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1
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Mullen N, Curneen J, Donlon PT, Prakash P, Bancos I, Gurnell M, Dennedy MC. Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks. Endocr Rev 2024; 45:125-170. [PMID: 37556722 PMCID: PMC10765166 DOI: 10.1210/endrev/bnad026] [Citation(s) in RCA: 1] [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: 01/16/2023] [Revised: 07/11/2023] [Accepted: 07/26/2023] [Indexed: 08/11/2023]
Abstract
Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine-learning algorithms have shown promise in the prediction of PA subtypes, while the development of noninvasive alternatives to adrenal vein sampling (including molecular positron emission tomography imaging) has made accurate localization of functioning adrenal nodules possible. In parallel, more selective approaches to targeting the causative aldosterone-producing adrenal adenoma/nodule (APA/APN) have emerged with the advent of partial adrenalectomy or precision ablation. Additionally, the development of novel pharmacological agents may help to mitigate off-target effects of aldosterone and improve clinical efficacy and outcomes. Here, we consider how each of these innovations might change our approach to the patient with PA, to allow more tailored investigation and treatment plans, with corresponding improvement in clinical outcomes and resource utilization, for this highly prevalent disorder.
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Affiliation(s)
- Nathan Mullen
- The Discipline of Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway H91V4AY, Ireland
| | - James Curneen
- The Discipline of Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway H91V4AY, Ireland
| | - Padraig T Donlon
- The Discipline of Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway H91V4AY, Ireland
| | - Punit Prakash
- Department of Electrical and Computer Engineering, Kansas State University, Manhattan, KS 66506, USA
| | - Irina Bancos
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
| | - Mark Gurnell
- Wellcome-MRC Institute of Metabolic Science, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK
| | - Michael C Dennedy
- The Discipline of Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway H91V4AY, Ireland
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Lorusso M, Rufini V, DE Crea C, Pennestrì F, Bellantone R, Raffaelli M. Integration of molecular imaging in the personalized approach of patients with adrenal masses. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2022; 66:104-115. [PMID: 35343669 DOI: 10.23736/s1824-4785.22.03449-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Adrenal masses are a frequent finding in clinical practice. Many of them are incidentally discovered with a prevalence of 4% in patients undergoing abdominal anatomic imaging and require a differential diagnosis. Biochemical tests, evaluating hormonal production of both adrenal cortex and medulla (in particular, mineralocorticoids, glucocorticoids and catecholamines), have a primary importance in distinguishing functional or non-functional lesions. Conventional imaging techniques, in particular computerized tomography (CT) and magnetic resonance imaging (MRI), are required to differentiate between benign and malignant lesions according to their appearance (size stability, contrast enhanced CT and/or chemical shift on MRI). In selected patients, functional imaging is a non-invasive tool able to explore the metabolic pathways involved thus providing additional diagnostic information. Several single photon emission tomography (SPET) and positron emission tomography (PET) radiopharmaceuticals have been developed and are available, each of them suitable for studying specific pathological conditions. In functional masses causing hypersecreting diseases (mainly adrenal hypercortisolism, primary hyperaldosteronism and pheochromocytoma), functional imaging can lateralize the involvement and guide the therapeutic strategy in both unilateral and bilateral lesions. In non-functioning adrenal masses with inconclusive imaging findings at CT/MR, [18F]-FDG evaluation of tumor metabolism can be helpful to characterize them by distinguishing between benign nodules and primary malignant adrenal disease (mainly adrenocortical carcinoma), thus modulating the surgical approach. In oncologic patients, [18F]-FDG uptake can differentiate between benign nodule and adrenal metastasis from extra-adrenal primary malignancies.
