Biological Day-to-Day Variation and Reference Change Limits of Serum Cortisol and Aldosterone in Healthy Young Men on Unrestricted Diets

Several factors are known to influence neuroendocrine secretion. A circadian rhythm with a clear episodic secretion of serum cortisol and aldosterone has been well described in several reports(1)(2). Recently, a gender-related seasonal periodicity in plasma cortisol was reported (3). However, in many of the studies on biological variability, the experimental setting has not reflected the routine daily living habits of the subjects. In the interpretation of laboratory results, especially in monitoring outpatients, the variability present in the routine environment should be taken into account. Data on biological variation are needed for the correct interpretation of serial laboratory results in clinical practice(4)(5). Changes may be significant even if the individual results all lie inside the population-based reference interval. A method for estimating the reference change limit, defined as the difference between two consecutive test results that is statistically significant in a given proportion of individuals, was first introduced by Harris and Yasaka (6). The 95% reference change limit corresponds to the critical difference for P <0.05. Because the previous studies on the day-to-day biological variation and the determination of reference change limits of serum cortisol and aldosterone have been few (3)(7)(8), we undertook this study to determine the biological day-to-day variation in serum concentrations of cortisol and aldosterone in serial measurements of blood samples collected on six mornings during a period of 9 days in eight male subjects. On the basis of these results, we have calculated …