Multiple endocrine neoplasia type 1 (MEN1) (OMIM) is an autosomal dominant syndrome with an estimated incidence in the general population of 1 to 2 per 100,000. The major endocrine features of MEN1 include the following:
- Parathyroid tumors and primary hyperparathyroidism (PHPT).
- Pancreatic neuroendocrine tumors (PNETs) of the duodenum.
- Pituitary tumors.
A diagnosis of MEN1 is made when an individual has two of these three major endocrine tumors. Familial MEN1 is defined as at least one MEN1 case plus at least one first-degree relative with one of these three tumors.[2,3,4] The age-related penetrance of MEN1 is 45% at age 30 years, 82% at age 50 years, and 96% at age 70 years.[2,5]
Parathyroid Tumors and PHPT
The most common features and often the first presenting signs of MEN1 are parathyroid tumors, which result in PHPT. These tumors occur in 80% to 100% of patients by age 50 years.[2,6,7,8] Unlike the solitary adenoma seen in sporadic cases, MEN1-associated parathyroid tumors are typically multiglandular and often hyperplastic. The average age at onset of PHPT in MEN1 is 20 to 25 years, in contrast to that in the general population, which is typically age 50 to 59 years. Parathyroid carcinoma in MEN1 is rare but has been described.[9,10,11,12]
Individuals with MEN1-associated PHPT will have elevated parathyroid hormone (PTH) and calcium levels in the blood. The clinical manifestations of PHPT are mainly the result of hypercalcemia. Mild hypercalcemia may go undetected and have few or no symptoms. More severe hypercalcemia can result in the following:
Since MEN1-associated hypercalcemia is directly related to the presence of parathyroid tumors, surgical removal of these tumors may result in normalization of calcium and PTH levels and relief of symptoms; however, high recurrence rates following surgery have been reported in some series.[13,14,15] (Refer to the Interventions section of this summary for more information.)
PNETs of the duodenum, the second most common endocrine manifestation in MEN1, occur in 30% to 80% of patients by age 40 years.[2,8] Gastrinomas represent 50% of the gastrointestinal neuroendocrine tumors in MEN1 and are the major cause of morbidity and mortality in MEN1 patients.[2,13] Gastrinomas are usually multicentric, with small (<0.5 cm) foci throughout the duodenum. Most result in peptic ulcer disease (Zollinger-Ellison syndrome), and half are malignant at the time of diagnosis.[13,16,17]
Other functioning PNETs seen in MEN1 include the following:
- Insulinomas (10%–20% penetrance).
- Vasoactive intestinal peptide tumors (~1% penetrance).
- Glucagonomas (1%–5% penetrance).
- Somatostatinomas (~1% penetrance).