|
1
|
Sodero G, Cipolla C, Camporesi A, Martino L, Costa S, Cannioto Z, Frassanito P, Tamburrini G, Veredice C, Maggio L, Munblit D, Raffaelli F, Piastra M, Zampino G, Valentini P, Buonsenso D. Endocrinologic Dysfunctions and Neuropsychiatric Sequelae in Pediatric Patients With a History of Central Nervous System Infection (ENDLESS): A Prospective Monocentric Study. Pediatr Infect Dis J 2025; 44:310-317. [PMID: 39787566 PMCID: PMC11888822 DOI: 10.1097/inf.0000000000004645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/23/2024] [Indexed: 01/12/2025]
Abstract
INTRODUCTION Central nervous system (CNS) infections represent some of the most critical pediatric health challenges, characterized by high mortality rates and a notable risk of long-term complications. Despite their significance, standardized guidelines for endocrinological follow-up of CNS infection survivors are lacking, leading to reliance on the expertise of individual centers and clinicians. MATERIALS AND METHODS Prospective monocentric observational study conducted at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, Italy. It included patients with a history of CNS infection, admitted to various pediatric departments of the hospital. The participants were selected based on a coded diagnosis of CNS infection and had completed their follow-up at the Pediatric Endocrinology Day Hospital after October 2019. RESULTS Eighty participants were included, comprising 53 patients with a prior CNS infection and 27 healthy controls, with a median age of 7.4 years (range 3.6-12.3 years). Endocrinologic alterations were detected in 13 patients, with 8 cases in those who had meningitis, 4 in encephalitis survivors, and 1 in a patient with a cerebral abscess. Patients with a history of CNS infections were shorter compared with healthy controls ( P = 0.027). Moreover, those who had meningitis exhibited an increased risk of developing epilepsy ( P = 0.01), neurosensory disabilities ( P = 0.034) and the need for ventriculoperitoneal shunt insertion ( P = 0.006). Patients with bacterial CNS infections were more prone to neurosensory and endocrine dysfunctions compared to those with viral or other infections. Significant differences were observed in hormone levels between previously infected patients and controls, specifically in TSH ( P < 0.001), ACTH ( P = <0.001), and cortisol ( P = 0.019). IGF-1 levels were considerably lower in the infection group, both in absolute terms and when adjusted for sex and age ( P < 0.001). The regression analysis suggested that the reduction in IGF-1 was more pronounced the earlier the CNS infection occurred, irrespective of infection type. CONCLUSIONS Our study found several endocrinologic imbalances in children who survived CNS infections.
Collapse
Affiliation(s)
- Giorgio Sodero
- From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Clelia Cipolla
- From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Anna Camporesi
- Pediatric Anesthesia and Intensive Care, V. Buzzi Children’s Hospital, Milano, Italy
| | - Laura Martino
- From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Simonetta Costa
- Division of Neonatology, Department of Pediatrics, University Hospital A Gemelli, Catholic University of the Sacred Heart, Rome, Italy
| | - Zemira Cannioto
- Neonatology Unit, “San Camillo-Forlanini” Hospital, Rome, Italy
| | - Paolo Frassanito
- Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Gianpiero Tamburrini
- Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Chiara Veredice
- From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Luca Maggio
- Neonatology Unit, “San Camillo-Forlanini” Hospital, Rome, Italy
| | - Daniel Munblit
- Division of Care in Long Term Conditions, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King’s College London, London, UK
- Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Research and Clinical Center for Neuropsychiatry, Moscow, Russia
| | - Francesca Raffaelli
- UOC Malattie Infettive, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Marco Piastra
- Pediatric ICU and Trauma Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy
- Institute of Anesthesia and Intensive Care, Catholic University of the Sacred Heart, Rome, Italy
| | - Giuseppe Zampino
- From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- UOC Malattie Infettive, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Piero Valentini
- From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- UOC Malattie Infettive, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Danilo Buonsenso
- From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Centro di Salute Globale, Università Cattolica del Sacro Cuore, Roma, Italia
- Area Pediatrica, Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Roma, Italia
| |
Collapse
|
|
2
|
Malavolta E, Cammisa I, Rotunno G, Pane LC, Arzilli F, Sodero G, Rigante D, Cipolla C. The Impact of Acquired Hypothyroidism on the Growth and Metabolic Profiles of Pediatric Patients: A Retrospective Monocentric Study. CHILDREN (BASEL, SWITZERLAND) 2025; 12:272. [PMID: 40150555 PMCID: PMC11941351 DOI: 10.3390/children12030272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/06/2025] [Accepted: 02/21/2025] [Indexed: 03/29/2025]
Abstract
Background: Hypothyroidism is the most common thyroid dysfunction in childhood, resulting from the decreased biological activity of thyroid hormones in tissues. Pediatric patients with hypothyroidism, when left untreated or when thyroid hormone levels fail to normalize despite treatment, may exhibit various complications such as growth retardation, obesity, and hypercholesterolemia. Aim: We conducted a monocentric retrospective study to evaluate potential differences in obesity rates and auxological parameters between healthy patients and children with hypothyroidism undergoing levothyroxine replacement therapy. Additionally, we examined possible differences in lipid and glucose metabolism between the two groups. Materials and Methods: We collected and analyzed data from the electronic medical records of 108 patients who were regularly followed up for thyroid dysfunction at the Pediatric Endocrinology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS from January 2016 to June 2024. We also included 104 healthy controls who underwent thyroid function testing during the same period, followed up in the same department for regular auxological check-ups. Results: Our findings revealed that patients with acquired hypothyroidism had a lower height z-score compared to healthy controls (t(210) = -2.6; p = 0.01). Additionally, they exhibited higher blood glucose and triglyceride levels, although these values remained within the normal range. Conclusions: We highlight the critical importance of the early diagnosis of hypothyroidism to initiate levothyroxine replacement therapy promptly and mitigate the long-term effects of hypothyroidism on children's growth.
Collapse
Affiliation(s)
- Elena Malavolta
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
| | - Ignazio Cammisa
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
| | - Giulia Rotunno
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
| | - Lucia Celeste Pane
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
| | - Federica Arzilli
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
| | - Giorgio Sodero
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
- Pediatric Department, Perrino Hospital, 72100 Brindisi, Italy
- Pediatric Endocrinology Unit, Perrino Hospital, 72100, Brindisi, Italy
| | - Donato Rigante
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
- Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore di Roma, 00168 Rome, Italy
| | - Clelia Cipolla
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (I.C.); (G.R.); (L.C.P.); (D.R.)
| |
Collapse
|
|
3
|
Korkmaz HA. Clinical Insight into Congenital Hypothyroidism Among Children. CHILDREN (BASEL, SWITZERLAND) 2025; 12:55. [PMID: 39857886 PMCID: PMC11763606 DOI: 10.3390/children12010055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/23/2024] [Accepted: 12/31/2024] [Indexed: 01/27/2025]
Abstract
Molecular, genetic, and technological advances have led to increased knowledge regarding neonatal thyroid hormone metabolism disorders. Maternal and fetal hypothyroidism, which can cause psychomotor dysfunction syndromes or low IQ levels, can lead to brain damage, reduced fetal growth and incidental fetal death. The treatment of congenital hypothyroidism detected by screening programs performed during the neonatal period provides normalization of growth, IQ levels, and the physical, mental, and motor development of infants. Therefore, the early diagnosis and treatment of congenital hypothyroidism will prevent the development of complications. In this article, the classification and management of neonatal thyroid diseases are reviewed in light of the current scientific literature.
Collapse
Affiliation(s)
- Hüseyin Anıl Korkmaz
- Department of Pediatrics, Division of Pediatric Endocrinology, Izmir Faculty of Medicine, University of Health Sciences, 35210 Izmir, Turkey; ; Tel: +90-(0232)-411-6000
- Department of Pediatrics, Division of Pediatric Endocrinology, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, 35210 Izmir, Turkey
| |
Collapse
|
|
4
|
Metwalley KA, Farghaly HS. Refractory hypothyroidism in children: an overview. J Pediatr Endocrinol Metab 2024; 37:841-849. [PMID: 39242350 DOI: 10.1515/jpem-2024-0306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 08/24/2024] [Indexed: 09/09/2024]
Abstract
Refractory hypothyroidism (RF) defined as raised serum levels of thyroid stimulating hormone (TSH) above upper limit of the reference range with or without the persistence of hypothyroid symptoms following a 6-week interval after the dosage was last increased to upper limits of dose per age. The most common cause of RH is inadequate compliance. In addition, diet, concomitant medication interactions, and gastrointestinal diseases can all result in l-thyroxine (LT4) malabsorption, which can cause RH. Moreover, weight gain, switching brands of LT4, poor storage of LT4, chronic liver disorders, cystic fibrosis, nephrotic syndrome, consumptive hypothyroidism, Addison's disease are significant contributors to RF in children. RH in children is frequently asymptomatic, when symptoms do occur, they are typically minor and resemble those of hypothyroidism. It is essential to identify RH early and treat its underlying cause in order to avoid overusing LT4, which can lead to cardiac and bone problems. Endocrinologists should handle children who they suspect of having RH methodically after making sure there is enough compliance. Searching for undiagnosed illnesses and/or other factors that can affect LT4 absorption could be part of this. We present this review after an extensive literature search and long-standing clinical experience. This review's objective is to shed light on the causes, clinical manifestations, investigations, and treatment of RH in children.
Collapse
Affiliation(s)
- Kotb Abbass Metwalley
- Pediatric Endocrinology Unit, Department of Pediatrics, Faculty of Medicine, 68796 Assiut University , Assiut, Egypt
| | - Hekma Saad Farghaly
- Pediatric Endocrinology Unit, Department of Pediatrics, Faculty of Medicine, 68796 Assiut University , Assiut, Egypt
| |
Collapse
|
|
5
|
Chen A, Luo Z, Zhang J, Cao X. Emerging research themes in maternal hypothyroidism: a bibliometric exploration. Front Immunol 2024; 15:1370707. [PMID: 38596686 PMCID: PMC11002152 DOI: 10.3389/fimmu.2024.1370707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 03/12/2024] [Indexed: 04/11/2024] Open
Abstract
Background Hypothyroidism, a prevalent endocrine disorder, carries significant implications for maternal and infant health, especially in the context of maternal hypothyroidism. Despite a gradual surge in recent research, achieving a comprehensive understanding of the current state, focal points, and developmental trends in this field remains challenging. Clarifying these aspects and advancing research could notably enhance maternal-infant health outcomes. Therefore, this study employs bibliometric methods to systematically scrutinize maternal hypothyroidism research, serving as a reference for further investigations. Objective Through bibliometric analysis, this study seeks to unveil key research focus areas, developmental trends, and primary contributors in Maternal Hypothyroidism. The findings offer insights and recommendations to inform future research endeavors in this domain. Methods Literature metrics analysis was performed on data retrieved and extracted from the Web of Science Core Collection database. The analysis examined the evolution and thematic trends of literature related to Maternal Hypothyroidism. Data were collected on October 28, 2023, and bibliometric analysis was performed using VOSviewer, CiteSpace, and the Bibliometrix software package, considering specific characteristics such as publication year, country/region, institution, authorship, journals, references, and keywords. Results Retrieved from 1,078 journals, 4,184 articles were authored by 18,037 contributors in 4,580 institutions across 113 countries/regions on six continents. Maternal Hypothyroidism research publications surged from 44 to 310 annually, a 604.54% growth from 1991 to 2022. The USA (940 articles, 45,233 citations), China Medical University (82 articles, 2,176 citations), and Teng, Weiping (52 articles, 1,347 citations) emerged as the most productive country, institution, and author, respectively. "Thyroid" topped with 233 publications, followed by "Journal of Clinical Endocrinology & Metabolism" (202) with the most citations (18,513). "Pregnancy" was the most cited keyword, with recent high-frequency keywords such as "outcome," "gestational diabetes," "iodine intake," "preterm birth," "guideline," and "diagnosis" signaling emerging themes in Maternal Hypothyroidism. Conclusions This study unveils developmental trends, global collaboration patterns, foundational knowledge, and emerging frontiers in Maternal Hypothyroidism. Over 30 years, research has predominantly focused on aspects like diagnosis, treatment guidelines, thyroid function during pregnancy, and postpartum outcomes, with a central emphasis on the correlation between maternal and fetal health.
