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| ==Historical Perspective== | | ==Historical Perspective== |
| An Italian anatomist, Luigi De Crecchio provided the earliest known description of a case of probable CAH. <blockquote>I propose in this narrative that it is sometimes extremely difficult and even impossible to determine sex during life. In one of the [[anatomy|anatomical]] theaters of the hospital..., there arrived toward the end of January a cadaver which in life was the body of a certain Joseph Marzo... The general physiognomy was decidedly male in all respects. There were no feminine curves to the body. There was a heavy beard. There was some delicacy of structure with muscles that were not very well developed... The distribution of [[pubic hair]] was typical of the male. Perhaps the lower extremities were somewhat delicate, resembling the female, and were covered with hair... The [[penis]] was curved posteriorly and measured 6 cm, or with stretching, 10 cm. The [[glans|corona]] was 3 cm long and 8 cm in circumference. There was an ample [[foreskin|prepuce]]. There was a first grade [[hypospadias]]... There were two folds of skin coming from the top of the penis and encircling it on either side. These were somewhat loose and resembled [[labia majora]].</blockquote> De Crecchio then described the internal organs, which included a normal [[vagina]], [[uterus]], [[fallopian tube|tubes]], and [[ovary|ovaries]]. <blockquote>It was of the greatest importance to determine the habits, tendencies, passions, and general character of this individual... I was determined to get as complete a story as possible, determined to get at the base of the facts and to avoid undue exaggeration which was rampant in the conversation of many of the people present at the time of the dissection.</blockquote> He interviewed many people and satisfied himself that Joseph Marzo "conducted himself within the sexual area exclusively as a male, "even to the point of contracting the "[[syphilis|French disease]]" on two occasions. The cause of death was another in a series of episodes of vomiting and diarrhea.
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| This account, translated by Alfred Bongiovanni from De Crecchio (Sopra un caso di apparenzi virili in una donna. ''Morgagni'' 7:154-188, 1865), contains nearly all the important themes and issues. Were this man's male [[gender identity]], [[gender role|role]], and [[sexual orientation|orientation]] determined by his anatomy, by his [[testosterone]], or by his [[sex of rearing]]? His presumed female [[chromosome]]s and [[gonad]]s obviously did not make him female. Yet despite his careful documentation of Marzo's unambiguous social role, De Crecchio rejects his male identity and describes him as "una donna," revealing the 19th century assumption that a person's "true sex" can be determined by inspection of internal organs. Then as now, such a case prompted "undue exaggeration" and much "conversation." And then as now, we see the conflict between the desire of the scientist to learn and understand, and the sense of violation of poor Joseph Marzo's privacy. Finally, were the episodes of vomiting and diarrhea the salt-wasting of CAH?
| | In 1563, Eustachius describes the adrenals (published by Lancisi in 1714). |
| | | In 1849, Thomas Addison, while searching for the cause of pernicious anemia, stumbles on a bronzed appearance associated with the adrenal glands called ''melasma suprarenale'' In 1855, Thomas Addison describes the clinical features and autopsy findings in 11 cases of diseases of the suprarenal capsules, at least 6 of which were tuberculous in origin. |
| The association of excessive sex steroid effects with diseases of the adrenal cortex have been recognized for over a century. The term ''adrenogenital syndrome'' was applied to both sex-steroid producing tumors and severe forms of CAH for much of the 20th century, before some of the forms of CAH were understood. '''Congenital adrenal hyperplasia,''' which also dates to the first half of the century, has become the preferred term to reduce ambiguity and to emphasize the underlying pathophysiology of the disorders.
| | In 1856, In adrenalectomy experiments, Brown-Séquard demonstrates that the adrenal glands are essential for life. |
| | | In 1896, William Osler prepares an oral glycerin extract derived from pig adrenals and demonstrates that it has clinical benefit in patients with Addison disease. |
| Much of our modern understanding and treatment of CAH comes from research conducted at [[Johns Hopkins Medical School]] in Baltimore in the middle of the 20th century. Lawson Wilkins, "founder" of [[pediatric endocrinology]], worked out the apparently paradoxical pathophysiology: that hyperplasia and overproduction of adrenal androgens resulted from impaired capacity for making cortisol. He reported use of adrenal cortical extracts to treat children with CAH in 1950. Genital reconstructive surgery was also pioneered at Hopkins. After application of [[karyotype|karyotyping]] to CAH and other [[intersex]] disorders in the 1950s, [[John Money]], JL Hampson, and JG Hampson persuaded both the scientific community and the public that sex assignment should not be based on any single biological criterion, and gender identity was largely learned and has no simple relationship with chromosomes or hormones. See [[Intersex]] for a fuller history, including recent controversies over reconstructive surgery.
