Multiple endocrine neoplasia

Definitions & Key takeaways

Multiple endocrine neoplasias, or MEN for short, are a group of inherited diseases that cause tumors to grow in the endocrine glands of the body. MEN tumors are classified into two broad categories based on their underlying mutations. There is MEN1 caused by a mutation in the MEN1 gene, and MEN2, which is caused by a mutation in the RET gene.

People with MEN1 present with tumors in the pituitary gland or parathyroid glands and pancreatic tumors. MEN2 is further divided into two subtypes: MEN2A and MEN2B. MEN2A is characterized by medullary thyroid cancer, pheochromocytoma, and parathyroid tumors; whereas MEN2B presents with medullary thyroid cancer, pheochromocytoma, and mucosal neuromas.

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Introduction0:00–0:34

The multiple endocrine neoplasias, or MEN for short, are a group of inherited diseases which cause tumors to grow in the endocrine glands of the body.
The endocrine glands affected in multiple endocrine neoplasia are the pituitary gland, the thyroid gland, the parathyroid glands, the adrenal glands and the pancreas.
So in multiple endocrine neoplasias there are tumors that form in these glands that lead to overproduction of hormones. Let’s start by going through the glands that are affected and what they do.

Physiology0:34–2:52

The pituitary gland is a pea-sized gland found at the base of the brain that makes hormones to control many of the other endocrine glands in the body.
These hormones include thyroid stimulating hormone which acts on the thyroid to make thyroid hormone, adrenal corticotropic hormone that acts on the adrenal glands to make cortisol, follicle stimulating hormone and luteinizing hormone which acts on the ovaries and testes to make estrogen in women and testosterone in men.
So it’s like the king of the endocrine glands telling them how much hormone to produce. The pituitary also makes growth hormone which makes you grow, prolactin which stimulates milk production in women, oxytocin which triggers milk release, antidiuretic hormone which help the kidneys reabsorb water, and melanocyte stimulating hormone helps the melanocytes create more melanin or pigment.
Next, in the neck is the thyroid gland which makes thyroid hormones that control the metabolic rate, as well as calcitonin, a hormone that decreases calcium levels.
Within the thyroid gland, are buried four parathyroid glands which make parathyroid hormone which increases calcium levels.
Lower down, there are the adrenal glands which sit just above each kidney and produce epinephrine and norepinephrine which are fight or flight hormones that increase cardiac output, dilate the pupils, and increase blood flow to the muscles.
Finally, there’s the pancreas which makes insulin to help lower blood sugar, and glucagon to help raise blood sugar. The pancreas also makes gastrin which increases hydrochloric acid production in the stomach, and vasoactive intestinal peptide which relaxes the intestinal wall allowing food to pass.

Causes2:52–4:09

Multiple endocrine neoplasias are caused by genetic mutations to one of two genes, either MEN1 or RET. Both of these genes have a dominant inheritance pattern, so you only need one copy of the mutated gene to get the disease.
The MEN1 gene is found on chromosome 11 and is a tumor suppressor gene, meaning it normally stops a cell from dividing uncontrollably.
AN MEN1 mutation causes MEN type 1. On the other hand, RET is a proto oncogene which promotes normal cell division, and when it mutates, it becomes an oncogene which promotes constant cell division.
Mutated RET causes multiple endocrine neoplasia type 2A and 2B. In multiple endocrine neoplasia type 1, there are three types of tumors: parathyroid, pancreatic, and pituitary.
The most common tumor is a parathyroid tumor. Increased parathyroid hormone causes increased bone breakdown which leads to hypercalcemia and calcium kidney stones.

Pathology4:09–6:35

Pancreatic tumors cause problems based on the type of hormone they produce. A gastrinoma produces gastrin which increases the amount of hydrochloric acid in the stomach and can cause peptic ulcers, abdominal pain, and vomiting.
Insulinomas cause hypoglycemia while a glucagonomas cause hyperglycemia. The pituitary gland develops non-cancerous tumors called adenomas which usually make an excess amount of at least one of the many hormones that are produced there.
Most commonly, there’s excess prolactin, which causes galactorrhea, or milk production in women who are not breast feeding, and gynecomastia in men, which is breast tissue growth.
Next, there can be excess growth hormone, which causes gigantism in children, meaning they’ll get really tall, or acromegaly in adults where they have enlarged hands and feet, a large forehead, and a prominent jaw.
A way to remember the two most common hormones released by pituitary adenomas is the phrase “lots of milk leads to giant kids”, where “lots of milk” refers to prolactin, and “giant kids” refers to growth hormone.
In multiple endocrine neoplasia 2A, the most common problem is thyroid medullary cancer which develops in virtually everyone with the disease.
This type of cancer develops from C-cells in the thyroid that produce calcitonin and can metastasize to other organs through the blood.
The adrenal glands form tumors called pheochromocytoma, which make too much epinephrine and norepinephrine. This results in high blood pressure, anxiety, and sweating.
People with multiple endocrine neoplasia type 2A can also develop parathyroid adenoma, but unlike type 1, only about half of the people will develop this type of tumor.
In multiple endocrine neoplasia type 2B, the type of tumors are the same as 2A except there is no parathyroid adenoma. Instead they have multiple neuromas, which are tumors that come from nerve tissue in the skin and mouth.

Symptoms6:35–7:16

Symptoms of multiple endocrine neoplasia depends on the type of tumor and the hormone produced, as well as from a mass effect and local inflammation from the tumor itself.
In MEN type 1, a pituitary adenoma might press on nearby brain tissue causing headaches, or it could press on the optic nerves causing vision problems.
In MEN type 2 A and B, thyroid tumor might compress nearby organs in the neck causing hoarseness, coughing, and trouble swallowing.
In MEN type 2B, neuromas typically grow on the tongue, lips and the roof of the mouth. Multiple endocrine neoplasia can be diagnosed by genetic testing to find the underlying genetic mutation.

Diagnosis and treatment7:16–7:48

The genetic defect can’t be treated but the tumors can be cured with surgery if caught early. If type 2 is diagnosed then a thyroidectomy will be performed to prevent medullary thyroid cancer.
The thyroid may also be removed in family members who carry the defective gene, to prevent thyroid cancer in the future.

Review7:48–8:21

All right, as a quick recap… Multiple endocrine neoplasias are divided into three types, type 1, type 2A, and type 2B. MEN type 1 causes parathyroid, pituitary, and pancreatic tumors.
Type 2A causes medullary thyroid cancer, pheochromocytoma, and parathyroid tumors. Type 2B is similar to 2A but typically has multiple neuromas instead of parathyroid tumors.