Mahvash disease is an autosomal recessive, hereditary
pancreatic neuroendocrine tumor syndrome.
The genetic defect that causes Mahvash disease is biallelic inactivating mutations of the
glucagon receptor
The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in the ...
gene (''GCGR'').
Mahvash disease was discovered by American physician Run Yu and his colleagues in 2008.
Mahvash disease is very rare. There have been over 10 cases of Mahvash disease described by the end of 2018.
Mahvash disease occurs in both females and males. Mahvash disease is also called “glucagon cell hyperplasia and neoplasia” or “glucagon cell adenomatosis” by some authors but Mahvash disease is a distinct disease entity while the two alternative terms are mostly histological descriptions.
Some patients with “glucagon cell hyperplasia and neoplasia” do not have glucagon receptor mutations.
Signs and symptoms
Most patients with Mahvash disease are diagnosed in adulthood. Patients with Mahvash disease usually present with vague abdominal discomfort. Imaging with CT or MRI identifies a very large pancreas with one or more tumors. Biochemical testing shows marked hyperglucagonemia (hundreds-fold elevated). If the tumors are resected, they are found to be
neuroendocrine tumor
Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lun ...
s that usually express glucagon. In the tumor margin, pancreatic alpha cell hyperplasia is pervasive, numerous large
islets composed of mostly alpha cells are evident, and multiple
microadenoma
Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.[neuroendocrine tumor
Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lun ...]
s often are present. The
pancreatic neuroendocrine tumors are the main health concern for patients with Mahvash disease. Although the tumors commonly are indolent, death due to liver metastasis has been reported.
Pathogenesis
Mahvash disease is a form of reactive panc