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Hydrocortisone for adrenal insufficiency
  1. C J Elder,
  2. P Dimitri
  1. The Department of Paediatric Endocrinology, Sheffield Children's NHS Foundation Trust, Sheffield, UK
  1. Correspondence to Professor Paul Dimitri, The Department of Paediatric Endocrinology, Sheffield Children's NHS Foundation Trust, Western Bank, Sheffield S10 2TH, UK; paul.dimitri{at}

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Thomas Addison first described Addison's disease in 1855 in patients who had adrenal tuberculosis, highlighting the importance of the adrenal cortex to survive. In 1952, a decade after the medical landmark discovery of cortisone as a treatment for inflammatory conditions, the first case of adrenal crisis and death in a patient on glucocorticoid therapy undergoing surgery was described,1 and thereafter, a spate of such cases was published;2 ,3 recommendations as to how these patients should be investigated and managed followed.4 ,5 It is now widely acknowledged that patients on long-term corticosteroids require increased steroid cover at times of stress, such as major surgery and significant febrile illness. A knowledge of how to treat adrenal insufficiency during times of (patho) physiological stress is paramount to prevent complications andϕ death.

Cortisol secretion

The hypothalamic-pituitary-adrenal (HPA) axis is integral to the body's maintenance of baseline homeostasis and its response to stress. The physiological secretion of cortisol is regulated by the main circadian oscillator in the suprachiasmatic nucleus, located in the hypothalamus.6 Each of the main components of the HPA axis is secreted in a pulsatile, circadian manner. The central clock is synchronised to the environment through signals from the retina, and efferent projections from the central clock induce the release of corticotropin-releasing hormone (CRH), which drives the HPA axis. In turn, cortisol induces the expression of peripheral clock genes, thus synchronising peripheral tissues with central circadian control. The height of the pulse amplitude for hypothalamic CRH and arginine vasopressin is characteristically at 4:00 a.m., with adrenocorticotropic hormone (ACTH) peaking between 4:00 a.m. and 6:00 a.m., and the resultant cortisol surge seen at 8:00 a.m. Circadian rhythm is absent in newborn babies and starts to establish itself during infancy but may not fully mature until 3 years of age or older. …

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  • Contributors PD and CJE have contributed to the preparation and review of this commissioned article.

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.