Collapse
Affiliation(s)
- Ailing Chen
- Research Institute for Reproductive Health and Genetic Diseases, Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, China
| | - Zouqing Luo
- Department of Obstetrics, Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, China
| | - Jinqiu Zhang
- Department of Pathology, Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, China
| | - Xiaohui Cao
- Department of Obstetrics, Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, China
| |
Collapse
|
|
6
|
Alfaro JM, Manrique R, Santamaría A, Álvarez E, Manes C, Jiménez M. Effects of endocrine disorders on maxillary and mandibular growth in Colombian children and adolescents: a cross-sectional study. Eur Arch Paediatr Dent 2024; 25:17-25. [PMID: 37999852 PMCID: PMC10942899 DOI: 10.1007/s40368-023-00850-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 09/15/2023] [Indexed: 11/25/2023]
Abstract
OBJECTIVE To establish the influence of overweight/obesity, medicated hypothyroidism, and medicated non-syndromic hypogrowth on maxillary and mandibular growth. MATERIALS AND METHODS The relation between 10 craniofacial anthropometric measurements and hypothyroidism (n = 216), overweight/obesity (n = 108), and non-syndromic hypogrowth (n = 250) were evaluated in patients aged 1-19 years and a control group of healthy patients (n = 587). A subgroup analysis was performed at the peak growth in all groups. RESULTS Patients with overweight/obesity and hypothyroidism showed increased craniofacial growth, while hypogrowth patients showed differences in zygomatic width and nasal base growth. Females with hypothyroidism and non-syndromic hypogrowth showed decreased head circumference at peak growth. Several anthropometric measurements were increased in patients with overweight/obesity, including head circumference. When all age groups were analyzed, overweight/obese and hypothyroidism patients showed increased zygomatic width while decreased hypogrowth. Overall, most craniofacial anthropometric measurements in overweight/obese patients were increased. Finally, the peak growth in males with hypothyroidism and subjects with non-syndromic hypogrowth was delayed compared to the control group (p < 0.05). CONCLUSIONS Children and adolescents with overweight/obesity and endocrine disorders showed alterations in craniofacial growth. Clinicians must be aware that the growth peak in these patients may be delayed when planning maxillary and mandibular orthopedic treatment.
Collapse
Affiliation(s)
- J M Alfaro
- Pediatric Endocrinologist, Pediatric Research Group, Medical School, CES Clinic, Medellín, Colombia
| | - R Manrique
- Epidemiology and Biostatistics Research Group, CES University, Medellín, Colombia
| | - A Santamaría
- LPH Research Group, Dental School, CES University, Medellín, Colombia
| | - E Álvarez
- Head and Neck Bioengineering Research Group, Dental School, CES University, Medellín, Colombia
| | - C Manes
- Master's Degree in Dental Sciences, CES University, Medellín, Colombia
| | - M Jiménez
- Master's Degree in Dental Sciences, CES University, Medellín, Colombia.
| |
Collapse
|
|
7
|
Cimino-Fiallos N, Hurt B. Hypothyroidism-Etiologies, Evaluation, and Emergency Care. Emerg Med Clin North Am 2023; 41:743-758. [PMID: 37758421 DOI: 10.1016/j.emc.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
Thyroid hormone affects every human organ system and is a vital component of metabolism. Common and easily treatable, hypothyroidism does not usually require emergency management. However, myxedema coma is the decompensated form of hypothyroidism and can be life threatening if not treated expediently.
Collapse
Affiliation(s)
- Nicole Cimino-Fiallos
- Meritus Health Emergency Department, 11116 Medical Campus Drive, Hagerstown, MD 21742, USA
| | - Brenten Hurt
- Department of Emergency Medicine, University of Maryland School of Medicine, 110 South Paca Street, Sixth Floor, Suite 200, Baltimore, MD 21201, USA.
| |
Collapse
|
|
8
|
Amayiri N, Spitaels A, Zaghloul M, Figaji A, Cavalheiro S, Muller HL, Elhassan M, Parkes J, Mushtaq N, Beltagy ME, Yousef YA, Esiashvili N, Sullivan M, da Costa MD, Dastoli P, Mubarak F, Bartels U, Chamdine O, Davidson A, Musharbash A, Alcasabas P, Bouffet E, Bailey S. SIOP PODC-adapted treatment guidelines for craniopharyngioma in low- and middle-income settings. Pediatr Blood Cancer 2023; 70:e28493. [PMID: 32790146 DOI: 10.1002/pbc.28493] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 05/21/2020] [Accepted: 05/26/2020] [Indexed: 12/16/2022]
Abstract
Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.
Collapse
Affiliation(s)
- Nisreen Amayiri
- Pediatric Oncology Department, King Hussein Cancer Center, Amman, Jordan
| | - Ariane Spitaels
- Division of Endocrinology, Department of Pediatric Medicine, Faculty of Health Sciences, UCT, Cape Town, South Africa
| | - Mohamed Zaghloul
- Radiation Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital, Cairo, Egypt
| | - Anthony Figaji
- Department of Neurosurgery, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa
| | - Sergio Cavalheiro
- Division of Neurosurgery, Pediatric Oncology Institute/GRAACC, Universidade Federal de São Paulo, Sao Paulo, Brazil
- Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Hermann L Muller
- Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, Oldenburg, Germany
| | - Moawia Elhassan
- Clinical Oncology department, National Cancer Institute, University of Gezira, Wad Madani, Sudan
| | - Jeannette Parkes
- Department of Radiation Oncology, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
| | - Naureen Mushtaq
- Department of Pediatric Hematology and Oncology, Aga Khan University Hospital, Karachi, Pakistan
| | - Mohamed El Beltagy
- Department of Neurosurgery, Kasr Al-Ainy School of Medicine, Children's Cancer Hospital Egypt, Cairo University, Cairo, Egypt
| | - Yacoub A Yousef
- Ophthalmology division/ Surgery department, King Hussein Cancer Center, Amman, Jordan
| | - Natia Esiashvili
- Radiation Oncology Department, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Michael Sullivan
- Department of Pediatric Hematology and Oncology, Royal Hospital for Sick Children, Melbourne, Victoria, Australia
| | - Marcos Devanir da Costa
- Division of Neurosurgery, Pediatric Oncology Institute/GRAACC, Universidade Federal de São Paulo, Sao Paulo, Brazil
- Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Patricia Dastoli
- Division of Neurosurgery, Pediatric Oncology Institute/GRAACC, Universidade Federal de São Paulo, Sao Paulo, Brazil
| | - Fatima Mubarak
- Radiology Department, Aga Khan University, Karachi, Pakistan
| | - Ute Bartels
- Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Canada
| | - Omar Chamdine
- Department of Pediatric Hematology Oncology and stem cell transplantation, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Alan Davidson
- Hematology-Oncology Service, Red Cross Children's Hospital, Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa
| | - Awni Musharbash
- Neurosurgery division/Surgery department, King Hussein Cancer Center, Amman, Jordan
| | - Patricia Alcasabas
- University of the Philippines-Philippine General Hospital, Manila, the Philippines
| | - Eric Bouffet
- Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Canada
| | - Simon Bailey
- Department of Pediatric Oncology, Great North Children's Hospital, Newcastle upon Tyne, UK
| |
Collapse
|
|
9
|
Năstase L, Cristea O, Diaconu A, Stoicescu SM, Mohora R, Pascu BM, Tala ST, Roșca I. Two Cases of Congenital Hypothyroidism Revealing Thyroid Agenesis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1887. [PMID: 37893606 PMCID: PMC10608129 DOI: 10.3390/medicina59101887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/16/2023] [Accepted: 10/19/2023] [Indexed: 10/29/2023]
Abstract
Congenital hypothyroidism (CH) may have major detrimental effects on growth and neurological development, but early intervention leads to excellent outcomes. CH is classified as transient or permanent, primary or secondary, with primary CH being the most common neonatal endocrine disorder. Most patients with CH do not present any typical signs and symptoms of hypothyroidism shortly after birth, partly due to transplacental maternal thyroid hormone transfer and residual neonatal thyroid function. This paper reports on two CH cases. During the initial Neonatal Intensive Care Unit (NICU) admission phase, CH was not suspected due to nonspecific signs. The distinct characteristics of our cases are as follows: both infants were admitted to the NICU for respiratory distress syndrome, requiring invasive mechanical ventilation, and both were born to diabetic mothers. Following extubation, they both showed similar neurological issues, including reduced muscle tone and feeding difficulties. Initially, those symptoms were attributed to delayed clearance of analgesic and sedative medication. However, symptoms progressively worsened over time. Subsequent tests revealed both meeting CH diagnostic criteria: an unusual ultrasound indicating thyroid agenesis and abnormal hormone levels. Guided by the pediatric endocrinology team, prompt hormonal treatment was started with improvements in neurocognitive function and feeding. Usually, CH screening involves blood samples from healthy newborns at 2-3 days of life. Abnormal results require confirmation, prompting treatment within two weeks. Certain NICU-admitted infants face higher diagnosis delays, as seen in those two cases where CH screening was postponed. Thus, for all neonates with persistent pathologies unresponsive to standard etiological treatment, conducting a comprehensive anamnestic evaluation of the medical history, along with maternal preconceptional and prenatal nutrition, is recommended.
Collapse
Affiliation(s)
- Leonard Năstase
- Neonatology Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 011061 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Octaviana Cristea
- Neonatology Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 011061 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Alexandra Diaconu
- Neonatology Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 011061 Bucharest, Romania
| | - Silvia-Maria Stoicescu
- Neonatology Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 011061 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Ramona Mohora
- Neonatology Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 011061 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Bogdan Mihai Pascu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Endocrinology Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 020395 Bucharest, Romania
| | - Simona Tania Tala
- Endocrinology Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 020395 Bucharest, Romania
| | - Ioana Roșca
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Neonatology Department, Clinical Hospital of Obstetrics and Gynecology “Prof. Dr. P. Sârbu”, 060251 Bucharest, Romania
| |
Collapse
|
|
10
|
Phillips JG, Fabian SB, Adkins EW, Kiell EP. Full Recovery of Sensorineural Hearing Loss in a Patient with Congenital Hypothyroidism. J Am Acad Audiol 2023; 34:225-229. [PMID: 37657487 DOI: 10.1055/a-2165-0789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/03/2023]
Abstract
BACKGROUND Congenital hypothyroidism (CH) is one of the most preventable causes of intellectual disability in the world. Screening programs have led to earlier detection of CH, and children with adequate thyroid supplementation can have minor long-term differences in overall neuropsychological testing compared to baseline. PURPOSE Despite early identification, up to one-fourth of children born with CH suffer from hearing loss even with early and adequate thyroid hormone supplementation. We present a unique case of an individual born with congenital hypothyroidism found to have sensorineural hearing loss. RESEARCH DESIGN Case report. STUDY SAMPLE Single subject. INTERVENTION Diagnosis of congenital hypothyroidism at 1 week of life and initiation of treatment with levothyroxine. DATA COLLECTION AND ANALYSIS Degree of hearing loss was measured with age-appropriate audiological testing at ages 4 weeks, 7 weeks, 3 months, 7 months, 9 months, 11 months, and 12 months. RESULTS The patient was treated early with thyroid hormone supplementation and demonstrated full recovery of hearing by age 12 months. CONCLUSIONS Despite the body of literature documenting hearing loss as an ongoing complication of CH, this patient demonstrates a unique case of full hearing recovery with early treatment.
