Multiple Endocrine Neoplasia Type 1 (MEN 1)

• • Also known as Wermer syndrome

  • Characterized by tumors of the parathyroid, anterior pituitary, and pancreas

  • Tumors may develop synchronously or metachronously, may be benign or malignant, and may be hyperplasia, adenomas, or carcinoma

  • Pancreatic tumors include functioning and nonfunctioning islet tumors such as gastrinoma, insulinoma, glucagonoma, VIPoma, somatostatinoma, pancreatic polypeptide tumors (PPomas)

  • Other tumors in MEN 1 can include adrenocortical tumors, thymic or bronchial carcinoid tumors, multiple lipomas, cutaneous angiofibromas and collagenomas

  • Syndrome is transmitted as autosomal dominant trait

  • Most common mutation is in the menin gene on 11q13

  • Trait has 100% penetrance but variable expressivity

Epidemiology

• • Syndrome often develops in the third and fourth decade of life

  • Male:female ratio is 1:1

  • No known racial predilection

  • 90-97% of patients have biochemical evidence of hyperparathyroidism

  • 30-80% manifest pancreatic islet cell tumors

  • 15-50% develop pituitary tumors

  • Gastrinomas with MEN 1 account for 20% of all cases of Zollinger-Ellison syndrome

Symptoms and Signs

• • Presentation depends on endocrine tissue involved and the overproduction of a specific hormone; symptoms may arise from tumor mass itself

  • Dyspepsia, abdominal pain, hematemesis

  • Syncope, tremulousness, diaphoresis, confusion, dizziness (hypoglycemia)

  • Symptoms of hypercalcemia, renal stones

  • Headaches, visual field defects, amenorrhea, galactorrhea, hypogonadism, acromegaly (pituitary dysfunction)

Laboratory Findings

• • Elevated serum calcium and intact parathyroid hormone

  • Elevated gastric acid secretion; elevated fasting serum gastrin level

  • Supervised fast with resultant hypoglycemia, elevated serum insulin level, and elevated serum C-peptide level

  • Elevated prolactin level

  • Direct genetic testing generally offered only for probands with definitive evidence of the MEN 1 syndrome; once the mutation is known, then direct genetic testing of at-risk family members is useful

Imaging Findings

• • Gastrinomas and other pancreatic islet cell tumors can be localized with CT scanning, angiography, or somatostatin receptor scintigraphy

• • Hyperparathyroidism is due to multiple parathyroid adenomas with 4 gland involvement

  • MEN 1-related hyperparathyroidism occurs earlier in life than nonfamilial primary hyperparathyroidism

• • CT scan, angiography, or somatostatin receptor scintigraphy to evaluate for pancreatic islet cell tumors

  • Sestamibi scan, cervical US, CT, or selective venous sampling to evaluate location of abnormality for persistent or recurrent hyperparathyroidism

  • Annual surveillance for adult gene carriers should include:

  • -History and physical exam

    -Calcium and parathyroid hormone measurement for hyperparathyroidism

    -Gastrin, pancreatic polypeptide, abdominal CT scan and somatostatin receptor scintigraphy for pancreatic tumor detection

    -Prolactin level for pituitary adenoma

    -Chest CT scan for thymic carcinoid tumor detection

• • Parathyroid disease treated with surgery

  • Treat parathyroid disease first

  • Pituitary tumors may require surgical ablation or irradiation but usually are managed medically

Surgery

Indications

• • Biochemical evidence of hyperparathyroidism

  • To remove/limit tumor growth of pancreatic tumors (as they are very often ...