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Affiliation(s)
- Margherita Lorusso
- PET/CT Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Vittoria Rufini
- Section of Nuclear Medicine, University Department of Radiological Sciences and Hematology, Università Cattolica del Sacro Cuore, Rome, Italy.,Division of Endocrine and Metabolic Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Carmela DE Crea
- Division of Endocrine and Metabolic Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy - .,Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesco Pennestrì
- Division of Endocrine and Metabolic Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Università Cattolica del Sacro Cuore, Rome, Italy
| | - Rocco Bellantone
- Division of Endocrine and Metabolic Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marco Raffaelli
- Division of Endocrine and Metabolic Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Università Cattolica del Sacro Cuore, Rome, Italy
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Barat M, Cottereau AS, Gaujoux S, Tenenbaum F, Sibony M, Bertherat J, Libé R, Gaillard M, Jouinot A, Assié G, Hoeffel C, Soyer P, Dohan A. Adrenal Mass Characterization in the Era of Quantitative Imaging: State of the Art. Cancers (Basel) 2022; 14:cancers14030569. [PMID: 35158836 PMCID: PMC8833697 DOI: 10.3390/cancers14030569] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/14/2022] [Accepted: 01/18/2022] [Indexed: 12/30/2022] Open
Abstract
Simple Summary Non-invasive characterization of adrenal lesions requires a rigorous approach. Although CT is the cornerstone of adrenal lesion characterization, a multimodality multiparametric imaging approach helps improve confidence in adrenal lesion characterization. Abstract Detection and characterization of adrenal lesions have evolved during the past two decades. Although the role of imaging in adrenal lesions associated with hormonal secretion is usually straightforward, characterization of non-functioning adrenal lesions may be challenging to confidently identify those that need to be resected. Although many adrenal lesions can be readily diagnosed when they display typical imaging features, the diagnosis may be challenging for atypical lesions. Computed tomography (CT) remains the cornerstone of adrenal imaging, but other morphological or functional modalities can be used in combination to reach a diagnosis and avoid useless biopsy or surgery. Early- and delayed-phase contrast-enhanced CT images are essential for diagnosing lipid-poor adenoma. Ongoing studies are evaluating the capabilities of dual-energy CT to provide valid virtual non-contrast attenuation and iodine density measurements from contrast-enhanced examinations. Adrenal lesions with attenuation values between 10 and 30 Hounsfield units (HU) on unenhanced CT can be characterized by MRI when iodinated contrast material injection cannot be performed. 18F-FDG PET/CT helps differentiate between atypical benign and malignant adrenal lesions, with the adrenal-to-liver maximum standardized uptake value ratio being the most discriminative variable. Recent studies evaluating the capabilities of radiomics and artificial intelligence have shown encouraging results.
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Affiliation(s)
- Maxime Barat
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 75014 Paris, France; (M.B.); (P.S.)
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
| | - Anne-Ségolène Cottereau
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Nuclear Medicine, Cochin Hospital, AP-HP, 75014 Paris, France;
| | - Sébastien Gaujoux
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Pancreatic and Endocrine Surgery, Pitié-Salpetrière Hospital, AP-HP, 75013 Paris, France
| | - Florence Tenenbaum
- Department of Nuclear Medicine, Cochin Hospital, AP-HP, 75014 Paris, France;
| | - Mathilde Sibony
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Pathology, Cochin Hospital, AP-HP, 75014 Paris, France
| | - Jérôme Bertherat
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Endocrinology, Cochin Hospital, AP-HP, 75014 Paris, France
| | - Rossella Libé
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Endocrinology, Cochin Hospital, AP-HP, 75014 Paris, France
| | - Martin Gaillard
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Digestive, Hepatobiliary and Endocrine Surgery, Cochin Hospital, AP-HP, 75014 Paris, France
| | - Anne Jouinot
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Endocrinology, Cochin Hospital, AP-HP, 75014 Paris, France
| | - Guillaume Assié
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Department of Endocrinology, Cochin Hospital, AP-HP, 75014 Paris, France
| | | | - Philippe Soyer
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 75014 Paris, France; (M.B.); (P.S.)
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
| | - Anthony Dohan
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 75014 Paris, France; (M.B.); (P.S.)
- Faculté de Médecine, Université de Paris, 75006 Paris, France; (A.-S.C.); (S.G.); (M.S.); (J.B.); (R.L.); (M.G.); (A.J.); (G.A.)