| | In 1905, Bulloch and Sequeira describe patients with congenital adrenal hyperplasia. |
| | | In 1929, Liquid extracts of cortical tissue are used to keep adrenalectomized cats alive indefinitely (Swingle and Pfiffner); subsequently, this extract was used successfully to treat a patient with Addison disease (Rowntree and Greene). |
| [[Hydrocortisone]], [[fludrocortisone]], and [[prednisone]] were available by the late 1950s. By 1980 all of the relevant steroids could be measured in blood by reference laboratories for patient care. By 1990 nearly all specific genes and enzymes had been identified.
| | In 1932, Harvey Cushing associates the polyglandular syndrome of pituitary basophilism, which he first described in 1912, with hyperactivity of the pituitary-adrenal glands. |
| | | In 1936,The concept of stress and its effect on pituitary-adrenal function are described by Selye. |
| However, the last decade has seen a number of new developments, discussed more extensively in [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency]]:
| | In 1937-1952,Isolation and structural characterization of adrenocortical hormones are reported by Kendall and Reichstein. |
| # debate over the value of [[genital reconstructive surgery]] and changing standards
| | In 1943, Li and colleagues isolate pure adrenocorticotropic hormone from sheep pituitary. |
| # debate over [[sex assignment]] of severely virilized XX infants
| | In 1950, Hench, Kendall, and Reichstein share the Nobel Prize in Medicine for describing the anti-inflammatory effects of cortisone in patients with rheumatoid arthritis. |
| # new treatments to improve height outcomes
| | In 1953,Isolation and analysis of the structure of aldosterone are reported by Simpson and Tait. |
| # [[newborn screening]] programs to detect CAH at birth
| | In 1956, Conn describes primary aldosteronism. |
| # increasing attempts to treat CAH before birth
| | In 1981, Characterization and synthesis of corticotropin-releasing hormone are reported by Vale. |
| | From 1980-present the molecular era: cloning and functional characterization of steroid receptors, steroidogenic enzymes, and adrenal transcription factors are reported, and the molecular basis for human adrenal diseases is defined. |
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| ==References== | | ==References== |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
Historical Perspective
In 1563, Eustachius describes the adrenals (published by Lancisi in 1714).
In 1849, Thomas Addison, while searching for the cause of pernicious anemia, stumbles on a bronzed appearance associated with the adrenal glands called melasma suprarenale In 1855, Thomas Addison describes the clinical features and autopsy findings in 11 cases of diseases of the suprarenal capsules, at least 6 of which were tuberculous in origin.
In 1856, In adrenalectomy experiments, Brown-Séquard demonstrates that the adrenal glands are essential for life.
In 1896, William Osler prepares an oral glycerin extract derived from pig adrenals and demonstrates that it has clinical benefit in patients with Addison disease.
In 1905, Bulloch and Sequeira describe patients with congenital adrenal hyperplasia.
In 1929, Liquid extracts of cortical tissue are used to keep adrenalectomized cats alive indefinitely (Swingle and Pfiffner); subsequently, this extract was used successfully to treat a patient with Addison disease (Rowntree and Greene).
In 1932, Harvey Cushing associates the polyglandular syndrome of pituitary basophilism, which he first described in 1912, with hyperactivity of the pituitary-adrenal glands.
In 1936,The concept of stress and its effect on pituitary-adrenal function are described by Selye.
In 1937-1952,Isolation and structural characterization of adrenocortical hormones are reported by Kendall and Reichstein.
In 1943, Li and colleagues isolate pure adrenocorticotropic hormone from sheep pituitary.
In 1950, Hench, Kendall, and Reichstein share the Nobel Prize in Medicine for describing the anti-inflammatory effects of cortisone in patients with rheumatoid arthritis.
In 1953,Isolation and analysis of the structure of aldosterone are reported by Simpson and Tait.
In 1956, Conn describes primary aldosteronism.
In 1981, Characterization and synthesis of corticotropin-releasing hormone are reported by Vale.
From 1980-present the molecular era: cloning and functional characterization of steroid receptors, steroidogenic enzymes, and adrenal transcription factors are reported, and the molecular basis for human adrenal diseases is defined.
References
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