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J Clin Endocrinol Metab. 2018 Apr 1;103(4):1459-1469. doi: 10.1210/jc.2017-01937.

Mean High-Dose l-Thyroxine Treatment Is Efficient and Safe to Achieve a Normal IQ in Young Adult Patients With Congenital Hypothyroidism.

Author information

Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Sozial-Pädiatrisches Zentrum, Charité Universitätsmedizin Berlin, Berlin, Germany.
Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, New South Wales, Sydney, Australia.
Head of Medical Faculty and Clinic, Universitätsklinikum Heidelberg, Heidelberg, Germany.



The optimal levothyroxine (LT4) dose to treat congenital hypothyroidism (CH) remains unclear, with debate over whether higher starting doses (>10 µg/kg) are necessary and safe for a normal intelligence quotient (IQ).


To examine psychomotor, metabolic, and quality of life (QoL) outcomes in patients with CH treated with a mean high initial LT4 dose.

Design, settings, participants:

A cross-sectional cohort study of patients with CH identified in the Berlin newborn screening program from 1979 to 2003; 76 patients with CH (mean age, 18 years; mean initial LT4 dose, 13.5 µg/kg) and 40 siblings completed the study.

Main outcome measures:

Psychomotor (Wechsler Intelligence Test, CNS Vital Signs), QoL (short form-36 Health Survey), anthropometric (body mass index, height), and metabolic (intima media thickness, laboratory parameters) outcomes were compared with those of healthy siblings. Mean values and percentage of episodes of elevated thyroxine (T4) and tri-jod-thyronin (T3) and suppressed thyrotropin (TSH) before age 2 years were analyzed. A meta-analysis of CH treatment studies was performed.


There were no significant differences in IQ, QoL, or other outcome measures in patients with CH compared with controls. Most T4 levels were high before age 2 years and during subsequent testing, but mean T3 and TSH levels remained normal. The meta-analysis showed a significant IQ difference in severe vs mild CH cases only when treatment started with an LT4 dose <10 µg/kg.


High initial LT4 dosing was effective and safely achieved optimal cognitive development in patients with CH, including those severely affected. Supranormal T4 values during infancy were not associated with impaired IQ in adolescence.

[Indexed for MEDLINE]

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