Collapse
Affiliation(s)
- Jacline G Phillips
- Department of Otolaryngology-Head and Neck Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
- Department of Otolaryngology-Head and Neck Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina
| | - Samantha B Fabian
- Department of Otolaryngology-Head and Neck Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
- Department of Otolaryngology-Head and Neck Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina
| | - Erin W Adkins
- Department of Otolaryngology-Head and Neck Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina
| | - Eleanor P Kiell
- Department of Otolaryngology-Head and Neck Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
- Department of Otolaryngology-Head and Neck Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina
| |
Collapse
|
|
11
|
Calcaterra V, Magenes VC, Siccardo F, Hruby C, Basso M, Conte V, Maggioni G, Fabiano V, Russo S, Veggiotti P, Zuccotti G. Thyroid dysfunction in children and adolescents affected by undernourished and overnourished eating disorders. Front Nutr 2023; 10:1205331. [PMID: 37841407 PMCID: PMC10576529 DOI: 10.3389/fnut.2023.1205331] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 09/06/2023] [Indexed: 10/17/2023] Open
Abstract
Eating disorders (ED) are one of the most prevalent chronic disorders in adolescents and young adults, with a significantly increasing prevalence in younger children, particularly in girls. Even if obesity in essence is not framed as an eating disorder and has always been considered a separate pathology, ED and obesity could be considered part of a continuum. It has become evident that one condition can lead to another, such as binge eating disorder (BED) and bulimia nervosa, and that they share the same repercussions in terms of psychosocial, metabolic, and nutritional health. This narrative review aims to investigate the hypothalamic-pituitary-thyroid axis in undernourished and overnourished patients with ED, including obesity, in order to highlight the relationship between weight control and thyroid function and its effects and to consider therapeutic and preventive strategies in children and adolescents. Literature data report that thyroid alterations occur in patients with ED, both underweight and overweight, and represent a continuum of changes depending on the severity and time course of the disease involving the endocrine system. Considering the relevant role thyroid hormones (TH) play not only in energy expenditure (EE) but also in metabolic control and cardiovascular risks related to dysmetabolism and mood regulation, continuous monitoring of thyroid homeostasis in patients with ED is mandatory to prevent severe complications and to start early treatment when necessary.
Collapse
Affiliation(s)
- Valeria Calcaterra
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Department of Pediatric, Buzzi Children's Hospital, Milan, Italy
| | | | | | - Chiara Hruby
- Department of Pediatric, Buzzi Children's Hospital, Milan, Italy
| | - Martina Basso
- Child and Adolescent Neuropsychiatry Unit (UONPIA), ASST-Fatebenefratelli-Sacco, Milan, Italy
| | - Veronica Conte
- Child and Adolescent Neuropsychiatry Unit (UONPIA), ASST-Fatebenefratelli-Sacco, Milan, Italy
| | - Giulia Maggioni
- Child and Adolescent Neuropsychiatry Unit (UONPIA), ASST-Fatebenefratelli-Sacco, Milan, Italy
| | - Valentina Fabiano
- Department of Pediatric, Buzzi Children's Hospital, Milan, Italy
- Department of Biomedical and Clinical Science, University of Milano, Milan, Italy
| | - Susanna Russo
- Child and Adolescent Neuropsychiatry Unit (UONPIA), ASST-Fatebenefratelli-Sacco, Milan, Italy
| | - Pierangelo Veggiotti
- Department of Biomedical and Clinical Science, University of Milano, Milan, Italy
- Pediatric Neurology Unit, Buzzi Children's Hospital, Milan, Italy
| | - Gianvincenzo Zuccotti
- Department of Pediatric, Buzzi Children's Hospital, Milan, Italy
- Department of Biomedical and Clinical Science, University of Milano, Milan, Italy
| |
Collapse
|
|
12
|
Zhang S, Zhou L, Zhang L, Wang Y, Wang H. Molecular genetic screening of full-term small for gestational age. BMC Pediatr 2023; 23:217. [PMID: 37147621 PMCID: PMC10161501 DOI: 10.1186/s12887-023-04030-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 04/24/2023] [Indexed: 05/07/2023] Open
Abstract
OBJECTIVE To examine the clinical application of genomic screening in newborns small for gestational age (SGA), hoping to provide an efficient technique for early discovery of neonatal diseases, which is necessary to elevate survival rates and the quality of life in infants. METHODS Totally 93 full-term SGA newborns were assessed. Dried blood spot (DBS) samples were obtained at 72 h after birth, and tandem mass spectrometry (TMS) and Angel Care genomic screening (GS, using Targeted next generation sequencing) were carried out. RESULTS All 93 subjects were examined by Angel Care GS and TMS. No children showing inborn errors of metabolism (IEM) were detected by TMS, while 2 pediatric cases (2.15%, 2/93) were confirmed as thyroid dyshormonogenesis 6 (TDH6) by Angel Care GS. Additionally, 45 pediatric cases (48.4%) had one or more variants conferring a carrier status for recessive childhood-onset disorders, with 31 genes and 42 variants associated with 26 diseases. The top three gene-related diseases with carrier status were autosomal recessive deafness (DFNB), abnormal thyroid hormone and Krabbe disease. CONCLUSIONS SGA is tightly associated with genetic variation. Molecular Genetic Screening allows early detection of congenital hypothyroidism and may be a potent genomic sequencing technique for screening newborns.
Collapse
Affiliation(s)
- Shuman Zhang
- Department of Neonatology, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Lingna Zhou
- Department of Medical Genetics, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Lin Zhang
- Department of Neonatology, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Yu Wang
- Department of Neonatology, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, China.
| | - Huaiyan Wang
- Department of Neonatology, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, China.
| |
Collapse
|
|
13
|
Al-Qahtani MH, ElYahia SA, AlQahtani AS, AlQahtani AJ, Alamer AA, AlQahtani SM, Yousef AA, Albuali WH, Awary BH, Aldajani AA, Al Ghamdi MA. Thyroid Disorders Spectrum in Pediatric Endocrine Clinic; Seven-Year Experience of a Teaching Hospital in Saudi Arabia. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10020390. [PMID: 36832519 PMCID: PMC9955412 DOI: 10.3390/children10020390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023]
Abstract
Thyroid disorders constitute one of the major endocrine disorders in pediatric service. It includes a range of congenital versus acquired anatomic and/or functional thyroid diseases in growing children that has a spectrum of severity from severe intellectual disability effect to subclinical mild pathologies. This study was designed to analyze the demographic characteristics, clinical pattern, and severity of thyroid disorders in the pediatric endocrine clinic patients at the teaching hospital of the university over a 7-year duration. A total number of 148 patients with thyroid disorders were seen in pediatric Endocrine clinic during the time between January 2015 and December 2021. Female patients constitute 64% of them. Acquired Hypothyroidism was the commonest disorder; 34% of the cases followed by the congenital hypothyroidism (CH), then Hashimoto's thyroiditis, and 5.8% for others. While a very small percentage was acquired hyperthyroidism. The majority of referrals were from dermatology and other service for the screening of thyroid disease as association with other autoimmune diseases with percentage of 28.3%. Next was neck swelling manifestation in 22.6%. Thyroid disorders in children, both congenital and acquired, constitute an important medical issue for pediatricians to be aware of its variable presentations, and its potential serious health consequences on the affected children if not diagnosed and treated earlier. Acquired hypothyroidism constitutes more percentage of the thyroid disorders followed in the pediatric endocrinology outpatient clinics. Congenital hypothyroidism is the second most common thyroid disorder in the outpatient unit, having the most potential complications. These results support the international studies with the female predominance in most of thyroid disorders.
Collapse
Affiliation(s)
- Mohammad H. Al-Qahtani
- Department of Pediatrics, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
- Correspondence:
| | - Sufian A. ElYahia
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | | | | | - Abdulaziz A. Alamer
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Sultan M. AlQahtani
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Abdullah A. Yousef
- Department of Pediatrics, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Waleed H. Albuali
- Department of Pediatrics, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Bassam H. Awary
- Department of Pediatrics, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Ala’a A. Aldajani
- Department of Pediatrics, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Mohammed A. Al Ghamdi
- Department of Pediatrics, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| |
Collapse
|
|
14
|
Liu R, Tian JL, Huang XL, Song YZ. Genetic Factors Causing Thyroid Dyshormonogenesis as the Major Etiologies for Primary Congenital Hypothyroidism: Clinical and Genetic Characterization of 33 Patients. J Clin Med 2022; 11:7313. [PMID: 36555929 PMCID: PMC9786654 DOI: 10.3390/jcm11247313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/01/2022] [Accepted: 12/07/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND AIMS Although the significance of primary congenital hypothyroidism (CH) is supported by an increasing amount of evidence, the clinical and genetic characteristics of this condition are still poorly understood. This study aimed to explore the underlying genetic etiologies in a cohort of primary CH patients. SUBJECTS AND METHODS The clinical data of 33 patients with primary CH were collected and analyzed via a cross-sectional study. Genetic analysis was performed by high-throughput sequencing and Sanger verification, and the pathogenicity of the novel missense variants was predicted using a variety of comprehensive bioinformatic tools. RESULTS Among the 33 patients, 22 (22/33, 66.7%) harbored pathogenic variants in the causative genes of thyroid dysgenesis or dyshormonogenesis, with DUOX2 (15/33, 45.5%) topping the list, followed by TG, TPO, DUOXA2 and PAX8. Four novel genetic variants were detected, including a pathogenic frameshift and three likely pathogenic missense variants. Positive neonatal screening for TSH, neonatal jaundice and abnormal thyroid morphology were the main positive findings among all cases. Although 31 of the total 33 CH patients exhibited normal anthropometric and social performance, the other 2 had poor prognosis in this study. CONCLUSIONS This study reported 33 new CH patients bearing four novel genetic variants, which enriched the variant spectrum of CH genes. In this cohort, genetic factors causing thyroid dyshormonogenesis were the main etiologies of CH development. Most patients exhibited a favorable prognosis; however, systematic management remains a challenge in achieving improved clinical outcomes for CH patients.
Collapse
Affiliation(s)
- Rui Liu
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Jing-Li Tian
- Department of Pediatrics, Huizhou No. 2 Women’s and Children’s Healthcare Hospital, Huizhou 516000, China
| | - Xiao-Ling Huang
- Neonatal Screening Center, Dongguan Maternal and Child Healthcare Hospital, Dongguan 523125, China
| | - Yuan-Zong Song
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| |
Collapse
|
|
15
|
Siano MA, Ametrano O, Barbato F, Sammarco E, Ranucci G, Pietrobattista A, Rossomando A, Mandato C. Consumptive Hypothyroidism due to Hepatic Hemangiomas: A Case Series and Review of the Literature. JPGN REPORTS 2022; 3:e270. [PMID: 37168485 PMCID: PMC10158424 DOI: 10.1097/pg9.0000000000000270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 10/06/2022] [Indexed: 05/13/2023]
Abstract
Consumptive hypothyroidism (CH) is a rare and potentially overlooked complication of hepatic hemangiomas (HH) overexpressing the enzyme deiodinase, which converts thyroxine (T4) to reverse triiodothyronine (rT3). Materials and methods Here, we report a case series of 3 patients and a systematic review of the literature. Results Hypothyroidism (mean serum TSH 52.03 mIU/L) was detected at a mean age of 4.6 months (range 3-6) in 3 infants with infantile hepatic hemangiomas, treated with thyroxine (mean dose 12 µg/kg/day). All received treatment with propranolol (1-3 mg/kg/day) from the mean age of 4 months. Hormonal treatment was stopped at a mean age of 20 months (range 12-30). Hypothyroidism reoccurred in a patient concurrently with the increase of liver lesions, requiring liver transplantation (LT) at age 39 months.Literature review retrieved 42 studies (48 patients): HH (n = 43) were isolated in 24 infants and associated with cutaneous hemangiomas in 19. Hemangiomas were only cutaneous in 5.In the first 43 patients, hypothyroidism was detected at a mean age of 1 month; 21 of 43 patients were prescribed propranolol alone (n = 8) or associated with other medicaments (n = 13); 2 of 43 patients underwent LT. Hormonal treatment consisted of T4 in 35 of 43 patients and T3 in 10.CH associated with only cutaneous and extrahepatic visceral hemangiomas (n = 5), detected at a mean age of 7 months (TSH mean levels at diagnosis of 150.3 mIU/L). Three of 5 patients received treatment with propranolol ± other medicaments. All 5 patients were treated with T4. Conclusions Periodical thyroid function assessment is necessary in patients with hepatic hemangiomas, particularly when lesions' size and number increase rapidly.
