Adult growth hormone deficiency (GHD) is an endocrine disorder associated with increased morbidity and poor quality of life. The purpose of this study was to describe the clinical characteristics, treatment patterns, and prevalence of individuals at risk for adult GHD and individuals with confirmed adult GHD in the United States (US).

Using Veradigm Network electronic health records linked to claims, this study identified adults with a high likelihood of adult GHD based on having ≥ 1 of the following between January 1, 2017 and December 31, 2021: diagnosis of hypopituitarism or ≥ 1 related condition, such as Cushing disease, ≥ 3 pituitary hormone deficiencies other than GHD, ≥ 3 pituitary hormone treatments other than growth hormone (GH), or ≥ 1 prescription for GH. Index date was the earliest qualifying event. Individuals were stratified by GH level on or before index date: confirmed adult GHD (< 3 ng/mL), at risk for adult GHD (no test result), ruled-out (≥ 3 ng/mL).

US prevalence of adult GHD was estimated to be between 0.2 (confirmed) and 37.0 (confirmed + at-risk) per 100,000. Among 268 individuals with confirmed adult GHD and 54,310 at risk for adult GHD, mean age was 50 years old, and a majority were female. GH treatment was initiated in 9.7% of confirmed individuals and 3.1% of those at risk for adult GHD. Among confirmed and at-risk individuals, prevalence of endocrine-related conditions was higher in treated individuals, whereas prevalence of several metabolic and cardiovascular comorbidities was higher in those untreated. Only 32.2% of individuals who initiated treatment during the follow-up period were persistent until the end of follow-up.

Our findings report US prevalence of adult GHD and suggest that adult GHD is commonly underdiagnosed in the US. Factors contributing to low rates of adult GHD diagnosis and treatment warrant further research.

Growth hormone deficiency (GHD) causes decreased growth rate in children, resulting in short stature in childhood and adulthood. Daily subcutaneous injections with growth hormone (GH) have been standard treatment. Newer weekly GH formulations now exist. This study estimates utilities associated with GHD treatment for both people with the disease and caregivers by employing time trade-off (TTO) methodology.

Three online surveys were conducted amongst the general population in the UK and Canada. Based on a pilot, data collection was conducted in two surveys only (Survey A and Survey B). In Survey A, adults aged ≥18 years evaluated health states as if they were receiving injections themselves. In Survey B, adults with a child <15 years evaluated health states as if they were administering injections to a child. The surveys assessed device complexity, injection frequency, injection pain, needle visibility and storage possibilities.

2026 and 2028 respondents completed Survey A and Survey B, respectively. Of these, 1782 respondents and 1678 respondents were valid for inclusion. Avoiding weekly injection pain was associated with a significant utility gain of 0.030 (95% CI 0.026-0.035, p<0.001) in Survey A and 0.044 (95% CI 0.038-0.051, p<0.001) in Survey B. Additionally, less complex injection devices and lower injection frequencies had a significant impact in both Survey A (0.020, 95% CI 0.016-0.025, p<0.001; 0.009, 95% CI 0.005-0.014, p<0.001) and Survey B (0.008, 95% CI 0.002-0.014, p=0.006; 0.009, 95% CI 0.003-0.014, p=0.003).

Several aspects are associated with a significant impact on utilities for people with GHD and potential caregivers. Treatment options without injection pain, a time-consuming and complex injection process and daily injections are expected to result in higher health-related quality of life. These results may inform future economic evaluations and treatment choices.

Brain magnetic resonance imaging (MRI) is mandatory or highly recommended in many pediatric endocrinological conditions to detect causative anatomic anomalies and rule out neoplastic lesions. However, MRI can also show findings associated with the underlying clinical condition, as well as unrelated "incidentalomas". These latter findings are often abnormalities with a high incidence in the general population for which there is no clear literature regarding their management, especially in pediatric patients. The present study aimed to evaluate the number of unnecessary performed MRIs in pediatric endocrinology.

Retrospective analysis on 584 MRI scans performed in 414 patients (254 growth hormone deficiency, 41 other causes of short stature, 116 central precocious puberty).

The MRI scans were completely normal in 67% of the individuals, and the prevalence of individuals who underwent more than one MRI was 18%, with no significant differences among the groups. The overall prevalence of incidentalomas was 17%. Among 170 repeated MRI scans, 147 (86%) were not required according to a dedicated protocol. Only five patients (four GHD, one Noonan) correctly repeated the MRI. All the repeated MRI scans did not reveal any progression in the findings. If we include the MRIs performed in cases of OCSS other than Noonan syndrome (n=32) and girls with CPP older than 6 years (n=89), an additional 121 MRIs could have been avoided, leading to a total number of unnecessary MRIs to 268 (46%).

Only a few specific neuroimaging findings in endocrinologic pediatric patients warrant further investigation, while too often repeated imaging is carried out unnecessarily. We advocate the importance of guidelines to reduce costs for both the healthcare system and patients' families, as well as to alleviate physical and psychological distress for patients and caregivers.

