Context: The Thr92Ala-DIO2 polymorphism may affect hypothyroid patients’ responses to levothyroxine (LT4) treatment.

Objective: To study whether the Thr92Ala-DIO2 polymorphism affects hypothyroid patients’ responses to levothyroxine (LT4) treatment.

Design: Secondary analysis of a randomized intervention study.

Setting: Primary care center.

Patients or Other Participants: 109 hypothyroid women aged 21-70 years with normal TSH levels grouped in homozygous Thr92-DIO2 (THR; n=39) and homozygous Ala92-DIO2 plus heterozygous (ALA; n=70) groups.

Intervention: Change in LT4 dose.

Main Outcome Measure: Cognitive testing examined declarative memory (paragraph recall) and executive function (letter cancelation, trail making, Iowa gambling task, N-back number correct/incorrect, and subject ordered pointing). Mood and health status were assessed with the profile of mood states (POMS) questionnaire, affective lability scale (ALS), and thirty-six item short-form health survey (SF-36).

Results: At baseline THR subjects had better memory scores vs. ALA subjects on the 2-back number correct test; ALA subjects performed better with the POMS, ALS, and SF-36 surveys relative to the THR group (controlling for age, sex, and education). Reassessment revealed lower LT4 dose did not change the existing cognitive differences between THR and ALA individuals. Lower LT4 worsened the performance of ALA patients, eliminated differences in POMS and ALS, and minimized differences in SF-36. An increase in LT4 dose did not affect existing differences between groups.

Conclusions: Results suggest carrying the Thr92Ala-DIO2 polymorphism could be a factor to consider when planning treatment for hypothyroidism and assessing outcomes. Further studies with larger cohorts are needed to confirm these results. 

Data collected through psychological testing. Processed through basic statistical analyses. 

Data sets are complete.