key: cord-0888884-pakfbt2r
authors: Choy, Kay W
title: Cortisol concentrations and mortality from COVID-19
date: 2020-09-15
journal: Lancet Diabetes Endocrinol
DOI: 10.1016/s2213-8587(20)30305-3
sha: 6c3b097bd75427763f88286fad775352016c9256
doc_id: 888884
cord_uid: pakfbt2r

nan

In their report on the association between high serum total cortisol concentrations and mortality from COVID-19, Tan and colleagues 1 appear to have overlooked the pulsatility of cortisol secretion. A recent study by Gibbison and colleagues 2 showed that both adrenocorticotropic hormone and cortisol are pulsatile in critical illness. The nadir of cortisol pulses in 35% of the patients in their study dropped below the threshold for deficiency in critical illness, as defined by international guidelines, although values shortly before and shortly after were well above this threshold. 2 On this basis, Gibbison and colleagues argue that the practice of point-testing of cortisol in critical illness should be stopped. 2 The use of aggregated, static models of serum total cortisol to predict mortality from COVID-19 should proceed with caution. Given the pulsatility, a significantly different serum total cortisol result might have been obtained if a sample was collected an hour earlier or later. 2 Tan and colleagues 1 have not reported on plasma adrenocorticotropic hormone concen trations, which would have been crucial in understanding the secretory dynamics of the hypothalamic-pituitaryadrenal axis function in patients with and without COVID-19. 2 During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisolmetabolising enzymes, contributes to hypercortisolaemia and hence adrenocorticotropic hormone suppression. 3 Because more than 90% of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without affecting free concentrations of the hormone. 4 A study by Hamrahian and colleagues 4 found that nearly autosomal dominant osteopetrosis are identical to those described for this 6000-year-old skeleton. The morphology was identical at the macroscopic, 3 radiographical, 9 and microscopic level, 10 indicating that the expression of autosomal dominant osteopetrosis has not changed for thousands of years. The emergence of such new datasets encourages a multidisciplinary cooperation between paleopathology and medical sciences to bridge the past and the future of rare diseases.

We declare no competing interests. We thank N Lobanova for the drawings, J Dorn for their work on the pictures, and K Mahlow for the CT scans. 40% of critically ill patients with hypoproteinaemia had subnormal serum total cortisol concentrations, even though their adrenal function was normal. While serum free cortisol measurement is not routinely available, serum total protein concentrations, or conditions that affect serum proteins (eg, liver disease), should be considered when interpreting serum total cortisol concentrations. 5 Lastly, the likely positive bias of the cortisol immunoassay (compared with the reference method gas chromatography-mass spectrometry), which has previously been reported in renal and ICU patients, 6 should be considered. This bias is related to the specificity of the immunoassay. 6 During critical illness and in renal impairment, changes in cortisol metabolism could lead to an accumulation of other steroids, which, because of similarities to the structure of cortisol, are recognised by the immunoassay. 6 Differences have been reported in the bias of the immunoassay compared with gas chromatography-mass spectrometry in the serum of patients with sepsis compared with patients routinely attending outpatient clinics. 6 I declare no competing interests.

Department of Pathology, The Northern Hospital, Epping, VIC 3076, Australia

Association between high serum total cortisol concentrations and mortality from COVID-19

Dynamic pituitary-adrenal interactions in the critically ill after cardiac surgery

Reduced cortisol metabolism during critical illness

Measurements of serum free cortisol in critically ill patients

Measuring cortisol in serum, urine and saliva-are our assays good enough?

The effect of serum matrix and gender on cortisol measurement by commonly used immunoassays