Cortisone

Cortisone
IUPAC name	17α,21-Dihydroxypregn-4-ene-3,11,20-trione
Tradename	Cortone, others
CAS number	53-06-5
DrugBank	DB01380
PubChem	222786
ChemSpiderID	193196
UNII	V27W9254FZ
ChEBI	16962
ChEMBL	1350
C	21
H	28
Molecular weight	360.444 g/mol
Melting point	220–224 °C
Smiles	O=C4\C=C2/[C@]([C@H]1[C@@](C(=O)CO)(C[C@@H](O)C1)C)(C[C@H]3C(=O)C[C@@H](O)[C@@]3(C)C2)CC4

Cortisone. It is a naturally occurring glucocorticoid hormone produced by the adrenal cortex and a crucial precursor in the steroidogenesis pathway leading to the active hormone cortisol. First isolated in the 1930s, its potent anti-inflammatory and immunosuppressive properties revolutionized the treatment of numerous conditions, from rheumatoid arthritis to asthma. While its systemic use is now limited due to significant adverse effects, cortisone and its synthetic derivatives remain foundational in modern endocrinology and pharmacology.

History

The isolation of cortisone was a landmark achievement in mid-20th century biochemistry. In 1936, Edward Calvin Kendall of the Mayo Clinic, working with Tadeus Reichstein and others, successfully isolated several compounds from the adrenal gland, which he designated Compounds A through F. Compound E was cortisone. The subsequent large-scale synthesis and clinical trials, famously led by Philip Showalter Hench also at the Mayo Clinic, demonstrated its dramatic effects in patients with rheumatoid arthritis. This breakthrough earned Kendall, Hench, and Reichstein the Nobel Prize in Physiology or Medicine in 1950. The initial production process, which required over 30 chemical steps from bile acids, was famously supported by research funding from Merck & Co..

Medical uses

Cortisone itself, often administered as cortisone acetate, is used in adrenal insufficiency as part of hormone replacement therapy to mimic the body's natural cortisol production. Its most widespread modern application is in localized injections for inflammatory conditions; for example, intra-articular injections for osteoarthritis of the knee or rotator cuff tendinitis, and injections for carpal tunnel syndrome. Topical formulations are used for inflammatory skin conditions like eczema and psoriasis. It is also a critical component in managing acute exacerbations of autoimmune diseases such as systemic lupus erythematosus and certain forms of vasculitis.

Mechanism of action

As a prodrug, cortisone must be converted to its active form, cortisol, by the enzyme 11β-hydroxysteroid dehydrogenase type 1, primarily in the liver. Cortisol then exerts its effects by diffusing into cells and binding to the glucocorticoid receptor, a type of nuclear receptor. This hormone-receptor complex translocates to the cell nucleus, where it regulates gene transcription. It suppresses the expression of pro-inflammatory proteins like cytokines (e.g., interleukin-1, tumor necrosis factor-alpha) and cyclooxygenase-2, while promoting the synthesis of anti-inflammatory proteins such as lipocortin-1. This genomic action underlies its potent immunosuppressive and metabolic effects.

Side effects and precautions

Systemic use of cortisone is associated with a wide array of adverse effects, particularly with long-term administration. These include iatrogenic Cushing's syndrome, characterized by moon face, central obesity, and hypertension. Metabolic disturbances such as hyperglycemia, diabetes mellitus, and dyslipidemia are common. Other serious risks include osteoporosis, increased susceptibility to infections like pneumonia, peptic ulcer disease, cataracts, glaucoma, and psychiatric disorders including insomnia and psychosis. Sudden withdrawal after prolonged use can precipitate an adrenal crisis due to hypothalamic-pituitary-adrenal axis suppression.

Chemistry and biosynthesis

Chemically, cortisone is a pregnane steroid, specifically 17α,21-dihydroxypregn-4-ene-3,11,20-trione. Its biosynthesis occurs in the zona fasciculata of the adrenal cortex from cholesterol. The pathway involves hydroxylation steps catalyzed by cytochrome P450 enzymes, with pregnenolone and progesterone as key intermediates. The final steps involve 17α-hydroxylation and 21-hydroxylation to form 11-deoxycortisol, which is then converted to cortisol by CYP11B1. Cortisone is produced from cortisol via the reverse action of 11β-hydroxysteroid dehydrogenase type 2, serving as an inactive metabolite.

Society and culture

The introduction of cortisone was hailed as a "miracle drug" in the popular press of the 1950s, dramatically altering public perception of chronic illness and the power of pharmaceutical science. Its story is intertwined with the rise of the modern pharmaceutical industry, exemplified by the efforts of Merck & Co. and competition from other firms like Pfizer. The drug's profound side effects later led to a cultural reckoning, influencing narratives in literature and film about medical hubris. It paved the way for the development of safer synthetic analogues like prednisone, dexamethasone, and budesonide, which remain staples in global medicine.

Category:Steroid hormones Category:Glucocorticoids Category:World Health Organization essential medicines