MEN syndromes Flashcards
MEN1
pituitary adenoma
parathyroid hyperplasia
pancreatic tumors
Wermer syndrome
MEN 2A
parathyroid hyperplasia
medullary thyroid carcinoma
Pheochomocytoma
MEN 2B
Mucosal neuromas
Marfanoid body habitus
medullary thyroid carcinoma
pheochromocytoma
The MEN syndromes
group of inherited diseases resulting in proliferative lesions (hyperplasia, adenomas, and carcinomas) of multiple endocrine organs
-occur at younger ages
- multiple endorine organs, synchronously or metachronously
- often multifocal
- usually preceded by asymptomatic stage of hyperplasia
(MEN-2 usually C-cell hyperplasia in the thyroid parenchyma adjacent to medullary thyroid carcinomas)
- more aggressive and recur in higher proportion of cases than similar sporadic endocrine tumors.
MEN 1: Parathyroid
Primary hyperparathyroidism- most common manifestation of MEN-1
initial manifestation of the disorder in most patients, appearing by age 40 to 50.
Both hyperplasia and adenomas.
MEN-1: Pancreas
tumors- leading cause of morbidity and mortality in persons with MEN-1.
aggressive, often present with metastatic disease.
multiple “microadenomas” scattered throughout the pancreas in conjunction with one or two dominant lesions.
MEN-1-associated pancreatic endocrine tumors are often functional; however, because pancreatic polypeptide is the most commonly secreted product, many tumors fail to produce an endocrine hypersecretion syndrome. Among those that do, Zollinger-Ellison syndrome (associated with gastrinomas) and hypoglycemia and neurologic manifestations (associated with insulinomas) are most common.
MEN-1: Pituitary
The most frequent anterior pituitary tumor encountered in MEN-1 is a prolactinoma; some patients develop acromegaly from somatotrophin-secreting tumors.
MEN-1: beyond the 3Ps
spectrum of this disease extends beyond the 3Ps.
The duodenum is the most common site of gastrinomas in individuals with MEN-1 (far in excess of the frequency of pancreatic gastrinomas), and synchronous duodenal and pancreatic tumors may be present in the same individual.
MEN-1 syndrome is caused by
germline mutations in the MEN1 tumor suppressor gene, which encodes a protein called menin
The dominant clinical manifestations of MEN-1 usually result from
peptide hormones that are overproduced and include such abnormalities as recurrent hypoglycemia due to insulinomas, intractable peptic ulcers in persons with Zollinger-Ellison syndrome, nephrolithiasis caused by PTH-induced hypercalcemia, or symptoms of prolactin excess from a pituitary tumor.
MEN-2 is subclassified into three distinct syndromes
MEN-2A, MEN-2B, and familial medullary thyroid cancer
Sipple syndrome
MEN-2A
characterized by pheochromocytoma, medullary carcinoma of the thyroid, and parathyroid hyperplasia
MEN-2A caused by
germline gain-of-function mutations in the RET proto-oncogene on chromosome 10q11.2
MEN 2B- differences from 2A
Patients develop medullary thyroid carcinomas, which are usually multifocal and more aggressive than in MEN-2A, and pheochromocytomas.
primary hyperparathyroidism is not present in MEN-2B.
MEN-2B - accompanied by neuromas or ganglioneuromas involving the skin, oral mucosa, eyes, respiratory tract, and gastrointestinal tract, and a marfanoid habitus, with long axial skeletal features and hyperextensible joints
Familial medullary thyroid cancer
a variant of MEN-2A
There is a strong predisposition to medullary thyroid cancer but not the other clinical manifestations of MEN-2A or MEN-2B
Routine genetic testing identifies RET mutation carriers earlier and more reliably in MEN-2 kindreds; all individuals carrying germline RET mutations are advised to undergo prophylactic thyroidectomy to prevent the inevitable development of medullary carcinomas
