Effects of Thyroid Function on Phosphodiester Concentrations in Skeletal Muscle and Liver: An In Vivo NMRS Study

Context Thyroid function is clinically evaluated by determination of circulating concentrations of thyrotropin (thyroid-stimulating hormone; TSH) and free thyroxine (fT4). However, a tissue-specific effector substrate of thyroid function is lacking. Energy-rich phosphorus-containing metabolites (PM) and phospholipids (PL) might be affected by thyroid hormone action and can be noninvasively measured by 31P nuclear magnetic resonance spectroscopy (NMRS). Objectives To measure the actions of peripheral thyroid hormones on PM and PL tissue concentrations. Design and Setting A longitudinal, prospective pilot study was performed. Participants Nine patients with hyperthyroidism (HYPER) and 4 patients with hypothyroidism (HYPO) were studied at baseline and 3 months after treatment. Main Outcome Measures High-field 1H/31P NMRS was used to assess profiles of PM, PL, and flux through oxidative phosphorylase in liver and skeletal muscle, as well as ectopic tissue lipid content. Results The concentrations of total skeletal muscle (m-) and hepatic (h-) phosphodiesters (PDE) and one of the PDE constituents, glycerophosphocholine (GPC), were lower in HYPER compared with HYPO (m-PDE: 1.4 ± 0.4 mM vs 7.4 ± 3.5 mM, P = 0.003; m-GPC: 0.9 ± 0.3 mM vs 6.7 ± 3.5 mM, P = 0.003; h-PDE: 4.4 ± 1.4 mM vs 9.9 ± 3.9 mM, P = 0.012; h-GPC: 2.2 ± 1.0 mM vs 5.1 ± 2.4 mM, P = 0.024). Both h-GPC (rho = −0.692, P = 0.018) and h-GPE (rho = −0.633, P = 0.036) correlated negatively with fT4. In muscle tissue, a strong negative association between m-GPC and fT4 (rho = −0.754, P = 0.003) was observed. Conclusions Thyroxine is closely negatively associated with the PDE concentrations in liver and skeletal muscle. Normalization of thyroid dysfunction resulted in a decline of PDE in hypothyroidism and an increase in hyperthyroidism. Thus, PDE might be a sensitive tool to estimate tissue-specific peripheral thyroid hormone action.