PROPHYLACTIC THYROIDECTOMY IN MEN IIA - DOES THE CALCITONIN LEVEL CORRELATE WITH TUMOR SPREAD

Background: The fate of patients with multiple endocrine neoplasia of type IIA (MEN II A) is determined by medullary thyroid carcinoma, whic h occurs in all cases. This has led to the therapeutic concept of prop hylactic thyroidectomy in affected family members with the goal of rem oving the thyroid before the manifestation of carcinoma. We investigat ed a prophylactically thyroidectomized MEN IIA population to determine whether the highly specific and sensitive tumor marker calcitonin cor relates with tumor spread. Patients and methods: Fifteen patients with MEN IIA (aged 4-24 years) who had undergone prophylactic thyroidectom y since 1990 were included in the study. Baseline and pentagastrin-sti mulated calcitonin levels were preoperatively determined in all cases. The indication for surgery was established on the basis of pathologic calcitonin levels in the first seven patients and on the basis of det ected RET proto-oncogene mutation in the other eight patients. Bilater al central lymphadenectomy was performed in all patients in addition t o thyroidectomy. Results: Histology demonstrated C-cell hyperplasia in five patients (aged 4-13 years), unilateral medullary microcarcinoma in six (aged 9-17 years) and a bilateral medullary microcarcinoma in t hree cases (aged 17-24 years). One 9-year-old boy with bilateral micro carcinoma already had a lymph node metastasis. The mean baseline calci tonin level correlated with the histologic findings (r=0.71, P=0.003) but there was no correlation between pentagastrin-stimulated calcitoni n levels and histology (r=0.21, P=0.47). Conclusion: In MEN IIA patien ts undergoing prophylactic thyroidectomy, baseline but not stimulated calcitonin levels already correlate with the histologic tumor stage at the stage of clinically occult C-cell hyperplasia or medullary microc arcinoma. However, biochemical screening cannot reliably discriminate the transition from C-cell hyperplasia to invasive microcarcinoma. Ind ividuals with MEN IIA should therefore undergo early prophylactic thyr oidectomy once the diagnosis is confirmed by molecular genetic testing .