MEN syndromes: Clinical

The multiple endocrine neoplasias, or MEN for short, are a group of inherited diseases which cause tumors to grow in endocrine glands, like the pancreas, pituitary, thyroid, adrenals, and parathyroid glands.

So in multiple endocrine neoplasias there’s overproduction of various hormones.

Multiple endocrine neoplasias are caused by a dominant mutation in either the MEN 1 gene which is a tumor suppressor gene or the RET gene which is a proto oncogene.

A MEN1 mutation causes MEN type 1, and a RET mutation causes MEN type 2A and 2B.

In multiple endocrine neoplasia type 1, there are three types of tumors: pituitary, parathyroid, pancreatic - 3 “p’s”.

But the gastrinomas that occur in the pancreas, are actually more often found in the duodenum, so to keep things accurate 2 “p’s” and a “g” for gastrointestinal gastrinoma is better.

Now in MEN1, the most common tumors are parathyroid tumors which create excess parathyroid hormone. That leads to bone breakdown, which causes serum calcium levels to rise, and that allows calcium kidney stones to form. This is similar to what happens in an isolated parathyroid adenoma.

The key differences are that MEN1-associated hyperparathyroidism has an earlier age of onset, around 25 years, and tends to affect 3 or 4 of the parathyroid glands, rather than just one.

A silver lining is that MEN1 associated hyperparathyroidism almost never progresses to a malignant parathyroid cancer.

Management of hyperparathyroidism can be surgical or nonsurgical.

Surgery is indicated in individuals who meet at least one criteria in the biochemical, skeletal, renal, or age categories.

The biochemical criteria are a moderately elevated serum parathyroid hormone, and a serum calcium level that’s adjusted for albumin, of over 12 milligrams per deciliter.

Skeletal criteria include diminished bone density, and previous asymptomatic vertebral fractures demonstrated on imaging studies.