The Mode of Excretion of Creatine and Creatine Metabolism in Thyroid Disease 1

Abstract

The yellow color yielded by the Jaffe reaction, which is commonly employed for the determination of creatinine and creatine, is not highly specific and is ill-adapted to visual colorimetry. For the measurement of the comparatively gross quantities of creatinine and creatine excreted in the urine, it has proved quite accurate; but the small amounts of creatinine found in normal blood can be measured only with uncertainty. For creatine of serum, it has proved even more unsatisfactory than for creatinine. So slight is the increase in color produced by alkaline picrate after serum filtrates are exposed to acid and heat that the very presence of creatine in normal serum has been doubted (1 to 3). In the plasma of infants and of women who excreted creatine in the urine, Hunter and Campbell (1) and Wilson and Plass (2) detected appreciable increments of chromogenic material after treatment aimed to convert creatine to creatinine. This led them to the tentative conclusion that creatinuria marked the appearance of creatine in the serum of which it was not a normal component.Discouraged by these experiences, subsequent observers have confined their attentions to studies of the excretion of creatine in the urine, in which it appears in measurable quantities and without appreciable amounts of interfering chromogenic substances. Consequently, opinions about the metabolism of this substance, especially in human subjects, are largely based on inference. The recent presentation by Peters (4) of a procedure adapted to the Evelyn-Molloy photoelectric colorimeter has made it possible to measure creatine in serum with reasonable accuracy and therefore to examine the relation of creatinuria to the concentration of creatine in blood serum.The present paper deals with the mode of excretion of creatine by normal adults and the na- METHODSBlood serum and urine were analyzed for creatinine and creatine by the Folin (5) method with the modifications devised by Peters (4) to adapt it to the Evelyn-Molloy photoelectric colorimeter. The most important of these are: (1) the use of a concentrated, but unsaturated solution of picric acid, containing 11.75 grams per liter instead of a saturated solution; and (2) the omission of hydrochloric acid as a dehydrating agent, since it was found that in tungstate filtrates, creatine is quantitatively converted to creatinine at autoclave temperature without the addition of acid. The error of the method does not exceed 0.1 mgm. per cent.Because of the variability of the concentrations of creatine and creatinine in urine, difficulty was at first experienced in bringing the color within the range of intensity suitable for the colorimeter. This was obviated by diluting all urines to a specific gravity of 1.010. From this diluted urine, a 1 to 20 dilution was made. This procedure brings the concentrations of creatine and creatinine regularly within the optimum colorimetric range.In a certain number of experiments, blood and urine were collected at approximately the same time, but the urine was not collected ...

Studies of Serum Creatine Tolerance. I. Findings in Normal Males and in Hyperthyroidism 12

“…The hospital patients were kept at bed rest during the tolerance periods, but the normal subjects and outpatients were permitted to indulge in limited ambulatory activity in the laboratory. The procedure followed was that of Tierney and Peters (6) with the following exceptions: (a) the inter-vals for collection of specimens were varied for reasons atinuria is governed by serum creatine concentration (6, discussed under Results below, (b) urine collections were 11, 12), and (c) autoclaving of specimens for the analysis omitted, since other data have demonstrated that in the of total creatinine was carried out in 12 ml. volumetric absence of renal disease, the presence or absence of cre-flasks rather than in colorimeter tubes so that any evapora- tion losses in autoclaving could be made up quantitatively with distilled water prior to transfer for colorimetry.…”

“…More recently Richardson and Shorr (2,3) and Thorn (4) have shown that hyperthyroid individuals excrete a larger proportion of a given dose of creatine than do comparable normal individuals, and that this "reduced tolerance" is partially or totally reversible by effective therapy. The development by one of us of a practical method for the determination of creatine in serum (5) led Tierney and J. P. Peters to investigate the effects of exogenous creatine on serum levels in normal humans and in thyroid disease (6). Their findings revealed that the increased creatinuria reflected increased serum concentrations, and that the "critical" serum level for the excretion of creatine was approximately 0.6 mg. %b.…”

“…It also seemed important to determine whether the increased tolerance noted by Tierney and Peters in one male (6) was a characteristic of this disease in men.…”

Urinary Excretion of Creatine in the Sheep

“…The values for the ratio of urinary creatine to creatinine are even higher with the present method than older values, calculated from the literature and summarized in Table 2, for sheep and some other ruminants. (Tierney and Peters 1943).…”

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

“…The complete absence of creatine from the urine at times may be due to the fact that there is a renal threshold so that it is excreted only when the serum concentration exceeds 0.58 mgm. per cent (35 Represents the liberation and excretion of creatine. This varies considerably depending upon the ability of the muscles to retain or liberate free creatine.…”