Cortisone is converted back to the active steroid cortisol by stereospecific hydrogenation at carbon 11 by the enzyme 11β-Hydroxysteroid dehydrogenase type 1, particularly in the liver.

[8] Oral use of cortisone has a number of potential systemic adverse effects, including asthma, hyperglycemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression, amenorrhoea, cataracts, glaucoma, Cushing's syndrome, increased risk of infections, and impaired growth.

In 1949, Philip S. Hench and colleagues discovered that large doses of injected cortisone were effective in the treatment of patients with severe rheumatoid arthritis.

[13] Kendall was awarded the 1950 Nobel Prize for Physiology or Medicine along with Philip Showalter Hench and Tadeusz Reichstein for the discovery of the structure and function of adrenal cortex hormones including cortisone.

[14][15] Both Reichstein and the team of O. Wintersteiner and J. Pfiffner had separately isolated the compound prior to the discovery made by Mason and Kendall, but failed to recognize its biological significance.

In the UK in the early 1950s, John Cornforth and Kenneth Callow at the National Institute for Medical Research collaborated with Glaxo to produce cortisone from hecogenin from sisal plants.

[19] Abuse and addiction to cortisone was the subject of the 1956 motion picture Bigger Than Life, produced by and starring James Mason.

Though it was a box-office flop upon its initial release,[20] many modern critics hail the film as a masterpiece and brilliant indictment of contemporary attitudes toward mental illness and addiction.