Congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Further information: Congenital adrenal hyperplasia
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Other names21-OH CAH
CT scan shows enlarged adrenals with masses consistent with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (image credit: NICHD/A. Mallappa, D. Merke)
SpecialtyEndocrinology 
SymptomsAndrogen excess and corticosteroid deficiencies
Frequency1:18,000 to 1:14,000 (classical forms);
1:1000 to 1:50 (nonclassical forms)

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a genetic disorder characterized by impaired production of cortisol in the adrenal glands.[1]

It is classified as an inherited metabolic disorder. CAH is an autosomal recessive condition since it results from inheriting two copies of the faulty CYP21A2 gene responsible for 21-hydroxylase enzyme deficiency. The most common forms of CAH are: classical form, usually diagnosed at birth, and nonclassical, late onset form, typically diagnosed during childhood or adolescence, although it can also be identified in adulthood when seeking medical help for fertility concerns or other related issues, such as PCOS or menstrual irregularities.[1] Carriers for the alleles of the nonclassical forms may have no symptoms, such form of CAH is sometimes called cryptic form.[2][3] Congenital adrenal hyperplasia due to 21-hydroxylase deficiency in all its forms accounts for over 95% of diagnosed cases of all types of congenital adrenal hyperplasia.[4] Unless another specific enzyme is mentioned, CAH in most contexts refers to 21-hydroxylase deficiency, and different mutations related to enzyme impairment have been mapped on protein structures of the enzyme.[5] It is one of the most common autosomal recessive genetic diseases in humans.[6][7][8]

Due to the loss of 21-hydroxylase function, patients are unable to efficiently synthesize cortisol. As a result, ACTH (Adrenocorticotropic hormone) levels increase, leading to adrenocortical hyperplasia and overproduction of cortisol precursors, which are used in the synthesis of sex steroids, which can lead to signs of androgen excess, including ambiguous genitalia in newborn girls and rapid postnatal growth in both sexes.[1] In severe cases of CAH in females, surgical reconstruction may be considered to create more female-appearing external genitalia. However, there is ongoing debate regarding the timing and necessity of surgery. The way CAH affects the organism is complicated, and not everyone who has it will show signs or have symptoms.[4] Individuals with CAH may face challenges related to growth impairment during childhood and fertility issues during adulthood. Psychosocial aspects such as gender identity development and mental health should also be taken into consideration when managing individuals with CAH.[1] Overall prognosis for individuals with appropriate medical care is good; however, lifelong management under specialized care is required to ensure optimal outcomes.[1]

Treatment for CAH involves hormone replacement therapy to provide adequate levels of glucocorticoids and mineralocorticoids. Regular monitoring is necessary to optimize hormone balance and minimize potential complications associated with long-term glucocorticoid exposure.[1]

  1. ^ a b c d e f Burdea L, Mendez MD (July 2023). "21-Hydroxylase Deficiency". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID 29630216.
  2. ^ Cite error: The named reference pmid28541281 was invoked but never defined (see the help page).
  3. ^ Dumić M, Brkljacić L, Mardesić D, Plavsić V, Lukenda M, Kastelan A (July 1985). "'Cryptic' form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in the Yugoslav population". Acta Endocrinol (Copenh). 109 (3): 386–92. doi:10.1530/acta.0.1090386. PMID 2992207.
  4. ^ a b Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. (November 2018). "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 103 (11): 4043–4088. doi:10.1210/jc.2018-01865. PMC 6456929. PMID 30272171.
  5. ^ Neves Cruz J, da Costa KS, de Carvalho TA, de Alencar NA (March 2020). "Measuring the structural impact of mutations on cytochrome P450 21A2, the major steroid 21-hydroxylase related to congenital adrenal hyperplasia". Journal of Biomolecular Structure & Dynamics. 38 (5): 1425–1434. doi:10.1080/07391102.2019.1607560. PMID 30982438. S2CID 115195169.
  6. ^ Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI (July 1985). "High frequency of nonclassical steroid 21-hydroxylase deficiency". American Journal of Human Genetics. 37 (4): 650–667. PMC 1684620. PMID 9556656.
  7. ^ Krone N, Arlt W (April 2009). "Genetics of congenital adrenal hyperplasia". Best Practice & Research. Clinical Endocrinology & Metabolism. 23 (2): 181–192. doi:10.1016/j.beem.2008.10.014. PMC 5576025. PMID 19500762.
  8. ^ Turcu AF, Nanba AT, Chomic R, Upadhyay SK, Giordano TJ, Shields JJ, et al. (May 2016). "Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency". European Journal of Endocrinology. 174 (5): 601–609. doi:10.1530/EJE-15-1181. PMC 4874183. PMID 26865584.
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