Subclinical Hypothyroidism, LT4 Treatment Do Not Affect Cognitive Function in Children

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doctor and young patient, thyroid, throat paint
Neurocognitive function in children is unimpaired by persistent idiopathic subclinical hypothyroidism and is not affected by levothyroxine supplementation.

Neurocognitive function in children is unimpaired by persistent idiopathic subclinical hypothyroidism and is not affected by levothyroxine supplementation, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

The neuropsychologic outcomes of subclinical hypothyroidism in children have not been well characterized and it is unclear whether long-term levothyroxine supplementation is warranted. The researchers performed a prospective case-control study to evaluate the effects of long-term levothyroxine treatment on neurocognitive outcomes in children aged 6 to 16 years with idiopathic subclinical hypothyroidism.

The study included 34 children (mean age, 9.1±2.6 years; 52.9% boys) with long-lasting idiopathic subclinical hypothyroidism and 34 healthy control children matched for age, sex, and socioeconomic status. Serum thyrotropin levels were measured after overnight fasting by electrochemiluminescence immunoassay. Neurocognitive function was assessed in both groups at baseline using the Wechsler Intelligence Scale for children, third edition, which includes 3 composite scores: verbal IQ, performance IQ, and full scale IQ. Neurocognitive function was reassessed at 2 years in children with subclinical hypothyroidism. In addition, levothyroxine supplementation was proposed in children with subclinical hypothyroidism and was administered at a starting dose of 50 µg/d for 2 years. The levothyroxine dose was then titrated individually every 6 months to maintain normal serum thyrotropin and free thyroxine levels.

Thyrotropin concentrations were increased in children with subclinical hypothyroidism (6.3±1.1 mU/L) compared with those in control children (2.6±0.8 mU/L; P <.001) at baseline, as expected. Neurocognitive scores were normal in children with and without subclinical hypothyroidism and no significant difference was observed in full-scale (100.4±11.3 vs 101.8±14.2, respectively), visual (99.7±13.7 vs 98.3±14.9, respectively), or performance (101.2±10.4 vs 105.0±10.4, respectively) IQ scores.

In total, 20 children elected to receive levothyroxine supplementation and 14 proceeded without any treatment. No difference in subclinical hypothyroidism duration was observed between the groups. Levothyroxine treatment was associated with normalization of thyrotropin levels (6.3±1.0 at baseline vs 2.8±1.4 mU/L at 2 years; P <.001). No change in thyrotropin levels was observed in untreated children (6.4±1.2 at baseline vs 6.3±0.9 mU/L at 2 years).

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No change in neurocognitive scores was seen in either group, and multiple regression analysis did not identify any significant correlations between IQ scores and thyrotropin levels.

The researchers acknowledged that the small study sample size represented a limitation to their findings and that random assignment of children with subclinical hypothyroidism to treatment groups would have prevented any potential biases in assignment of therapy.

“[T]he results of this study provide evidence that neurocognitive function in children is not impaired by mild and persistent untreated idiopathic [subclinical hypothyroidism], and does not benefit from 2 years of [levothyroxine] supplementation,” the study authors concluded. “Our findings support the current practice to not routinely recommend [levothyroxine] therapy in all children with serum [thyrotropin] values less than 10 mIU/l.”

The researchers also noted that additional randomized studies are needed to fully establish the effects of subclinical hypothyroidism and levothyroxine treatment on neurocognitive function in children, and that “[f]or now, the decision to initiate therapy should be based on consideration of individual factors and clinical judgment.”

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Capalbo D, Alfano S, Polizzi M, et al. Cognitive function in children with idiopathic subclinical hypothyroidism: Effects of 2 years of levothyroxine therapy. J Clin Endocrinol Metab. 2020;105(3):dgaa046.