The Association of Insulin Resistance with Subclinical Thyrotoxicosis

Background: Although overt thyrotoxicosis is associated with reduced insulin sensitivity (IS), the effects of subclinical thyrotoxicosis (SCTox) (i.e., suppressed serum thyroid-stimulating hormone with free thyroxine and tri-iodothyronine within the reference range) on glucose metabolism are not clear. SCTox may be of endogenous origin or due to ingestion of supraphysiological amounts of thyroid hormone. Our hypotheses were that reduced IS is present in SCTox and that the degree of reduction differs between SCTox of endogenous and exogenous origin. Methods: The study population consisted of 125 premenopausal, normal-weight women, divided into four groups: exogenous SCTox due to L-T4 treatment for benign goiter or hypothyroidism (SCTox-ExogG) (n-53), endogenous SCTox (SCTox-Endog) (n-12), exogenous SCTox due to L-T4 treatment for differentiated thyroid cancer (SCTox-ExogDTC) (n-20), and finally euthyroid women (C) (n = 40) as a control group. After a mixed meal challenge, glucose and insulin were determined at baseline and 120 minutes later. IS was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) index, quantitative IS check index (QUICKI), and 2 hours IS Avignon's index amended by Aloulou for mixed food. Secretion by pancreatic B-cells was calculated by HOMA-B index. Comparison among groups was done by analysis of variance followed by Tukey test. Linear regression analysis of T3 versus HOMA-IR was calculated. Results: IS was reduced in all types of SCTox when compared with C. All SCTox groups had significantly higher levels of insulin (baseline and postmeal) and HOMA-IR and lower values of QUICKI and Aloulou when compared with controls. SCTox-Endog, however, had higher baseline insulin levels and HOMA-IR and a lower QUICKI index than the rest of the SCTox groups. Although within the normal range, total T4, free T4, and T3 levels were also significantly higher in the SCTox groups than in euthyroids. In SCTox-Endog, T3/T4 ratio was increased above the rest of SCTox groups. A moderate linear relationship between T3 and HOMA-IR was found in the whole population. Conclusions: IR is associated with SCTox of either endogenous or exogenous origin. However, based on our findings of lower IS compared with the rest of the SCTox groups, the endogenous subclinical form might have an even larger metabolic impact.