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Introduction: Neuroendocrine neoplasms encompass well-differentiated tumors (NETs) and poorly differentiated carcinomas (neuroendocrine carcinomas [NECs]), which are distinguished by their clinical behavior and molecular characteristics. They can cause paraneoplastic syndromes, such as ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS), necessitating prompt recognition and management due to severe hypercortisolism., Case Presentation: A 66-year-old patient with a 3-year history of metastatic mixed neuroendocrine-non-neuroendocrine neoplasm with a NEC and adenocarcinoma component originating from the vulva presented to the emergency department with dyspnea and fatigue. Upon clinical examination, we found widespread hyperpigmentation, a moon-face appearance, hirsutism, buffalo hump, and muscle atrophy. Laboratory investigations revealed severe hypokalemia (2.3 mmol/L), elevated serum cortisol (1,726 nmol/L) and ACTH (194 ng/L) levels. Urinary free cortisol measurement was 21-fold the upper limit of the reference range (3,614.0 nmol/24 h), and cortisol concentration did not decrease after 1mg-dexamethasone suppression test (1,812 nmol/L for an expected value <50 nmol/L), confirming the ACTH-dependent CS. Thoracoabdominal computed tomography (CT) scan demonstrated progressive neoplastic disease in the liver, kidney, lymph nodes, peritoneum, and lungs. Brain magnetic resonance imaging indicated multifocal metastatic infiltration but no evidence of pituitary adenoma. Interestingly, despite a previously negative 68 Ga-DOTATATE positron emission tomography (PET)/CT performed 1 year prior, there was moderate somatostatin receptor (SSTR) expression in lymphatic, pulmonary, peritoneal, and bone tissues, suggesting the presence of a component with redifferentiation and re-expression of the SSTR. After the workup, the patient was admitted to a supportive care facility. Hypercortisolism symptoms were effectively managed with an adrenal enzyme inhibitor (ketoconazole) in combination with somatostatin analogs. Unfortunately, the patient was too frail to benefit from peptide receptor radionuclide therapy (PRRT)., Conclusion: This redifferentiation phenomenon in neuroendocrine tumors should be further investigated as patients might be, under certain conditions, eligible for PRRT. Therefore, we suggest that newly occurring paraneoplastic syndromes in patients with NEC should always be evaluated using 68 Ga-DOTATATE PET/CT., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: Hereditary pheochromocytoma (hPCC) commonly develops bilaterally, causing adrenal insufficiency when standard treatment, radical adrenalectomy (RA), is performed. Partial adrenalectomy (PA) aims to preserve adrenal function, but with higher recurrence rates. This study compares outcomes of PA versus RA in hPCC., Methods: Patients with hPCC due to pathogenic variants in RET, VHL, NF1, MAX, and TMEM127 from 12 European centers (1974-2023) were studied retrospectively. Stratified analysis based on surgery type and initial presentation was conducted. The main outcomes included recurrence, adrenal insufficiency, metastasis, and mortality., Results: The study included 256 patients (223 RA, 33 PA). Ipsilateral recurrence rates were 9/223 (4%) after RA versus 5/33 (15%) after PA (P = 0.02). Metastasis and mortality did not differ between groups. Overall, 103 patients (40%) underwent bilateral adrenalectomy either synchronously or metachronously (75 RA, 28 PA). Of these, 46% developed adrenal insufficiency after PA.In total, 191 patients presented with initial unilateral disease, of whom 50 (26%) developed metachronous contralateral disease, most commonly in RET, VHL, and MAX. In patients with metachronous bilateral disease, adrenal insufficiency developed in 3/4 (75%) when PA was performed as the first operation followed by RA, compared to 1/7 (14%) when PA was performed as the second operation after prior RA (P = 0.09)., Conclusion: In patients with hPCC undergoing PA, local recurrence rates are higher than after RA, but metastasis and disease-specific mortality are similar. Therefore, PA seems a safe method to preserve adrenal function in patients with hPCC, in cases of both synchronous and metachronous bilateral disease, when performed as a second operation., Competing Interests: Conflict of interest: None., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Biallelic loss-of-function variants in the IYD gene cause hypothyroidism resulting from iodine wasting. We describe 8 patients (from 4 families in which the parents are first cousins) who are homozygous for a variant in IYD (including a novel missense deleterious variant, c.791C>T [P264L], in 1 family). Seven patients presented between 5 and 16 years of age with a large goiter, overt hypothyroidism, and a high serum thyroglobulin. The goiter subsided with levothyroxine therapy in most. Upon stopping levothyroxine in 5 patients, goiter and hypothyroidism reappeared in 3. In these 3 patients, a rising serum thyroglobulin concentration preceded hypothyroidism and goiter and urinary iodine excretion was low. In patients who remained euthyroid, urinary iodine was normal. In conclusion, these patients bearing biallelic pathogenic variants in IYD developed a large goiter, a high serum thyroglobulin, and overt hypothyroidism when their iodine intake was low., Competing Interests: Conflict of interest: C.H., N.D., and C.B. are members of the MTG-8 Study Group of the European Reference Network for Rare Endocrine Disease, Endo-ERN., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)