21-hydroxylase deficiency historical perspective
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor-In-Chief: Mehrian Jafarizade, M.D  Ahmad Al Maradni, M.D. 
Congenital adrenal hyperplasia was first discovered in 1865 by an Italian pathologist, Luigi De Crecchio. Explanation of hormonal aspects and molecular characteristics remained unclear until 1980. From 1980 scientists started to describe enzymes and molecular basis of 21-hydroxyase deficiency.
Landmark events in the understanding and discovery of adrenal hormones include the following:
- In 1563, Eustachius described the adrenal glands. The findings were later on published by Lancisi in 1714.
- In 1849, Thomas Addison, while searching for the cause of pernicious anemia, found a bronze colored growth associated with the adrenal glands. Then in 1855, Thomas Addison described clinical findings in 11 cases of adrenal disorders.
- In 1856, while conducting adrenalectomy experiments, Brown-Séquard found that the adrenal glands are necessary for life.
- In 1865, the Italian pathologist, Dr. Luigi De Crecchio was the first to describe 21-hydroxylase deficiency. Dr. Crecchio found large adrenal glands in a male autopsy, who had female internal organs.
- In 1896, William Osler prepared an extraction derived from pig adrenals and showed that it had clinical benefit in patients with Addison disease.
- In 1905, Bulloch and Sequeira described patients with congenital adrenal hyperplasia.
- In 1936, Selye described the concept of stress and its effect on pituitary-adrenal function.
- In 1937-1952, Kendall and Reichstein, described the basic structure of adrenocortical hormones.
- In 1943, Li and colleagues isolated adrenocorticotropic hormone from sheep pituitary.
- In 1950, Hench, Kendall, and Reichstein shared the Nobel Prize in Medicine for describing the anti-inflammatory effects of cortisone in patients with rheumatoid arthritis.
- In 1956, Conn described primary aldosteronism.
- In 1963 congenital adrenal hyperplasia was described as a complex disorder, caused by different enzyme deficiencies.
- In 1965, the diagnostic approach to congenital adrenal hyperplasia was established by measuring the levels of adrenal steroids in amniotic fluid.
The molecular era
- 1980 - present has been termed as the molecular era; highlights during this era are as follows:
- Cloning and functional characterization of steroid hormone receptors was discovered.
- Steroidogenic enzymes were described.
- Adrenal transcription factors were reported.
- Molecular basis for adrenal diseases was described.
- ↑ Delle Piane L, Rinaudo PF, Miller WL (2015). "150 years of congenital adrenal hyperplasia: translation and commentary of De Crecchio's classic paper from 1865". Endocrinology. 156 (4): 1210–7. doi:10.1210/en.2014-1879. PMID 25635623.
- ↑ Melmed, Shlomo (2016). Williams textbook of endocrinology. Philadelphia, PA: Elsevier. ISBN 978-0323297387.=
- ↑ HENCH PS, KENDALL EC (1949). "The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone; compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis". Proc Staff Meet Mayo Clin. 24 (8): 181–97. PMID 18118071.
- ↑ Biglieri EG, Herron MA, Brust N (1966). "17-hydroxylation deficiency in man". J. Clin. Invest. 45 (12): 1946–54. doi:10.1172/JCI105499. PMC 292880. PMID 4288776.
- ↑ History of Congenital Adrenal Hyperplasia. Texas department of state health services (2016). http://www.dshs.state.tx.us/newborn/histor~1.shtm Accessed on February 4, 2016