ESPE Abstracts

Background: Hyperthyrotropinaemia (HTT) describes the biochemical condition of elevated thyroid stimulating hormone (TSH) with normal thyroid hormone concentration. The aetiology of this condition is likely multifactorial but factors such as maternal thyroid disease and presence of trisomy 21 (T21) are thought to play an important role. HTT can be identified during newborn screening for congenital hypothyroidism (CHT), or when thyroid investigations are performed for other indications. The clinical significance or long-term implications of this condition are widely debated, and its management is controversial. Management options include prospective monitoring of thyroid function or early initiation of low dose thyroxine therapy. The objectives of this study were to examine the natural history of this condition and to quantify clinical outcomes and variation in clinical practice with the goal of informing evidence-based management of this cohort.

Methods: A retrospective, observational multi-centre review was performed over a five-year period. Centres included the national newborn screening centre and two tertiary maternity hospitals in Dublin, Ireland. Infants were recruited based on the biochemical inclusion criteria of serum TSH 5.5-10 mU/L with normal FT4 value, during their first month of life. All term infants with mild HTT were included.

Results: A total of 426 study participants were included. The prevalence of mild HTT in term infants was 0.7% and incidence was 2 to 13 per 1000 live births. T21 was present in 3.5%(n = 15) participants. Aggregated TSH concentrations were 2.79mU/L higher in infants with T21 (P =0.000). A mixed linear regression model estimated that overall TSH values decreased by 0.01mU/L every day, after adjusting for the effect of T21 (P = 0.000). In 98.4%(n = 419) of participants, TSH normalised without intervention. In 1.6%(n = 7) TSH values increased, and thyroid hormone therapy was commenced at a mean age of 85 days, with median TSH concentration 15.2 mU/L at treatment initiation. In participants whose TSH normalised, a regression model predicted that resolution of HTT occurred at 71 days of age in patients without T21 or maternal thyroid disease (P = 0.000).

Conclusions: This study describes the largest cohort of neonates with mild HTT to date. Infants with T21 had consistently higher TSH values and longer time to normalisation compared to infants without. Outcome data revealed an overall downward trend in TSH values and ultimate resolution of HTT in the majority of participants. These data are reassuring and support a conservative management approach of monitoring prior to treatment initiation in these patients.