T4 plus T3 Treatment in Children with Hypothyroidism and Inappropriately Elevated Thyroid-Stimulating Hormone despite Euthyroidism on T4 Treatment

Abstract

Aims: To evaluate the effect of addition of T3 to L-T4 treatment in children with congenital hypothyroidism (CH) who have inappropriately elevated thyroid-stimulating hormone (TSH) levels despite high normal serum T4 levels on L-T4 treatment. Methods: Ten children (age 7.1 ± 2 years) with CH whose TSH levels were persistently high despite euthyroidism and can only be normalized with hyperthyroidism were included. L-T4 treatment was switched to T3+L-T4 combination (Bitiron® tablet 50 µg L-T4 + 12.5 µg triiodothyronine). The patients received 50% of their usual L-T4 dose as L-T4 and the remaining half as T3 in a 4:1 ratio. The dose of T3+L-T4 was titrated to achieve normal TSH levels. Thyroid hormones and biochemical markers were followed for 1 year. Results: Euthyrotropinemia was achieved at the 7th month (mean) of combination (T3+L-T4) treatment. Serum T4 and fT4 were lower and T3 was higher during combination compared to L-T4 treatment. LDL-cholesterol decreased and ALP increased in the euthyrotropinemic state. Vital signs were similar at hyperthyrotropinemia and euthyrotropinemia. Conclusion: T3+L-T4 treatment provides euthyrotropinemia without causing hyperthyroidism in children with CH and inappropriate hyperthyrotropinemia. Our data strongly suggest that decreased negative feedback due to lower T3 levels at the pituitary level is the main reason for persistent hyperthyrotropinemia.

Persistent hyperthyrotropinemia in congenital hypothyroidism: successful combination treatment with levothyroxine and liothyronine

“…We have found, as in one previous study (22), that adding a small dose of liothyronine caused normalization or near-normalization of TSH in all patients without causing excess levels of thyroid hormones. This provides a simple and well-tolerated solution to the problem of persistent hyperthyrotropinemia.…”

“…Infants with congenital hypothyroidism are a special case since among them the need to achieve normal thyroid hormone exposure of the brain is of greater importance. Recently, a study of combined treatment in children, focusing on the physiological effects, was published (22) . We report here our experience with combined L-T4 and liothyronine treatment of eight patients with persistent hyperthyrotropinemia with particular focus on dose requirements.…”

Liothyronine Improves Biochemical Control of Congenital Hypothyroidism in Patients with Central Resistance to Thyroid Hormone

“…The median age of our cohort at the time of LT3 initiation was 3.5 years, compared with mean ages of 6.2 years and 7.1 years in prior cohorts (one of which excluded patients under 4 years of age). 15, 16 Importantly, our study includes three patients started on LT3 before the age of 3 years, demonstrating that LT3 appears effective in normalizing thyroid hormone levels at the age when maintaining euthyroidism is most critical for neurodevelopment. The median initial dose of LT3 in our cohort (0.29 μg/kg/day) is lower than those in prior studies (0.3–0.66 μg/kg/day), in which locally available LT3 formulations may have constrained the investigators to a minimum administered LT3 dose of 6.25 μg, 15, 16 whereas doses as low as 2.5 μg are available in many areas of the world.…”

“…15, 16 The most significant limitation of both studies was the lack of a comparison group treated with LT4 monotherapy, without which it is difficult to determine whether the observed improvement in TSH and T4 was due to the addition of LT3 or to the normal resolution of central resistance to thyroid hormone. To address this critical issue, we included a monotherapy comparison group in our analysis of LT3 treatment.…”

“…Prior case series of such patients have shown that combined therapy with LT3 and LT4 may help normalize TSH while keeping T3 and T4 in the normal range. 15, 16 However, these studies were limited by several factors, most notably their failure to control for the natural history of central resistance to thyroid hormone to resolve over time in patients with congenital hypothyroidism. 3 …”