Thyroxine overuse and clinical indices guiding successful treatment withdrawal

Levothyroxine (LT4) is commonly prescribed, but there is evidence strongly suggesting that a significant proportion of these patients are on treatment without solid evidence of hypothyroidism. Small trials on treatment discontinuation, did not detect any predictors of success. Therefore, we conducted this study in an attempt to identify predicting factors for successful LT4 withdrawal.

In 802 consecutive patients (83% females, mean age 48 ± 16 years) on LT4 treatment for 8.8 ± 7.3 years without a solid diagnosis of hypothyroidism, therapy was abruptly discontinued. A total of 387 persons were followed up for up to 4 months (group A) and 415 individuals who were euthyroid at 4 months post LT4 discontinuation, were followed up for up to 60 months (group B). Recurrent hypothyroidism was defined if thyrotropin (TSH) level exceeded 4.5mIU/L.

Among the entire cohort, 182 patients (23%) became hypothyroid, 40% of group A and 7% of group B (p < 0.001). The Τhyroid treatment Discrimination Index (T4RxDI), the product of TSH levels multiplied by the daily LT4 dose divided by BMI, was calculated. In group A, successful LT4 withdrawal was strongly indicated by a T4RxDI value < 2.78 (72% sensitivity, 66% specificity), while in group B, the corresponding value was 3.75 (100% sensitivity, 48% specificity).

Our findings reveal considerable overuse of LT4 and propose a T4RxDI product of < 3 as a valuable predictive factor of recurrent hypothyroidism, justifying a treatment discontinuation trial. If hypothyroidism does not resume within 4 months, the risk of developing long-term hypothyroidism is likely to be minimal.