In children with RET protooncogene mutation curative treatment of medullary thyroid carcinoma (MTC) is possible by prophylactic thyroidectomy. Long term treatment of athyroid children and adolescents carries some problems. We evaluated the long term follow-up of operated gene carriers. In 41 MEN 2A/FMTC gene carriers (28 families) prophylactic thyroidectomy was carried out between the age of 4 to 21 years. 18 families carried mutations in exon 11 codon 634, one in codon 630, 3 families in exon 10 codons 618 or 620 and 6 families in exons 13–15, codons 790,791, 804 or 891. Histology showed no C-cell hyperplasia (CCH) in 2, CCH in 15 patients and MTC in 24 patients (T1 n=21, T2 n=1, T3 n=1, Tx n=1). No patient had lymph node involvement (N0 n=30, Nx n=11). After prophylactic thyroidectomy 35 patients were cured demonstrated by normal basal and pentagastrin stimulated calcitonin levels. In 6 patients either basal or pentagastrin stimulated calcitonin was elevated. In two patients carrying a 634 mutation other endocrinopathies than MTC manifested during follow-up. A 12 year old boy developed pHPT 5 years after thyroidectomy and a 28 year old women had bilateral adrenalectomy 12 years after thyroidectomy. In the follow-up (x=7.6 y, mean 8 y, range 0.2–18.5 y) under thyroxine substitution therapy in many patients TSH was elevated: after one month in 82% (x=54 mU/l, median 44mU/l), after one year in 35% (x=40, median 15 mU/l), even after 5 years 32% of TSH levels were elevated (×=9 mU/l, median 5 mU/l). Therefore sufficient age- and weight-dependent thyroxine dosage has to be substituted directly after thyroidectomy. During follow-up dose adjustment and control intervals of 3 months are necessary in specialized centres. If prophylactic thyroidectomy is done at early ages cure rate is high. Despite this encouraging results thyroxine substitution therapy in the follow-up carries some problems concerning optimal dosage and non-compliance. Therefore TSH has to be estimated in the follow-up every 3 months, especially in children and adolescents.
