Effects of Thyroid on Creatine Metabolism With a Discussion of the Mechanism of Storage and Excretion of Creatine Bodies 1

Abstract

The vast literature which has accumulated on the metabolism of creatine has been reviewed in a number of monographs (1 to 4). The discovery of phosphocreatine in muscle (5, 6) was followed by extensive work on the enzyme system controlling the creatine-phosphocreatine cycle and the role of this cycle in muscular contraction (7,8).The synthesis of creatine from its precursors has recently been elucidated using isotopes (9, 10) and experiments on isolated tissues (11). It has been demonstrated that administration of androgens having a methyl group in the 17-position leads to an outpouring of creatine into the urine, presumably through an increased synthesis of creatine (12 to 14).In spite of all this work, the mechanism by which various physiological and pathological conditions influence the excretion of creatine and creatinine is still little understood. The elucidation of these problems depends on the one hand on the study of the synthesis of creatine from its precursors, and on the other hand, upon an understanding of the factors which govern the storage of creatine and phosphocreatine in the muscles, and the liberation and excretion of creatine and creatinine in the urine. The effects of thyroid on the excretion of creatine are so marked that they present an opportunity to study these questions. In this paper we shall survey briefly knowledge which has accumulated on the relationship of thyroid to creatine metabolism and add to it observations which we have made. We shall then discuss the bearing of these findings upon the mechanism of the storage and excretion of creatine and creatinine.

Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report

“…In addition, it has also been reported that increased s-Cr levels under hypothyroidism might be associated with increased circulating Cr, suggesting hypothyroidism might increase s-Cr levels independent of GFR. These mechanisms include increased release of Cr from muscle tissue due to myopathy and rhabdomyolysis [16], and increased conversion from creatine into creatinine [17]. Indeed, in our case, re-evaluation of renal function revealed no increase in 24-h Ccr after the levothyroxine treatment despite the apparent improvement in s-Cr levels.…”

Studies on Amino Acid Metabolism. Ii. Blood Glycine and Total Amino Acids in Various Pathological Conditions, With Observations on the Effects of Intravenously Administered Glycine 1

“…The relation between glycine and creatine and the role of the latter in the metabolism of muscle have been studied extensively (7,11,12,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). It is likely that in the myopathy of thyrotoxicosis (44) and in myopathies in general (34) there is no impairment of creatine synthesis, but rather of creatine storage and utilization.…”

Thyrotoxic muscle disease

“…It follows from this that thyrotoxic patients have a reduced tolerance to ingested creatine (Thorn & Eder, 1946;Wilkins & Fleischmann, 1946). Urinary creatine is virtually absent in normal adult males, though values of up to 50 mg/day may be found in women (Documenta Geigy, 1962).…”