Multiple Endocrine Neoplasia Syndrome Type 1 (MEN 1) is a rare familial syndrome, with a prevalence of approximately 1 out of 30000. The individual inherits one mutated allele, situated on chromosome 11q13, from one parent. Women and men are equally affected, and it occurs in all racial groups. About 10% of the cases arise from de novo MEN1 mutations.

Genetics of MEN1
The gene is a classical tumor suppressor gene. Carrying a mutated gene gives rise to predominantly endocrine, but also non-endocrine, lesions. The tumor lesions are multiple, and among the affected organs are the parathyroids, the pituitary, the endocrine pancreas, thymus, adrenal cortex, fat tissue and skin. Temporal onset and penetrance of the various lesions vary, and may be different even within families harboring the same mutation. More than 1300 different mutations, of which more than 70% causes a truncated protein, have been reported. Around 30% of sporadic (non-familial) endocrine pancreatic tumors also have gene mutations.

Lesions in MEN1
The endocrine lesions can be functioning, i. e. giving rise to clinically elevated hormonal serum levels causing discomfort for the patient, and may even be lethal if untreated. Examples of functioning tumors are insulinoma, gastrinoma, prolactinoma and PTH-producing parathyroid adenoma. Non-functioning tumors do not cause overt clinical symptoms related to released hormones or peptides.

The endocrine tumors in MEN 1 most often have an indolent growth pattern, and the majority is benign such as the lesions in the parathyroids, the pituitary and adrenal gland. They can however anyway cause discomfort to the patient due to excessive hormone release or by crowding surrounding normal tissue. The MEN 1 skin lesions (angiofibromas and collagenomas) and lipomas (fat tumors) are benign.

The malignant MEN 1 lesions derive from the endocrine pancreas, the duodenum or thymus, and eventually approximately 50% of MEN 1 carriers will develop a malignant tumor. The most common cause of death in MEN 1 is endocrine pancreatic tumor, which are most often non-functioning and spread at diagnosis.

Hyperparathyroidism in a young patient (<45 years) should be investigated to find out if the lesion is MEN 1 related, and an endocrine pancreatic tumor should always be suspected to be part of the MEN 1 syndrome.

MEN 1 lesions:

Endocrine lesions *

Non endocrine lesions *


Lesions at MEN1

* Penetrance at 40 years of age (Falchetti et al).

Hyperparathyroidism normally occurs in around 5% of the population, with the highest prevalence in postmenopausal women. In MEN 1 however, practically every individual carrying the mutation will develop adenomas in all four parathyroid glands. For the individual developing severe symptoms (weakness, constipation, pain in muscles and bone, thinning of bones etc from the excess of blood calcium) the treatment of choice is surgery. One gland, or part of one gland, is left to prevent hypocalcaemia, and the patient is closely monitored for recurring hyperparathyroidism.

The endocrine pancreatic tumors developed in MEN 1 are often multiple, and the majority of tumors are non-functioning. The most common functioning tumor in MEN 1 is insulinoma, and in the majority of cases benign with regard to spreading. However, the release of insulin causes hypoglycemia typically giving symptoms like sweating, tremor, hunger, palpitations, seizures or loss of consciousness. The prognosis for a patient with a radically resected insulinoma is very good.

Gastrinomas, also common tumors in MEN 1, arise from scattered endocrine cells situated in the duodenum, or more rarely from pancreatic islets. The syndrome is called Zollinger-Ellison and historically gave rise to life-threatening ulcers of the stomach or the duodenum. Now the excess hormone release is efficiently controlled by acid pump inhibitors. Surgical resection of the duodenum can potentially cure the patient.

The pituitary tumors in MEN 1 are benign and arise in the anterior part of the gland. The majority of the lesions produce prolactin, causing oligo- or amenorrhea, galactorrhea and infertility in women and erectile dysfunction, decreased body hair and gynecomastia in men. Both sexes may suffer from low bone density and low libido. Hormone release can often be controlled using dopamine inhibitors, which also causes shrinking of the tumor. Other pituitary tumors in MEN 1 may be producing ACTH or growth hormone.

In the department of Endocrine Oncology an MEN 1 biochemical screening program has been developed and used since the 1980s. Affected family members come in regularly, from an early age, for follow-up and treatments. Combining biochemical and radiological follow-up with early surgical intervention at the department of Endocrine Surgery have proven successful (the Uppsala protocol).