Abstract
Sufficient thyroid iodine uptake is needed to ensure effective radioactive iodine (RAI) treatment, which is mediated by the sodium-iodide symporter (NIS). Activation of AMP-activated-protein-kinase (AMPK), leads to decreased NIS expression and thyroid iodine uptake in in vitro and animal models. Clinically relevant conditions that lead to AMPK activation include metformin use and hypocaloric conditions. Here, we aim to assess the effects of metformin and hypocaloric diet on thyroid iodine uptake in healthy volunteers. Healthy male volunteers were included and randomized. Group 1 (n = 8) received metformin, group 2 (n = 7) followed a hypocaloric diet (1500 kcal/day), superposed on a moderate iodine restriction diet; Baseline measurements included thyroid iodine-123 (I-123) uptake and TSH, fT4, T3 and rT3 levels. After two weeks, thyroid function and I-123 uptake measurements were repeated. Baseline characteristics were similar between groups. Levels of TSH and fT4 were similar after each intervention. T3 decreased after hypocaloric diet and metformin (−0.2 ± 0.19 nmol/L, p = 0.0327; respectively −0.13 ± 0.13 nmol/L, p = 0.0282), resulting in decreased T3/rT3 ratios. There was no significant difference in thyroid I-123 uptake after each intervention. In conclusion, metformin treatment and hypocaloric diet resulted in a significant decrease in T3 levels and T3/rT3 ratios in healthy volunteers, without significant effects on thyroid iodine uptake. We found no indications that metformin or hypocaloric diet will have clinically relevant effects on RAI uptake.
Highlights
The specific thyroid iodine uptake is mediated by the sodium iodide symporter (NIS)[3]
There were no significant differences in percentage of change in I-123 uptake. These results indicate that hypocaloric dieting or metformin use did not result in significant changes in thyroid I-123 uptake in healthy volunteers. This is the first study investigating the effects of energy depletion by metformine or hypocaloric diet, both important AMPK activators, on thyroid iodine uptake in humans
We showed that hypocaloric dieting or metformin lead to a significant decrease in s-T3 levels and a significantly decreased T3/rT3 ratio whereas thyroid iodine uptake was not influenced
Summary
The specific thyroid iodine uptake is mediated by the sodium iodide symporter (NIS)[3]. Previous research has shown that activation of the master sensor for energy depletion, 5′ adenosine monophosphate-activated-protein-kinase (AMPK), leads to decreased NIS expression and iodine uptake in in vitro studies and animal models[6,7,8]. Uptake through reduced transcription and increased degradation of NIS6–8 These results show that modulation of AMPK activity influences NIS expression and RAI uptake. Reduced caloric intake leads to AMPK activation, and could result in reduced NIS expression and RAI uptake[9]. Preparation for RAI treatment in DTC consists of either thyroid hormone withdrawal for 3–4 weeks or administration of recombinant human TSH (rhTSH) in order to stimulate thyroid iodine uptake[2]. An iodine depleted diet which is often used in preparation for RAI therapy, is accompanied by decreased appetite and caloric intake[18]
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