- Correspondence:
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4
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Viëtor CL, Creemers SG, van Kemenade FJ, van Ginhoven TM, Hofland LJ, Feelders RA. How to Differentiate Benign from Malignant Adrenocortical Tumors? Cancers (Basel) 2021; 13:cancers13174383. [PMID: 34503194 PMCID: PMC8431066 DOI: 10.3390/cancers13174383] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/18/2021] [Accepted: 08/24/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Adrenocortical carcinoma is a rare cancer with a poor prognosis. Adrenal tumors are, however, commonly identified in clinical practice. Discrimination between benign and malignant adrenal tumors is of great importance to determine the appropriate treatment and follow-up strategy. This review summarizes the current diagnostic strategies and challenges to distinguish benign from malignant adrenal lesions. We will focus both on radiological and biochemical assessments, enabling diagnosis of the adrenal lesion preoperatively, and on histopathological and a wide variety of molecular assessments that can be done after surgical removal of the adrenal lesion. Furthermore, new non-invasive strategies such as liquid biopsies, in which blood samples are used to study circulating tumor cells, tumor DNA and microRNA, will be addressed in this review. Abstract Adrenocortical carcinoma (ACC) is a rare cancer with a poor prognosis. Adrenal incidentalomas are, however, commonly identified in clinical practice. Discrimination between benign and malignant adrenal tumors is of great importance considering the large differences in clinical behavior requiring different strategies. Diagnosis of ACC starts with a thorough physical examination, biochemical evaluation, and imaging. Computed tomography is the first-level imaging modality in adrenal tumors, with tumor size and Hounsfield units being important features for determining malignancy. New developments include the use of urine metabolomics, also enabling discrimination of ACC from adenomas preoperatively. Postoperatively, the Weiss score is used for diagnosis of ACC, consisting of nine histopathological criteria. Due to known limitations as interobserver variability and lack of accuracy in borderline cases, much effort has been put into new tools to diagnose ACC. Novel developments vary from immunohistochemical markers and pathological scores, to markers at the level of DNA, methylome, chromosome, or microRNA. Molecular studies have provided insights into the most promising and most frequent alterations in ACC. The use of liquid biopsies for diagnosis of ACC is studied, although in a small number of patients, requiring further investigation. In this review, current diagnostic modalities and challenges in ACC will be addressed.
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Affiliation(s)
- Charlotte L. Viëtor
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, 3015GD Rotterdam, The Netherlands; (C.L.V.); (T.M.v.G.)
| | - Sara G. Creemers
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands; (S.G.C.); (L.J.H.)
| | - Folkert J. van Kemenade
- Department of Pathology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands;
| | - Tessa M. van Ginhoven
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, 3015GD Rotterdam, The Netherlands; (C.L.V.); (T.M.v.G.)
| | - Leo J. Hofland
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands; (S.G.C.); (L.J.H.)
| | - Richard A. Feelders
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands; (S.G.C.); (L.J.H.)
- Correspondence:
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5
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Yan J, Zhang T, Zhao K. Application of molecular probes in nuclear imaging of neuroendocrine tumors. Zhejiang Da Xue Xue Bao Yi Xue Ban 2021; 50:131-137. [PMID: 34117850 PMCID: PMC8675064 DOI: 10.3724/zdxbyxb-2021-0031] [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: 08/03/2020] [Accepted: 11/25/2020] [Indexed: 11/25/2022]
Abstract
Neuroendocrine tumors are a type of heterogeneous tumors originating from neuroendocrine cells derived from the neural crest，which can secrete a variety of amines and peptide hormones.Based on different molecular biomarkers，histologic types and differentiation degrees，individualized nuclear imaging can provide information for the early diagnosis，clinical staging，treatment guidance，and detection of the recurrence and metastasis of neuroendocrine tumor. In this paper，we review the development and application of nuclear medicine molecular imaging probes such as glucose analogs，somatostatin analogues，amine precursors，hormone analogs and enzyme inhibitors in the diagnosis and treatment of neuroendocrine tumors.
