An unusual association of hyperparathyroidism, ectopic GHRH secrection and bronchial carcinoid in a MEN1 family

Introduction: MEN1 is characterized by tumors of parathyroid glands, pituitary and pancreas. Pituitary tumors frequently produce PRL and GH, but acromegaly due to ectopic GHRH secretion has been reported in <1% of cases. Here we present a case of two patients belonging to a MEN1 family (c.207delC; p.P69PfsX118 mutation (ENST00000377313), affected by primary hyperparathyroidism, in association with acromegaly due to ectopic GHRH secretion and bronchial carcinoid, respectively. Case report: A 18-year-old boy came to our observation with clinical, biochemical findings and scintigraphic image diagnostic of primary hyperparathyroidism. He successfully underwent subtotal parathyroidectomy. Given the young age and the presence of multiple parathyroid hyperplasia, the patient underwent genetic analysis that revealed the presence of a MEN1 gene mutation. Despite the absence of signs and symptoms, acromegaly due to ectopic GHRH secretion was diagnosed (RMN negative for pituitary adenoma and GHRH level: 60.14 ng/ml, normal 9.4±5.5). Search for an ectopic tumor through chest-abdominal TC scan, total-body PET/CT and 111 In-Pentreotide (Octreoscan) was unsuccessful, and treatment with somatostatin analogs was started. Recently, scintigraphy with somatostatin analogs (68-Ga-DOTATOC-PET) showed three focal areas in the pancreatic tail. Distal pancreasectomy revealed a multiple pancreatic neuroendocrine tumors. The evaluation of the patient’s mother, revealed the presence of primary hyperparathyroidism, elevated gastrin, chromogranin A, pancreatic polypeptide and a 4 cm-lung mass radiologically evident. The patient underwent subtotal right pneumonectomy and the histological analysis was consistent with the diagnosis of a typical bronchial carcinoid secreting the above polypeptides. Conclusions: In this report we emphasize the uncommon presence of acromegaly due to pancreatic ectopic GHRH secretion and bronchial carcinoid in two patients belonging to a MEN1 family. An early and full diagnostic procedure appears to be important in order to recognize this rare syndrome that may be lethal as happened to the proband aunt who died for a malignant gastrinoma.