Multiple Endocrine Neoplasia Type 1

What causes the syndrome?

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder that affects patients by causing endocrine and non-endocrine tissue tumors. The true prevalence of this condition is underestimated and varies from 0.2 - 2.0 per 100,000 people. This is a complicated disorder with multiple manifestations that can be remembered with the "3P's": Primary hyperparathyroidism, Pancreatic and duodenal neuroendocrine tumors, and Pituitary tumors. There is a very low likelihood that a patient who has the genetic susceptibility to MEN1 will express any of these diseases before the age of 10. Most often this syndrome presents between the ages of 20 and 40 years of age. The patient must have two of the three "P's" to have a clinical diagnosis of multiple endocrine neoplasia type 1. However, in family members of known MEN1 patients, the presence of one"P" his diagnostic. In order to confirm the diagnosis the patient will need genetic testing. The gene responsible for MEN1 was identified in 1997 and is located on a chromosome 11q13. This gene is called MEN1 and it codes for a protein called menin. Menin is a tumor suppressor gene which controls cell growth, cell death, and genetic stability. To date more than 400 different medications have been reported in this team. 90% of these mutations are inherited and 10% can arise sporadically without a genetic predisposition.

Pituitary tumors

The pituitary tumors in MEN1 patients are less frequent than primary hyperparathyroidism or pancreatic and duodenal neuroendocrine tumors. These pituitary tumors can develop in up to 60% of MEN1 patients. The mean age of diagnosis of a pituitary tumor in these types of patients is about 38 years of age. In the majority of MEN1 patients the pituitary tumors are macroadenomas, most of which are prolactinomas. Monitoring for pituitary tumor development in these patient should generally include yearly measurement of blood prolactin and insulin like growth factor-1. Dr. Jogi and Dr. Elhaj are endocrinologists in Houston who are trained to manage these pituitary tumors. Imaging of the pituitary with MRI may be required every 2-3 years.

Primary hyperparathyroidism

Most patients with multiple endocrine neoplasia 1 will have hypercalcemia due to primary hyperparathyroidism by their 30's, but it has been found as young as age 19. This is the initial clinical and biochemical manifestation of multiple endocrine neoplasia type I. Patients generally have a symmetrical hyperplasia of the parathyroid glands or multiple adenomas involving all of the parathyroid glands. The timing a parathyroid surgery (parathyroidectomy) is very important. In patient's with multiple endocrine neoplasia type I-related-primary-hyperparathyroidism all of the parathyroid tissue is involved. Therefore, any treatment for the parathyroid is technically palliative. Unfortunately destroying or removing all of the parathyroid tissue can result in a condition called permanent hypoparathyroidism. Hypoparathyroidism, which causes hypocalcemia, is far worse than hyperparathyroidism. In patients with mild disease, it may be appropriate to delay surgery until the serum calcium is 1 mg/dL or more above the upper limit of the normal reference range. The preferred surgical treatment for hyperparathyroidism related to multiple endocrine neoplasia type I is a subtotal parathyroidectomy with a transcervical thymectomy. The exact type of surgery may be decided by your surgeon. The endocrinologists at Houston Thyroid and Endocrine will carefully help you get the correct treatment.

Pancreatic and duodenal neuroendocrine tumors

These tumors represent the second most frequent manifestation in multiple endocrine neoplasia type I and continue to be the #1 cause of tumor-related-death in these patients. These tumors become apparent in 50-75% of patients with MEN1. More than 80% of these patients had changes that can be found on pathology specimens of the pancreas. Insulinoma is the most common functioning pancreatic neuroendocrine tumor that is found in these types of patients younger than age 25. At insulinoma is tumor of the pancreas that secretes insulin at high levels on regulated by the amount of sugar that is in the blood; therefore patient's have very low blood sugars during the day and at night. The endocrinology specialists at Houston Thyroid and Endocrine diagnose these tumors with specific blood testing. Endocrinologists work inconceert with endocrine surgeons to manage these conditions. Although patients with multiple endocrine neoplasia type 1 have multiple pancreatic tumors, only about one or two tumors are the source of insulin excess. All pancreatic neuroendocrine tumors are capable of becoming malignant, and this is especially true for the nonfunctioning tumors. The other tumors that can occur include glucagonomas, neuroendocrine tumors that hypersecrete vasoactive intestinal poly-peptide, and obviously malignant non-functioning tumors that tend to spread throughout the body. All these types of tumors require an aggressive surgical approach that includes removal of 80% of the pancreas, removal of the spleen, and removal of associated lymph nodes. This is a very specialized surgery that requires an experienced surgeon. Metastases located in the liver which secrete hormones can be successfully managed through a combination of liver surgery, radiofrequency thermoablation, and hepatic artery embolization. Octreotide and systemic chemotherapy can also be used for palliation.

Gastrinomas are the most common functioning tumors in the duodenum of patients with multiple endocrine neoplasia. These tumors induce secretion of excessive amounts of gastrin which results in very high acid levels in the stomach. This condition is called Zollinger-Ellison Syndrome. Almost one third of patients with Zollinger-Ellison syndrome have MEN-1. Proton pump inhibitors, which are medications used for gastroesophageal reflux disease disease (GERD), are an effective way of managing the hormonal consequences of gastric acid excess, but they do not prevent the conversion of these hormone secreting tumors into malignant tumors. More than 90% of the gastrinomas that are found and multiple endocrine neoplasia type I come from the duodenum. The definitive treatment for a gastrinoma is a surgery which involves removal of part of the pancreas, removal of lymph nodes that are associated, and enucleation of residual tumors.