Multiple endocrine neoplasia type 2A (MEN2A) is an inherited condition that involves a tumor of excessive growth of at least two of the thyroid gland, parathyroid gland, and adrenal glands. It is an uncommon condition that affects approximately 1 in 35,000 individuals.
MEN2A is caused by a mutation on chromosome 10 of the RET proto-oncogene. This leads to failure of the tumor suppressor gene.
Characteristics of MEN2A
There are three types of multiple endocrine neoplasia: type 1 (MEN1), type 2B (MEN2A) and type 2B (MEN2B). The defining characteristic of MEN2 is a mutation in the RET proto-oncogene, which leads increased risk of the growth of a tumor in the endocrine glands, such as the thyroid gland, adrenal glands, and parathyroid gland.
Medullary thyroid cancer (MTC) affects majority of patients with MEN2A and is often the first sign of the condition. Phaeochromocytoma affects up to half of patients and hyperparathyroidism affects approximately 1 in 5 of patients. The kidney may also be affected and other associated conditions include nephrolithiasis and nephrocalcinosis.
Symptoms associated with MEN2A can vary significantly, depending on the area of the endocrine that is experiencing excessive or tumor growth. Most patients first notice symptoms between 30 and 50 years of age, although the onset of symptoms can vary greatly.
Parathyroid hyperplasia affects the majority of patients with the condition. However, only 20% experience symptoms linked to high levels of calcium in the blood, which is usually associated with this. In fact, most patients are with parathyroid hyperplasia are only identified as a result of the removal of the thyroid gland. For patients with hypercalcemia, it is recommended for the parathyroid gland to be removed.
Other symptoms that may present in patients with MEN2A include:
- Excessive sweating
- Itchy skin
- Lump or growth at the base of the neck
There are several diagnostic tests that can be used in the diagnosis of MEN2A.
- Blood tests to investigate changes in hormone levels
- 24-hour urine collection test can detect elevated levels of catecholamines and metabolites such as vanillyl-mandelic acid in the urine.
- Magnetic resonance imaging (MRI) to detect changes in the abdomen following elevated levels of catecholamines in the urine.
- Metaiodobenzylguanidine (MIBG) scans to determine the location of phaeochromocytomas.
- Ultrasound imaging to investigate presence and nature of thyroid tumors.
- Fine-needle aspiration to determine nature of thyroid tumors.
Genetic testing and screening is also available for patients with a family history of the condition. This test is highly sensitive and can accurately determine individuals with the gene mutation that put them at risk of developing endocrine tumors.
The primary aim of treatment for patients with MEN2A is to reduce morbidity and mortality of patients. This can be through prophylactic removal of the thyroid gland or regular screening for MTC to enable early intervention when necessary.
Other treatments may include:
- Bilateral adrenalectomy for patients with adrenal medullary hyperplasia or phaeochromocytoma
- Total thyroidectomy for patients with a known genetic mutation
- Subtotal parathyroidectomy for patients with hyperparathyroidism
- Cervical thymectomy for patients with hyperparathyroidism
The prognosis for patients with MEN2A is typically better than that for patients with MEN2B.
If a mutation in the RET proto-oncogene is confirmed, genetic counseling is required to inform the patient about the familial nature of the condition and the best options for family planning.