Multiple endocrine neoplastic syndrome II A type
Last reviewed: 23.04.2024
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Multiple endocrine neoplastic syndrome IIA type (MEN type IIA syndrome, multiple endocrine adenomatosis, type IIA syndrome, Sipple syndrome) is a hereditary syndrome and is characterized by medullary thyroid cancer, pheochromocytoma and hyperparathyroidism. The clinical picture depends on the affected glandular elements. Hormonal tests and imaging studies help detect tumors that, when possible, are surgically removed. Mutations in the receptor tyrosine kinase of proto-oncogenes suggest that this dominant oncogene is responsible for the presence of MEN-type IIA syndrome.
[Symptoms of the syndrome MEN IIA
Symptoms of MEN type IIA depend on the type of tumor.
Forms
Thyroid
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 multicenter.
Adrenal glands
Pheochromocytoma usually occurs in the adrenal glands. Pheochromocytoma occurs in 40-50% of patients with MEEN type IIA syndrome in relatives, and in some related cases, pheochromocytoma accounts for 30% of deaths. Unlike sporadic pheochromocytomas, family varieties of the MEN-IIA syndrome begin with medullary hyperplasia of the adrenal gland and are multicenter and bilateral in more than 50% of cases. Vnadr-adrenal pheochromocytomas are rare. Pheochromocytomas are almost always benign, but some, as a rule, arise repeatedly.
Pheochromocytomas that occur against the background of MEN syndrome usually produce adrenaline disproportionately to norepinephrine, in contrast to sporadic cases.
Hypertensive crisis on the background of pheochromocytoma is often an observed symptom. Hypertension in patients with MEEN IIA type with pheochromocytoma is more often paroxysmal than in the usual sporadic case. Patients with pheochromocytomas may experience a paroxysmal heartbeat, anxiety, headaches, or sweating, sometimes the course of the disease is asymptomatic.
Parathyroid glands
About 20% of patients have symptoms of hyperparathyroidism (which may be long-standing), with hypercalcemia, kidney stone disease, nephrocalcinosis, or kidney failure. In the remaining 25% of cases without clinical or biochemical signs of hyperparathyroidism, parathyroid hyperplasia is occasionally detected during surgery for a medullary parathyroid carcinoma. Hyperparathyroidism often affects several glands, like diffuse hyperplasia or multiple adenomas.
Other manifestations of MEEN IIA type
The incidence of Hirschsprung disease in children with at least one relative with MEN-IIA syndrome increased; Zollinger-Ellison syndrome is rare in patients with MEN-type IIA syndrome.
Diagnostics of the syndrome MEN IIA
Syndrome MEEN IIA type is assumed in patients with bilateral pheochromocytoma, family history of MEN disease or at least two characteristic endocrine manifestations. The diagnosis is confirmed by genetic testing. Many relatives are under constant surveillance, after the bilateral case of pheochromocytoma has been identified in the index case.
Medullary thyroid carcinoma is diagnosed by plasma calcitonin level after pentagastrin and Ca infusion. In most patients with palpable thyroid disorders, the level of the main calcitonin increases; at the initial stage of the disease, the basal levels can be normal, and the medullary carcinoma can be diagnosed only with artificially created adverse conditions for the infusion of Ca and pentagastrin. Early diagnosis of medullary thyroid carcinoma is very important, since the tumor can be removed while it can be localized.
Since pheochromocytoma can be asymptomatic, its diagnosis can be very difficult.
The most sensitive studies are analyzes of free plasma metanephryls and fractionated urinary catecholamines (in particular, adrenaline). CT or MRI promotes the localization of pheochromocytoma or the establishment of a bilateral lesion.
Genetic testing used to confirm the diagnosis is very accurate. Relatives of the first generation and any relatives from the patient case index should also undergo genetic testing. Annual testing for hyperparathyroidism and pheochromocytoma should begin in early childhood and continue until the end of a person's life. Testing for hyperparathyroidism is performed with the measurement of Ca in the serum. Testing for pheochromocytoma includes questions about symptoms, blood pressure measurements and laboratory tests.
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Treatment of the syndrome MEN IIA
In patients with pheochromocytoma, either medullary carcinoma of the thyroid gland, or hyperparathyroidism of pheochromocytoma should be removed in the first place; even if the course of the disease is asymptomatic, such a tumor significantly increases the risk of other operations. Chemotherapy is largely ineffective in treating residual or metastatic medullary thyroid carcinomas, but radiotherapy can prolong survival.
In the case of gene transfer, preventive thyroidectomy is recommended in infancy or early childhood, since untreated medullary thyroid carcinoma is a fatal disease.