Triiodothyronine supplementation improves lipid parameters in central hypothyroidism: a randomized controlled trial ('4 T study')

A normal thyroid function is critical for regular metabolism, wellbeing and cognitive function. Hypercholesterolaemia and increased creatine kinase levels are typical findings in hypothyroidism. In central hypothyroidism replacement therapy is mainly depending on clinical information which hampers optimal dosing of thyroxin (T4). In a placebo controlled, randomized trial 36 patients with central hypothyroidism including TSH deficiency were studied following a double blind cross-over design. 29 patients (age: 52±2; f/m: 7/22; deficient pituitary axes: 3.6±0.1; mean±SEM) completed the study after treatment for three five-week periods: 'P', usual doses of T4 (1±0.05µg/kg bw); 'T', optimized T4 treatment (1.6µg/kg bw T4); 'C', combination of triiodothyronine (T3; 10% of 1.6µg/kg bw) and T4. Biochemical parameters and Achilles tendon reflex time (ART) were assessed at the end of each treatment period. Heart rate (65±2/min) and blood pressure (125/80mmHg) did not change significantly. However, after period P, patients had a higher BMI than during T and C (29.5±0.7 vs. 29.0±0.7 vs. 28.9±0.7kg/m2; p<0.03). Unfavourable lipid parameters were higher during P, but improved during T and more pronounced after C. Cholesterol: 226±7 vs. 198±9 vs. 194±7, p<0.001; triglycerides: 184±23 vs. 191±24 vs. 168±22, p<0.05; VLDL: 39±4 vs. 42±5 vs. 35±4, p<0.03; LDL: 135±7 vs. 116±5 vs. 114±6, p<0.001; HDL 52±2 vs. 47±3 vs. 45±3mg/dl, p<0.001. Creatine kinase was higher during P and than in T and C: 159±16 vs. 127±13 vs. 106±10 U/l; p<0.001. Prolonged ART in phase P (389±0.08) and T (380±0.9) normalized during C treatment (364±0.08 ms; p<0.01; normal range: 360±3 ms). In conclusion, thyroxin treatment with a dose of 1.6µg/kg bw and additional supplementation of T3 improves unfavourable lipid parameters in patients with central hypothyroidism. Additional, Achilles tendon reflex time and creatine kinase are reduced during combination treatment indicating deficiency of biological active thyroid hormone during 'usual dose' T4 treatment.