Collapse
Affiliation(s)
- Maria Anna Siano
- From the Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Università di Salerno, Baronissi (Salerno), Italy
| | - Orsola Ametrano
- Department of Pediatric Dermatology, Santobono-Pausilipon Children Hospital, Naples, Italy
| | - Filomena Barbato
- Department of Pediatric Dermatology, Santobono-Pausilipon Children Hospital, Naples, Italy
| | - Elena Sammarco
- Department of Pediatric Dermatology, Santobono-Pausilipon Children Hospital, Naples, Italy
| | - Giusy Ranucci
- Department of Pediatrics, Santobono-Pausilipon Children Hospital, Naples, Italy
| | | | - Alessia Rossomando
- From the Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Università di Salerno, Baronissi (Salerno), Italy
| | - Claudia Mandato
- From the Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Università di Salerno, Baronissi (Salerno), Italy
- Department of Pediatrics, Santobono-Pausilipon Children Hospital, Naples, Italy
| |
Collapse
|
|
16
|
Segev N, Arora S, Khoury J, Yayah Jones NH, Chuang J. Frequency and Severity of Hypothyroidism During TKI Therapy in the Pediatric and Young Adult Population. J Pediatr Hematol Oncol 2022; 44:e964-e967. [PMID: 35973039 DOI: 10.1097/mph.0000000000002527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 07/05/2022] [Indexed: 11/25/2022]
Abstract
Tyrosine kinase inhibitors that target vascular endothelial growth factor receptor [VEGFR-TKI] are a class of targeted therapies approved for treatment of several malignancies and are increasingly used in the pediatric population. Development of hypothyroidism during VEGFR-TKI therapy is well described in adults; however, there are no available data in children. Importantly, hypothyroidism during childhood can negatively impact growth and neurodevelopment. This retrospective study is the first to document frequency and severity of VEGFR-TKI induced hypothyroidism in pediatric and young adult patients. Patients included were ≤25 years of age and treated with at least one VEGFR-TKI between 2010 and 2018 at Cincinnati Children's Hospital Medical Center. After review of clinical and demographic data, 69 patients were identified. Of these, 19 (27.5%) developed thyroid dysfunction defined as Thyroid-stimulating hormone≥5 mIU/mL during therapy. Twelve of those patients had overt hypothyroidism with documentation of low free thyroxine and/or levothyroxine initiation. Mean exposure time to VEGFR-TKI before thyroid dysfunction was 2.8 (0.5-10.4) months. These results suggest moderate risk of developing thyroid dysfunction during VEGFR-TKI therapy in pediatric and young adult patients. Baseline thyroid hormone screening should be performed and repeated frequently during the first year of therapy in the pediatric population.
Collapse
Affiliation(s)
- Natalie Segev
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Shruthi Arora
- Division of Pediatric Endocrinology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
| | - Jane Khoury
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Nana-Hawa Yayah Jones
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Janet Chuang
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| |
Collapse
|
|
17
|
Abstract
Iodine is a micronutrient needed for the production of thyroid hormones, which regulate metabolism, growth, and development. Iodine deficiency or excess may alter the thyroid hormone synthesis. The potential effects on infant development depend on the degree, timing, and duration of exposure. The iodine requirement is particularly high during infancy because of elevated thyroid hormone turnover. Breastfed infants rely on iodine provided by human milk, but the iodine concentration in breast milk is determined by the maternal iodine intake. Diets in many countries cannot provide sufficient iodine, and deficiency is prevented by iodine fortification of salt. However, the coverage of iodized salt varies between countries. Epidemiological data suggest large differences in the iodine intake in lactating women, infants, and toddlers worldwide, ranging from deficient to excessive intake. In this review, we provide an overview of the current knowledge and recent advances in the understanding of iodine nutrition and its association with thyroid function in lactating women, infants, and toddlers. We discuss risk factors for iodine malnutrition and the impact of targeted intervention strategies on these vulnerable population groups. We highlight the importance of appropriate definitions of optimal iodine nutrition and the need for more data assessing the risk of mild iodine deficiency for thyroid disorders during the first 2 years in life.
Collapse
Affiliation(s)
- Maria Andersson
- Nutrition Research Unit, University Children’s Hospital Zurich, CH-8032 Zürich, Switzerland
| | - Christian P Braegger
- Nutrition Research Unit, University Children’s Hospital Zurich, CH-8032 Zürich, Switzerland
| |
Collapse
|
|
18
|
Emeksiz C, Yilmaz N, Tüzüner T, Baygin O. Dental age estimation with two different methods in paediatric patients with hypothyroidism. Arch Oral Biol 2022; 139:105450. [PMID: 35525016 DOI: 10.1016/j.archoralbio.2022.105450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 04/28/2022] [Accepted: 04/29/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVE This case-control study aimed to evaluate dental age estimation in children with hypothyroidism using two different methods in order to contribute to the literature about the most accurate method. DESIGN In the study, panoramic radiographs of 80 patients with hypothyroidism aged 5-13 years and 80 randomly selected age and sex-matched healthy patients were examined retrospectively. The Cameriere's and the Nolla's methods were used for the dental age estimation. Dental ages and their differences with chronological ages were compared according to group and sex. RESULTS No statistically significant difference in estimated dental age was found between the hypothyroidism and control groups using both methods (p > 0.05). Among all the males and females included in this study, the dental ages of the females calculated by Nolla's method were significantly lower than those of the males according to the chronological ages (p < 0.05). For females, in both the hypothyroidism (p < 0.001) and control (p = 0.001) groups, the dental age estimated by Cameriere's method was significantly closer to the chronological age compared to Nolla's method, although there was no statistically significant difference for males. CONCLUSION Although the dental age of children with hypothyroidism showed similar results to that of healthy children, it is concluded that Cameriere's method led to more accurate results than Nolla's method in females for both healthy patients and patients with hypothyroidism.
Collapse
Affiliation(s)
- Cansu Emeksiz
- Karadeniz Technical University, Faculty Of Dentistry, Department of Pediatric Dentistry, Turkey.
| | - Nagehan Yilmaz
- Karadeniz Technical University, Faculty Of Dentistry, Department of Pediatric Dentistry, Turkey.
| | - Tamer Tüzüner
- Karadeniz Technical University, Faculty Of Dentistry, Department of Pediatric Dentistry, Turkey.
| | - Ozgul Baygin
- Karadeniz Technical University, Faculty Of Dentistry, Department of Pediatric Dentistry, Turkey.
| |
Collapse
|
|
19
|
Uthayaseelan K, Kadari M, Subhan M, Saji Parel N, Krishna PV, Gupta A, Uthayaseelan K. Congenital Anomalies in Infant With Congenital Hypothyroidism: A Review of Pathogenesis, Diagnostic Options, and Management Protocols. Cureus 2022; 14:e24669. [PMID: 35663669 PMCID: PMC9162097 DOI: 10.7759/cureus.24669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/02/2022] [Indexed: 12/02/2022] Open
Abstract
Thyroid hormones (TH) regulate growth, nervous system myelination, metabolism, and physiologic functions in nearly every organ system. Congenital hypothyroidism (CH) is one of the most common endocrinopathies in children and has potentially devastating neurologic and developmental consequences. The etiology and clinical manifestations of hypothyroidism in children differ from adults. And hence, pediatric medical care requires a detailed understanding of thyroid function and dysfunction in children. The perinatal risk factors include female sex, preterm birth, low birth weight, postmature birth, additional birth abnormalities, and being delivered in multiple births. In countries where newborn screening is practiced, CH is detected after birth through screening tests. It aids in determining the underlying cause, though some patients may be able to start treatment without these tests. Early detection and treatment prevent irreversible and permanent nervous system damage. Thus, in addition to exploring the development of CH, this article has also covered the epidemiological data, clinical aspects, and management stemming from pediatric hypothyroidism.
Collapse
|
|
20
|
Chu SY, Wen CC, Weng CY. Gender Differences in Caring for Children with Genetic or Rare Diseases: A Mixed-Methods Study. CHILDREN (BASEL, SWITZERLAND) 2022; 9:627. [PMID: 35626804 PMCID: PMC9139271 DOI: 10.3390/children9050627] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/31/2022] [Accepted: 04/22/2022] [Indexed: 06/15/2023]
Abstract
As a factor in parenting stress, gender differences in caring for children with genetic or rare diseases warrant research attention; therefore, this study explored gender differences in parenting stress, health outcomes, and illness perceptions among caregivers of pediatric genetic or rare disease populations to improve the understanding of such gender differences. Applying a concurrent triangulation mixed-methods design, we conducted a questionnaire survey to assess study measures for 100 family caregivers (42 men and 58 women), which included a free-text response item to probe caregivers' subjective perceptions of the children's illness. The gender differences hypothesis was tested with statistics and the qualitative data about illness perception was analyzed by directed content analysis. Most female caregivers served as the primary caregivers and provided more caregiving, while they experienced significantly increased levels of parenting stress and depressive symptoms compared with male caregivers. Female caregivers perceived the conditions of their children's diseases to be highly symptomatic, with negative consequences and requiring disease control. By contrast, male caregivers had stronger perceptions regarding the negative effects of the disease on the children's quality of life. The gender discrepancy in viewpoints of illness perception sequence may contribute to female caregivers' higher levels of stress and depressive symptoms than males.
Collapse
Affiliation(s)
- Shao-Yin Chu
- Genetic Counseling Center, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung-Yang Road, Hualien 97074, Taiwan; (S.-Y.C.); (C.-Y.W.)
- Department of Pediatrics, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung-Yang Road, Hualien 97074, Taiwan
- Department of Medicine, College of Medicine, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97074, Taiwan
| | - Chin-Chen Wen
- Department of Human Development and Psychology, College of Humanities and Social Sciences, Tzu Chi University, No. 67, Jieren St., Hualien 97074, Taiwan
| | - Chun-Ying Weng
- Genetic Counseling Center, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung-Yang Road, Hualien 97074, Taiwan; (S.-Y.C.); (C.-Y.W.)
| |
Collapse
|
|
21
|
Abstract
Congenital hypothyroidism (CH) is a disorder of thyroid hormone deficiency which develops secondary to incomplete thyroid development or inadequate thyroid hormone production. State-mandated newborn screening throughout the United States has increased the detection rate of CH, allowing for early intervention. Although the overall mortality rate of CH is low, delayed or omitted treatment can lead to devastating neurocognitive outcomes. As such, CH is regarded as the leading cause of preventable intellectual disability in children. Early identification, facilitated by astute neonatal nursing and medical care, is contingent upon an active working knowledge of the disease process and awareness of the limitations of the newborn screen.
Collapse
|
|
22
|
Odenwald B, Fischer A, Röschinger W, Liebl B, Schmidt H, Nennstiel U. Long-Term Course of Hypothyroidism Detected through Neonatal TSH Screening in a Population-Based Cohort of Very Preterm Infants Born at Less than 32 Weeks of Gestation. Int J Neonatal Screen 2021; 7:ijns7040065. [PMID: 34698071 PMCID: PMC8544474 DOI: 10.3390/ijns7040065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/01/2021] [Accepted: 10/06/2021] [Indexed: 12/27/2022] Open
Abstract
After several decades of successful newborn screening (NBS) for congenital hypothyroidism, the optimal hypothyroidism NBS algorithm for very preterm infants is still controversial. Due to concerns about an elevated risk of a false-negative initial thyroid-stimulation hormone (TSH) screening, repeat NBS has been implemented for this group. While transient hypothyroidism is known to be more frequent among very preterm infants, the prevalence of permanent hypothyroidism is generally assumed to be the same as in more mature newborns. This study analyses screening and long-term follow-up data from the population-based cohort of 51 infants born from 1999-2017 at less than 32 weeks of gestation and diagnosed with hypothyroidism after NBS in the German Federal State of Bavaria (total number of infants screened 2,107,864). Severe permanent hypothyroidism was always detected at initial TSH screening unless there was a known confounding factor. Cases detected by repeat screening after a negative initial screen most frequently proved to be transient, less frequently mild permanent, or a definitive diagnosis was not possible because of inadequate re-evaluation of the thyroid axis. The prevalence of both permanent and transient hypothyroidism was elevated compared to a cohort of children from the same region born at a higher gestational age. The results seem to support the need for the repeated NBS of very preterm infants. However, as the recommendation to treat mild hypothyroidism is not based on high quality evidence, important issues for future research include treatment outcome studies or even a general review of whether this diagnosis meets the screening criteria. Meanwhile, involving a paediatric endocrinologist in treatment decisions is crucial for optimising the benefit of hypothyroidism screening for this particularly vulnerable group.
