source: Endocrine Society

year: 2015

authors: Celestino Neves, César Esteves, Helena Greenfield, Miguel Pereira, Oksana Sokhatska, Carmo Palmares, Davide Carvalho, Luís Delgado, José Luís Medina

Introduction:
It is possible that the higher cardiovascular risk in Graves’ disease (GD) may be due not only to hemodynamic changes induced by the hyperthyroid state, but also to alterations in the cardiovascular risk factor profile.

Aim:
The aim of our study is to evaluate the association between thyroid function in GD and lipoprotein profile, homocysteine, folate, vitamin B12, high-sensitivity C-reactive protein (hs-CRP) and insulin resistance.

Patients and Methods:
We studied 104 subjects with Graves’ disease (GD) (55 with euthyroidism and 49 with hyperthyroidism). Hyperthyroidism was defined as increased levels of serum fT3 (>3.71pg/mL) and/or fT4 (>1.48ng/dL) in the presence of low TSH levels (<0.35mUI/mL). Euthyroidism was defined as levels of TSH, fT3 and fT4 within the normal range (0.35-4.94mUI/mL, 1.71-3.71pg/mL and 0.70-1.48ng/dL, respectively).

The laboratory data obtained included thyroid function tests [TSH, free T3 (fT3) and free T4 (fT4)] and levels of antithyroid antibodies (TRAb, anti-TPO and anti-Tg), total cholesterol (total-C), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (apoB), apolipoprotein A1 (apoA1), lipoprotein(a) [Lp(a)], hs-CRP, homocysteine, folate and vitamin B12. We also determined the Homeostasis Model Assessment for insulin resistance (HOMA-IR) and beta-cell function (HOMA-b), the Quantitative Insulin Sensitivity Check Index (QUICKI), the Hepatic Insulin Sensitivity Index (HISI), the Whole-Body Insulin Sensitivity Index (WBISI) and the Insulinogenic Index (IGI), in order to evaluate insulin resistance. For this purpose, a 75 g OGTT was performed, and venous blood samples were obtained every 30 minutes, for 120 minutes, for measurements of plasma glucose, insulin and C-peptide.

Results:
Significantly higher median levels of TRAb were found in the hyperthyroid patients. On the other hand, levels of folate [5.1 (3.6-6.5) vs 6.9 (5.1-9.4), p=0.001] and WBISI [4.39 (2.49-6.15) vs 5.50 (4.08-7.79), p=0.015)] were significantly lower in the hyperthyroid group. It was observed that patients with higher levels of TRAb (OR=1.166; p=0.004) or hs-CRP (OR=3.064; p=0.042) had a higher risk of being hyperthyroid. The same observation was established for subjects with higher values of HOMA-IR (OR= 1.613; p=0.025) or IGI (OR=2.933; p=0.046). On the other hand, patients with higher levels of folate had a lower risk of being hyperthyroid. In the euthyroid group, TSH levels were positively correlated with WBISI values (r=0.291; p=0.047) and the levels of fT3 and vitamin B12 were negatively correlated (r=-0.358; p=0.01).

Conclusions:
The hyperthyroidism in Graves’ disease is associated with insulin resistance and diminished levels of folate.

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