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Affiliation(s)
- Jing Yan
- Department of PET，the First Affiliated Hospital，Zhejiang University School of Medicine，Hangzhou 310003，China
| | - Tingting Zhang
- Department of PET，the First Affiliated Hospital，Zhejiang University School of Medicine，Hangzhou 310003，China
| | - Kui Zhao
- Department of PET，the First Affiliated Hospital，Zhejiang University School of Medicine，Hangzhou 310003，China
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6
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Silins I, Sundin A, Nordeman P, Jahan M, Estrada S, Monazzam A, Lubberink M, Aigbirhio F, Hellman P, Antoni G. Para-chloro-2-[ 18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging. Int J Med Sci 2021; 18:2187-2196. [PMID: 33859526 PMCID: PMC8040415 DOI: 10.7150/ijms.51206] [Citation(s) in RCA: 13] [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: 08/03/2020] [Accepted: 03/01/2021] [Indexed: 01/11/2023] Open
Abstract
Introduction: [11C]Metomidate ([11C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [11C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T1/2=109.5 min) etomidate analogue, para-chloro-2-[18F]fluoroethyl etomidate; [18F]CETO, as an adrenal PET tracer. Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [18F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [11C]MTO. Results: The binding of [18F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro Kd of 0.66 nM. Non-specific uptake of [18F]CETO in NHP liver was found to be low compared to that of [11C]MTO. Conclusions: High specificity of [18F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [11C]MTO. Non-specific binding to the liver was significantly lower than that of [11C]MTO. [18F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Per Hellman
- Department of Surgical Sciences, Uppsala University
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7
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Sherlock M, Scarsbrook A, Abbas A, Fraser S, Limumpornpetch P, Dineen R, Stewart PM. Adrenal Incidentaloma. Endocr Rev 2020; 41:bnaa008. [PMID: 32266384 PMCID: PMC7431180 DOI: 10.1210/endrev/bnaa008] [Citation(s) in RCA: 169] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 04/06/2020] [Indexed: 12/14/2022]
Abstract
An adrenal incidentaloma is now established as a common endocrine diagnosis that requires a multidisciplinary approach for effective management. The majority of patients can be reassured and discharged, but a personalized approach based upon image analysis, endocrine workup, and clinical symptoms and signs are required in every case. Adrenocortical carcinoma remains a real concern but is restricted to <2% of all cases. Functional adrenal incidentaloma lesions are commoner (but still probably <10% of total) and the greatest challenge remains the diagnosis and optimum management of autonomous cortisol secretion. Modern-day surgery has improved outcomes and novel radiological and urinary biomarkers will improve early detection and patient stratification in future years to come.
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Affiliation(s)
- Mark Sherlock
- Department of Endocrinology, Beaumont Hospital, Dublin, Ireland
- Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Andrew Scarsbrook
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St James University Hospital, Leeds, UK
| | - Afroze Abbas
- Department of Endocrinology, Leeds Teaching Hospitals NHS Trust, St James University Hospital, Leeds, UK
| | - Sheila Fraser
- Department of Endocrine Surgery, Leeds Teaching Hospitals NHS Trust, St James University Hospital, Leeds, UK
| | - Padiporn Limumpornpetch
- Faculty of Medicine & Health, University of Leeds, Worsley Building, Clarendon Way, Leeds, UK
| | - Rosemary Dineen
- Department of Endocrinology, Beaumont Hospital, Dublin, Ireland
- Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Paul M Stewart
- Faculty of Medicine & Health, University of Leeds, Worsley Building, Clarendon Way, Leeds, UK
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8
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Ahmed AA, Thomas AJ, Ganeshan DM, Blair KJ, Lall C, Lee JT, Morshid AI, Habra MA, Elsayes KM. Adrenal cortical carcinoma: pathology, genomics, prognosis, imaging features, and mimics with impact on management. Abdom Radiol (NY) 2020; 45:945-963. [PMID: 31894378 DOI: 10.1007/s00261-019-02371-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Most tumors are either metastatic or locally invasive at the time of diagnosis. Differentiation between ACC and other adrenal masses depends on clinical, biochemical, and imaging factors. This review will discuss the genetics, pathological, and imaging feature of ACC.
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Affiliation(s)
- Ayahallah A Ahmed
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Aaron J Thomas
- Department of Radiology, Baylor College of Medicine, Houston, TX, USA
| | - Dhakshina Moorthy Ganeshan
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Katherine J Blair
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Chandana Lall
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL, USA
| | - James T Lee
- Department of Radiology, University of Kentucky, Lexington, Kentucky, USA
| | - Ali I Morshid
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Mouhammed A Habra
- Departments of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Khaled M Elsayes
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
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Abstract
OBJECTIVE To review the current evidence and guidelines for diagnosis and management of incidental adrenal masses with a focus on the recent changes made by the American College of Radiology (ACR) Incidental Findings Committee. CONCLUSION Incidentally detected adrenal nodules are a commonly encountered finding estimated to occur in 5-7% of the adult population. By following current recommendations, radiologists can improve patient care by efficiently determining which masses require further diagnostic testing and which masses can be considered benign and not require further follow-up.