Collapse
Affiliation(s)
- Birgit Odenwald
- Newborn Screening Centre/State Institute of Health, Bavarian Health and Food Safety Authority, 85764 Oberschleissheim, Germany;
- Correspondence: (B.O.); (U.N.)
| | - Aline Fischer
- Paediatric and Youth Medicine Clinic, Klinikum Dritter Orden, 80638 Munich, Germany;
| | - Wulf Röschinger
- Newborn Screening Unit, Becker and Colleagues Laboratory, 81737 Munich, Germany;
| | - Bernhard Liebl
- Newborn Screening Centre/State Institute of Health, Bavarian Health and Food Safety Authority, 85764 Oberschleissheim, Germany;
| | - Heinrich Schmidt
- Paediatric Endocrinology, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University, 80337 Munich, Germany;
| | - Uta Nennstiel
- Newborn Screening Centre/State Institute of Health, Bavarian Health and Food Safety Authority, 85764 Oberschleissheim, Germany;
- Correspondence: (B.O.); (U.N.)
| |
Collapse
|
|
23
|
Błażewicz A, Wiśniewska P, Skórzyńska-Dziduszko K. Selected Essential and Toxic Chemical Elements in Hypothyroidism-A Literature Review (2001-2021). Int J Mol Sci 2021; 22:10147. [PMID: 34576309 PMCID: PMC8472829 DOI: 10.3390/ijms221810147] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Thyroid hormones are known for controlling metabolism of lipids, carbohydrates, proteins, minerals, and electrolytes and for regulating body temperature. Normal thyroid status depends on the chemical/elemental composition of body fluids and tissues, which changes depending on physiological state, lifestyle and environment. A deficiency or excess of certain essential chemical elements (selenium, zinc, copper, iron or fluorine) or exposure to toxic (cadmium or lead) or potentially toxic elements (manganese or chromium) interacts with thyroid hormone synthesis and may disturb thyroid homeostasis. In our review, accessible databases (Scopus, PubMed and Web of Science) were searched for articles from 2001-2021 on the influence of selected chemical elements on the development of hypothyroidism. Our review adopted some of the strengths of a systematic review. After non-eligible reports were rejected, 29 remaining articles were reviewed. The review found that disruption of the physiological levels of elements in the body adversely affects the functioning of cells and tissues, which can lead to the development of disease.
Collapse
Affiliation(s)
- Anna Błażewicz
- Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Faculty of Biomedicine, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland;
| | - Patrycja Wiśniewska
- Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Faculty of Biomedicine, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland;
| | - Katarzyna Skórzyńska-Dziduszko
- Department of Human Physiology, Faculty of Medicine, Medical University of Lublin, 11 Radziwiłłowska Street, 20-080 Lublin, Poland;
| |
Collapse
|
|
24
|
Pituitary Macroadenoma and Severe Hypothyroidism: The Link between Brain Imaging and Thyroid Function. Case Rep Pediatr 2021; 2021:2360855. [PMID: 34434587 PMCID: PMC8382546 DOI: 10.1155/2021/2360855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 07/30/2021] [Accepted: 08/04/2021] [Indexed: 11/24/2022] Open
Abstract
In case of primary hypothyroidism, reactive pituitary hyperplasia can manifest as pituitary (pseudo) macroadenoma. We report the case of a 12-year-old boy who was evaluated for impaired growth velocity and increased body weight. Because of low insulin-like growth factor 1 levels and poor response to the growth hormone stimulation test, brain magnetic resonance imaging was performed and a pituitary macroadenoma was found. Treatment with levothyroxine was started, and thyroid function was evaluated approximately every 40 days to titrate the dosage. After few months of therapy, the size of the macroadenoma decreased and growth hormone secretion normalized. The pituitary returned to normal size in approximately 5 years. The boy went through puberty spontaneously and reached a normal adult height. In a patient affected by primary hypothyroidism, reactive pituitary hyperplasia can cause growth hormone deficiency; however, growth hormone secretion usually normalizes after starting levothyroxine treatment. Pituitary macroadenoma can be difficult to distinguish from severe pituitary hyperplasia; however, pituitary macroadenomas are rare in childhood, and our clinical case underlines how the hormonal evaluation is essential to achieve a correct diagnosis and prevent unnecessary surgery in a context of pituitary mass.
Collapse
|
|
25
|
Eckert A, Galler A, Papsch M, Hess M, Holder M, Döing C, Bierkamp-Christophersen D, Hammer E, Pappa A, Lanzinger S. Are psychiatric disorders associated with thyroid hormone therapy in adolescents and young adults with type 1 diabetes? J Diabetes 2021; 13:562-571. [PMID: 33325120 DOI: 10.1111/1753-0407.13145] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 12/08/2020] [Accepted: 12/10/2020] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND To evaluate the association between thyroid autoimmunity and psychiatric disorders (depression, anxiety, eating disorder, schizophrenia or attention-deficit/hyperactivity disorder) among adolescents and young adults with type 1 diabetes (11-25 years). METHODS We compared 9368 type 1 diabetes patients with thyroid autoimmunity (3789 of them treated with levothyroxine) with 62 438 type 1 diabetes patients without any thyroid disease from a multicentre diabetes patient follow-up registry (DPV) in terms of psychiatric disorders. Thyroid autoimmunity was defined as documented diagnosis of Hashimoto thyroiditis or positive antibodies against thyroid peroxidase or thyroglobulin. Multivariable logistic regression models were used to calculate odds ratios for the respective psychiatric disorders in type 1 diabetes patients with thyroid autoimmunity (overall and stratified by levothyroxine therapy) compared to type 1 diabetes patients without thyroid diseases (reference). RESULTS Of the 9368 patients with thyroid autoimmunity, 62% were female with a median (Q1-Q3) age of 16.3 (14.2-17.6) years. Thyroid autoimmunity (with or without levothyroxine therapy) revealed a slight, but significant higher chance for depression (odds ratio [OR], 1.35, 95% confidence interval [CI], 1.19, 1.52), eating disorder (OR, 1.25, CI, 1.03, 1.51), attention-deficit/hyperactivity disorder (OR, 1.22, CI, 1.07, 1.39) and schizophrenia (OR, 1.63, CI, 1.04, 2.56). In individuals with prescribed levothyroxine therapy because of thyroid dysfunction significantly higher odds for depression (OR, 1.63, CI, 1.34, 1.99), anxiety (OR, 1.60, CI, 1.18, 2.18), and attention-deficit/hyperactivity disorder (OR, 1.71, CI, 1.38, 2.12) were observed compared to reference. Thyroid autoimmunity without required levothyroxine therapy revealed no differences to the reference group. CONCLUSIONS Patients on levothyroxine had significantly higher odds for psychiatric disorders, but thyroid autoimmunity in terms of high antibody levels only did not show higher odds for any psychiatric disorder.
Collapse
Affiliation(s)
- Alexander Eckert
- Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany
- German Centre for Diabetes Research (DZD), Neuherberg, Germany
| | - Angela Galler
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Paediatric Endocrinology and Diabetology, Berlin Institute of Health, Sozialpädiatrisches Zentrum, Berlin, Germany
| | - Matthias Papsch
- Department of Paediatrics and Adolescent Medicine, Marienhospital GmbH, Gelsenkirchen, Germany
| | - Melanie Hess
- Department of Paediatric Endocrinology/Diabetology, University Childrens Hospital Beider Basel UKBB, Basel, Switzerland
| | - Martin Holder
- Department of Paediatric Endocrinology and-Diabetology, Hospital Stuttgart, Stuttgart, Germany
| | - Carsten Döing
- Department of General Paediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | | | - Elke Hammer
- Department of Paediatrics, Paediatric Endocrinology and Diabetology, Catholic Childrens Hospital Wilhelmstift, Hamburg, Germany
| | - Angeliki Pappa
- Department of Paediatrics and Adolescent Medicine, University Hospital RWTH Aachen, Aachen, Germany
| | - Stefanie Lanzinger
- Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany
- German Centre for Diabetes Research (DZD), Neuherberg, Germany
| |
Collapse
|
|
26
|
Shi M, Manouchehri AM, Shaffer CM, Vaitinadin NS, Hellwege JN, Salem JE, Davis LK, Simmons JH, Roden DM, Shoemaker MB, Ferguson JF, Mosley JD. Genetic Thyrotropin Regulation of Atrial Fibrillation Risk Is Mediated Through an Effect on Height. J Clin Endocrinol Metab 2021; 106:2124-2132. [PMID: 33895829 PMCID: PMC8208678 DOI: 10.1210/clinem/dgab272] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 03/31/2021] [Indexed: 12/23/2022]
Abstract
CONTEXT A genetic predisposition to lower thyrotropin (TSH) levels is associated with increased atrial fibrillation (AF) risk through undefined mechanisms. OBJECTIVE Defining the genetic mediating mechanisms could lead to improved targeted therapies to mitigate AF risk. METHODS We used 2-sample mendelian randomization (MR) to test associations between TSH-associated single-nucleotide variations and 16 candidate mediators. We then performed multivariable mendelian randomization (MVMR) to test for a significant attenuation of the genetic association between TSH and AF, after adjusting for each mediator significantly associated with TSH. RESULTS Four candidate mediators (free thyroxine, systolic blood pressure, heart rate, and height) were significantly inversely associated with genetically predicted TSH after adjusting for multiple testing. In MVMR analyses, adjusting for height significantly decreased the magnitude of the association between TSH and AF from -0.12 (SE 0.02) occurrences of AF per SD change in height to -0.06 (0.02) (P = .005). Adjusting for the other candidate mediators did not significantly attenuate the association. CONCLUSION The genetic association between TSH and increased AF risk is mediated, in part, by taller stature. Thus, some genetic mechanisms underlying TSH variability may contribute to AF risk through mechanisms determining height occurring early in life that differ from those driven by thyroid hormone-level elevations in later life.
