Congenital adrenal hyperplasia

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Congenital adrenal hyperplasia ~~(CAH)~~, ~~also~~previously known as adrenogenital syndrome, is a ~~form~~group of seven autosomal recessive disorders relating to an enzyme deficiency affecting adrenal ~~hyperplasia~~ ~~related~~steroidogenesis.

Epidemiology

The incidence is highly variable depending on the enzyme deficiency ranging from 1 in 200-1000 for non-classic 21-alpha-hydroxylase deficiency, 1 in 10,000-20,000 for classic 21-alpha-hydroxylase deficiency through to very rare (<30 cases reported of P450 cholesterol side-chain cleavage enzyme deficiency) ⁸.

Clinical presentation

There are a variety of ~~autosomal recessive disorders in adrenal steroidogenesis; characterized by low cortisol~~phenotypes depending on the production or lack thereof glucocorticoid, ~~low aldosterone,~~mineralocorticoid and ~~androgen excess~~/or sex steroids. Common clinical presentations include ⁸:

~~Clinical presentation~~

virilization~~/genital ambiguity of female fetuses~~ / atypical genitalia in females (due to androgen excess)
precocious puberty, hirsutism, oligomenorrhea/amenorrhea, female infertility
electrolyte imbalance related to a salt-losing crisis (neonatal salt wasting)
dehydration
testicular masses

hypertension

Neonatal screening for 21-alpha-hydroxylase deficiency is present in many countries ⁸.

Pathology

Congenital adrenal hyperplasia is ana group of seven autosomal recessive ~~disorder~~disorders of congenital cortisol synthesis ~~enzyme~~involving a deficiency of one of the following enzymes ⁸:

21-alpha-hydroxylase ~~deficiency~~: ~90-95% of cases ^5,8
11-beta-hydroxylase ~~deficiency~~
17-alpha-hydroxylase
3-beta-hydroxysteroid dehydrogenase type 2
steroidogenic acute regulatory protein
P450 cholesterol side-chain cleavage enzyme
P450 oxidoreductase

The adrenal glands are most commonly affected, followed by the gonads ⁹.

Associations

Approximately 30%

Radiographic features

~~Ultrasound~~

Features of adrenal hyperplasia may be present ⁹:

~~bilateral~~diffusely enlarged adrenal glands~~: size criteria are still debated (some suggest limb width >4 mm and length >20 mm)~~
wrinkled surface of adrenals (cerebriform pattern)
~~cerebriform pattern of the~~lobulated adrenal glands~~: characteristic sign~~
~~normal ultrasound appearances~~ may ~~also~~ be ~~seen~~present
~~testicular~~

Testicular masses may be identified representing ~~adrenal rest tissue (see the article on~~ testicular adrenal ~~rests~~rest tumours (majority of males ⁹).

Treatment and prognosis

Management relies on replacing the deficient glucocorticoid, mineralocorticoid, and/or sex steroid as well as anti-hypertensive treatment ⁸.

Differential diagnosis

normal neonatal adrenal: can be differentiated from congenital adrenal hyperplasia (CAH) by the characteristic cerebriform appearance on sonography in CAH

