Endocrine Abstracts

JOINT1070

Introduction: Multiple Endocrine Neoplasia type 1 (MEN-1) is a rare hereditary syndrome characterized by the development of multiple NETs that significantly disrupt endocrine function. Both Cushing’s Disease (CD) and prolactinoma is uncommon, with less than 1% presenting with multiple pituitary neuroendocrine tumors (PitNET). Similarly, insulinoma represents an infrequent finding in MEN1. This case highlights the intricate diagnostic and therapeutic challenges posed by MEN1.

Case Presentation: A 28-year-old male presented with rapid weight gain and abdominal striae. Physical examination showed cushingoid and hypogonadal facies, acanthosis nigricans, BMI 40.4 kg/m², BP 142/73 mmHg, and violaceous striae. Elevated nighttime salivary cortisol 0.478 µg/dl (0-0.208) and 24-hour urinary free cortisol 187.0 µg/24h (4.3-176.0) confirmed hypercortisolism. Elevated ACTH 40.8 pg/ml (1.5-12.4), a 7 mm PitNET at MRI, and petrosal sinus sampling confirmed CD diagnosis. Complete laboratory tests: prolactin 65.6 ng/ml (4.04-15.2), testosterone 0.80 ng/ml (2.8-8.0), PTH 229.0 pg/ml (15-65), hypercalcemia 3.16 mmol/l(2.15-2.50). Abdominal imaging identified 6 pancreatic lesions consistent with pNETs (major at head: 21x14mm). DEXA Z score: femoral neck-1.5, distal wrist -1.8. Genetic testing for MEN-1: positive (c.825-1G>A mutation). Hypercalcemia was temporarily controlled with zoledronic acid, deferring parathyroidectomy. Initial management focused on CD treatment due to detected complications: hypogonadotropic hypogonadism, secondary hypothyroidism, class 3 obesity, hypertension, osteopenia. Post-transsphenoidal surgery, morning plasma cortisol was 18.5 µg/dl; histopathology revealed only a prolactin-secreting PitNET. During hospitalization, additional functional studies of pNETs were performed, confirming endogenous hyperinsulinemia (glucose: 47 mg/dl, C-peptide: 7.28 ng/ml, insulin: 33.0 µU/ml), with normal levels of VIP, gastrin, somatostatin, and glucagon. 68-Ga-NOTA-PET revealed multiple pNETs, with biospy guided by ecoendoscopy identifying a well-differentiated G1 pNET. Due to persistent CD and confirmed insulinoma without localization, cabergoline, lanreotide, and continuous glucose monitoring were initiated. Metyrapone started 1 month after improved cortisol levels (24-hour urinary free cortisol: 61.6 µg/24h), with documented symptomatic hypoglycemia post-metyrapone despite prior initiation of lanreotide. The patient is awaiting a 68-Ga-NOTA-exendin-4 PET scan in Switzerland to localize the insulinoma and guide for possible minimal invasive treatment options, along with the potential consideration of reoperation for CD and parathyroidectomy.

Discussion: This case underscores the complexity of managing MEN1 in a young patient with CD, prolactinoma, primary hyperparathyroidism, and multiple pNETs, including an insulinoma. Management of MEN1 requires careful prioritization, as not all conditions can be addressed simultaneously. Localizing the insulinoma is crucial to minimize the risks associated with invasive pancreatic surgery, while timely treatment of CD is essential due to its associated complications.