Medical expert of the article
New publications
Multiple endocrine neoplastic syndrome type II A
Last reviewed: 07.07.2025
All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
Multiple endocrine neoplastic syndrome type IIA (MEN syndrome type IIA, multiple endocrine adenomatosis, syndrome type IIA, Siple syndrome) is an inherited syndrome characterized by medullary thyroid cancer, pheochromocytoma, and hyperparathyroidism. The clinical picture depends on the glandular elements involved. Hormonal tests and imaging studies help detect tumors, which are removed surgically when possible. Mutations in the receptor tyrosine kinase proto-oncogene suggest that this dominant oncogene is responsible for the presence of MEN syndrome type IIA.
Symptoms of MEN syndrome IIA
Symptoms of MEN IIA depend on the type of tumor.
Forms
Thyroid gland
Almost all patients suffer from medullary thyroid cancer. The tumor usually develops in childhood and begins with hyperplasia of the thyroid gland. Tumors are often multicentric.
Adrenal glands
Pheochromocytoma usually arises in the adrenal glands. Pheochromocytoma occurs in 40-50% of patients with MEN IIA in their family, and in some related cases, pheochromocytoma accounts for 30% of deaths. Unlike sporadic pheochromocytomas, familial MEN IIA begins with medullary hyperplasia of the adrenal glands and is multicentric and bilateral in more than 50% of cases. Extra-adrenal pheochromocytomas are rare. Pheochromocytomas are almost always benign, but some tend to recur.
Pheochromocytomas arising in the setting of MEN syndrome usually produce epinephrine disproportionately to norepinephrine, in contrast to sporadic cases.
Hypertensive crisis in the setting of pheochromocytoma is a frequently observed symptom. Hypertension in MEN IIA patients with pheochromocytoma is more often paroxysmal, as opposed to the usual sporadic case. Patients with pheochromocytomas may experience paroxysmal palpitations, anxiety, headaches, or sweating, and sometimes the disease is asymptomatic.
[ 8 ], [ 9 ], [ 10 ], [ 11 ], [ 12 ]
Parathyroid glands
About 20% of patients have symptoms of hyperparathyroidism (which may be longstanding), with hypercalcemia, nephrolithiasis, nephrocalcinosis, or renal failure. In the remaining 25% of cases without clinical or biochemical evidence of hyperparathyroidism, parathyroid hyperplasia is discovered incidentally during surgery for medullary parathyroid carcinoma. Hyperparathyroidism often involves multiple glands, as does diffuse hyperplasia or multiple adenomas.
Other manifestations of MEN IIA type
The incidence of Hirschsprung disease has increased in children with at least one relative with MEN IIA; Zollinger-Ellison syndrome is rare in patients with MEN IIA.
Diagnostics of MEN syndrome IIA
MEN IIA syndrome is suspected in patients with bilateral pheochromocytoma, a family history of MEN, or at least two characteristic endocrine manifestations. The diagnosis is confirmed by genetic testing. Many relatives are followed closely after bilateral pheochromocytoma is identified in the index case.
Medullary thyroid carcinoma is diagnosed by measuring plasma calcitonin levels after pentagastrin and Ca infusion. Most patients with palpable thyroid abnormalities have elevated basal calcitonin levels; early in the disease, basal levels may be normal, and medullary thyroid carcinoma may be diagnosed only when artificially unfavorable conditions are created to infuse Ca and pentagastrin. Early diagnosis of medullary thyroid carcinoma is important so that the tumor can be removed while it can be localized.
Because pheochromocytoma can be asymptomatic, its diagnosis can be very difficult.
The most sensitive tests are free plasma metanephrines and fractionated urinary catecholamines (particularly adrenaline). CT or MRI helps localize pheochromocytoma or establish the presence of bilateral lesions.
Genetic testing used to confirm the diagnosis is very accurate. First-degree relatives and any relatives in the patient's index case should also undergo genetic testing. Annual testing for hyperparathyroidism and pheochromocytoma should begin in early childhood and continue for the rest of the person's life. Testing for hyperparathyroidism is done by measuring serum Ca. Testing for pheochromocytoma involves questions about symptoms, blood pressure measurements, and laboratory tests.
Who to contact?
Treatment of MEN syndrome IIA
In patients with pheochromocytoma, medullary thyroid carcinoma, or hyperparathyroidism, the pheochromocytoma should be removed first; even if the disease is asymptomatic, it greatly increases the risk of other surgeries. Chemotherapy is largely ineffective in treating residual or metastatic medullary thyroid carcinomas, but radiation therapy may prolong survival.
In gene carriers, prophylactic thyroidectomy in infancy or early childhood is recommended, as untreated medullary thyroid carcinoma is fatal.