26-28: Other Syndromes of Multiple Endocrine Neoplasia

Patients with Carney complex develop adrenocortical nodular hyperplasia that can produce skin abnormalities, Cushing syndrome, GH-secreting pituitary adenomas or hyperplasia with acromegaly, thyroid tumors, gonadal Sertoli cell tumors, myxomas of the heart and breast, and other malignancies. With McCune-Albright syndrome, precocious puberty (particularly girls) develops due to gonadal hypersecretion. Multiple adrenal nodules can rarely cause Cushing syndrome. Hyperthyroidism results from autonomously functioning thyroid nodules. Acromegaly is caused by GH-secreting pituitary tumors. Patients also have fibrous dysplasia of bones and hypophosphatemia, and bone fractures are common. Sudden death has been reported. Type 2 von Hippel Lindau (VHL) syndrome is associated with pheochromocytomas, pancreatic/duodenal neuroendocrine tumors, hyperparathyroidism, and pituitary tumors as well as hemangiomas and renal cell carcinomas. Hypoxia inducible factor 2A (HIF2A) germline mutations predispose to pheochromocytomas, pancreatic/duodenal somatostatinomas, as well as erythrocytosis and retinal abnormalities. Neurofibromatosis type 1 (NF-1) is associated with pheochromocytomas and pancreatic/duodenal somatostatinomas as well as neurofibromas and hypothalamic hamartomas. Beckwith Wiedemann syndrome is associated with an increased risk of malignancies, particularly Wilms tumor and hepatoblastoma, but also neuroblastoma, adrenocortical carcinoma, neuroblastoma, pheochromocytoma, and paraganglioma.