The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.

BACKGROUND: Levothyroxine (l-T4) is commonly employed to correct hormone deficiency in children with congenital hypothyroidism (CH) and in adult patients with iatrogenic hypothyroidism. OBJECTIVE: To compare the daily weight-based dosage of the replacement therapy with l-T4 in athyreotic adult patients affected by CH and adult patients with thyroid nodular or cancer diseases treated by total thyroidectomy. DESIGN AND METHODS: A total of 36 adult patients (27 females and nine males) aged 18-29 years were studied; 13 patients (age: 21.5±2.1, group CH) had athyreotic CH treated with l-T4 since the first days of life. The remaining 23 patients (age: 24±2.7, group AH) had hypothyroidism after total thyroidectomy (14 patients previously affected by nodular disease and nine by thyroid carcinoma with clinical and biochemical remission). Patient weight, serum free thyroid hormones, TSH, thyroglobulin (Tg), anti-Tg, and anti-thyroperoxidase antibodies were measured. Required l-T4 dosage was evaluated. At the time of the observations, all patients presented free thyroid hormones within the normal range and TSH between 0.8 and 2 µIU/ml. RESULTS: Patients had undetectable Tg and anti-thyroid antibodies. The daily weight-based dosage of the replacement therapy with l-T4 to reach euthyroidism in patients of group CH was significantly higher than that in those of group AH (2.16±0.36 vs 1.73±0.24 µg/kg, P<0.005). Patients of group CH treated with l-T4 had significantly higher serum TSH levels than patients of group AH (P=0.05) as well as higher FT4 concentrations. CONCLUSIONS: To correct hypothyroidism, patients of group CH required a daily l-T4 dose/kg higher than group AH patients, despite higher levels of TSH. The different requirement of replacement therapy between adult patients with congenital and those with surgical athyroidism could be explained by a lack of thyroid hormones since fetal life in CH, which could determine a different set point of the hypothalamus-pituitary-thyroid axis.

Congenital hypothyroidism and late-onset goiter: identification and characterization of a novel mutation in the sodium/iodide symporter of the proband and family members.

BACKGROUND: Iodide transport defects (ITDs), rare causes of congenital hypothyroidism (CH), have been shown to arise from abnormalities of the sodium/iodide symporter (NIS). We describe a 16-year-old girl with CH caused by an ITD resulting from a novel mutation of NIS. SUMMARY: A 16-year-old girl with CH diagnosed by a neonatal screening program received early treatment with L-thyroxine replacement therapy. A (123)I scan had failed to reveal any iodide uptake by the thyroid and salivary glands; thus, thyroid agenesis was diagnosed. Thyroglobulin (Tg) was not measured when she was a neonate or infant. Unexpectedly, at the age of 14.5 years, a nodular goiter and high serum Tg concentrations (303 ng/mL; normal, <50) were identified. Her thyroid radioactive iodine uptake was very low as was the saliva to plasma iodide ratio (0.5). Analysis of her NIS gene revealed an in-frame six-nucleotide deletion of the coding sequence (1206-1211delGTCGGC) corresponding to the deletion of amino acids 287 and 288 of the human NIS protein located at the beginning of the VIII transmembrane segment. The proband was homozygous for this deletion, whereas both unrelated parents and her brother were heterozygous. COS-7 cells transfected with the mutant NIS failed to concentrate iodide, confirming that the mutation was the direct cause of the ITD in this patient. CONCLUSIONS: We describe a patient with CH caused by a previously not described mutation of the NIS gene that was inherited from her parents. We therefore recommend that thyroid ultrasonography be performed in CH patients with low radioactive iodine uptake and elevated serum Tg.