-<p><strong>Congenital adrenal hyperplasia (CAH)</strong>, also known as <strong>adrenogenital syndrome</strong>, is a form of <a href="/articles/adrenal-hyperplasia">adrenal hyperplasia</a> related to a variety of autosomal recessive disorders in adrenal steroidogenesis; characterized by low cortisol, low aldosterone, and androgen excess.</p><h4>Clinical presentation</h4><ul>
~~-<li>virilization/genital ambiguity of female fetuses (due to androgen excess)</li>~~
~~-<li>electrolyte imbalance related to a salt-losing crisis </li>~~
+<p><strong>Congenital adrenal hyperplasia</strong>, previously known as <strong>adrenogenital syndrome</strong>, is a group of seven autosomal recessive disorders relating to an enzyme deficiency affecting adrenal steroidogenesis.</p><h4>Epidemiology</h4><p>The incidence is highly variable depending on the enzyme deficiency ranging from 1 in 200-1000 for non-classic 21-alpha-hydroxylase deficiency, 1 in 10,000-20,000 for classic 21-alpha-hydroxylase deficiency through to very rare (<30 cases reported of P450 cholesterol side-chain cleavage enzyme deficiency) <sup>8</sup>.</p><h4>Clinical presentation</h4><p>There are a variety of phenotypes depending on the production or lack thereof glucocorticoid, mineralocorticoid and/or sex steroids. Common clinical presentations include <sup>8</sup>:</p><ul>
+<li>virilization / atypical genitalia in females (due to androgen excess)</li>
+<li>precocious puberty, hirsutism, oligomenorrhea/amenorrhea, <a href="/articles/female-infertility">female infertility</a>
+</li>
+<li>electrolyte imbalance related to a salt-losing crisis (neonatal salt wasting)</li>
~~-</ul><h4>Pathology</h4><p>Congenital adrenal hyperplasia is an autosomal recessive disorder of congenital cortisol synthesis enzyme deficiency:</p><ul>~~
~~-<li>21-alpha-hydroxylase deficiency: ~90% of cases <sup>5</sup>~~
+<li>hypertension</li>
+</ul><p>Neonatal screening for 21-alpha-hydroxylase deficiency is present in many countries <sup>8</sup>.</p><h4>Pathology</h4><p>Congenital adrenal hyperplasia is a group of seven autosomal recessive disorders of congenital cortisol synthesis involving a deficiency of one of the following enzymes <sup>8</sup>:</p><ul>
+<li>21-alpha-hydroxylase: ~90-95% of cases <sup>5,8</sup>
~~-<li>11-beta-hydroxylase deficiency </li>~~
~~-</ul><h4>Radiographic features</h4><h5>Ultrasound</h5><ul>~~
~~-<li>bilateral enlarged adrenal glands: size criteria are still debated (some suggest limb width >4 mm and length >20 mm)</li>~~
~~-<li>wrinkled surface of adrenals</li>~~
~~-<li>~~
~~-<a href="/articles/cerebriform-pattern-of-the-adrenal-glands">cerebriform pattern of the adrenal glands</a>: characteristic sign</li>~~
~~-<li>normal ultrasound appearances may also be seen</li>~~
~~-<li>testicular masses may be identified representing adrenal rest tissue (see the article on <a href="/articles/testicular-adrenal-rests-1">testicular adrenal rests</a>)</li>~~
-</ul><h4>Differential diagnosis</h4><ul><li>normal neonatal adrenal: can be differentiated from congenital adrenal hyperplasia (CAH) by the characteristic cerebriform appearance on sonography in CAH</li></ul>
+<li>11-beta-hydroxylase</li>
+<li>17-alpha-hydroxylase</li>
+<li>3-beta-hydroxysteroid dehydrogenase type 2</li>
+<li>steroidogenic acute regulatory protein</li>
+<li>P450 cholesterol side-chain cleavage enzyme</li>
+<li>P450 oxidoreductase</li>
+</ul><p>The <a title="Adrenal glands" href="/articles/adrenal-gland">adrenal glands</a> are most commonly affected, followed by the gonads <sup>9</sup>.</p><h5>Associations</h5><p>Approximately 30%</p><h4>Radiographic features</h4><p>Features of <a href="/articles/adrenal-hyperplasia">adrenal hyperplasia</a> may be present <sup>9</sup>:</p><ul>
+<li>diffusely enlarged adrenal glands</li>
+<li>wrinkled surface of adrenals (cerebriform pattern)</li>
+<li>lobulated adrenal glands may be present</li>
+</ul><p>Testicular masses may be identified representing <a href="/articles/testicular-adrenal-rests-1">testicular adrenal rest tumours</a> (majority of males <sup>9</sup>).</p><h4>Treatment and prognosis</h4><p>Management relies on replacing the deficient glucocorticoid, mineralocorticoid, and/or sex steroid as well as anti-hypertensive treatment <sup>8</sup>.</p><h4>Differential diagnosis</h4><ul><li>normal neonatal adrenal: can be differentiated from congenital adrenal hyperplasia (CAH) by the characteristic cerebriform appearance on sonography in CAH</li></ul>

References changed:

