Mild neonatal hyperthyrotrophinaemia is an increasingly common diagnosis. It is more common in males and is often transient, but predictors of success of trial-off therapy were not identified. Further studies are needed to determine optimum L-thyroxine dosing and to determine whether treatment improves neurocognitive outcomes.

To determine whether the large doses of thyroxine treatment early in life adversely affect bone mass, we measured bone mass of 20 congenital hypothyroid (CH) patients (8.4 +/- 2.2 years) who were diagnosed and treated since birth. Starting thyroxine dose and current dose were 8.5 +/- 1.9 micrograms/kg/day and 3.1 + 1.2 micrograms/kg/day respectively. Thyroid function and serum biochemical tests for calcium homeostasis were normal at the time of study. Bone mass was measured by dual energy X-ray absorptiometry. Nine siblings served as controls. The patients' bone mineral density was within the normal range of population controls, and was not different from the sibling controls. The patients also had height-adjusted bone mineral content equal to the expected height-adjusted values in the siblings. Our studies indicate that the large doses of thyroxine therapy for CH do not cause osteopenia in childhood.

We examined the patterns of TSH, T(4), and treatment schedules from diagnosis to 4 yr of age in 125 children (50 males anf 75 females) with congenital hypothyroidism (CH). Subjects were divided into 3 groups based on their thyroid scans: 1) athyreosis (n = 31), 2) dysgenesis (n = 54; 49 lingual and 5 hypoplastic), and 3) dyshormonogenesis (n = 40). Follow-up evaluation was carried out at 2-4 wk and 3, 6, 9, 12, 24, 36, and 48 months of age. Median gestational age, age at onset of therapy, and starting L-T(4) dose were similar in the three groups. In infants with athyreosis median screening TSH levels were higher (P < 0.02) and confirmatory T(4) levels were lower than in the other two groups (P < 0.01 vs. dysgenetic; P < 0.05 vs. dyshormonogenetic CH). During the first 6 months of therapy, mean TSH levels were highest in the athyrotic group, intermediate in the dysgenetic group, and lowest in the dyshormonogenetic group. In children with athyreosis, TSH levels normalized by 12 months of age. At 12 months dysgenetic patients had the highest TSH levels (P < 0.05). During the entire study period, TSH levels were lowest in patients with dyshormonogenesis (except at 48 months) and normalized earlier. Mean T(4) levels normalized by 2-4 weeks in all groups. At 3 and 6 months, the percentage of patients who required dose changes was highest in the athyrotic group, and at 12 months it was highest in the dysgenetic group. The athyrotic group received the highest dose of L-T(4), and dyshormonogenetic group received the lowest dose. We conclude that treatment and follow-up schedules for CH may differ in the three etiological categories based on the different hormonal patterns and responses to therapy. Children with athyreosis need close monitoring particularly early in life, whereas those with dysgenesis and dyshormonogenesis require more attention later in life.