Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment?

J Clin Endocrinol Metab. 2013 Nov;98(11):4499-506. doi: 10.1210/jc.2013-2175. Epub 2013 Aug 26.


Background: Optimal treatment of children with congenital hypothyroidism (CHT) is still debated. Our objective was to evaluate whether early undertreatment (UT) and overtreatment (OT) influence cognitive development at age 11 years.

Methods: Sixty-one patients (27 severe CHT, 34 mild CHT) were psychologically tested at ages 1.8 (Mental Development Index), 6 [intelligence quotient (IQ) 6], and 11 years (IQ11). Scores for cognitive development were related to initial levels of TSH normalization (fast, moderate, or slow) and to total durations of the UT and OT episodes within the first 2 years of life (no, short, or long UT/OT). UT and OT were defined as a free T4 (fT4) concentration below or above the individual fT4 steady-state concentration range (±2 SD).

Results: Patients with fast and moderate TSH normalization had higher Mental Development Index scores than patients with slow TSH normalization; 14.2 and 7.7 points higher, respectively (P = .001). TSH normalization had no significant effect on IQ11. Patients with long and short overtreatment had IQ11s that were -17.8 and -13.4 points lower, respectively, than the IQ11s of patients with no overtreatment (P = .014). UT without OT was associated with normal development scores, but UT with OT was associated with -14.7 points lower IQ11s than UT without OT (P = .005).

Conclusions: Our study suggests that CHT overtreatment during the first 2 years leads to lowered cognitive outcomes at 11 years, whereas undertreatment, if not complicated by overtreatment, results in a normal cognitive development. Fast TSH normalization at initial treatment leads to above-normal development scores at a young age but does not affect IQ at age 11 years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / drug effects
  • Brain / growth & development
  • Brain / physiology
  • Child
  • Child Development*
  • Cognition / drug effects
  • Cognition / physiology
  • Congenital Hypothyroidism / drug therapy*
  • Congenital Hypothyroidism / physiopathology*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Intelligence / drug effects
  • Intelligence / physiology
  • Intelligence Tests
  • Longitudinal Studies
  • Male
  • Prospective Studies
  • Thyrotropin / administration & dosage*
  • Thyrotropin / blood
  • Thyroxine / administration & dosage*
  • Thyroxine / blood


  • Thyrotropin
  • Thyroxine