Cardiovascular disease is one of the most important complications in girls and women with Turner syndrome (TS). Although the latest international guideline provides useful suggestions for the management of cardiovascular diseases in TS, some unknown cardiac conditions warrant physicians' attention and awareness. Here, we have reported two adult cases wherein significant cardiovascular diseases were detected during the transition period. The first case patient was diagnosed with aortic crank deformity and left subclavian artery aneurysm at 14 years based on the report of cardiac catheterization, computed tomography angiography, and cardiac magnetic resonance imaging, which had remained undetected by annual evaluations using transthoracic echocardiography (TTE). This case emphasizes the importance of cardiac reevaluation during the transition period. The second case patient was diagnosed with moderate mitral valve regurgitation (MR) due to mitral valve prolapse at 18 years through TTE, although the first evaluation at 7 years by TTE detected slight MR without any clinical concerns. The condition however progressed to severe MR at 28 years, requiring mitral valvuloplasty. MR is the most common valve disease worldwide, which makes it challenging to comprehend whether the condition is a complication. However, the condition requiring surgery at this age is extremely rare, which implies the possibility of early progression. Because almost all literature on cardiovascular complications in TS is cross-sectional, further information about longitudinal cardiovascular conditions is vital for optimal care for girls and women with TS. The two cases reported in this article provide significant information for improving lifelong cardiovascular health issues in TS.

Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is one of the main causes of short stature in children and adolescents. The aim of this study is to evaluate the epidemiology of pediatric GHD worldwide, since no other systematic review has been published so far.

We searched PubMed, Embase, and Web of Science up to July 2023 to find epidemiological studies involving children with GHD. Two review authors independently screened articles, extracted data and performed the quality assessment.

We selected 9 epidemiological studies published from 1974 to 2022. The range of prevalence was 1/1107-1/8,646. A study based on a registry of GH users in the Piedmont region (Italy) reported the highest mean prevalence. In the included studies, the mean incidence ranged from 1/28,800 to 1/46,700 cases per year. One study reported a 20-year cumulative incidence of 127/100,000 for boys and 93/100,000 for girls. Studies were heterogeneous in terms of population (age and GHD etiology) and diagnostic criteria. As for the methodological quality of included studies, all but one study satisfied the majority of the checklist items.

The included studies are mostly European, so the provided estimates cannot be considered global. International multicentre studies are needed to compare epidemiological estimates of GHD among different ethnical groups. Considering the considerable cost of human recombinant GH, the only available therapy to treat GHD, understanding accurate epidemiological estimates of GHD in each country is fundamental for resource allocation.

Pituitary hormone deficiency, hypopituitarism, is a dysfunction resulting from numerous etiologies, which can be complete or partial, and is therefore heterogeneous. This heterogeneity makes it difficult to interpret the results of scientific studies with these patients.Adequate treatment of etiologies and up-to-date hormone replacement have improved morbidity and mortality rates in patients with hypopituitarism. As GH replacement is not performed in a reasonable proportion of patients, especially in some countries, it is essential to understand the known consequences of GH replacement in each subgroup of patients with this heterogeneous dysfunction.In this review on hypopituitarism, we will address some particularities regarding insulin resistance, which is no longer common in these patients with hormone replacement therapy based on current guidelines, metabolic syndrome and its relationship with changes in BMI and body composition, and to vascular complications that need to be prevented taking into account the individual characteristics of each case to reduce mortality rates in these patients.

Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real-world treatment.

German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first-year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 to 2018 to determine specific parameters for GH treatment optimization.

All patient groups started GH treatment at a relatively high chronological age (2007-2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016-2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups, female patients were underrepresented compared to male patients (GHD 32.3%, SGA 43.6%) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients, GH therapy was started below the registered dose recommendation (30.0 μg/kg/day and 33.7 μg/kg/day, respectively). In the first year of treatment, the mean GH dose was increased moderately (GHD: 30.7, SGA: 35.7, TS: 40.8 μg/kg/day). There was no significant change of GH dosing over time from 2007 to 2018. The IoR was comparable between time-groups for all 3 diagnoses.

This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at the start of treatment. This is in accordance with important parameters used in prediction models.

Adult growth hormone deficiency (AGHD) is often underdiagnosed and undertreated, leading to costly comorbidities. Previously, we developed an algorithm to identify individuals in a commercially insured US population with high, moderate, or low likelihood of having AGHD. Here, we estimate and compare direct medical costs by likelihood level.

Retrospective, observational analysis using the Truven Health MarketScan database to analyze direct medical costs relating to inpatient and outpatient claims, outpatient prescription claims, medication usage, clinical utilization records, and healthcare expenditures. Patients were categorized into groups based on algorithmically determined likelihoods of AGHD. Likelihood groups were further stratified by age and sex. Trajectories of annual costs (USD) by likelihood level were also investigated.

The study cohort comprised 135 million US adults (aged ≥18 years). Individuals ranked as high-likelihood AGHD had a greater burden of comorbid illness, including cardiovascular disease and diabetes, than those ranked moderate- or low-likelihood. Those in the high-likelihood group had greater mean total direct medical monthly costs ($1844.51 [95% confidence interval (CI): 1841.24;1847.78]) than those in the moderate- ($945.65 [95% CI: 945.26;946.04]) and low-likelihood groups ($459.10 [95% CI: 458.95;459.25]). Outpatient visits accounted for the majority of costs overall, although cost per visit was substantially lower than for inpatient services. Costs tended to increase with age and peaked around the time that individuals were assigned a level of AGHD likelihood. Total direct medical costs in individuals with a high likelihood of AGHD exceeded those for individuals with moderate or low likelihood.

