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Letters to the Editor |
1 Department of Animal Physiology, NW I, University of Bayreuth, 95440 Bayreuth, Germany, Fax 49-921-552477
To the Editor:
Considerable previous work in humans has investigated the influence of increased fluid ingestion on the excretion of free glucocorticosteroids. In agreement with the results of Lloyd (1) published in 1952, later investigators claimed a stimulatory influence of water diuresis on urinary free cortisol (UFC) in healthy individuals (2)(3)(4)(5). Corticosteroids were measured by colorimetric methods (1)(2) or by more-specific competitive binding assays (3)(4)(5). These observations contrast, however, with recent work showing that UFC excretion is not increased during water diuresis (6)(7)(8).
The reason for the differing results is not known, but they may depend on the varying fluid volumes ingested and/or on the time/length of urine sampling. In my opinion, however, they may also be explained by the use of nonspecific protein binding assays because UFC values in previous investigations (3)(4)(5) were higher than UFC amounts measured by more-specific methods such as chromatography/RIA (9)(10) and HPLC(11)(12)(13). Thus, the cited results (1)(2)(3)(4)(5)(6)(7)(8) led me to suppose that water diuresis may stimulate the urinary excretion of a cortisol precursor/metabolite rather than cortisol itself [see also Ref. (5)].
Increased cortisone excretion should be considered in view of the facts that (a) urinary free cortisone excretion is 2–4 times higher than UFC (6)(10)(11)(13), (b) cortisone significantly cross-reacts with the binding protein (3)(4) or cortisol antibody (5) of the "cortisol" assays (Table 1
), and (c) Hatfield and Shuster (2) reported in 1957 that "The excretion of free cortisone was greater at higher rates of urine but the results were too few for statistical analysis". Lewicka et al. [Table 1 of Ref. (6)] listed in detail the amounts of urinary free corticosteroids and urine excreted per day; although not mentioned by the authors, the amounts of urinary free cortisone can be seen to have a positive relationship with the 24-h urine volumes (r = 0.82; n = 24; P <0.001). No such correlation existed between the 24-h urine volume and urinary excretion of free cortisol, tetrahydrocortisol, tetrahydrocortisone, or 18-hydroxycorticosterone.
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In summary, this short review indicates that a water load increases urinary cortisone excretion in healthy individuals. In contrast, urinary cortisol excretion seems not to be affected by increasing urine volumes. Thus, previous studies claiming a positive relationship between UFC and urine volume should be regarded with caution because UFC values may represent the sum of cortisol and cortisone. However, it is difficult to determine the influence of cortisone on UFC excretion in quantitative terms because interference by cortisone depends not only on its cross-reactivity with the binding protein but also on the diuresis-induced increase in cortisone excretion, which changes markedly with time of day: water diuresis in the morning (zenith of adrenal activity) presumably has a more pronounced effect on cortisone excretion than water diuresis in the evening (nadir of adrenal activity). Thus, it may be assumed that cortisone interference will be greater in those individuals who ingest substantial volumes of fluid in the morning. To exclude false UFC values, future measurements of UFC should include a chromatographic step in the cortisol assay (10), or investigators should use specific methods such as HPLC (11)(12)(13) or thin-layer chromatography/steroid derivatization with isonicotinic acid hydrazide (14).
References
The following articles in journals at HighWire Press have cited this article:
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  M. Boscaro and G. Arnaldi Approach to the Patient with Possible Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3121 - 3131. [Abstract] [Full Text] [PDF]
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 M. Fenske HIGH COGNITIVE DIETARY RESTRAINT IS ASSOCIATED WITH INCREASED CORTISOL EXCRETION IN POSTMENOPAUSAL WOMEN: A COMMENT J Gerontol A Biol Sci Med Sci, April 1, 2007; 62(4): 465 - 465. [Full Text] [PDF]
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