Immunometabolic signatures predict recovery from thyrotoxic myopathy in patients with Graves' disease

Abstract

Background Thyroid hormone excess induces protein energy wasting, which in turn promotes muscle weakness and bone loss in patients with Graves' disease. Although most studies have confirmed a relationship between thyrotoxicosis and muscle dysfunction, few have measured changes in plasma metabolites and immune cells during the development and recovery from thyrotoxic myopathy. The aim of this study was to identify specific plasma metabolites and T-cell subsets that predict thyrotoxic myopathy recovery in patients with Graves' disease. Methods One hundred patients (mean age, 40.0 ± 14.2 years; 67.0% female), with newly diagnosed or relapsed Graves' disease were enrolled at the start of methimazole treatment. Handgrip strength and Five Times Sit to Stand Test performance time were measured at Weeks 0, 12, and 24. In an additional 35 patients (mean age, 38.9 ± 13.5 years; 65.7% female), plasma metabolites and immunophenotypes of peripheral blood were evaluated at Weeks 0 and 12, and the results of a short physical performance battery assessment were recorded at the same time. ResultsIn both patient groups, methimazole-induced euthyroidism was associated with improved handgrip strength and lower limb muscle function at 12 weeks. Elevated plasma metabolites including acylcarnitines were restored to normal levels at Week 12 regardless of gender, body mass index, or age (P trend <0.01). Senescent CD8 + CD28 À CD57 + Tcell levels in peripheral blood were positively correlated with acylcarnitine levels (P < 0.05) and decreased during thyrotoxicosis recovery (P < 0.05). High levels of senescent CD8 + T cells at Week 0 were significantly associated with small increases in handgrip strength after 12 weeks of methimazole treatment (P < 0.05), but not statistically associated with Five Times Sit to Stand Test performance. Conclusions Restoring euthyroidism in Graves' disease patients was associated with improved skeletal muscle function and performance, while thyroid hormone-associated changes in plasma acylcarnitines levels correlated with muscle dysfunction recovery. T-cell senescence-related systemic inflammation correlated with plasma acylcarnitine levels and was also associated with small increases in handgrip strength.

Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves’ Disease

“…We selected treatment period for 12 weeks. Because we previously published a paper about thyrotoxic myopathy in patient with GD [ 14 ]. In that paper, we found that skeletal muscle function and thyroid hormone levels were recovered in most GD patients treated with methimazole for 12 weeks.…”

“…Details have been described previously [ 14 ]. Briefly, for whole metabolite extraction, 10 µL of plasma was added to 240 µL of water and 250 µL of ice-cold methanol before being vortexed and centrifuged (14,000 ×g, 4°C, 15 minutes).…”

Autoimmune Diseases in Patients With Myotonic Dystrophy Type 2

“…These findings have profound diagnostic implications, since symptoms of DM2 and a variety of AIDs often overlap, like in the case of Hashimoto or Graves that can give rise to myopathy and myotonia ( 12 , 13 ). This can result in earlier diagnosis of DM2 on the one hand or lead to DM2 being completely missed, since myotonia and myopathy might be interpreted as part of a thyroid disease.…”

“…The AIDs seen exclusively in the Dutch patient sample included aplastic anemia, uveitis anterior, Churg-Strauss syndrome, and autoimmune hepatitis, while the Serbian database included myasthenia gravis, neuromyelitis optica, celiac disease, and psoriasis. These findings have profound diagnostic implications, since symptoms of DM2 and a variety of AIDs often overlap, like in the case of Hashimoto or Graves that can give rise to myopathy and myotonia (12,13). This can result in earlier diagnosis of DM2 on the one hand or lead to DM2 being completely missed, since myotonia and myopathy might be interpreted as part of a thyroid disease.…”

Sclerostin as a Putative Myokine in Sarcopenia

“…Moreover, further studies are needed to clarify the role of sclerostin in the muscle-bone relationship in a variety of racial and ethnic populations. Since it has been recognized that many hormones and growth factors regulate muscle mass and protein metabolism [ 7 , 11 , 12 ], it would be valuable to investigate the role of sclerostin in the myopathies of endocrine disorders.…”