Understanding the trajectory of healthcare costs in AGHD may help rationalize allocation of healthcare resources.

Over the past 4 decades, the clinical care of people living with HIV (PLWH) evolved from treatment of acute opportunistic infections to the management of chronic, noncommunicable comorbidities. Concurrently, our understanding of adipose tissue function matured to acknowledge its important endocrine contributions to energy balance. PLWH experience changes in the mass and composition of adipose tissue depots before and after initiating antiretroviral therapy, including regional loss (lipoatrophy), gain (lipohypertrophy), or mixed lipodystrophy. These conditions may coexist with generalized obesity in PLWH and reflect disturbances of energy balance regulation caused by HIV persistence and antiretroviral therapy drugs. Adipocyte hypertrophy characterizes visceral and subcutaneous adipose tissue depot expansion, as well as ectopic lipid deposition that occurs diffusely in the liver, skeletal muscle, and heart. PLWH with excess visceral adipose tissue exhibit adipokine dysregulation coupled with increased insulin resistance, heightening their risk for cardiovascular disease above that of the HIV-negative population. However, conventional therapies are ineffective for the management of cardiometabolic risk in this patient population. Although the knowledge of complex cardiometabolic comorbidities in PLWH continues to expand, significant knowledge gaps remain. Ongoing studies aimed at understanding interorgan communication and energy balance provide insights into metabolic observations in PLWH and reveal potential therapeutic targets. Our review focuses on current knowledge and recent advances in HIV-associated adipose tissue dysfunction, highlights emerging adipokine paradigms, and describes critical mechanistic and clinical insights.

This study aimed to detect white matter changes and different effects of thyroid hormone on the white matter integrity in young adult male patients with childhood-onset growth hormone deficiency (CO-GHD), compared with healthy people.

Magnetic resonance imaging (structural imaging and diffusion tensor imaging) was performed in 17 young adult male patients with CO-GHD and 17 healthy male controls. The white matter volume, mean diffusivity (MD) values and fractional anisotropy (FA) values were quantified and compared between two groups (CO-GHD group vs. control group). We assessed the interaction effects between thyroid hormone and groups (CO-GHD group vs. control group) on white matter integrity.

Patients with CO-GHD exhibited similar white matter volumes compared with controls. However, compared with the controls, patients with CO-GHD showed a significant reduction in FA values in six clusters and a substantial increase in MD values in four clusters, mainly involving the corticospinal tracts, corpus callosum and so on. Moreover, after correcting for insulin-like growth factor-1 levels, the significant interaction effects between groups (CO-GHD group vs. control group) and serum free thyroxine levels on MD values were noted in three clusters, mainly involving in superior longitudinal fasciculus and sagittal stratum.

In conclusion, young males with CO-GHD showed white matter changes in multiple brain regions and different effects of thyroid hormone on the white matter integrity.

Daily administration of growth hormone (GH) treatment has been in clinical use for treatment for GH deficiency (GHD) in adults for more than 30 years. Numerous studies have demonstrated evidence that GH treatment improves body composition, cardiovascular risk factors and quality of life with few side effects. Less frequent GH injections are hypothesized to improve adherence and several long-acting GH (LAGH) formulations have been developed and a few have been approved and marketed. Different pharmacological modifications have been applied and the pharmacokinetics and pharmacodynamics of LAGH are different to each other and to those of daily injections and require different dosing and monitoring specific for each LAGH. Studies have shown improved adherence with LAGH, and short-term efficacy and side effects are comparable between daily GH injections and LAGHs. Long-term treatment with daily GH injections is effective and safe, while long-term studies for LAGHs are awaited. In this review challenges, benefits, and risks of treatment with daily and long-acting GH preparations will be compared.

GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear.

We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels.

We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst.

Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (β = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [β] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (β = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters.

The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

Congenital combined pituitary hormone deficiency (cCPHD) is the loss of ≥2 pituitary hormones caused by congenital factors.

We aimed to estimate the national incidence of cCPHD diagnosed before age 18 years and in subgroups.

Patients with cCPHD were identified in the Danish National Patient Registry and Danish hospital registries in the period 1996-2020. Hospital files were reviewed and incidences calculated using background population data. Incidence was the main outcome measure.

We identified 128 patients with cCPHD; 88 (68.8%) were males. The median (range) age at diagnosis was 6.2 (0.01-19.0) years. The median (25th;75th percentile) number of hormone deficiencies at diagnosis was 3 (3; 4) at <1 year vs 2 (2; 2) at 1-17 years, P < .0001. Abnormal pituitary magnetic resonance imaging findings were seen in 70.3% (83/118). For those born in Denmark aged <18 years at diagnosis (n = 116/128) the estimated national incidence (95% CI) of cCPHD was 10.34 (7.79-13.72) per 100 000 births, with an annual incidence rate of 5.74 (4.33-7.62) per million. In subgroup analysis (diagnosis <1 vs 1-17 years), the incidence was highest in the 1-17 years subgroup, 7.97 (5.77-11.00) vs 1.98 (1.39-2.84) per 100 000 births, whereas the annual incidence rate was highest at <1 year, 19.8 (13.9-28.4) vs 4.69 (3.39-6.47) per million births.

cCPHD had the highest incidence rate and the most hormone deficiencies in those diagnosed at <1 year. The incidence was highest in the 1-17 years age group, underscoring the need for multiple pituitary hormone investigations throughout childhood and adolescence in children with only 1 hormone deficiency.

Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection.

This study was undertaken by the growth hormone (GH) scientific study group in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives, and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with growth hormone deficiency (GHD) was compiled. Each member was asked to determine the: (1) importance of the data field and (2) ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect.

A total of 246 items were compiled and 27 were removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GHD on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months, and 9 every 12 months.

In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the MDS requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting GH.

Growth hormone is meaningfully involved in the processes of tooth cells differentiation and tissue formation. The aim of the study was to evaluate the occurrence of dental anomalies: microdontia, macrodontia, hypodontia and developmental defects of enamel (DDE) amongst a group of isolated growth hormone deficient (GHD) patients and healthy children. This cross-sectional study was based on a group of 101 Caucasian children: 33 with GHD (mean age 10.94, SD 2.51) and 68 being healthy, normal height subjects (mean age 10.4, SD 2.38). The dental examination in primary and permanent teeth was carried out by one trained and calibrated dentist, in accordance with the WHO guidelines. It was observed that 33% of GHD patients suffer from dental anomalies (hypodontia, microdontia or macrodontia), the difference between the study group and the control group was statistically significant (33% vs 4%, p < 0.001). Hypodontia and microdontia/macrodontia were the most common problems affecting 18% and 21% of the GHD individuals, respectively. The prevalence of DDE did not differ significantly between GHD group and the control group (58% vs 48%, p > 0.05). As children with GHD present more dental anomalies than their healthy coevals, clinicians should be aware of the possible oral health problems associated with GHD and consider dental screening and management as part of the patient's overall health care plan.

Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

Jintrolong® is a long-acting PEGylated recombinant human growth hormone (PEG-rhGH) developed for weekly injection in patients with pediatric growth hormone deficiency (PGHD). Although PEG modification of therapeutic proteins is generally considered safe, concerns persist about the potential for adverse vacuolation in tissues with long-term exposure to PEG-included therapies, particularly in children. We assessed the safety of Jintrolong® in cynomolgus monkeys with an examination of vacuolation in the brain choroid plexus (CP) and reported long-term clinical safety data obtained from children with PGHD. The toxicity of Jintrolong® was assessed following the 52-week administration with doses at 0.3, 1, or 3 mg/kg/week. The levels of vacuolation of CP in animals were dose-dependent and at least partially reversible after a 104- or 157-week recovery period. Vacuolation in the CP epithelium did not lead to obvious subcellular structural or cell functional abnormalities. Compared with the clinical dose of 0.2 mg/kg/week Jintrolong® in PGHD patients, exposure in monkeys under NOAEL 3 mg/kg/week exhibited safety margins greater than 120.5, the predicted minimum dose to induce vacuolation in monkeys is equivalent to 1.29 mg/kg/week in humans, which is 6.45-fold higher than the clinical dose. The safety data acquired in clinical trials for Jintrolong® were also analyzed, which included phase III (360 patients), phase IV (3,000 patients) of 26-week treatment, and a follow-up study with treatment lasting for 3 years. There was no statistically significant difference in the incidence of adverse reactions between the Jintrolong® group and the daily rhGH control group (no PEG), and no new adverse effects (AE) were observed in the Jintrolong® group at the clinical therapeutic dose of 0.2 mg/kg/week.

The aim of the work was to investigate the bone mineral density (BMD) in middle-aged male patients with both childhood-onset (CO) and adulthood-onset (AO) adult growth hormone deficiency (AGHD). In this retrospective cross-sectional study in a major medical center in China, dual X-ray absorptiometry was performed in 50 male AGHD patients (average age was 35.2±9.8 years) and 50 age- and BMI-matched non-athletic healthy men. BMD was compared between AGHD patients and controls. Compared with healthy controls, AGHD group had significantly decreased IGF-1 (p1<0.001) and IGF-1 SDS (p1<0.001). Serum testosterone levels were significantly lower in AGHD patients (p1<0.001), mainly in AO AGHD patients (p3<0.001). The BMD of the femoral neck, trochanter, femoral shaft, total hip, and lumbar spine were significantly lower in all AGHD patients compared with healthy controls (all p1<0.05), especially in CO AGHD patients (all p2<0.05). Multiple stepwise linear regression indicated AGHD was negatively correlated with BMD at each site (β<0, p<0.05). Additionally, serum testosterone level was an independent influencing factor of BMD of the femoral neck (β=0.256, p=0.018) and lumbar spine (β=0.219, p=0.040). BMD was significantly reduced in AGHD patients, especially in CO AGHD patients. Our data suggested that the status of growth hormone deficiency and testosterone level were important for maintaining of bone mineral density in middle-aged male patients with AGHD.

The aim of the study was to evaluate the dental and bone age delay and occlusal traits of children with growth hormone deficiency (GHD) and idiopathic short stature (ISS).

