The Synthesis, Storage, and Excretion of Creatine, Creatinine, and Glycocyamine in Progressive Muscular Dystrophy and the Effects of Certain Hormones on These Processes

Abstract

The diminished excretion of creatinine in progressive muscular dystrophy is a more striking and specific phenomenon than the excess excretion of creatine, marked though this is. While creatinuria is invariably encountered in all cases of long-standing dystrophy, the extent to which the excretion of creatinine is decreased provides a more reliable indication of the severity of the disease since an excess output of creatine may occur physiologically in normal human subjects and in many pathological conditions not known to be associated with muscle disease. In progressive muscular dystrophy the residual muscle mass, as inferred from the excretion of creatinine, provides a useful index of the state of the disease at any given time. Although there is excessive creatinuria in progressive muscular dystrophy, there is no evidence that a deprivation of methyl stores occurs through a loss of urinary creatine. The loss of methyl groups contained in the excess creatine is, under ordinary conditions of diet, almost exactly compensated for by a drop in the excretion of methyl groups in the urinary creatinine. Testosterone propionate, administered over variable periods of time, resulted in the retention of creatine both in normal male children and in male children with progressive muscular dystrophy, as shown in the normal subjects by a diminution in creatine output, and in both by an excess creatinuria for variable periods of time following withdrawal of the hormone. An increase in the excretion of creatine in progressive muscular dystrophy occurred following the administration of methyl testosterone. Neither testosterone propionate nor methyl testosterone appeared to effect any consistent change in the output or urinary creatinine. No effects on the excretion of creatine and creatinine were observed following the prolonged administration of concentrate of gonadotropic and thyrotropic principles of the hypophysis, or from the administration of desoxycorticosterone acetate to patients with progressive muscular dystrophy. Except in one case, in which marked improvement was observed following the administration of testosterone propionate, no effects on the clinical course of the patients with progressive muscular dystrophy were observed as a result of treatment by any of the various hormones employed in this study.

The Origin of Urinary Creatine in Progressive Muscular Dystrophy 1

“…In man there is reason to believe that most or all creatine synthesis occurs in the liver (9) and it is, therefore, suggested that in progressive muscular dystrophy the creatinuria is a consequence of-an imbalance between normal hepatic creatine synthesis, and markedly diminished creatine uptake by-muscle. This view is in accord with that expressed by Hoagland, Gilder, and Shank (10).…”

Nutritional Status Evaluation in Patients Affected by Bethlem Myopathy and Ullrich Congenital Muscular Dystrophy

“…Creatinine is derived from the metabolism of creatine, which is transformed into phosphocreatine and used by muscles as an energetic substrate (Hoagland et al, 1945 ). A higher production of creatinine is linked to a higher use of phosphocreatine and, consequently, to greater muscular efficiency.…”

Serum Creatinine and Renal Function

“…Pathophysiologic states associated with muscle wasting and reduced muscle mass also feature reduced creatinine generation. Such conditions include chronic glucocorticoid therapy (9), hyperthyroidism (10), muscular dystrophy (11, 12), muscular paralysis (10, l3, 14), dermatomyositis and polymyositis (10), and all causes of negative nitrogen balance (5).…”