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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. [ABSTRACT FROM AUTHOR]

Context: Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate.Objective: The aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients.Methods: Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease.Results: Five of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively.Conclusion: Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered. [ABSTRACT FROM AUTHOR]

Context: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE results in an increase of progression-free survival and quality of life in patients with progressive well-differentiated neuroendocrine neoplasms (NENs).Objective: To study the effect of 177Lu-DOTATATE in patients with carcinoid syndrome and radiologically stable or newly diagnosed disease treated solely for the purpose of symptom reduction.Design: Retrospective cohort study.Setting: Tertiary care hospital.Patients: 22 patients with a metastatic midgut NEN, elevated urinary 5-hydroxyindolacetic acid excretion and flushing and/or diarrhea despite treatment with a somatostatin analog, without documented disease progression.Intervention: PRRT with 177Lu-DOTATATE (intended cumulative dose: 29.6 GBq) with a primary aim to reduce symptoms.Results: After PRRT, mean bowel movement frequency (BMF) decreased from 6.1 ± 3.4 to 4.6 ± 3.6 per day (p=0.009). Flushes decreased from 4.3 ± 2.9 to 2.4 ± 2.7 flushes per day (p=0.002). A decrease of BMF of more than 30% occurred in 47% of patients with baseline BMF of 4 or more (n=17). In patients with ≥2 episodes of flushing a day (n=15), 67% of patients had more than 50% decrease of daily flushing. A decrease in urinary 5-hydroxyindolacetic acid excretion of more than 30% was seen in 56% of patients. The EORTC-C30 diarrhea subscale score showed a trend towards improvement by an average of 16.7 ± 33.3 points (p=0.11).Conclusion: PRRT with 177Lu-DOTATATE effectively reduced diarrhea and flushing in patients with carcinoid syndrome and can be considered for symptomatic treatment of carcinoid syndrome insufficiently controlled with somatostatin analogs. [ABSTRACT FROM AUTHOR]

Objectives: Inoperable or metastatic paragangliomas (PGLs) and malignant pheochromocytomas (PCCs) are rare tumours with limited options for systemic treatment. Aim of thi s study was to assess the safety and efficacy of the radiolabelled somatostatin analogue (177LutetiumDOTA0-Tyr3)octreotate (177Lu-DOTATATE) for the treatment of PGLs and PCCs. Methods: Patients with histologically proven inoperable or malignant PGLs and PCCs treated with 177Lu-DOTATATE at our centre were retrospectively analysed. Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gb per cycle. Response was assessed with u se of RECIST 1.1. Results: Thirty patients were included: 17 with parasympathetic, 10 with sympathetic PGLs and 3 with PCCs. Grade 3/4 subacute haematotoxicity occurred in 6 (20%) of patients. A reversible subacute adverse event due to cardiac failure following possible catecholamine release occurred in two patients. Best tumour response was partial response in 7 (23%) and stable disease in 20 (67%), whereas 3 (10%) patients had progressive disease. In 20 patients with baseline disease progression, tumour control was observed in 17 (85%); t he median progression-free survival was 91 months in patients with parasympathetic PGLs, 13 months in patients wi th sympathetic PGLs and 10 months in patients with metastatic PCCs. Conclusion: This study suggests that PRRT with 177Lu-DOTATATE is a safe and effective treatment option for patient s with inoperable or malignant PGL and PCC. [ABSTRACT FROM AUTHOR]

Objective: To determine if urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion is of prognostic value for overall survival (OS) in patients with a gastrointestinal neuroendocrine tumour (NET) and to compare the prognostic value with patient characteristics, ENETS/WHO grading, ENETS TNM staging and biomarkers. Design and methods: Data was collected from patients with a gastrointestinal NET or a NET with gastrointestinal metastases and available 5-HIAA excretion in 24-h urine samples. Laboratory results were stratified for urinary 5-HIAA and chromogranin A (CgA): <2x upper limit of normal (ULN), 2-10x ULN, or >10x ULN. For neuron-specific enolase (NSE), this was the reference range or >1x ULN. OS was compared using Kaplan-Meier and log-rank tests, and hazard ratios were calculated using Cox regression for univariate and multivariate analyses. Results: A total of 371 patients were included, 46.6% female with a mean age of 59.9years. OS was shortest in patients with urinary 5-HIAA excretion >10x ULN vs reference range (median 83 months vs 141 months, P = 0.002). In univariate analysis, urinary 5-HIAA excretion >10x ULN was a negative predictor (HR 1.62, 95% CI: 1.09-2.39). However, in multivariate analysis, only age (HR 1.04, 95% CI: 1.01-1.08), grade 3 disease (HR 5.09, 95% CI: 2.20-11.79), NSE>1x ULN (HR2.36, 95% CI: 1.34-4.14) and CgA >1 Ox ULN (HR 3.61, 95% CI: 1.56-8.34) remained as the predictors. Conclusion: Urinary 5-HIAA excretion >10x ULN is a negative predictor for OS. However, when added to other biomarkers and grading, it is no longer a predictor for OS. Therefore, it should only be determined to assess carcinoid syndrome and not for prognostic value. [ABSTRACT FROM AUTHOR]