Congenital hypothyroidism (CH) affects 1:2.0003.000 newborns. In most cases, the cause is a developmental defect (dysgenesia) or an arrested migration (ectopia) of the thyroid gland. In the remaining cases TSH resistance or defects in iodide transport or thyroid hormonogenesis account for CH. The differential diagnosis is aimed to recognize permanent CH forms and to achieve an etiologic diagnosis for accurate management and genetic counselling. Appropriate investigations are in most cases performed at 34 years of age, after 1 month L-thyroxine withdrawal. In this study, a novel rhTSH (Thyrogen®) protocol has been tested after approval by Institutional Ethical Committee and informed consent in 8 patients, aged 17 months-12 years, during L-T4 treatment. In the presence of a normally positioned thyroid gland at ultrasound, 2 i.m. injections (0.004 mg/kg) were administered at days 1 and 2, and thyroid uptake with 123I+ perchlorate test (200500 mg of KClO4) were performed at day 3. In the case of apparent agenesia, 3 rhTSH injections were administered at days 13, with neck scintigraphy uptake at days 3 and 4. In all cases, blood was sampled at baseline and at day 3 for TSH and thyroglobulin (Tg) levels. Side effects were not observed in any patients. Basal TSH levels were normal at baseline and peaked at day 3 (range: 1547 mU/l). Tg levels increased after stimulation in 7/8 patients. At scintigraphy, in a patient previously classified as affected with agenesia, a sublingual thyroid (ectopia) was revealed. Two patients had a large thyroid with a positive perchlorate test (discharge=100%, indicating a total organification defect), while 5 patients had a normally positioned gland with normal uptake and negative perchlorate test (indicating transient CH or partial TSH resistance). In conclusion, we report a novel rhTSH protocol for the differential diagnosis of CH performed during L-T4 treatment in childhood. This test not only led to the correct diagnosis in all cases but also allowed the specific patient management and the targeted genetic analyses. rhTSH test represents a valid alternative to L-T4 withdrawal, avoiding untoward effects of transient hypothyroidism in CH infants.
01 - 05 Apr 2006
European Society of Endocrinology