Multiple endocrine neoplasia type 2A (MEN 2A) is a hereditary disease that is caused by the mutations of a RET proto-oncogene and is a subtype of MEN syndrome. Pathology arises in endocrine glands, and MEN 2A specifically causes medullary thyroid cancer, pheochromocytoma, and hyperparathyroidism.
Multiple endocrine neoplasia type 2A (MEN 2A) is the most frequently occurring form of MEN 2, and many patients have a positive family history of endocrine cancers. Those with MEN 2A characteristically develop medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid adenomas or hyperplasia, with a prevalence of up to 95%, 50%, and 30% respectively. Symptoms arise as a result of the tumors present, however, some individuals may remain asymptomatic.
MTC is often the first clinical manifestation of the disease and usually becomes symptomatic by the third decade of life . As MTC results from hyperplasia of the C-cells in the thyroid gland, diarrhea is a common complaint, albeit poor prognostic factor, resulting from hypersecretion of calcitonin  . A neck mass is often seen on presentation, with symptoms of local spread such as difficulty swallowing, change in voice, neck pain, and dyspnea. Lymphadenopathy occurs as a result of tumor metastasis to the lymph nodes. The tumor has a propensity to metastasize, often to the liver, bones, and lungs . This usually takes place before patients seek medical attention.
Pheochromocytomas are largely benign, and mainly arise from the adrenal glands and secrete catecholamines, although in MEN 2A they predominantly secrete adrenalin . A minority of patients may present with pheochromocytoma as the first sign of disease, and in contrast to sporadic cases, they are more likely to be bilateral . Furthermore, the symptoms they produce are often insidious and may be paroxysmal . Typical manifestations include palpitations, tachycardia, hypertension, excessive sweating, headaches, anxiety, and hypertensive crisis.
Parathyroid adenomas may cause hypercalcemia, increased calcium excretion in urine, and renal stones. Some patients with MEN 2A additionally present with cutaneous lichen amyloidosis (CLA) often on the upper back, seen as dark itchy desquamating papules .
Genetic testing is the preferred diagnostic test, performed on patients and their relatives as a screening test. It can also be performed antenatally. The presence of two of the neoplasms belonging to multiple endocrine neoplasia type 2A is enough to make a clinical diagnosis. Depending on the gene mutation found, the finding has a role in management and prognosis of the condition. Other screening tools include screening for MEN 2A characteristic tumors and their biochemical markers in family members yearly.
Laboratory and imaging studies for each of the tumors is as follows: