The Clinical Outcome of Prospective Screening for Multiple Endocrine Neoplasia Type 2A

Abstract

An important question facing physicians who care for families with multiple endocrine neoplasia type 2a is whether prospective screening to detect early abnormalities of the thyroid, parathyroid, or adrenal glands favorably influences the ultimate course of the disease. An 18-year study of a large family has allowed us to examine the effect of early treatment on the clinical course of the disease. Of 22 patients who underwent thyroidectomy for early C-cell abnormalities, 19 remained free of detectable medullary thyroid carcinoma according to all criteria, at a mean of 11 years after thyroidectomy. None of the 22 patients had evidence of parathyroid disease either at the time of surgery or after a mean follow-up of 10 years. Prospective screening for adrenal medullary abnormalities by means of measurement of 24-hour urinary epinephrine excretion and the ratio of urinary epinephrine to norepinephrine was predictive of pheochromocytoma in 10 of 11 patients (with a false negative result in one patient) but was not useful in diagnosing adrenal medullary hyperplasia. We conclude that regular, prospective screening and early treatment of the manifestations of multiple endocrine neoplasia can prevent metastasis of medullary thyroid carcinoma and the morbidity and mortality caused by pheochromocytoma.

Pheochromocytomas detected by biochemical screening in predisposed subjects are associated with lower prevalence of clinical and biochemical manifestations and smaller tumors than pheochromocytomas detected by signs and symptoms

“…In the patients with a documented hereditary predisposition, several patients developed an additional pheochromocytoma in the contralateral adrenal gland, especially in the case of MEN 2A syndrome (5). In the sporadic group, there were several patients with malignant pheochromocytomas.…”

“…In 12-24% of cases of an apparently sporadic presentation, a pheochromocytoma is caused by germline mutations in the von Hippel-Lindau gene (VHL), the RET gene (leading to MEN2), the neurofibromatosis type I gene (NF1), or one of the SDH genes encoding for subunits B, D, and C of mitochondrial succinate dehydrogenase (2)(3)(4)(5)(6)(7)(8).…”

Review of Multiple Endocrine Neoplasia Type 2A in Children: Therapeutic Results of Early Thyroidectomy and Prognostic Value of Codon Analysis

“…16 In our opinion, both consequent genetic and yearly preoperative biochemical screening starting in the first year of life is mandatory to monitor individual biology of the Ccell disease in MEN-2A patients and to plan ETT between 2 to 5 years of age. If biochemical screening demonstrates an abnormality, ETT should be performed immediately at any age.…”

“…[7][8][9][10][11][12] The only potentially curative treatment for medullary thyroid carcinoma is surgical removal of all thyroid tissue, [13][14][15] a goal that is not regularly achieved in patients with clinically manifest MTC. 16 The molecular bases of MEN-2A and MEN-2B are missense mutations in the RET protooncogene, a transmembrane tyrosine kinase receptor located on chromosome 10q11.2. In MEN 2A, the most frequent germ line mutations involve the extracellular domain of rearranged during transfection (RET) at codons 609, 611, 618, 620, 630, and 634.…”

Carcinoma medular da tireóide

“…Parentes de primeiro grau de um caso índice de CMT são submetidos a um destes testes a partir de 3 a 5 anos de idade, e repete-se anualmente até os 35 anos, ou até a positividade do mesmo (77,78).…”