The study group included 46 patients aged 5 to 14 years: 15 with ISS, 17 with GHD before growth hormone treatment, and 14 with GHD during substitution therapy. The control group consisted of 46 age and sex-matched subjects of normal height. A calibrated dentist assessed all subjects in terms of dental age and occlusal characteristics. Bone age was evaluated only in GHD and ISS children as a part of a hospital's diagnostic protocol.

The subgroup of GHD before treatment differed significantly concerning dental age delay from their healthy peers (- 0.34 and 0.83 year, respectively, p = 0.039). Dental age delay in short stature children was less marked than bone age delay (- 0.12 and - 1.76, respectively, p < 0.00001). Dental crowding was recorded in 57% of ISS patients and 53% of GHD children before treatment compared to only 22% of the control subjects (p = 0.027 and p = 0.021, respectively).

Dental age was retarded in GHD children before growth hormone (GH) therapy, but the delay does not seem clinically significant. ISS children and GHD children before therapy showed marked bone age delay and tendency to crowding.

The different pace of teeth eruption and skeletal growth in short stature children should be considered when planning their dental treatment.

To evaluate circulating soluble α-klotho (sαKL) levels in GHD children before and after 12 months of GH treatment (GHT).

Auxological and basal metabolic parameters, oral glucose tolerance test for glucose and insulin levels, insulin sensitivity indices and klotho levels were evaluated before and after 12 months of follow-up in 58 GHD children and 56 healthy controls.

At baseline, GHD children showed significantly lower growth velocity standard deviation score (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001), GH peak and area under the curve (AUC) after arginine test (ARG) (both p < 0.001) and glucagon stimulation test (GST) (p < 0.001 and 0.048, respectively), IGF-1 (p < 0.001), with higher BMI (SDS) (p < 0.001), WC (SDS) (p = 0.003) and sαKL (p < 0.001) than controls. After 12 months of GHT, GHD children showed a significant increase in height (SDS) (p < 0.001), growth velocity (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001) IGF-1 (p < 0.001), fasting insulin (p < 0.001), Homa-IR (p < 0.001) and sαKL (p < 0.001) with a concomitant decrease in BMI (SDS) (p = 0.002) and WC (SDS) (p = 0.038) than baseline. At ROC curve analysis, we identified a sαKL cut-off to discriminate controls and GHD children of 1764.4 pg/mL in females and 1339.4 pg/mL in males. At multivariate analysis, the independent variables significantly associated with sαKL levels after 12 months of GHT were the oral disposition index (p = 0.004, β = 0.327) and IGF-1 (p = 0.019, β = 0.313).

Gender-related sαKL may be used as a marker of GHD combined to GH and IGF-1. Insulin and IGF-1 are independently associated with sαKL values after 12 months of GHT.

In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions.

Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces.

From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year). The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up.

This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.

Adult growth hormone deficiency (AGHD) is an underdiagnosed disease associated with increased morbidity and mortality. Identifying people who may benefit from growth hormone (GH) therapy can be challenging, as many AGHD symptoms resemble those of aging. We developed an algorithm to potentially help providers stratify people by their likelihood of having AGHD.

The algorithm was developed with, and applied to, data in the anonymized Truven Health MarketScan® claims database. Patients. A total of 135 million adults in the US aged ≥18 years with ≥6 months of data in the Truven database. Measurements. Proportion of people with high, moderate, or low likelihood of having AGHD, and differences in demographic and clinical characteristics among these groups.

Overall, 0.5%, 6.0%, and 93.6% of people were categorized into groups with high, moderate, or low likelihood of having AGHD, respectively. The proportions of females were 59.3%, 71.6%, and 50.4%, respectively. People in the high- and moderate-likelihood groups tended to be older than those in the low-likelihood group, with 58.3%, 49.0%, and 37.6% aged >50 years, respectively. Only 2.2% of people in the high-likelihood group received GH therapy as adults. The high-likelihood group had a higher incidence of comorbidities than the low-likelihood group, notably malignant neoplastic disease (standardized difference -0.42), malignant breast tumor (-0.27), hyperlipidemia (-0.26), hypertensive disorder (-0.25), osteoarthritis (-0.23), and heart disease (-0.22).

This algorithm may represent a cost-effective approach to improve AGHD detection rates by identifying appropriate patients for further diagnostic testing and potential GH replacement treatment.

Growth hormone (GH) deficiency develops early in patients with hypothalamic-pituitary disorders and is therefore common among these patients. GH deficiency in adults is associated with increased morbidity, increased body fat mass, abdominal obesity, dyslipidaemia, reduced exercise capacity, impaired cardiac function as well as reduced self-reported well-being and impaired quality of life. Since recombinant human GH became available as replacement therapy more than 25 years ago, randomised controlled trials and long-term studies, together with meta-analyses, have shown improved outcomes in adult patients with hypopituitarism receiving GH. Many of the features associated with GH deficiency in adults improve, or even normalize, and the safety profile is reassuring. The increased interest in GH deficiency in adults with hypothalamic-pituitary disorders has also contributed to the identification of other factors of importance for an outcome such as the replacement of other pituitary hormone deficiencies, and the management of the underlying hypothalamic-pituitary disease, most commonly a pituitary tumour. In this narrative review, we summarize the burden of GH deficiency in adults with hypopituitarism, the impact of GH replacement on the outcome, as well as safety. Based on currently available data, GH replacement should be considered routine management of adults with hypopituitarism.

