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Article: G. H. Trevor Wheler, David Brandon, Aaron Clemons, Crystal Riley, John Kendall, D. Lynn Loriaux, and J. David Kinzie Cortisol Production Rate in Posttraumatic Stress Disorder J Clin Endocrinol Metab 2006; 0: jc.2006-0061v1 [Abstract]

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Cortisol dynamics unaltered in PTSD

G.H.Trevor Wheler, David Brandon, Aaron Clemons, Crystal Riley, John Kendall, D. Lynn Loriaux, J. David Kinzie   (22 January 2007)

Cortisol production rate in posttraumatic stress

Martin Friedrich Fenske   (30 October 2006)

Cortisol dynamics unaltered in PTSD 22 January 2007
G.H.Trevor Wheler Oregon Health and Sciences University, David Brandon, Aaron Clemons, Crystal Riley, John Kendall, D. Lynn Loriaux, J. David Kinzie Send letter to journal: Re: Cortisol dynamics unaltered in PTSD whelert{at}ohsu.edu G.H.Trevor Wheler, et al.	Fenske provides several useful comments concerning the limitations of the use of commercially available RIA kits for determination of urinary cortisol levels. We agree that urinary free cortisol is notoriously dependent on the laboratory in which it is measured and can be affected by the presence of various analytes. For example, in our RIA kit, cortisone cross-reactivity was approximately 2%. We, therefore, crosschecked cortisol levels in urine using gas chromatography mass spectrometry. It is common knowledge that a blank effect is magnified by high urine volume, but the effect on cortisol measurement is generally artificially high, not low, as found in this study. We found no significant difference in cortisol levels between post-traumatic stress disorder and control groups. These data fit with all other measured parameters of cortisol dynamics, including the cortisol production rate. The results indicate that cortisol dynamics are unaltered in this group of post-traumatic stress disorder subjects, not on medication, and in the unprovoked state compared to control subjects.
Cortisol production rate in posttraumatic stress 30 October 2006
Martin Friedrich Fenske, Scientist, Biologist University of Bayreuth Send letter to journal: Re: Cortisol production rate in posttraumatic stress martin.fenske{at}uni-bayreuth.de Martin Friedrich Fenske	I read with interest the paper of Wheler et al. (1) who reported in their brief report on urinary free cortisol (UFC) excretion in human suffering from posttraumatic stress disorder. In their discussion, they stated "the only parameter that differed statistically in posttraumatic stress disorder patients compared with control subjects was decreased urinary cortisol. However, we found no difference in distribution of cortisol or its metabolites in urine that could have explained this finding" (p. 3488). I believe there are shortcomings in the study that make the interpretation of their results difficult or even impossible. The first of these limitations is that UFC was measured with a commercial RIA (Coat-A-count RIA, Diagnostic Products) after dichloromethane extraction. The authors did not consider previous warnings that cortisol RIA methods with clinical use to determine excessive cortisol production are unsuitable for physiological studies." (ref. 2, p.4003). Second, they did not provide information about whether cortisone significantly cross-reacts with the C antiserum, which could lead to falsely increased UFC values (for discussion, see ref. 3). Third, the authors did not consider the possible influence of high urine volume. We have recently shown that UFC excretion correlates with increasing urine volume (4, 5), confirming previous results (for further literature, see ref. 5). In my opinion, interpretation of UFC excretion is only possible if patients’ fluid intake is strictly controlled and urine volume is considered an important pre-analytical parameter. References 1. Wheler GHT, Brandon D, Clemons A, Riley C, Kendall J, Loriaux L, Kinzie JD. 2006. Cortisol production rate in posttraumatic stress disorder. J Clin Endocrinol Metab 91:3486-3489. 2. Murphy BEP. 2003. Commercial radioimmunoassays do not measure urinary free cortisol accurately and should not be used for physiological studies. J Clin Endocrinol Metab 88:4001-4004. 3. Fenske M. 2004. How much "urinary free cortisol" is really cortisol during water diuresis in healthy individuals. Clin Chem 50:1102-1104. 4. Fenske M. 2006. Thin-layer chromatographic competitive protein-binding assay for cortisol and cortisone, and its application to urine samples from healthy men undergoing water diuresis. Chromatographia 63:383-388. 5. Fenske M. 2006. Urinary free cortisol and cortisone excretion in healthy individuals: influence of water loading. Steroids, in press: doi:10.1016/ j.steroids.2006.08.004.