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<\/p>\nThe cortisol to cortisone shunt requires 2 isoforms of the 11beta-hydroxysteroid dehydrogenase enzyme. The liver and kidneys play a significant role in the physiologic regulation of cortisol action.<\/p>\n
Cortisol can bind both glucocorticoid and mineralocorticoid receptors, and indeed under normal physiological conditions, plasma levels of cortisol are up to 1,000-fold higher than that of aldosterone. 11beta-hydroxysteroid dehydrogenase type 2 (11\u03b2-HSD2) inactivates physiological concentrations of cortisol and thus protects the mineralocorticoid receptor from direct activation by cortisol[1].<\/p>\n
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Fig. 1 The Cortisol-to-Cortisone Shunt<\/strong><\/p>\n The two isoforms of 11beta-hydroxysteroid dehydrogenase\u00a0play essential roles in the cortisol-to-cortisone shunt. 11beta-hydroxysteroid dehydrogenase type 1 (11\u03b2 HSD1) converts inactive cortisone to active cortisol in the liver, which subsequently binds its cognate hepatic glucocorticoid receptor (GCR)(dark arrows). 11beta-hydroxysteroid dehydrogenase type 2 (11\u03b2 HSD2) converts active cortisol to inactive cortisone at the level of the kidney, thus protecting the mineralocorticoid receptor (MCR) from activation by cortisol<\/a>(white arrows)[2].<\/p>\n Data derived from references[3\u20135]\n Treatment of adrenal crises<\/strong><\/p>\n Patients with adrenal crises because of Addison\u2019s disease do not require concomitant fludrocortisone (mineralocorticoid) administration if their total daily dose of steroids is greater than or equal to 50mg of hydrocortisone, or steroid equivalent.<\/em> Supraphysiologic doses of hydrocortisone, given during an emergency, will activate the mineralocorticoid receptor and thus provide additional \u201cmineralocorticoid coverage.\u201d<\/em> Patients managed with methylprednisolone<\/em> may, and those taking dexamethasone <\/em>will require mineralocorticoid due to limited binding of the former and zero binding of the latter to mineralocorticoid receptors [6].<\/p>\nComparison of the isoforms of 11\u03b2 HSD<\/h2>\n\n
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\n\t 11\u03b2 HSD1<\/td> 11\u03b2 HSD2<\/td>\n<\/tr>\n \n\t Increases circulating levels of cortisol<\/td> Promotes physiological cortisol resistance<\/td>\n<\/tr>\n \n\t Absent from the kidney<\/td> Present in the kidney<\/td>\n<\/tr>\n \n\t Absent from sweat and salivary glands<\/td> Present in sweat and salivary glands<\/td>\n<\/tr>\n \n\t Present in the liver<\/td> Absent from the liver<\/td>\n<\/tr>\n \n\t Present in osteoblasts and osteocytes<\/td> Absent from bone<\/td>\n<\/tr>\n \n\t Present in adipose tissue<\/td> Absent from adipose tissue<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n Clinical Pearl<\/h2>\n