EFFECTS OF THYROID ON CREATINE METABOLISM WITH A DISCUSSION OF THE MECHANISM OF STORAGE AND EXCRETION OF CREATINE BODIES 1

Abstract

A review of the literature and original studies reported suggest that thyroid hormone (1) decreases the concn. of both creatine and phosphocreatine in the muscles; (2) increases the urinary output of creatine and decreases that of creatinine. The authors show that when thyroid is administered to a hypothyroid patient, there is at first a loss of stores of creatine from the muscles over a period of 30-60 days. After this period the daily output of creatine + creatinine returns to the pretreatment level but the proportion of creatine is increased and that of creatine is decreased. Thyroid deficiency does not interfere with the synthesis of creatine brought about by methyl testosterone but does prevent the loss of creatine stores which usually occurs when methyl testosterone is discontinued. When treated myxedematous patients were allowed to lapse into the hypothyroid state by withdrawing thyroid therapy while they continued to receive methyl testosterone, there was an abrupt cessation of creatinuria over a period of about 2 wks. This suggested that the withdrawal of thyroid caused increased storage of creatine. The writers discuss the mechanism of storage and excretion of creatine and present 2 theories concerning the origin of creatinine. They point out that alterations in the excretion of creatine and creatinine could be caused by changes (1) in the rate of synthesis of creatine from its precursors; (2) in the ability of the muscles to store or to liberate creatine; (3) in the rate or direction of the creatine-phosphocreatine cycle; (4) in the rate of conversion of creatine or of phosphocreatine into creatinine. Analysis of the observations made on the effects of thyroid suggests that (1) it has negligible effect upon the synthesis of creatine from its precursors; (2) it decreases the storage of creatine by the muscles; (3) it decreases the amt. of creatine which is converted into creatinine. It is not known whether the changes in the creatine stores of the muscle occur independently or are associated with changes in muscle protoplasm or of tissue fluid. It is not known whether thyroid influences the conversion of creatine into creatinine directly or through an effect upon the enzymes controlling the creatine-phosphocreatine cycle.