Aim: To determine the final diagnosis of patients with subclinical hypothyroidism (SCH), and to perform mutation screening of the thyroid peroxidase gene (TPO).
Methods: Infants with SCH without an identified etiology were included in the study. Patients with thyroid dysgenesis were excluded. Children > or = 2 years of age, and still on L-thyroxine (LT4) treatment underwent a diagnostic algorithm. After LT4 was discontinued for 4 weeks, thyroid function tests (TFT) were obtained. A perchlorate discharge test (PDT) was performed in patients with normal thyroid ultrasound but abnormal TFT. Sequence analysis of TPO was studied in all children who underwent a PDT.
Results: Forty-eight patients (23 males and 25 females) completed the trial. Among these children, 19 (39.5%) had transient SCH, and 29 (60.5%) had permanent SCH. Among patients with permanent SCH, 19 had thyroid hypoplasia, six had partial iodide organification defect with positive PDT, and four had other dyshormonogenesis with negative PDT. Mean LT4 dose before the medication ceased was 1.2 +/- 0.5 microg/kg/day in transient cases, and 1.7 +/- 0.4 in those with permanent SCH (p < 0.05). No TPO mutation was detected. However, in five patients, seven different previously known TPO polymorphisms were detected: c.102C > G, L4L; > A, A576A; c.2088C > T, D666D; c.2263A > C, T725P; c.2630 T >C, V847A.
Conclusions: LT4 treatment should be stopped after the age of 2 years in infants with SCH without a definite pathology of the thyroid gland to exclude cases with transient hypothyroidism. Additionally, we should consider particularly thyroid gland hypoplasia, and also partial defects in iodide organification in infants with SCH.