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Objective: To report clinical, hormonal and structural effects of CYP11B1 pathogenic variations in Indian patients with 11β‐hydroxylase deficiency (11βOHD) and find hormonal criteria that accurately distinguish 11βOHD from 21α‐hydroxylase deficiency (21OHD). Design: Retrospective record review of genetically diagnosed patients with 11βOHD. Patients and Measurements: Clinical features, hormonal parameters at diagnosis (by immunoassay) and recent follow‐up of 13 genetically proven 11βOHD patients managed at our centre were retrospectively reviewed. ACTH‐stimulated serum adrenal steroids (measured by LC‐MS/MS) of 11βOHD were compared with those of simple virilizing and non‐classic 21OHD. Structural analysis of the observed pathogenic variations was performed by computational modelling. Results: Nine (four females) and four (all females) patients had classic and non‐classic disease, respectively. All 11βOHD patients had elevated ACTH‐stimulated serum 11‐deoxycortisol (26.5–342.7 nmol/L) whereas none had elevated serum 17‐hydroxyprogesterone (4.2–21.2 nmol/L); both hormonal parameters distinguished 11βOHD from 21OHD with 100% accuracy. ACTH‐stimulated serum cortisol, but not 11‐deoxycortisol, clearly distinguished classic (<70 nmol/L) from non‐classic (>160 nmol/L) disease. Thirteen (eight novel, two recurrent) pathogenic variants were observed. Only missense mutations were observed among patients with non‐classic disease. Computational modelling predicted the possible affection of enzyme structure and function for all the observed missense mutations. Conclusions: This first Indian study describes 13 11βOHD patients, including four with the rarer non‐classic variant. A total of eight novel pathogenic variants were identified in our study, highlighting regional genetic heterogeneity. Measurement of ACTH‐stimulated adrenal steroids by LC‐MS/MS will help avoid the misdiagnosis of 11βOHD as 21OHD and has potential to distinguish classic from non‐classic 11βOHD. [ABSTRACT FROM AUTHOR]

Introduction: Radionuclide therapy is a promising treatment modality in metastatic pheochromocytoma/paraganglioma (PPGL). There is scarce data on 131I-metaiodobenzyl guanidine (131I-MIBG) therapy from the Indian subcontinent. Hence, we aim to study the safety and effectiveness of low-dose, low-specific activity (LSA) 131I-MIBG therapy in patients with symptomatic, metastatic PPGL. Methods: Clinical, hormonal, and radiological response parameters and side effects of LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL were retrospectively reviewed. World health organizations' (WHO) symptomatic, hormonal, and tumor response, and response evaluation criteria in solid tumors (RECIST1.1) criteria were used to assess the response. Results: Seventeen (PCC: 11, sympathetic PGL: 06) patients (15 with disease progression) received low-dose LSA 131I-MIBG therapy. Complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) were 18% (3/17), 24% (4/17), 18% (3/17), and 41% (7/17), respectively, for WHO symptomatic response; 20% (2/10), 10% (1/10), 30% (3/10), and 40% (4/10), respectively, for WHO hormonal response; and 19% (3/16), 6% (1/16), 31% (5/16), and 44% (7/16), respectively for tumor response based on RECIST1.1. All patients with symptomatic PD and 50% (2/4) with hormonal PD had progression as per RECIST1.1 criteria. Side effects included thrombocytopenia, acute myeloid leukemia, mucoepidermoid carcinoma, and azoospermia in 6% (1/17) each. Conclusions: Our study reaffirms the modest efficacy and safety of low-dose, LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL. Symptomatic, but not hormonal, progression after 131I-MIBG therapy correlates well with tumor progression and should be further evaluated with imaging. In resource-limited settings, anatomic imaging alone may be used to assess tumor response to 131I-MIBG therapy. [ABSTRACT FROM AUTHOR]