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Affiliation(s)
- Daniel I Glazer
- Division of Abdominal Imaging and Intervention, Department of Radiology, Harvard Medical School, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
| | - William W Mayo-Smith
- Division of Abdominal Imaging and Intervention, Department of Radiology, Harvard Medical School, Brigham and Women's Hospital, 1620 Tremont Street, Boston, MA, 02120, USA
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10
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Asban A, Patel AJ, Reddy S, Wang T, Balentine CJ, Chen H. Cancer of the Endocrine System. ABELOFF'S CLINICAL ONCOLOGY 2020:1074-1107.e11. [DOI: 10.1016/b978-0-323-47674-4.00068-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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11
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Abstract
Cross-sectional imaging can make a specific diagnosis in lesions, such as myelolipomas, cysts, and hemorrhage, and is often sufficient to distinguish benign from malignant adrenal processes. CT and MRI are useful studies to identify pheochromocytomas and cortisol-secreting or androgen-secreting tumors. In patients with primary aldosteronism, adrenal venous sampling remains the most accurate localizing study and should be performed in all patients older than 35. Radiolabeled isotope studies serve as second-line diagnostic tests for malignant adrenal tumors, primary or metastatic, as well as for pheochromocytoma. Nuclear imaging studies should follow a robust hormonal diagnosis and be correlated with findings on cross-sectional imaging.
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Affiliation(s)
- Mishal Mendiratta-Lala
- Department of Radiology, University of Michigan Health System, 1500 East Medical Center Drive, B1D502, Ann Arbor, MI 48109-5030, USA
| | - Anca Avram
- Department of Radiology, University of Michigan Health System, 1500 East Medical Center Drive, B1G505, Ann Arbor, MI 48109-5030, USA
| | - Adina F Turcu
- Department of Internal Medicine, University of Michigan Health System, Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5911, USA
| | - N Reed Dunnick
- Department of Radiology, University of Michigan Health System, 1500 East Medical Center Drive, B1G503, Ann Arbor, MI 48109-5030, USA.
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Wong K, Chondrogiannis S, Fuster D, Ruiz C, Marzola M, Giammarile F, Colletti P, Rubello D. Additional value of hybrid SPECT/CT systems in neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas. Rev Esp Med Nucl Imagen Mol 2017. [DOI: 10.1016/j.remnie.2016.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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13
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Wong KK, Chondrogiannis S, Fuster D, Ruiz C, Marzola MC, Giammarile F, Colletti PM, Rubello D. Additional value of hybrid SPECT/CT systems in neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas. Rev Esp Med Nucl Imagen Mol 2016; 36:103-109. [PMID: 27793631 DOI: 10.1016/j.remn.2016.09.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 09/15/2016] [Accepted: 09/15/2016] [Indexed: 10/20/2022]
Abstract
The aim of this review was to evaluate the potential advantages of SPECT/CT hybrid imaging in the management of neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas. From the collected data, the superiority of fused images was observed as providing both functional/molecular and morphological imaging compared to planar imaging. This provided an improvement in diagnostic imaging, with significant advantages as regards: (1) precise locating of the lesions; (2) an improvement in characterization of the findings, resulting higher specificity, improved sensitivity, and overall greater accuracy, (3) additional anatomical information derived from the CT component; (4) CT-based attenuation correction and potential for volumetric dosimetry calculations, and (5) improvement on the impact on patient management (e.g. in better defining treatment plans, in shortening surgical operating times). It can be concluded that SPECT/CT hybrid imaging provides the nuclear medicine physician with a powerful imaging modality in comparison to planar imaging, providing essential information about the location of lesions, and high quality homogeneous images.
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Affiliation(s)
- K K Wong
- Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Nuclear Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
| | - S Chondrogiannis
- Department of Nuclear Medicine, Radiology, NeuroRadiology, Medical Physics, Clinical Laboratory, Molecular Laboratory, Microbiology, Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - D Fuster
- Department of Nuclear Medicine, Hospital Clínic, Barcelona, Spain
| | - C Ruiz
- Department of Nuclear Medicine, Hospital Clínic, Barcelona, Spain
| | - M C Marzola
- Department of Nuclear Medicine, Radiology, NeuroRadiology, Medical Physics, Clinical Laboratory, Molecular Laboratory, Microbiology, Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - F Giammarile
- Nuclear Medicine Department, University of Lyon, Lyon, France
| | - P M Colletti
- Department of Nuclear Medicine, University of Southern California, Los Angeles, CA, USA
| | - D Rubello
- Department of Nuclear Medicine, Radiology, NeuroRadiology, Medical Physics, Clinical Laboratory, Molecular Laboratory, Microbiology, Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy.