The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19th century. Its non-acquired variant (naGHD) is, at childhood onset, a rare syndrome of multiple etiologies, predominantly characterized by severe and permanent growth failure culminating in short stature. It is still difficult to diagnose GHD and, in particular, to ascertain impaired GH secretion in comparison to levels in normally-growing children. The debate on what constitutes an optimal diagnostic process continues. Treatment of the GH deficit via replacement with cadaveric pituitary human GH (pit-hGH) had first been demonstrated in 1958, and opened an era of therapeutic possibilities, albeit for a limited number of patients. In 1985, the era of recombinant hGH (r-hGH) began: unlimited supply meant that substantial long-term experience could be gained, with greater focus on efficacy, safety and costs. However, even today, the results of current treatment regimes indicate that there is still a substantial fraction of children who do not achieve adult height within the normal range. Renewed evaluation of height outcomes in childhood-onset naGHD is required for a better understanding of the underlying causes, whereby the role of various factors - diagnostics, treatment modalities, mode of treatment evaluation - during the important phases of child growth - infancy, childhood and puberty - are further explored.

Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established.

This is a retrospective chart review of all random GH levels obtained in neonates ≤28 days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD.

The study included 138 neonates with the mean age of 9.07 ± 6.6 days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73 ± 1.19 ng/ml) as compared to the ARF-GHD (9.4 ± 7.96 ng/ml, p = .002) and non-GHD groups (14.86 ± 14.42 ng/ml, p = .027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5 ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD.

This study demonstrates that random GH levels obtained in the first 28 days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Growth hormone (GH) deficiency (GHD) in adults is characterized by abnormal body composition, unfavorable cardiovascular risk factors, and poor quality of life. The diagnosis is made within appropriate clinical settings and according to established guidelines. Numerous studies have shown that GH treatment improves body composition, cardiovascular risk factors, physical capacity, and quality of life while issues on safety, in particular long-term safety, remain.

Short- and long-term safety of GH replacement in adults with GHD.

Adults with GHD are an inhomogeneous group of patients and GH replacement requires individual considerations. Most adverse effects are mild and transient and related to fluid retention and GH dose. In patients without comorbidities long-term GH treatment is safe and development of diabetes, cardiovascular disease, or tumors are not increased. Furthermore, mortality is not increased. Patients with risk factors should be identified before GH treatment is initiated and an optimal balance between benefit and risk established. Studies with sufficient duration and power to identify the development of cardiovascular diseases and cancers are still awaited. Effective management of comorbidities can be expected to decrease morbidity and mortality and improve quality of life. Studies with long-acting GH formulations are ongoing and available data indicate similar effects and short-time safety.

Growth hormone (GH) therapy has been studied as treatment for clinical manifestations of adult-onset growth hormone deficiency (AO-GHD), including cardiovascular risk, bone health, and quality of life. Patients with AO-GHD typically also have significant history of pituitary pathology and hypopituitarism, which raises the question of what proportion of their clinical presentation can be attributed to GHD alone. Currently, much of the existing data for GH therapy in AO-GHD come from uncontrolled retrospective studies and observational protocols. These considerations require careful reassessment of the role of GH as a therapeutic agent in adult patients with hypopituitarism.

We contrast results from placebo-controlled trials with those from uncontrolled and retrospective studies for GH replacement in patients with hypopituitarism. We also examine the evidence for the manifestations of AO-GHD being attributed to GHD alone, as well as the data on adults with congenital, life-long untreated isolated GHD.

The evidence for increased morbidity and mortality in hypopituitary patients with GHD, and for the benefits of GH therapy, are conflicting. There remains the possibility that the described clinical manifestations of AO-GHD may not be due to GHD alone, but may also be related to underlying pituitary pathology, treatment history and suboptimal hormone replacement.

In the setting of inconsistent data on the benefits of GH therapy, treatment of AO-GHD remains an individualized decision. There is a need for more randomized, placebo-controlled studies to evaluate the long-term outcomes of GH therapy in adults with hypopituitarism.

Adult onset growth hormone (GH) deficiency (AGDH) is a potentially underdiagnosed condition, caused by damage to the pituitary gland. AGHD is treated with growth hormone replacement therapy. A large variety of clinical symptoms and changes in the metabolic homeostasis can be observed and quantified. New large animal models are needed for future drug development.

In this study, we evaluate methods for a new large non-primate animal model of GH deficiency in post pubertal Göttingen Minipigs (minipig). Lesions in the pituitary gland were made by stereotaxic monopolar thermo-coagulation guided by magnetic resonance imaging (MRI), and pituitary function was evaluated using insulin tolerance test (ITT) with measurements of growth hormone secretion induced by hypoglycemia.

Lesions were successfully applied to the pituitary gland without any damage to surrounding tissue including the hypothalamus, which was confirmed by post-operative MRI and post mortem histology. Plasma levels of GH during ITT showed no decrease in secreted levels one week after surgery compared to levels obtained before surgery.

Compared to other GH insufficiency models, eloquent brain tissue is spared. Furthermore, alternatively to rodent models, a large animal model would allow the use of human intended equipment to evaluate disease. Using the minipig avoids social, economical and ethical issues, compared with primates.

