Effects of supra-physiological levothyroxine dosages on lipids, lipoproteins and liver parameters in healthy volunteers: A randomized controlled crossover study

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B Sjouke, L.P.B. Elbers, B. van Zaane, R.M. Stoekenbroek, J.J.P. Kastelein, G.K. Hovingh, V.E.A. Gerdes

Voorzitter(s): prof. dr. M.M.E. Schneider, UMCU, Utrecht & dr. L.J.M. de Heide, Zorgroep Noorderbreedt, Leeuwarden

Woensdag 22 april 2015

15:00 - 16:00u in Zaal 0.4

Categorieën: parallelsessie (case reports/research)

Parallel sessie: Parallelsessie 3: Case reports/research

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Background:
We recently observed that treatment with the liver specific thyroid hormone agonist eprotirome resulted in significant increases in liver parameters and a modest decrease in atherogenic lipids and lipoproteins in euthyroid patients with familial hypercholesterolemia. It is unknown whether the effects of eprotirome on liver parameters were due to either a drug specific effect or induced ‘local hyperthyroidism’. We studied the effects of supra-physiological levothyroxine dosages on liver parameters, plasma lipids and lipoproteins.

Methods:
We performed a post-hoc analysis of a single blind, randomized controlled, cross-over trial, comprising two studies. In both, healthy volunteers received levothyroxine or no medication for 14 days. In Study A, 16 individuals received 0.3mg/day. In Study B, 12 individuals received 0.45/0.60mg/day (body weight dependent).

Results:
Reductions in total cholesterol (TC) (change after levothyroxine usage: -11% and -15% in study A and B, respectively), LDL-cholesterol (-13% and -17%) and ApoB levels (-8% and -16%) were observed, compared with the control period (change after no medication: TC +6% and -4%, for study A and B respectively; LDL-C +6% and -5%; ApoB +4% and -7%); p < 0.001 for all differences between study periods. Thyroid hormone excess did not clinically significantly affect ASAT, ALAT, Gamma-GT, alkaline phosphatase, total or conjugated bilirubin levels, in both studies.

Conclusion:
Supra-physiological thyroid hormone levels were associated with reductions in TC, LDL-C and ApoB levels but not with increased liver parameters. This may suggest that the effects of eprotirome on liver parameters as previously reported were compound specific rather than thyroid hormone-dependent.