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15
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Wong KK, Gandhi A, Viglianti BL, Fig LM, Rubello D, Gross MD. Endocrine radionuclide scintigraphy with fusion single photon emission computed tomography/computed tomography. World J Radiol 2016; 8:635-655. [PMID: 27358692 PMCID: PMC4919764 DOI: 10.4329/wjr.v8.i6.635] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 11/09/2015] [Accepted: 03/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To review the benefits of single photon emission computed tomography (SPECT)/computed tomography (CT) hybrid imaging for diagnosis of various endocrine disorders.
METHODS: We performed MEDLINE and PubMed searches using the terms: “SPECT/CT”; “functional anatomic mapping”; “transmission emission tomography”; “parathyroid adenoma”; “thyroid cancer”; “neuroendocrine tumor”; “adrenal”; “pheochromocytoma”; “paraganglioma”; in order to identify relevant articles published in English during the years 2003 to 2015. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (case reports, reviews, meta-analyses and abstracts) concerning the application of SPECT/CT to endocrine imaging were analyzed to provide a descriptive synthesis of the utility of this technology.
RESULTS: The emergence of hybrid SPECT/CT camera technology now allows simultaneous acquisition of combined multi-modality imaging, with seamless fusion of three-dimensional volume datasets. The usefulness of combining functional information to depict the bio-distribution of radiotracers that map cellular processes of the endocrine system and tumors of endocrine origin, with anatomy derived from CT, has improved the diagnostic capability of scintigraphy for a range of disorders of endocrine gland function. The literature describes benefits of SPECT/CT for 99mTc-sestamibi parathyroid scintigraphy and 99mTc-pertechnetate thyroid scintigraphy, 123I- or 131I-radioiodine for staging of differentiated thyroid carcinoma, 111In- and 99mTc- labeled somatostatin receptor analogues for detection of neuroendocrine tumors, 131I-norcholesterol (NP-59) scans for assessment of adrenal cortical hyperfunction, and 123I- or 131I-metaiodobenzylguanidine imaging for evaluation of pheochromocytoma and paraganglioma.
CONCLUSION: SPECT/CT exploits the synergism between the functional information from radiopharmaceutical imaging and anatomy from CT, translating to improved diagnostic accuracy and meaningful impact on patient care.
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Jadvar H, Shulkin BL. Other Neoplasms. CLINICAL NUCLEAR MEDICINE IN PEDIATRICS 2016:337-347. [DOI: 10.1007/978-3-319-21371-2_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Imaging Features of Various Adrenal Neoplastic Lesions on Radiologic and Nuclear Medicine Imaging. AJR Am J Roentgenol 2015; 205:554-63. [PMID: 26295641 DOI: 10.2214/ajr.15.14467] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE The purpose of this review is to describe the features of diverse adrenal neoplastic lesions on radiologic and nuclear medicine imaging. CONCLUSION Various neoplastic lesions with or without malignant potential can occur in the adrenal gland. Knowledge of imaging features of adrenal lesions on radiologic and nuclear medicine imaging will facilitate differential diagnosis and assessment of malignant potential.
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Abstract
Adrenocortical carcinoma (ACC) is rare but one of the most malignant endocrine tumors. This article reviews and summarizes the current knowledge about the treatment of ACC. The epidemiology and molecular events involved in the pathogenesis of ACC are briefly outlined. The different diagnostic tools to distinguish benign from malignant adrenocortical tumors, including biochemical analysis and imaging, are discussed. The surgical treatment of ACC has evolved in the last 2 decades. The different surgical alternatives for the treatment of ACC in the context of primary, recurrent, or metastatic disease are reviewed, and the remaining challenges and controversies are discussed.
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Affiliation(s)
- Gustavo G Fernandez Ranvier
- Division of Metabolic, Endocrine and Minimally Invasive Surgery, Department of Surgery, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Box 1259, New York, NY 10029, USA
| | - William B Inabnet
- Department of Surgery, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, First Ave at 16th St, Baird Hall, 16th Floor, Suite 20, New York, NY 10003, USA.