Collapse
Affiliation(s)
- Mingjian Shi
- Department of Biomedical Informatics & Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | - Ali M Manouchehri
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | - Christian M Shaffer
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | | | - Jacklyn N Hellwege
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | - Joe-Elie Salem
- Département de Pharmacologie, APHP, Sorbonne Université, INSERM, UNICO-GRECO Cardio-oncology Program, F75013 Paris, France
| | - Lea K Davis
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | - Jill H Simmons
- Division of Pediatric Endocrinology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | - Dan M Roden
- Department of Biomedical Informatics & Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
- Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37212, USA
| | - M Benjamin Shoemaker
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | - Jane F Ferguson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
| | - Jonathan D Mosley
- Department of Biomedical Informatics & Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
- Correspondence: Jonathan D. Mosley, MD, PhD, Vanderbilt University Medical Center, 1285 Medical Research Building IV, Nashville, TN 37232, USA.
| |
Collapse
|
|
27
|
Arrieta M, Ramos Gaspar R, Santos AL. Paleopathological diagnosis of a proportionate short stature on a female skeleton from the Coimbra collection: Turner syndrome versus other causes. INTERNATIONAL JOURNAL OF PALEOPATHOLOGY 2021; 33:234-244. [PMID: 34023583 DOI: 10.1016/j.ijpp.2021.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 05/04/2021] [Accepted: 05/04/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVE This paper discusses the possible etiologies for the proportionate short stature of a female individual and provides data to allow the diagnosis of future cases of Turner Syndrome (TS) in paleopathology. MATERIALS Skeleton of a 26-years-old maid, from the Coimbra Identified Skeletal Collection, who died of measles in 1920. METHODS Macroscopic examination, imaging techniques, and metric analysis. RESULTS Her estimated height is 138.91-144.3 cm, approximately three standard deviations below the average female stature for early 20th century Portugal. The crural, brachial, humero-femoral, and intermembral indexes show a proportionate body, uncommon in dwarfism. Small skull with prominent frontal, maxillary prognathism, enamel hypoplasia, cribra orbitalia, porotic hyperostosis, proliferative reaction in the petrous portion of the temporal, obliterated sagittal suture, oval foramen magnum, and small mandible with masculine features. The sternal ends of the ribs are wider and vertebrae present developmental defects (e.g. atlas with both left transverse foramina and posterior tubercle open, absence of the right transverse foramen in the axis, sacrum with six vertebrae). CONCLUSIONS The differential diagnosis point to a possible case of Turner Syndrome. SIGNIFICANCE This study describes the features of Turner Syndrome and provide detail metric analysis of this individual, which will be useful for future paleopathological diagnoses. LIMITATIONS The confirmation of the diagnosis will only be possible through genetic analysis. SUGGESTIONS FOR FURTHER RESEARCH Reanalysis of skeletal individuals with short stature to detect possible cases of Turner Syndrome.
Collapse
Affiliation(s)
- Mario Arrieta
- CONICET - Laboratorio de Biarqueología, Universidad Nacional de Río Cuarto, Ruta Nac. 36 - Km. 601, X5804BYA, Río Cuarto, Córdoba, Argentina.
| | - Rosa Ramos Gaspar
- Coimbra Hospital and Universitary Centre (CHUC), Portugal; Department of Life Sciences, Research Centre for Anthropology and Health (CIAS), University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal.
| | - Ana Luisa Santos
- Department of Life Sciences, Research Centre for Anthropology and Health (CIAS), University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal.
| |
Collapse
|
|
28
|
Li L, Liu W, Zhang L, Wang F, Wang F, Gu M, Wang X, Liu S. Identification and analyzes of DUOX2 mutations in two familial congenital hypothyroidism cases. Endocrine 2021; 72:147-156. [PMID: 32803677 DOI: 10.1007/s12020-020-02437-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Mutations in DUOX2 are the frequent cause of congenital hypothyroidism (CH), a common neonatal metabolic disorder characterized by great phenotypic variability. CH can be traditionally subclassified into two subtypes: thyroid dysgenesis (TD) and thyroid dyshormonogenesis. The objectives of this study were to analyze the genetic data of two familial CH cases, to elucidate the pathogenesis from the perspective of genetics and to review and summarize the previous findings. METHODS Targeted regions sequencing (TRS) technology covering all exons and intron-exon boundaries of 35 known and potential CH-related candidate target genes in combination with Sanger sequencing were performed to identify the likely pathogenic mutations of the six patients with familial CH. RESULTS In family 1, two DUOX2 missense mutations, namely, c.1060C>T/p.R354W in exon 10 and c.3200C>T/p.S1067L in exon 25, were found. Patient 1 (P1), P2 and P3 were transient CH (TCH) patients with eutopic thyroid glands of normal size and function. In family 2, only the mutation c.3200C>T/p.S1067L was identified. P4, P5, and P6 were diagnosed with permanent CH (PCH), which requires lifelong levothyroxine (L-T4) treatment. Furthermore, both P4 and P5 harbored properly located thyroid glands, whereas P6 had a mildly reduced gland. P1, P3, P6, and other family members carrying monoallelic or biallelic DUOX2 mutations showed no obvious abnormal clinical symptoms or signs, while P2, P4, and P5 showed umbilical hernias. CONCLUSIONS The present study suggests that the phenotypic features resulting from DUOX2 mutations vary greatly. The p.R354W and p.S1067L alterations or the combination of the two alterations in DUOX2 are probably only predisposing to CH and DUOX2 may be involved in the morphogenesis of the human thyroid gland. Simultaneously, the compensation of DUOX1 for the loss of DUOX2, undetectable pathogenic mutations, the effects of environmental factors, epigenetic mechanisms and the involvement of multiple genes cannot be excluded in the explanation of these genetic results.
Collapse
Affiliation(s)
- Liangshan Li
- Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Clinical Laboratory, Medical College of Qingdao University, Qingdao, China
| | - Wenmiao Liu
- Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Liqin Zhang
- Child Health Care Department, Qingdao Women and Children's Hospital, Qingdao, China
| | - Fang Wang
- Endocrinology Department, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Fengqi Wang
- Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Maosheng Gu
- Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China
| | - Xiuli Wang
- Neonatal Screening Center, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China.
| | - Shiguo Liu
- Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, China.
| |
Collapse
|
|
29
|
Yang LL, Liang SS. Study on pathogenic genes of dwarfism disease by next-generation sequencing. World J Clin Cases 2021; 9:1600-1609. [PMID: 33728303 PMCID: PMC7942040 DOI: 10.12998/wjcc.v9.i7.1600] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/10/2020] [Accepted: 12/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There are many factors that lead to dwarfism, and the mechanism has not yet been elucidated. Next-generation sequencing may identify candidate-related gene mutations, which may clarify the molecular cause.
AIM To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations.
METHODS Physical and laboratory characteristics, including clinical examination, growth hormone drug challenge test, serum insulin-like growth factor-1 (IGF-1), IGF binding protein 3, other related tests, imaging examination, and chromosome karyotyping, were analyzed. Next-generation sequencing was performed to analyze pathogenicity variability.
RESULTS In the 39 dwarfism patients, 10 had pathogenicity variability. Gene variation was found in the OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes. Of the 10 patients with pathogenicity variability, the related physical characteristics included double breast development and growth hormone deficiency, enuresis and indirect inguinal hernia on the left, two finger distance of 70.2 cm, head circumference of 49.2 cm, ischium/lower body length of 1.8 cm, weak limb muscles, and partial growth hormone deficiency. After 6 mo of growth hormone therapy, the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2 ± 170.3 to 285.0 ± 166.0 and 3.9 ± 1.4 to 4.2 ± 1.1, respectively.
CONCLUSION OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes may be related to the incidence of dwarfism, and more research needs to be performed to elucidate the mechanism.
Collapse
Affiliation(s)
- Lv-Lv Yang
- Department of Pediatrics, Quanzhou First Hospital, Quanzhou 362000, Fujian Province, China
| | - Shi-Shan Liang
- Department of Pediatrics, Quanzhou First Hospital, Quanzhou 362000, Fujian Province, China
| |
Collapse
|
|
30
|
van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, Cassio A, Heinrichs C, Beauloye V, Pohlenz J, Rodien P, Coutant R, Szinnai G, Murray P, Bartés B, Luton D, Salerno M, de Sanctis L, Vigone M, Krude H, Persani L, Polak M. Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid 2021; 31:387-419. [PMID: 33272083 PMCID: PMC8001676 DOI: 10.1089/thy.2020.0333] [Citation(s) in RCA: 229] [Impact Index Per Article: 57.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background: An ENDO-European Reference Network (ERN) initiative was launched that was endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology with 22 participants from the ENDO-ERN and the two societies. The aim was to update the practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). A systematic literature search was conducted to identify key articles on neonatal screening, diagnosis, and management of primary and central CH. The evidence-based guidelines were graded with the Grading of Recommendations, Assessment, Development and Evaluation system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Summary: The recommendations include the various neonatal screening approaches for CH as well as the etiology (also genetics), diagnostics, treatment, and prognosis of both primary and central CH. When CH is diagnosed, the expert panel recommends the immediate start of correctly dosed levothyroxine treatment and frequent follow-up including laboratory testing to keep thyroid hormone levels in their target ranges, timely assessment of the need to continue treatment, attention for neurodevelopment and neurosensory functions, and, if necessary, consulting other health professionals, and education of the child and family about CH. Harmonization of diagnostics, treatment, and follow-up will optimize patient outcomes. Lastly, all individuals with CH are entitled to a well-planned transition of care from pediatrics to adult medicine. Conclusions: This consensus guidelines update should be used to further optimize detection, diagnosis, treatment, and follow-up of children with all forms of CH in the light of the most recent evidence. It should be helpful in convincing health authorities of the benefits of neonatal screening for CH. Further epidemiological and experimental studies are needed to understand the increased incidence of this condition.
Collapse
Affiliation(s)
- Paul van Trotsenburg
- Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
| | - Athanasia Stoupa
- Pediatric Endocrinology, Gynecology and Diabetology Department, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Universitaire Necker Enfants Malades, Paris, France
- Université de Paris, Paris, France
- INSERM U1163, IMAGINE Institute, Paris, France
- INSERM U1016, Cochin Institute, Paris, France
| | - Juliane Léger
- Department of Pediatric Endocrinology and Diabetology, Reference Center for Growth and Development Endocrine Diseases, Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Paris, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1141, Paris, France
| | - Tilman Rohrer
- Department of Pediatric Endocrinology, University Children's Hospital, Saarland University Medical Center, Homburg, Germany
| | - Catherine Peters
- Department of Pediatric Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom
| | - Laura Fugazzola
- Department of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Alessandra Cassio
- Department of Pediatric Endocrinology, Unit of Pediatrics, Department of Medical & Surgical Sciences, University of Bologna, Bologna Italy
| | - Claudine Heinrichs
- Pediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium
| | - Veronique Beauloye
- Unité d'Endocrinologie Pédiatrique, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Joachim Pohlenz
- Department of Pediatrics, Johannes Gutenberg University Medical School, Mainz, Germany
| | - Patrice Rodien
- Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, Service EDN, CHU d'Angers, Institut MITOVASC, Université d'Angers, Angers, France
| | - Regis Coutant
- Unité d' Endocrinologie Diabetologie Pédiatrique and Centre des Maladies Rares de la Réceptivité Hormonale, CHU-Angers, Angers, France
| | - Gabor Szinnai
- Department of Pediatric Endocrinology, University Children's Hospital Basel, University of Basel, Basel, Switzerland
| | - Philip Murray
- European Society for Pediatric Endocrinology
- Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - Beate Bartés
- Thyroid Group, European Patient Advocacy Group Patient Representative (ePAG), Association Vivre sans Thyroide, Léguevin, France
| | - Dominique Luton
- Department of Obstetrics and Gynecology, University Hospitals Paris Nord Val de Seine (HUPNVS), Assistance Publique Hôpitaux de Paris (APHP), Bichat Hospital, Paris, France
- Department Risks and Pregnancy (DHU), Université de Paris, Inserm U1141, Paris, France
| | - Mariacarolina Salerno
- Pediatric Endocrine Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Luisa de Sanctis
- Department of Public Health and Pediatrics, University of Turin, Regina Margherita Children's Hospital, Turin, Italy
| | - Mariacristina Vigone
- Department of Pediatrics, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Heiko Krude
- Institut für Experimentelle Pädiatrische Endokrinologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Luca Persani
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
- Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
| | - Michel Polak
- Pediatric Endocrinology, Gynecology and Diabetology Department, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Universitaire Necker Enfants Malades, Paris, France
- Université de Paris, Paris, France
- INSERM U1163, IMAGINE Institute, Paris, France
- INSERM U1016, Cochin Institute, Paris, France
- Paris Regional Newborn Screening Program, Centre régional de dépistage néonatal, Paris, France
- Centre de Référence Maladies Endocriniennes de la Croissance et du Développement, INSERM U1016, IMAGINE Institute, Paris, France
- ENDO-European Reference Network, Main Thematic Group 8, Paris, France
| |
Collapse
|
|
31
|
van den Broek S, Lupattelli A, Frank AS, Haug LS, Nordeng H. Thyroid hormone replacement therapy in pregnancy and motor function, communication skills, and behavior of preschool children: The Norwegian Mother, Father, and Child Cohort Study. Pharmacoepidemiol Drug Saf 2020; 30:716-726. [PMID: 33314561 PMCID: PMC8247290 DOI: 10.1002/pds.5184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 12/08/2020] [Indexed: 12/17/2022]
Abstract
PURPOSE Limited research has focused on the association between prenatal thyroid hormone replacement therapy (THRT) and motor function, communication skills, and behavior in preschool children. Here, we estimated the association between THRT during pregnancy and the first trimester and these developmental outcomes. METHODS This study was based on the Norwegian Mother, Father, and Child Cohort Study (MoBa) and other national registries. We included mother-child pairs exposed to THRT during pregnancy (n = 663), after delivery (n = 728), or unexposed (n = 28 040). Exposure to THRT was defined according to filled prescriptions. Child outcomes, presented as T-score differences, were parent-reported using the Ages and Stages Questionnaire, Strengths and Difficulties Questionnaire, and Child Behavior Checklist. RESULTS Of 29 431 mother-child pairs, 2.3% were prenatally exposed to THRT. We found no difference between prenatally exposed and unexposed children in regards to gross motor function (β: 0.17, 95% CI -1.19, 1.54), fine motor function (β: -0.17, 95% CI -1.14, 0.80), communication (β: -0.31, 95% CI -1.58, 0.96), externalizing (β: -0.03, 95% CI -1.07, 1.01), internalizing (β: 0.89, 95% CI -0.20, 1.97), or social behaviors (β: -0.04, 95% CI -0.92, 0.84). Somatic complaints were higher in THRT-exposed children (β: 0.98, 95% CI 0.08, 1.87), and children whose mothers were exposed after delivery had more sleep problems than unexposed children (β: 0.99, 95% CI 0.24, 1.74). CONCLUSIONS Children prenatally exposed to THRT have developmental outcomes as positive as unexposed children on motor function, communication, and behavior. The association with somatic complaints and sleep were not clinically relevant.
