medwireNews: Treating patients with congenital hypothyroidism with a high dose of levothyroxine (LT4) from infancy does not compromise their IQ in young adulthood, report researchers.

The 76 patients (68% female) in the study had received an average LT4 dose of 13.5 µg/kg per day (ranging from 4.4 to 20.8 µg/kg per day), starting at a median of 8 days old (ranging from 1 to 77 days).

When assessed at an average age of 18.1 years, the patients had an average IQ of 102.5, which was comparable to the 102.3 average IQ among 40 of their healthy siblings. These values were adjusted for variables including individual socioeconomic status, which significantly correlated with IQ.

Fifteen of the children had severe congenital hypothyroidism (thyroxine [T4] ≤2 μg/dL), and most (83%) had thyroid dysgenesis.

Heiko Krude (Charité Universitätsmedizin Berlin, Germany) and co-researchers combined their findings with those from another 438 patients identified in a systematic review, and this showed no IQ differences between children with severe and mild/moderate congenital hypothyroidism if they were given LT4 doses greater than 10 µg/kg per day.

By contrast, severely affected children had significantly poorer IQs than those with mild or moderate hypothyroidism if they were given LT4 doses of 8 to 10 µg/kg per day or less than 8 µg/kg per day.

Together, this indicates that a high starting LT4 dose “not only enables an optimal cognitive development that is indistinguishable from the control group but also helps close the developmental gap between patients with severe and mild [congenital hypothyroidism] forms”, write the researchers in The Journal of Clinical Endocrinology & Metabolism.

The children’s free T4 levels were high during the first 24 months of life, at an average of 14.9 μg/dL, but triiodothyronine (T3) and thyroid-stimulating hormone (TSH) levels were normal, at respective averages of 1.79 ng/mL and 3.49 mU/L.

The team stresses that the high T4 levels did not result in overt clinical hyperthyroidism and that previous research has also shown normal T3 and TSH levels despite high T4 in children receiving LT4 for congenital hypothyroidism, but not in those treated for acquired hypothyroidism.

“Therefore the higher T4 levels in [congenital hypothyroidism] patients might not represent a state of ‘overtreatment’ but rather reflect a higher need of T4 to reach normal T3 levels at least in the brain-structures that regulate TSH”, they suggest.

The researchers conclude that “high dose treatment of [congenital hypothyroidism] seems to be necessary to reach optimal cognitive development, while at the same time is safe in not causing clinical symptoms of hyperthyroidism.”

Eleanor McDermid

J Clin Endocrinol Metab 2018; Advance online publication

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