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20
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Antonini SR, Leal LF, Cavalcanti MM. Pediatric adrenocortical tumors: diagnosis, management and advancements in the understanding of the genetic basis and therapeutic implications. Expert Rev Endocrinol Metab 2014; 9:445-464. [PMID: 30736208 DOI: 10.1586/17446651.2014.941813] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Adrenocortical tumors (ACTs) may be sporadic or related to inherited genetic syndromes. Uncovering the molecular defects underlying these genetic syndromes has revealed key signaling pathways involved in adrenocortical tumorigenesis. Although the understanding of ACT biology has improved, to date, very few potential prognostic molecular markers of childhood ACTs have been identified. In this review, we summarize the current knowledge of the epidemiology, clinical presentation, diagnosis, prognosis and treatment options for pediatric patients with ACTs. A review of the genetic basis of adrenocortical tumorigenesis is presented, focusing on the main molecular abnormalities involved in the tumorigenic process and potential novel therapy targets that have been generated, or are being generated, with the discovery of these molecular defects.
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Affiliation(s)
| | - Letícia F Leal
- a Department of Pediatrics, Ribeirao Preto Medical-School - University of Sao Paulo, Sao Paulo, Brazil
| | - Marcelo M Cavalcanti
- a Department of Pediatrics, Ribeirao Preto Medical-School - University of Sao Paulo, Sao Paulo, Brazil
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Abstract
Adrenocortical carcinoma (ACC) is an orphan malignancy that has attracted increasing attention during the last decade. Here we provide an update on advances in the field since our last review published in this journal in 2006. The Wnt/β-catenin pathway and IGF-2 signaling have been confirmed as frequently altered signaling pathways in ACC, but recent data suggest that they are probably not sufficient for malignant transformation. Thus, major players in the pathogenesis are still unknown. For diagnostic workup, comprehensive hormonal assessment and detailed imaging are required because in most ACCs, evidence for autonomous steroid secretion can be found and computed tomography or magnetic resonance imaging (if necessary, combined with functional imaging) can differentiate benign from malignant adrenocortical tumors. Surgery is potentially curative in localized tumors. Thus, we recommend a complete resection including lymphadenectomy by an expert surgeon. The pathology report should demonstrate the adrenocortical origin of the lesion (eg, by steroidogenic factor 1 staining) and provide Weiss score, resection status, and quantitation of the proliferation marker Ki67 to guide further treatment. Even after complete surgery, recurrence is frequent and adjuvant mitotane treatment improves outcome, but uncertainty exists as to whether all patients benefit from this therapy. In advanced ACC, mitotane is still the standard of care. Based on the FIRM-ACT trial, mitotane plus etoposide, doxorubicin, and cisplatin is now the established first-line cytotoxic therapy. However, most patients will experience progress and require salvage therapies. Thus, new treatment concepts are urgently needed. The ongoing international efforts including comprehensive "-omic approaches" and next-generation sequencing will improve our understanding of the pathogenesis and hopefully lead to better therapies.
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Affiliation(s)
- Martin Fassnacht
- Department of Internal Medicine IV, Hospital of the University of Munich, Ziemssenstrasse 1, 80336 München, Germany.
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Treglia G, Giovanella L, Rufini V. PET and PET/CT imaging in thyroid and adrenal diseases: an update. Hormones (Athens) 2013; 12:327-33. [PMID: 24121375 DOI: 10.1007/bf03401299] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Positron emission tomography (PET) and PET/computed tomography (PET/CT) with different tracers are imaging methods increasingly used in patients with thyroid and adrenal diseases. The aim of this article is to provide an overview based on literature data about the usefulness of PET imaging in this setting. PET and PET/CT with different tracers have been used in patients with thyroid diseases including differentiated thyroid carcinoma, medullary thyroid carcinoma, and poorly differentiated and anaplastic thyroid carcinoma. The usefulness of 18F-FDG-PET and PET/CT in assessing indeterminate thyroid nodules at fine needle aspiration biopsy and the clinical relevance of thyroid incidental 18F-FDG uptake has also been evaluated. Currently, great interest is being shown in a variety of PET tracers that target specific characteristics of adrenal gland function, allowing a more accurate characterization of adrenal masses and staging of adrenal tumors. Since PET/CT using different tracers is an expensive diagnostic tool which necessitates ionizing radiation exposure, cost-effectiveness studies are needed in order to define the appropriate use of this diagnostic method in various endocrine disorders.
