Abstract
Background Fasting during Ramadan may be challenging for patients on levothyroxine(LT4), as the drug has a narrow therapeutic index and is administered on an empty stomach. The majority of Muslims who fast in Ramadan have two meals per day, iftar immediately after sunset and suhoor just before dawn. This study aimed to evaluate the impact of LT4 timing during Ramadan on thyroid-stimulating hormone(TSH) levels in patients who underwent total thyroidectomy to determine the best timing for intake and identify the predictors of TSH level changes. Methods We conducted a parallel, double-blind, randomized controlled trial on Saudi patients diagnosed with hypothyroidism who underwent total thyroidectomy. Patients were required to have stable thyroid function for six months prior to the study period and fast ≥ 20 days of Ramadan. Participants were randomized to one of three times for LT4 administration: Group A, 30 minutes pre-iftar(n=48); Group B, 3 hours post-iftar(n= 47); or Group C, 1 hour pre-suhoor(n=47). The number of participants in the final analysis (excluding patients who dropped out) was as follows:Group A,(n=31);Group B,(n= 34); and Group C,(n=22). The changes in TSH and free T4 levels two weeks before and after Ramadan were compared. Factors associated with a change in TSH levels were examined through multivariable analysis. Results TSH levels significantly increased in Group B(1.7±1.8 vs. 3.1±3.9 mU/L, p=0.003) and Group C(2±1.7 vs. 5.5±10 mU/L, p=0.011), but not Group A(1.8±1.6 vs. 3.3±4.2 mU/L,p=0.158). The change in free T4 levels was comparable among the groups: Group A, 16.5±2.7 vs. 15.9±3.2 mcg/dL, p=0.144; Group B, 15.8±3.8 vs. 16.3±3.6 mcg/dL, p=0.620; and Group C, 17.5±2.8 vs. 17.3±3.9 mcg/dL, p=0.770. In multivariable linear regression analysis, the following variables were significantly independently associated with TSH level change: age, weight gain, and the number of nonadherence days to LT4 where β=-0.2, p=0.026; β=+0.2, p=0.026; and β=+0.5, p<0.0001, respectively. Conclusions Fasting patients who took LT4 pre-iftar did not experience significant changes in TSH, whereas those who took LT4 post-iftar or pre-suhoor did. TSH changes during Ramadan may be associated with age(inverse association), weight gain, and the number of non-adherence to LT4 days. Trial registration SCTR Application no. 2112.