MEN Syndromes

Question 1

Definition of MEN

Answer 1

Multiple endocrine neoplasias (MEN) are inherited disorders characterized by the development of tumors in multiple endocrine glands. These tumors can affect various glands, such as the parathyroid glands, pituitary gland, pancreas, adrenal glands, and thyroid gland.
There are several subtypes of MEN, each associated with specific gene mutations.

Question 2

Classification and types of MEN

Answer 2

There are three main subtypes of multiple endocrine neoplasias, classified as MEN 1, MEN 2A, and MEN 2B:

MEN 1:
Also known as Wermer syndrome, MEN 1 is caused by mutations in the MEN1 gene. Tumors associated with MEN 1 typically involve three main endocrine glands: the parathyroid glands, pancreas, and pituitary gland. Common tumors in MEN 1 include parathyroid adenomas/hyperplasia, pancreatic neuroendocrine tumors (PNETs), and pituitary adenomas.

MEN 2A:
MEN 2A is caused by mutations in the RET (rearranged during transfection) gene. This subtype is characterized by tumors in the thyroid gland, adrenal glands, and parathyroid glands. The main tumors associated with MEN 2A are medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenomas.

MEN 2B:
MEN 2B is also caused by mutations in the RET gene. It is the rarest and most aggressive form of MEN. Tumors associated with MEN 2B include medullary thyroid carcinoma, pheochromocytoma, and a characteristic mucosal neuroma syndrome, which affects the oral and gastrointestinal mucosa.

Question 3

Diagnosis of MEN

Answer 3

The diagnosis of MEN is based on clinical features, family history, and genetic testing. Diagnostic steps may include:

Medical history and physical examination: Evaluation of symptoms, family history, and the presence of characteristic signs associated with specific MEN subtypes.
Genetic testing: Analysis of specific genes (MEN1 and RET) to identify mutations associated with MEN subtypes.
Hormone and biochemical testing: Measurement of hormone levels and biochemical markers associated with tumors, such as calcium and parathyroid hormone (PTH) levels in MEN 1 or calcitonin and catecholamines in MEN 2.
Imaging studies: Imaging techniques like ultrasound, CT scan, MRI, or scintigraphy may be used to identify and assess tumors in various endocrine glands.

Question 4

Symptoms of MEN

Answer 4

Hypercalcemia (elevated calcium levels) in MEN 1

Hyperparathyroidism (overactive parathyroid glands) in MEN 1 and MEN 2A

Pituitary dysfunction and hormone imbalances in MEN 1

Thyroid nodules or enlargement and medullary thyroid carcinoma in MEN 2A and MEN 2B

Pheochromocytoma symptoms, such as hypertension, palpitations, and sweating, in MEN 2A and MEN 2B

Mucosal neuromas, marfanoid habitus, and gastrointestinal issues in MEN 2B

Question 5

Treatment of MEN

Answer 5

Surgical removal: Surgery is often the primary treatment for tumors that are localized and resectable. The extent of surgery depends on the involved glands and tumors.

Medications: Medications may be used to control hormone excess, manage symptoms, or target specific tumors.

Surveillance: Regular follow-up and surveillance are essential to monitor tumor growth, hormone levels, and screen for the development of new tumors.

Genetic counseling: Genetic counseling and testing are recommended for individuals with MEN to assess the risk of passing on the condition to offspring and provide guidance on family planning.