Enhanced activity of the purine mucleotide cycle of the exercising muscle in patients with hyperthyroidism

Myopathy frequently develops in patients with hyperthyroidism, but its prec ise mechanism is not clearly understood. In this study we focused on the pu rine nucleotide cycle, which contributes to ATP balance in skeletal muscles . To investigate purine metabolism in muscles, we measured metabolites rela ted to the purine nucleotide cycle using the semiischemic forearm test. We examined the following four groups: patients with untreated thyrotoxic Grav es' disease (untreated group), patients with Graves' disease treated with m ethimazole (treated group), patients in remission (remission group), and he althy volunteers (control group). To trace the glycolytic process, we measu red glycolytic metabolites (lactate and pyruvate) as well as purine metabol ites (ammonia and hypoxanthine). In the untreated group, the levels of lactate, pyruvate, and ammonia releas ed were remarkably higher than those in the control group. Hypoxanthine rel ease also increased in the untreated group, but the difference among the pa tient groups was not statistically significant. The accelerated purine cata bolism did not improve after 3 months of treatment with methimazole, but it was completely normalized in the remission group. This indicated that long -term maintenance of thyroid function was necessary for purine catabolism t o recover. We presume that an unbalanced ATP supply or conversion of muscle fiber type may account for the acceleration of the purine nucleotide cycle under thyr otoxicosis. Such acceleration of the purine nucleotide cycle is thought to be in part a protective mechanism against a rapid collapse of the ATP energ y balance in exercising muscles of patients with hyperthyroidism.