Adrenal steroid hormone responses to exercise under thermal stress: potential role for non classic congenital adrenal hyperplasia in heat illness susceptibility

We queried whether adrenal insufficiency attributable to non-classic congenital adrenal hyperplasia (21 hydroxylase deficiency, 21OHD) might contribute to heat illness susceptibility. Patients referred to a specialist heat illness clinic (n=2 with prior hyponatraemia; n=16 lacking documentary evidence) and controls (n=16) underwent laboratory Heat Tolerance Assessment (HTA: 60-90 min walking, 60% relative intensity, 34 ° C heat), synthetic adrenocorticotrophic hormone stimulation (heat illness only) and CYP21A2 genotyping (hyponatraemic heat illness only). Copeptin, cortisol, 17-hydroxyprogesterone and 21 deoxycortisol were assayed from blood at baseline and post-HTA, with precursor product [17-hydroxyprogesterone + 21 deoxycortisol] expressed relative to cortisol. Saliva and urine were assayed for free cortisol (one hyponatraemic case, controls). Versus controls, normonatraemic heat illness exhibited greater (P<0.05) serum cortisol across HTA, while hyponatraemic heat illness showed blunted responses in aldosterone, and free cortisol (salivary cortisol 1.6 and 1.6 vs 6.0 [4.2, 19.4] and 4.2 [3.8, 19.2] nmol.L-1; urine cortisol 19 vs 117 +/- 71 nmol.L-1). Hyponatraemic heat illness demonstrated elevated precursor product consistent with 21OHD, and multiple CYP21A2 mutations. One normonatraemic case of heat illness also showed elevated precursor product. These data support potential for 21OHD to precipitate heat illness under sustained physical stress and advance a case for targeted genetic screening.