The lesions did not remove all GH production, but proof of concept is demonstrated. In addition, the ITT is presented as a safe and efficient method to diagnose GH deficiency in minipigs.

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPG). Methods: Recommendations are based on diligent reviews of clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2019 updated guideline contains 58 numbered recommendations: 12 are Grade A (21%), 19 are Grade B (33%), 21 are Grade C (36%), and 6 are Grade D (10%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 357 citations of which 51 (14%) are evidence level (EL) 1 (strong), 168 (47%) are EL 2 (intermediate), 61 (17%) are EL 3 (weak), and 77 (22%) are EL 4 (no clinical evidence). Conclusion: This CPG is a practical tool that practicing endocrinologists and regulatory bodies can refer to regarding the identification, diagnosis, and treatment of adults and patients transitioning from pediatric to adult-care services with growth hormone deficiency (GHD). It provides guidelines on assessment, screening, diagnostic testing, and treatment recommendations for a range of individuals with various causes of adult GHD. The recommendations emphasize the importance of considering testing patients with a reasonable level of clinical suspicion of GHD using appropriate growth hormone (GH) cut-points for various GH-stimulation tests to accurately diagnose adult GHD, and to exercise caution interpreting serum GH and insulin-like growth factor-1 (IGF-1) levels, as various GH and IGF-1 assays are used to support treatment decisions. The intention to treat often requires sound clinical judgment and careful assessment of the benefits and risks specific to each individual patient. Unapproved uses of GH, long-term safety, and the current status of long-acting GH preparations are also discussed in this document. LAY ABSTRACT This updated guideline provides evidence-based recommendations regarding the identification, screening, assessment, diagnosis, and treatment for a range of individuals with various causes of adult growth-hormone deficiency (GHD) and patients with childhood-onset GHD transitioning to adult care. The update summarizes the most current knowledge about the accuracy of available GH-stimulation tests, safety of recombinant human GH (rhGH) replacement, unapproved uses of rhGH related to sports and aging, and new developments such as long-acting GH preparations that use a variety of technologies to prolong GH action. Recommendations offer a framework for physicians to manage patients with GHD effectively during transition to adult care and adulthood. Establishing a correct diagnosis is essential before consideration of replacement therapy with rhGH. Since the diagnosis of GHD in adults can be challenging, GH-stimulation tests are recommended based on individual patient circumstances and use of appropriate GH cut-points. Available GH-stimulation tests are discussed regarding variability, accuracy, reproducibility, safety, and contraindications, among other factors. The regimen for starting and maintaining rhGH treatment now uses individualized dose adjustments, which has improved effectiveness and reduced reported side effects, dependent on age, gender, body mass index, and various other individual characteristics. With careful dosing of rhGH replacement, many features of adult GHD are reversible and side effects of therapy can be minimized. Scientific studies have consistently shown rhGH therapy to be beneficial for adults with GHD, including improvements in body composition and quality of life, and have demonstrated the safety of short- and long-term rhGH replacement. Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; AHSG = alpha-2-HS-glycoprotein; AO-GHD = adult-onset growth hormone deficiency; ARG = arginine; BEL = best evidence level; BMD = bone mineral density; BMI = body mass index; CI = confidence interval; CO-GHD = childhood-onset growth hormone deficiency; CPG = clinical practice guideline; CRP = C-reactive protein; DM = diabetes mellitus; DXA = dual-energy X-ray absorptiometry; EL = evidence level; FDA = Food and Drug Administration; FD-GST = fixed-dose glucagon stimulation test; GeNeSIS = Genetics and Neuroendocrinology of Short Stature International Study; GH = growth hormone; GHD = growth hormone deficiency; GHRH = growth hormone-releasing hormone; GST = glucagon stimulation test; HDL = high-density lipoprotein; HypoCCS = Hypopituitary Control and Complications Study; IGF-1 = insulin-like growth factor-1; IGFBP = insulin-like growth factor-binding protein; IGHD = isolated growth hormone deficiency; ITT = insulin tolerance test; KIMS = Kabi International Metabolic Surveillance; LAGH = long-acting growth hormone; LDL = low-density lipoprotein; LIF = leukemia inhibitory factor; MPHD = multiple pituitary hormone deficiencies; MRI = magnetic resonance imaging; P-III-NP = procollagen type-III amino-terminal pro-peptide; PHD = pituitary hormone deficiencies; QoL = quality of life; rhGH = recombinant human growth hormone; ROC = receiver operating characteristic; RR = relative risk; SAH = subarachnoid hemorrhage; SDS = standard deviation score; SIR = standardized incidence ratio; SN = secondary neoplasms; T3 = triiodothyronine; TBI = traumatic brain injury; VDBP = vitamin D-binding protein; WADA = World Anti-Doping Agency; WB-GST = weight-based glucagon stimulation test.

In Italy, the utilization and the reimbursement of Growth Hormone (rGH) therapy by the National Health System (Servizio Sanitario Nazionale) are regulated by the "Note #39" included in the "Notes for the use of drugs" by the Italian Medicines Agency (AIFA), which are published in the Official Gazette, thus having the force of law. The "Note #39" establishes the diagnosis for which the reimbursement is granted and confirms the assignment of the national health surveillance on the use of GH therapy to the Italian National Institute of Health, requesting its computerization.