Collapse
Affiliation(s)
- Sophie van den Broek
- PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.,Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Angela Lupattelli
- PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
| | - Anna S Frank
- PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
| | - Line Småstuen Haug
- Department of Environmental Exposure and Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
| | - Hedvig Nordeng
- PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.,Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway
| |
Collapse
|
|
32
|
Scoville DW, Kang HS, Jetten AM. Transcription factor GLIS3: Critical roles in thyroid hormone biosynthesis, hypothyroidism, pancreatic beta cells and diabetes. Pharmacol Ther 2020; 215:107632. [PMID: 32693112 PMCID: PMC7606550 DOI: 10.1016/j.pharmthera.2020.107632] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/15/2020] [Indexed: 12/16/2022]
Abstract
GLI-Similar 3 (GLIS3) is a member of the GLIS subfamily of Krüppel-like zinc finger transcription factors that functions as an activator or repressor of gene expression. Study of GLIS3-deficiency in mice and humans revealed that GLIS3 plays a critical role in the regulation of several biological processes and is implicated in the development of various diseases, including hypothyroidism and diabetes. This was supported by genome-wide association studies that identified significant associations of common variants in GLIS3 with increased risk of these pathologies. To obtain insights into the causal mechanisms underlying these diseases, it is imperative to understand the mechanisms by which this protein regulates the development of these pathologies. Recent studies of genes regulated by GLIS3 led to the identification of a number of target genes and have provided important molecular insights by which GLIS3 controls cellular processes. These studies revealed that GLIS3 is essential for thyroid hormone biosynthesis and identified a critical function for GLIS3 in the generation of pancreatic β cells and insulin gene transcription. These observations raised the possibility that the GLIS3 signaling pathway might provide a potential therapeutic target in the management of diabetes, hypothyroidism, and other diseases. To develop such strategies, it will be critical to understand the upstream signaling pathways that regulate the activity, expression and function of GLIS3. Here, we review the recent progress on the molecular mechanisms by which GLIS3 controls key functions in thyroid follicular and pancreatic β cells and how this causally relates to the development of hypothyroidism and diabetes.
Collapse
Affiliation(s)
- David W Scoville
- Cell Biology Group, Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
| | - Hong Soon Kang
- Cell Biology Group, Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
| | - Anton M Jetten
- Cell Biology Group, Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
| |
Collapse
|
|
33
|
Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options. Int J Mol Sci 2020; 21:ijms21165927. [PMID: 32824723 PMCID: PMC7460638 DOI: 10.3390/ijms21165927] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 08/14/2020] [Accepted: 08/16/2020] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor β (THR-β) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.
Collapse
|
|
34
|
Chen Y, Tai HY. Levothyroxine in the treatment of overt or subclinical hypothyroidism: a systematic review and meta-analysis. Endocr J 2020; 67:719-732. [PMID: 32238664 DOI: 10.1507/endocrj.ej19-0583] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The goal of this study was to review relevant randomized controlled trials in order to determine the clinical efficacy of levothyroxine in the treatment of overt or subclinical hypothyroidism. Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through December 2019 were considered for inclusion. For each study, we assessed odds ratios (ORs), mean difference (MD), and 95% confidence interval (95%CI) to assess and synthesize outcomes. We included 25 studies with totally 1,735 patients in the meta-analysis. In the patients with hypothyroidism, compared with L-T4, L-T4 plus L-T3 significantly decreased TSH levels and increased FT3 levels. Compared with placebo, L-T4 significantly increased FT4 levels and decreased TSH levels. In patients with subclinical hypothyroidism, compared with placebo, L-T4 significantly decreased SBP, TSH, T3 and TC and increased FT3 and FT4.
Collapse
Affiliation(s)
- Yan Chen
- Department of Endocrinology, Wuwei People's Hospital, Wuwei, Gansu Province, China
| | - Hai-Yan Tai
- Department of Endocrinology, Wuwei People's Hospital, Wuwei, Gansu Province, China
| |
Collapse
|
|
35
|
Upper and Lower Limb Strength and Body Posture in Children with Congenital Hypothyroidism: An Observational Case-Control Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17134830. [PMID: 32635579 PMCID: PMC7370191 DOI: 10.3390/ijerph17134830] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 06/26/2020] [Accepted: 07/01/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Congenital hypothyroidism (CH) is an endocrine disease with a precocious significant impairment of growth and neuromotor development. Thyroid hormones are essential for central nervous system development, maturation, and myelination. Furthermore, thyroid hormone deficiency affects the function of several systems, including the musculoskeletal system. The disease has a significant incidence in the general population (1:3000-1:2000 newborns in Italy). The aim of the present study was to evaluate any differences in upper and lower limb strength, body sway, and plantar loading distribution in children with CH compared to healthy children. METHODS In this study, the case group was composed of children with CH (CHG), while the control group included healthy children (CG). Both groups comprised 19 children (CHG: female = 12; CG: female = 9). The maximum isometric handgrip strength and explosive-elastic lower limb strength were assessed with the handgrip test and the Sargent test, respectively. The stabilometric and baropodometric analyses were used to measure the Center of Pressure displacements and the plantar loading distribution between feet, respectively. The differences between groups were analyzed by a univariate analysis of covariance using as covariates weight and height with the significant level set at < 0.05. RESULTS We found that CHG children were shorter and thinner than CG ones (p < 0.05). No significant difference in the upper and lower limb strength was found between groups. CHG exhibited a significant greater Sway Path Length (p < 0.01) and Ellipse Surface (p < 0.05) than CG. Moreover, CHG displayed an asymmetric plantar loading distribution with a significant lower percentage in the right than in the left foot (p < 0.05). Moreover, a significant lower plantar loading percentage in the right foot of CHG than in the right foot of CG was observed (p < 0.05). CONCLUSIONS These findings seem to suggest that CH does not affect muscle strength in early treated children. However, these patients show poor postural control ability and asymmetric plantar loading distribution. Increasing the physical activity in these children could improve their body posture.
Collapse
|
|
36
|
Cannavò L, Aversa T, Corica D, Pepe G, Pajno GB, Alibrandi A, Wasniewska M. Authors' response to "Harder than just hitting a bulls-eye: treatment for hypothyroidism in children might have more than just one target". Endocrine 2020; 69:231-232. [PMID: 32323092 DOI: 10.1007/s12020-020-02318-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 04/13/2020] [Indexed: 11/24/2022]
Affiliation(s)
- Laura Cannavò
- Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, 98122, Messina, ME, Italy
| | - Tommaso Aversa
- Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, 98122, Messina, ME, Italy.
| | - Domenico Corica
- Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, 98122, Messina, ME, Italy
| | - Giorgia Pepe
- Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, 98122, Messina, ME, Italy
| | - Giovanni Battista Pajno
- Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, 98122, Messina, ME, Italy
| | - Angela Alibrandi
- Department of Economics, University of Messina, 98122, Messina, ME, Italy
| | - Malgorzata Wasniewska
- Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, 98122, Messina, ME, Italy
| |
Collapse
|
|
37
|
Gonzalez-Velazquez C, Xing MH, Urken ML. Harder than just hitting a bulls-eye: treatment for hypothyroidism in children might have more than just one target. Endocrine 2020; 69:230. [PMID: 32162183 DOI: 10.1007/s12020-020-02254-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 03/03/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Camilo Gonzalez-Velazquez
- Thyroid, Head and Neck Cancer (THANC) Foundation, 10 Union Square East, Suite 5B, New York, NY, 10003, USA
| | - Monica H Xing
- Thyroid, Head and Neck Cancer (THANC) Foundation, 10 Union Square East, Suite 5B, New York, NY, 10003, USA.
| | - Mark L Urken
- Thyroid, Head and Neck Cancer (THANC) Foundation, 10 Union Square East, Suite 5B, New York, NY, 10003, USA
| |
Collapse
|
|
38
|
Halcrow SE, Miller MJ, Snoddy AME, Fan W, Pechenkina K. Growing up different in Neolithic China: A contextualised case study and differential diagnosis of a young adult with skeletal dysplasia. INTERNATIONAL JOURNAL OF PALEOPATHOLOGY 2020; 28:6-19. [PMID: 31841791 DOI: 10.1016/j.ijpp.2019.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 10/16/2019] [Accepted: 11/03/2019] [Indexed: 06/10/2023]
Abstract
This paper presents a case study of a young adult from the late Neolithic Yangshao cultural period site (∼3300-2900 years BC) of Guanjia () located in Henan Province on the Central Plains of China, who has evidence for skeletal dysplasia characterised by proportional stunting of the long bones and a small axial skeleton, generalised osteopenia, and non-fusion of epiphyses. We provide a detailed differential diagnosis of skeletal dysplasia with paediatric onset and conclude that this is likely a form of hypopituitarism or hypothyroidism, an extremely rare finding within the archaeological context. This paper highlights the issues of distinguishing the forms of proportional dwarfism in palaeopathology because of the considerable variation in manifestation of these conditions. Finally, we assess whether there were any health and social implications for this person and community through the consideration of a bioarchaeology of care approach across the lifecourse, burial context, and information on social perceptions of 'difference' in the community. ：： （3300～2900）。，，，，。，，。。，。，、、""，。.
