Plasma branched chain amino acids are lower in short-term profound hypothyroidism and increase in response to thyroid hormone supplementation

Abstract

Branched chain amino acids (BCAA) are implicated in the pathogenesis of cardiometabolic diseases conceivably by affecting insulin resistance and mitochondrial dysfunction. Circulating BCAA levels may predict (subclinical) atherosclerosis, diabetes and hypertension development but the factors involved in BCAA regulation are incompletely understood. Given the key role of thyroid hormones on many metabolic processes including protein metabolism, we aimed to determine effects of thyroid dysfunction on circulating BCAA. Effects of short-term profound hypothyroidism on plasma BCAA were determined in 17 patients who had undergone total thyroidectomy for differentiated thyroid carcinoma. Patients were studied during hypothyroidism, i.e. after thyroidectomy, and after thyroid hormone supplementation. Plasma BCAA (sum of valine, leucine and isoleucine) and alanine were measured by nuclear magnetic resonance spectroscopy. During hypothyroidism (median thyroid-stimulating hormone 81 (IQR 67–120.5) mU/L), plasma BCAA were lower (255 (IQR 222–289) µmol/L) compared to a euthyroid reference population (n = 5579; 377 µmol/L (2.5th to 97.5th percentile 258–548), p < 0.001). After 20 weeks of thyroid hormone supplementation (thyroid-stimulating hormone 0.03 (IQR 0.01–0.14 mU/L) plasma BCAA had increased (328 (IQR 272–392) µmol/L, p = .001), but plasma alanine concentrations were unaltered (p = .50). Changes in body weight in response to thyroid hormone supplementation were correlated with changes in plasma BCAA (r = 0.721 p = .001, but not with changes in cholesterol or glucose (p > .80). In conclusion, plasma BCAA concentrations are lower during short-term profound hypothyroidism in humans, and increase in response to thyroid hormone supplementation. Changes in BCAA and in body weight after reversal of the hypothyroid state appear to be interrelated.