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Affiliation(s)
- Giorgio Treglia
- Department of Nuclear Medicine and PET/CT Center, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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18F-fluorocholine uptake in a case of adrenal incidentaloma: possible diagnostic pitfall or potential tool for adrenocortical tumors characterization? Clin Nucl Med 2013; 38:e83-4. [PMID: 23334144 DOI: 10.1097/rlu.0b013e318251e43b] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The understanding of radiotracer's physiological biodistribution as well as the potential source of false-positive results is crucial for an accurate diagnostic interpretation of (18)F-fluorocholine PET/CT examination in patients with prostate cancer. We illustrate the results of whole-body (18)F-fluorocholine PET/CT in a 79-year-old man with biochemical suspicion of prostate adenocarcinoma relapse. PET/CT study showed a focally increased (18)F-fluorocholine uptake, characterizing an incidentally found adrenocortical adenoma. Finally, we draw oncologists' attention to the possible false-positive results of (18)F-fluorocholine PET related to benign and unsuspected adrenocortical lesions in patients with a history of prostate malignancy.
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Bourdeau I, MacKenzie-Feder J, Lacroix A. Recent advances in adrenocortical carcinoma in adults. Curr Opin Endocrinol Diabetes Obes 2013; 20:192-7. [PMID: 23549307 DOI: 10.1097/med.0b013e3283602274] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Adrenocortical cancer (ACC) is a rare and often aggressive malignancy. The overall 5-year survival rate of ACC is less than 30% in part owing to advanced stage of the disease at diagnosis and limited efficiency of therapies when initial surgery is not curative. So far, studies with large cohorts of patients affected by ACC were lacking because of the rarity of the disease; however, recent international and multicenter collaborative studies provide new insights in the management of ACC. RECENT FINDINGS This review summarizes recent findings in the genetic, hormonal evaluation, imaging, and therapies of ACC in adults. There is new promise for the use of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography and metomidate in initial diagnosis and follow-up. Limited studies support benefit of specific surgical approaches such as loco-regional lymph node dissection and metastasectomy in specific subgroups. New developments in the use of mitotane therapy and its drug interactions, on adjuvant radiotherapy and prospective data on combined chemotherapy, have appeared recently. SUMMARY These recent findings will provide more evidence-based recommendations in the future to better assist clinicians in the management of patients with ACC. However, there is still an important need to understand the molecular mechanisms underlying this disease to design better therapeutic approaches.
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Affiliation(s)
- Isabelle Bourdeau
- Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.
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Hahner S, Kreissl MC, Fassnacht M, Haenscheid H, Bock S, Verburg FA, Knoedler P, Lang K, Reiners C, Buck AK, Allolio B, Schirbel A. Functional characterization of adrenal lesions using [123I]IMTO-SPECT/CT. J Clin Endocrinol Metab 2013; 98:1508-18. [PMID: 23426614 DOI: 10.1210/jc.2012-3045] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
CONTEXT Adrenal tumors are highly prevalent and represent a wide range of different pathological entities. Conventional imaging often provides only limited information on the origin of these lesions. Novel specific imaging methods are, therefore, of great clinical interest. OBJECTIVE We evaluated [(123)I]iodometomidate ([(123)I]IMTO) imaging for noninvasive characterization of adrenal masses. DESIGN/SETTING This was a prospective monocentric diagnostic study in a tertiary care center. PATIENTS AND INTERVENTION A total of 51 patients with an adrenal lesion underwent [(123)I]IMTO imaging after injection of 185 MBq of [(123)I]IMTO. Sequential planar whole-body scans until 24 hours postinjection and single photon emission computed tomography (SPECT)/computed tomography imaging 4 to 6 hours postinjection were performed. MAIN OUTCOME MEASURE Sensitivity and specificity of [(123)I]IMTO imaging for the noninvasive characterization of adrenal lesions were measured. RESULTS Adrenocortical tissue showed high and specific tracer uptake with a short investigation time and low radiation exposure. Qualitative analysis of SPECT/computed tomography data resulted in a sensitivity of 89% and a specificity of 85% for differentiating adrenocortical tumors from lesions of nonadrenocortical origin. Receiver-operating characteristic analysis of semiquantitative data revealed a sensitivity of 83% and a specificity of 86% for identification of adrenocortical lesions at a cutoff value of tumor to liver ratio of 1.3. CONCLUSIONS [(123)I]IMTO is a highly specific radiotracer for imaging of adrenocortical tissue with a short investigation time and low radiation exposure. Because of the general availability of SPECT technology, [(123)I]IMTO scintigraphy has the potential to become a widely used tool to noninvasively characterize the biology of adrenal lesions.
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Affiliation(s)
- Stefanie Hahner
- Endocrinology & Diabetes Unit, University Hospital Würzburg, Oberdürrbacher Strasse 6, D-97080 Würzburg, Germany
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