Objectives: Pediatric pheochromocytoma and paraganglioma (PPGL) are rare tumors with limited data on the diagnostic performance of 68Ga-DOTA(0)-Tyr(3)-octreotate positron emission tomography–computed tomography (68Ga-DOTATATE PET/CT). We have described our experience of 68Ga-DOTATATE PET/CT in overall and von Hippel Lindau (VHL)-associated pediatric PPGL and compared its sensitivity with that of 131I-meta-iodobenzyl-guanidine (131I-MIBG), 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT), and contrast-enhanced CT (CECT). Methods: Retrospective evaluation of consecutive PPGL patients (age: ≤20 years), who had undergone at least one functional imaging [131I-MIBG, 18F-FDG PET/CT, and/or 68Ga-DOTATATE PET/CT], was done. Composite of anatomical and all the performed functional imaging scans, image comparator (IC), was considered as the gold standard for sensitivity analysis. Results: In a cohort of 32 patients (16 males, age at diagnosis: 16.4 ± 2.68 years), lesion-wise sensitivity of 68Ga-DOTATATE PET/CT (95%) was higher than that of both 18F-FDG-PET/CT (80%, p=0.027) and 131I-MIBG (65%, p=0.0004) for overall lesions, than that of 18F-FDG-PET/CT (100 vs. 67%, p=0.017) for primary PPG, and than that of 131I-MIBG (93 vs. 42%, p=0.0001) for metastases. In the VHL (n=14), subgroup, 68Ga-DOTATATE PET/CT had higher lesion-wise sensitivity (100%) compared to 18F-FDG PET/CT (74%, p=0.045) and 131I-MIBG (64%, p=0.0145). Conclusions: In our pediatric PPGL cohort, overall lesion-wise sensitivity of 68Ga-DOTATATE PET/CT was higher than that of 18F–FDG PET/CT and 131I-MIBG scintigraphy. Hence, we recommend 68Ga-DOTATATE PET/CT as the preferred modality in pediatric PPGL. 68Ga-DOTATATE PET/CT may evolve as a preferred imaging modality for disease surveillance in VHL. [ABSTRACT FROM AUTHOR]

Pituitary adenomas (PA) account for approximately 15% of all intracranial neoplasms. Pituitary adenomas can be of different subtypes based on the cell of origin or associated hormone hypersecretion (non-functioning pituitary adenoma, prolactinoma, somatotropinoma, corticotropinoma, thyrotropinoma, and gonadotropinoma). Functioning PAs are associated with relatively higher morbidity and mortality because of associated hormone hypersecretion syndromes. Diagnosis of functioning PA is established by biochemical confirmation of hormone hypersecretion and demonstration of a pituitary lesion on imaging. Trans-sphenoidal surgical resection of tumor represents the first-line treatment for most tumor types, except for prolactinomas where medical therapy with dopamine agonists is preferred. Radiotherapy (RT) and medical therapy are the other options for the management of PA. It is important to individualize treatment options based on tumor type, patient's clinical condition, expertise of surgeon, affordability and patient preferences. In the first part of this series, we review the presentation and management of adrenocorticotropic hormone secreting, gonadotropin secreting and aggressive PA. Despite several recent advances, the diagnosis and management of Cushing's disease is still a challenge. Modifications in magnetic resonance imaging techniques like volume interpolated 3D spoiled gradient echo sequence have improved the sensitivity to detect microcorticotropinomas. Pituitary RT, preferably conventional RT, is a useful second-line therapy for the management of CD. Besides the conventional drugs, few drugs such as pasireotide and osilodrostat have been approved by US FDA recently, whereas several others are in pipeline which provide hope for a better outcome in CD patients. Temozolomide is a useful drug for the management of aggressive PA. [ABSTRACT FROM AUTHOR]

Context: Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%‐80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18‐24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect. Objective: To determine long‐term outcome of CRT and its predictors in CD patients. Design, Setting and Patients: This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post‐RT follow‐up. The dose delivered was 45 Gy in 25 fractions over 5 weeks. Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut‐off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed. Results: The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12‐48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3‐120) months after RT, while 13 (31%) patients had persistent disease at last follow‐up. There were no significant predictors of disease remission after CRT. Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri‐RT cabergoline. Peri‐CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016). Conclusion: Use of cabergoline in the peri‐CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD. [ABSTRACT FROM AUTHOR]

Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. Results: Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16-58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12-155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26-1196 mg; interquartile range: 104-416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3-4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves. Conclusion: Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure. [ABSTRACT FROM AUTHOR]