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

Abstract

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.

Keywords: hyperthyroidism; hypothyroidism; nuclear magnetic resonance spectroscopy; phosphodiesters; thyroid hormone action.