The aim of this work was to realize a dedicated electronic Clinical Report Form based on the mandatory data requested by the Note #39 and allowing the online reporting of the rGH prescriptions by the regional accredited centers.

This interface is at the base of the national database of the Italian Registry of GH Treatment, which allows obtaining and managing correct and complete data to provide public health surveillance on GH therapy, both at national and local levels, necessary for policymakers decisions. In addition, this national database could be a useful instrument for improving knowledge about aspects of this treatment still under discussion.

Treatment with recombinant human growth hormone (rhGH) has been shown to improve adult height in pediatric patients with GH deficiency (GHD). However, reassessment of patients after they reach their final height shows some of them have permanent GH deficiency (PGHD), while others had a transient deficiency (TGHD). The study objective was to assess, in a cohort of pediatric patients with GHD, potential differences in response to treatment with rhGH depending on whether deficiency is permanent or transient.

A retrospective study of 89 patients with GHD, who were monitored from diagnosis to adult height. Clinical, auxological, radiographic and laboratory variables were collected at diagnosis, after the first year of treatment, and when they had reached their adult height.

PGHD was found in 28% of patients. Initial height was -2.46 ± 0.86 SD and -2.24 ± 0.68 SD in subjects with PGHD and TGHD respectively. Peak GH level at diagnosis was 4.26 ± 2.78 and 6.20 ± 2.01 ng/mL (p < 0.01) in the PGHD and TGHD groups respectively. After the first year of treatment, increase in growth velocity was greater in the PGHD group: 4.33 ± 3.53 SD vs. 2.95 ± 2.54 SD in the PGHD group (p = 0.043). Final height was -0.81 ± 0.87 SD in the PGHD and -0.95 ± 0.83 SD in the TGHD group (p = 0.47).

Patients with PGHD had a better short- and long-term response to rhGH. They also showed lower GH levels in stimulation tests at diagnosis, as previously reported.

Growth hormone (GH) has been identified as an important regulator of the immune response. We have previously shown that adults with isolated GH deficiency (IGHD) due to a mutation in the GH releasing hormone receptor (GHRHR) gene, have a greater chance of having periodontitis. However, the interaction of GH with periodontal tissues is still unknown, and this population has emerged as a unique model to investigate this issue. Therefore, we evaluated the microbiological and immunological periodontal profiles of such individuals.

Nineteen IGHD and 19 controls matched by age, sex, diabetes, and smoking status, were enrolled in this case-control study. Periodontal clinical parameters (probing depth [PD] and clinical attachment loss [AL]) were measured at six sites per tooth. Immune mediators (C-reactive protein, matrix metalloproteinase [MMP]-8, MMP-9, interleukin [IL]-1α, IL-6, IL-8, tumor necrosis factor [TNF]-α, adiponectin, and leptin) were analyzed by enzyme-linked immunosorbent assay (ELISA) in the gingival crevicular fluid (GCF) in four non-adjacent sites for each participant (two with PD ≤3 mm [shallow sites] and two with PD ≥7 mm or the worst PD found in the mouth [deep sites]). Bacterial quantification (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) of subgingival biofilm samples collected from these same sites was performed by quantitative real-time polymerase chain reaction (qPCR).

IGHD individuals presented higher values of PD and AL, and increased levels of CRP, IL-8, MMP-8, and adiponectin in the GCF. Bacterial quantification did not identify differences between the two groups.

IGHD alters the local immune response in periodontal pockets leading to greater attachment loss, and GH stands out as an important hormone to be evaluated in the pathogenesis of periodontitis.

To discuss the rationale of developing long-acting growth hormone (LAGH) preparations, to describe the technologies designed to prolong GH action, and to address key issues regarding efficacy, safety, and monitoring while on treatment.

Recombinant human GH is currently approved for daily use and has been shown to restore longitudinal growth, and improve body composition with relatively few side-effects in children and adults with GH deficiency, respectively. However, daily injections can be inconvenient, painful and distressing for some patients, resulting in decreased adherence and efficacy. Over a dozen pharmaceutical companies have designed LAGH preparations that are at various stages of development using a number of different methods to prolong GH action.

LAGH will represent an advancement over daily recombinant human GH injections because of fewer injections that may offer increased acceptance, tolerability, and therapeutic flexibility to patients that potentially can improve treatment outcomes. However, given the unphysiological profile of LAGH preparations, long-term surveillance of efficacy and safety are needed. This review summarizes recent developments of LAGH preparations, and highlights the importance of long-term surveillance registries to assess for efficacy and safety that will be essential for understanding the impact of prolonged exposure to these compounds.

Growth hormone (GH) is produced primarily by anterior pituitary somatotroph cells. Numerous acute human (h) GH treatment and long-term follow-up studies and extensive use of animal models of GH action have shaped the body of GH research over the past 70 years. Work on the GH receptor (R)-knockout (GHRKO) mice and results of studies on GH-resistant Laron Syndrome (LS) patients have helped define many physiological actions of GH including those dealing with metabolism, obesity, cancer, diabetes, cognition and aging/longevity. In this review, we have discussed several issues dealing with these biological effects of GH and attempt to answer the question of whether decreased GH action may be beneficial.