Collapse
Affiliation(s)
- Siân E Halcrow
- Department of Anatomy, University of Otago, New Zealand.
| | | | | | - Wenquan Fan
- Henan Provincial Institute of Cultural Relics and Archaeology, Zhengzhou, China
| | - Kate Pechenkina
- Department of Anthropology, Queens College, City University of New York, United States
| |
Collapse
|
|
39
|
Wang F, Zang Y, Li M, Liu W, Wang Y, Yu X, Li H, Wang F, Liu S. DUOX2 and DUOXA2 Variants Confer Susceptibility to Thyroid Dysgenesis and Gland- in-situ With Congenital Hypothyroidism. Front Endocrinol (Lausanne) 2020; 11:237. [PMID: 32425884 PMCID: PMC7212429 DOI: 10.3389/fendo.2020.00237] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 03/31/2020] [Indexed: 12/18/2022] Open
Abstract
Background: Thyroid dysgenesis (TD), which is caused by gland developmental abnormalities, is the most common cause of congenital hypothyroidism (CH). In addition, advances in diagnostic techniques have facilitated the identification of mild CH patients with a gland-in-situ (GIS) with normal thyroid morphology. Therefore, TD and GIS account for the vast majority of CH cases. Methods: Sixteen known genes to be related to CH were sequenced and screened for variations by next-generation sequencing (NGS) in a cohort of 377 CH cases, including 288 TD cases and 89 GIS cases. Results: In our CH cohort, we found that DUOX2 (21.22%) was the most commonly variant pathogenic gene, while DUOXA2 was prominent in TD (18.75%) and DUOX2 was prominent in GIS (34.83%). Both biallelic and triple variants of DUOX2 were found to be most common in children with TD and children with GIS. The most frequent combination was DUOX2 with DUOXA1 among the 61 patients who carried digenic variants. We also found for the first time that biallelic TG, DUOXA2, and DUOXA1 variants participate in the pathogenesis of TD. In addition, the variant p.Y246X in DUOXA2 was the most common variant hotspot, with 58 novel variants identified in our study. Conclusion: We meticulously described the types and characteristics of variants from sixteen known gene in children with TD and GIS in the Chinese population, suggesting that DUOXA2 and DUOX2 variants may confer susceptibility to TD and GIS via polygenic inheritance and multiple factors, which further expands the genotype-phenotype spectrum of CH in China.
Collapse
Affiliation(s)
- Fengqi Wang
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China
- Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yucui Zang
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China
- Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Miaomiao Li
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China
- Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wenmiao Liu
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China
- Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yangang Wang
- Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaolong Yu
- Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hua Li
- Department of Rheumatology and Immunology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Fang Wang
- Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China
- *Correspondence: Fang Wang
| | - Shiguo Liu
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China
- Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China
- Shiguo Liu
| |
Collapse
|
|
40
|
Kucharska AM, Witkowska-Sȩdek E, Labochka D, Rumińska M. Clinical and Biochemical Characteristics of Severe Hypothyroidism Due to Autoimmune Thyroiditis in Children. Front Endocrinol (Lausanne) 2020; 11:364. [PMID: 32733376 PMCID: PMC7360718 DOI: 10.3389/fendo.2020.00364] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 05/11/2020] [Indexed: 01/04/2023] Open
Abstract
Introduction: In the majority of countries, autoimmune thyroiditis is the main cause of acquired hypothyroidism in children. Typically, the natural course of the disease is initially insidious and the diagnosis is incidental. There are some children who develop severe hypothyroidism without a proper diagnosis. The aim of the study was to analyze the clinical and biochemical profiles of children with severe primary hypothyroidism due to autoimmune thyroiditis. Materials and Methods: We analyzed the records of 354 patients diagnosed between 2009 and 2019 with autoimmune thyroiditis. Only patients with TSH above 100 μIU/mL, associated with decreased free thyroxine and the presence of antithyroid antibodies, were enrolled in the study. The analysis encompassed clinical symptoms, thyroid and biochemical status, bone age, and imaging. Results: Twenty-six children were enrolled in the study. The mean age at diagnosis was 10.26 ± 3.3 years, with a female preponderance of 1.8:1. The most frequent symptom was growth impairment (77%) and weight gain (58%). Goiters were present in 42% of patients. Less common findings were pituitary hypertrophy (four patients) and hypertrichosis (three patients). Median values at the time of diagnosis were TSH 454.3 uIU/ml (295.0-879.4), anti-TPO antibodies 1,090 IU/ml, and anti-Tg antibodies 195 IU/ml. Anti-TSHR ab were evaluated only in six out of the 26 patients. The characteristic biochemical profile was correlated with the grade of hypothyroidism, and the strongest correlations were found with CBC parameters, lipid profile, aminotransferases, and creatine. Conclusion: In children with severe hypothyroidism, the most sensitive symptoms are growth arrest and weight gain despite the fact that, in some children, the auxological parameters at presentation could be within normal values for the population. The specific biochemical profile closely correlates to the severity of thyroid hormone deficiency and involves mostly erythropoiesis, liver function, and kidney function. Pituitary enlargement should be considered in each child with severe hypothyroidism. It is necessary to conduct prospective studies evaluating the actual frequency of anti-TSHR antibodies and pituitary enlargement in children with extremely high TSH, especially those presenting without goiters.
Collapse
|
|
41
|
Villagomez AN, Muñoz FM, Peterson RL, Colbert AM, Gladstone M, MacDonald B, Wilson R, Fairlie L, Gerner GJ, Patterson J, Boghossian NS, Burton VJ, Cortés M, Katikaneni LD, Larson JCG, Angulo AS, Joshi J, Nesin M, Padula MA, Kochhar S, Connery AK. Neurodevelopmental delay: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2019; 37:7623-7641. [PMID: 31783983 PMCID: PMC6899448 DOI: 10.1016/j.vaccine.2019.05.027] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 05/09/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Adrienne N Villagomez
- University of Colorado School of Medicine, Aurora, CO, USA; Children's Hospital of Colorado, Aurora, CO, USA
| | - Flor M Muñoz
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Robin L Peterson
- University of Colorado School of Medicine, Aurora, CO, USA; Children's Hospital of Colorado, Aurora, CO, USA
| | - Alison M Colbert
- University of Colorado School of Medicine, Aurora, CO, USA; Children's Hospital of Colorado, Aurora, CO, USA
| | - Melissa Gladstone
- Department of Women and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | | | - Rebecca Wilson
- University of Colorado School of Medicine, Aurora, CO, USA; Children's Hospital of Colorado, Aurora, CO, USA
| | - Lee Fairlie
- Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa
| | - Gwendolyn J Gerner
- Kennedy Krieger Institute, Baltimore, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jackie Patterson
- University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Nansi S Boghossian
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Vera Joanna Burton
- Kennedy Krieger Institute, Baltimore, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | | | - Jennifer C G Larson
- Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA
| | - Abigail S Angulo
- University of Colorado School of Medicine, Aurora, CO, USA; Children's Hospital of Colorado, Aurora, CO, USA
| | - Jyoti Joshi
- Center for Disease Dynamics Economics & Policy, Amity Institute of Public Health, Amity University, India
| | - Mirjana Nesin
- Division of Microbiology and Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Michael A Padula
- Children's Hospital of Philadelphia, Department of Pediatrics, Philadelphia, PA, USA
| | - Sonali Kochhar
- Global Healthcare Consulting, India; University of Washington, Seattle, USA; Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Amy K Connery
- University of Colorado School of Medicine, Aurora, CO, USA; Children's Hospital of Colorado, Aurora, CO, USA.
| |
Collapse
|
|
42
|
Leung AKC, Leung AAC. Evaluation and management of the child with hypothyroidism. World J Pediatr 2019; 15:124-134. [PMID: 30734891 DOI: 10.1007/s12519-019-00230-w] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 01/14/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes. DATA SOURCES A PubMed search was completed in Clinical Queries using the key terms "hypothyroidism". RESULTS Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. CONCLUSIONS To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2 weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.
Collapse
Affiliation(s)
- Alexander K C Leung
- Department of Pediatrics, The University of Calgary, and The Alberta Children's Hospital, #200, 233 - 16th Avenue NW, Calgary, AB, T2M 0H5, Canada.
| | | |
Collapse
|
|
43
|
Vukovic R, Zeljkovic A, Bufan B, Spasojevic-Kalimanovska V, Milenkovic T, Vekic J. Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review. Front Endocrinol (Lausanne) 2019; 10:868. [PMID: 31920978 PMCID: PMC6914680 DOI: 10.3389/fendo.2019.00868] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 11/27/2019] [Indexed: 12/19/2022] Open
Abstract
Hashimoto autoimmune thyroiditis (AIT) is the most common cause of acquired hypothyroidism in the pediatric population. Development of AIT is mediated mainly by cellular immune response directed toward thyroid autoantigens, leading to inflammation and impaired function of thyroid gland. Both thyroid dysfunction and inflammation affect the metabolism of plasma lipoproteins. The alterations in lipid profile worsen with the advancement of hypothyroidism, ranging from discrete changes in euthyroid AIT patients, to atherogenic dyslipidemia in the overt hypothyroidism. In this review, characteristics of dyslipidemia in pediatric AIT patients, and the consequences in respect to the risk for cardiovascular disease (CVD) development are discussed. Additionally, benefit of L-thyroxine treatment on serum lipid profile in pediatric AIT patients is addressed. Finally, potential usefulness of novel lipid biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), non-cholesterol sterols, low-density lipoprotein particle size and number, and high-density lipoprotein structure and functionality in AIT patients is also covered. Further longitudinal studies are needed in order to elucidate the long-term cardiovascular outcomes of dyslipidemia in pediatric patients with Hashimoto AIT.
Collapse
Affiliation(s)
- Rade Vukovic
- Department of Pediatric Endocrinology, Mother and Child Healthcare Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
- *Correspondence: Rade Vukovic
| | - Aleksandra Zeljkovic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Biljana Bufan
- Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | | | - Tatjana Milenkovic
- Department of Pediatric Endocrinology, Mother and Child Healthcare Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia
| | - Jelena Vekic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| |
Collapse
|
|
44
|
Vigone MC, Capalbo D, Weber G, Salerno M. Mild Hypothyroidism in Childhood: Who, When, and How Should Be Treated? J Endocr Soc 2018; 2:1024-1039. [PMID: 30187015 PMCID: PMC6117400 DOI: 10.1210/js.2017-00471] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 07/20/2018] [Indexed: 12/12/2022] Open
Abstract
Mild hypothyroidism, also known as subclinical hypothyroidism (SH), is biochemically defined as serum TSH levels above the upper limit of the reference range, in the presence of normal serum concentrations of total T4 and free T4 (FT4). In the neonatal period, mild hypothyroidism can be defined by the presence of a TSH value between 6 and 20 mIU/L and normal FT4 levels. After the neonatal period, SH can be defined mild if TSH ranges between 4.5 and 10 mIU/L. The management of mild hypothyroidism in childhood is challenging. The major concern is to establish whether this condition should always be considered an expression of mild thyroid dysfunction. Indeed, the effects of untreated mild hypothyroidism are still not completely defined. In the neonatal period, concern exists about neurocognitive outcome; in children, although there is no clear evidence of alterations in growth or neurocognitive development, subtle cardiovascular abnormalities have been documented. Therefore, there is still uncertainty about the need of treatment across all ages, and the management should be based on the age of the child, the etiology, and the degree of TSH elevation, as well as on other patient factors. This review updates current evidences on diagnosis and management of mild hypothyroidism in childhood.
Collapse
Affiliation(s)
| | - Donatella Capalbo
- Department of Pediatrics, University Hospital Federico II, Naples, Italy
| | - Giovanna Weber
- Department of Pediatrics, Vita-Salute San Raffaele University, Milano, Italy
| | - Mariacarolina Salerno
- Department of Translational Medical Sciences-Pediatric Section, University of Naples Federico II, Naples, Italy
| |
Collapse
|
|
45
|
Diagnose and treat paediatric hypothyroidism promptly to achieve optimal growth and developmental outcomes. DRUGS & THERAPY PERSPECTIVES 2018. [DOI: 10.1007/s40267-017-0472-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
46
|
Mehmetoğlu F. Rectal Atresia and Congenital Hypothyroidism: An Association or Coincidence? European J Pediatr Surg Rep 2018; 6:e7-e10. [PMID: 29326865 PMCID: PMC5762197 DOI: 10.1055/s-0037-1612610] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 11/04/2017] [Indexed: 11/20/2022] Open
Abstract
Rectal atresia is a rare anorectal malformation, and its association with other anomalies is even more rare. This study presents a unique case of co-twin in which the surviving newborn male underwent surgery due to rectal atresia. Newborn screening tests identified congenital hypothyroidism. The surgical treatment consisted of three stages and thyroid hormones were replaced.
Collapse
Affiliation(s)
- Feride Mehmetoğlu
- Department of Pediatric Surgery, Dortcelik Children's Hospital, Bursa, Turkey
| |
Collapse
|