title: Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype.
abstract: The objective of this study was to describe a multiple endocrine neoplasia type 1 (MEN1) family characterized by primary hyperparathyroidism, in association with acromegaly because of ectopic growth hormone-releasing hormone (GHRH) secretion by a pancreatic neuroendocrine tumor in a young man and with a bronchial carcinoid in his mother. We investigate the clinical, radiological imaging, histopathologic findings, and therapy. An 18-year-old man successfully underwent subtotal parathyroidectomy for primary hyperparathyroidism. A subsequent genetic analysis showed a MEN1 gene mutation. Three years later, acromegaly because of ectopic GHRH secretion was diagnosed (pituitary MRI negative and elevated GHRH levels). A search for an ectopic tumor was unsuccessful and somatostatin analog therapy was started. Successively, scintigraphy with somatostatin analogs (68-Ga-DOTATOC-PET) showed three focal areas in the pancreatic tail. Distal pancreatectomy showed multiple pancreatic neuroendocrine tumors and hormonal status was normalized. Afterwards, the evaluation of the patient's mother, carrying the same mutation, indicated a primary hyperparathyroidism and a 4 cm lung mass. The patient underwent subtotal pneumonectomy and the histological analysis was consistent with the diagnosis of a typical bronchial carcinoid. In conclusion, an atypical phenotype may be recorded in MEN1 families, thus emphasizing the importance of the new imaging and surgical techniques in the diagnosis and treatment of such a rare disease.
authors.affiliation: Department of Clinical Sciences and Community Health, Endocrinology and Diabetology Unit, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. elisasala@yahoo.it
authors.forename: Elisa
authors.initials: E
authors.lastname: Sala
authors.forename: Emanuele
authors.initials: E
authors.lastname: Ferrante
authors.forename: Elisa
authors.initials: E
authors.lastname: Verrua
authors.forename: Elena
authors.initials: E
authors.lastname: Malchiodi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantovani
authors.forename: Marcello
authors.initials: M
authors.lastname: Filopanti
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrero
authors.forename: Andrea
authors.initials: A
authors.lastname: Pietrabissa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vanoli
authors.forename: Stefano
authors.initials: S
authors.lastname: La Rosa
authors.forename: Maria C
authors.initials: MC
authors.lastname: Zatelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Uberta
authors.initials: U
authors.lastname: Verga
mesh_terms: D000172:Acromegaly / Q000209:etiology; D000293:Adolescent; D001984:Bronchial Neoplasms / Q000235:genetics / Q000601:surgery; D002276:Carcinoid Tumor / Q000235:genetics / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D040941:Heredity; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000209:etiology; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D009154:Mutation; D018358:Neuroendocrine Tumors / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D016105:Parathyroidectomy; D010375:Pedigree; D010641:Phenotype; D011013:Pneumonectomy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D013007:Growth Hormone-Releasing Hormone