1. Chambrier E, Heinrichs C, Avni F. Sonographic Appearance of Congenital Adrenal Hyperplasia in Utero. J Ultrasound Med. 2002;21(1):97-100. <a href="https://doi.org/10.7863/jum.2002.21.1.97">doi:10.7863/jum.2002.21.1.97</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/11794409">Pubmed</a>
2. Sivit C, Hung W, Taylor G, Catena L, Brown-Jones C, Kushner D. Sonography in Neonatal Congenital Adrenal Hyperplasia. AJR Am J Roentgenol. 1991;156(1):141-3. <a href="https://doi.org/10.2214/ajr.156.1.1898548">doi:10.2214/ajr.156.1.1898548</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/1898548">Pubmed</a>
3. Hernanz-Schulman M, Brock J, Russell W. Sonographic Findings in Infants with Congenital Adrenal Hyperplasia. Pediatr Radiol. 2002;32(2):130-7. <a href="https://doi.org/10.1007/s00247-001-0592-4">doi:10.1007/s00247-001-0592-4</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/11819084">Pubmed</a>
4. Bryan P, Caldamone A, Morrison S, Yulish B, Owens R. Ultrasound Findings in the Adreno-Genital Syndrome (Congenital Adrenal Hyperplasia). J Ultrasound Med. 1988;7(12):675-9. <a href="https://doi.org/10.7863/jum.1988.7.12.675">doi:10.7863/jum.1988.7.12.675</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/3070057">Pubmed</a>
5. Carlson A, Obeid J, Kanellopoulou N, Wilson R, New M. Congenital Adrenal Hyperplasia: Update on Prenatal Diagnosis and Treatment. J Steroid Biochem Mol Biol. 1999;69(1-6):19-29. <a href="https://doi.org/10.1016/s0960-0760(99)00059-x">doi:10.1016/s0960-0760(99)00059-x</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/10418977">Pubmed</a>
6. New M. An Update of Congenital Adrenal Hyperplasia. Ann N Y Acad Sci. 2004;1038(1):14-43. <a href="https://doi.org/10.1196/annals.1315.009">doi:10.1196/annals.1315.009</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/15838095">Pubmed</a>
7. Teixeira S, Elias P, Andrade M, Melo A, Elias Junior J. The Role of Imaging in Congenital Adrenal Hyperplasia. Arq Bras Endocrinol Metabol. 2014;58(7):701-8. <a href="https://doi.org/10.1590/0004-2730000003371">doi:10.1590/0004-2730000003371</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/25372578">Pubmed</a>
8. El-Maouche D, Arlt W, Merke D. Congenital Adrenal Hyperplasia. The Lancet. 2017;390(10108):2194-210. <a href="https://doi.org/10.1016/s0140-6736(17)31431-9">doi:10.1016/s0140-6736(17)31431-9</a>
8. El-Maouche D, Arlt W, Merke D. Congenital Adrenal Hyperplasia. The Lancet. 2017;390(10108):2194-210. <a href="https://doi.org/10.1016/s0140-6736(17)31431-9">doi:10.1016/s0140-6736(17)31431-9</a>
9. Morani A, Jensen C, Habra M et al. Adrenocortical Hyperplasia: A Review of Clinical Presentation and Imaging. Abdom Radiol. 2019;45(4):917-27. <a href="https://doi.org/10.1007/s00261-019-02048-6">doi:10.1007/s00261-019-02048-6</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/31093730">Pubmed</a>
9. Morani A, Jensen C, Habra M et al. Adrenocortical Hyperplasia: A Review of Clinical Presentation and Imaging. Abdom Radiol. 2019;45(4):917-27. <a href="https://doi.org/10.1007/s00261-019-02048-6">doi:10.1007/s00261-019-02048-6</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/31093730">Pubmed</a>
10. Nermoen I & Falhammar H. Prevalence and Characteristics of Adrenal Tumors and Myelolipomas in Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis. Endocrine Practice. 2020;26(11):1351-65. <a href="https://doi.org/10.4158/ep-2020-0058">doi:10.4158/ep-2020-0058</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/33471666">Pubmed</a>
1. Chambrier ED, Heinrichs C, Avni FE. Sonographic appearance of congenital adrenal hyperplasia in utero. J Ultrasound Med. 2002;21 (1): 97-100. <a href="http://www.jultrasoundmed.org/content/21/1/97.full">J Ultrasound Med (full text)</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/11794409">Pubmed citation</a><span class="ref_v3"></span>
2. Sivit CJ, Hung W, Taylor GA et-al. Sonography in neonatal congenital adrenal hyperplasia. AJR Am J Roentgenol. 1991;156 (1): 141-3. <a href="http://dx.doi.org/10.2214/ajr.156.1.1898548">doi:10.2214/ajr.156.1.1898548</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/1898548">Pubmed citation</a><span class="auto"></span>
3. Hernanz-Schulman M, Brock JW, Russell W. Sonographic findings in infants with congenital adrenal hyperplasia. Pediatr Radiol. 2002;32 (2): 130-7. <a href="http://dx.doi.org/10.1007/s00247-001-0592-4">doi:10.1007/s00247-001-0592-4</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/11819084">Pubmed citation</a><span class="auto"></span>
4. Bryan PJ, Caldamone AA, Morrison SC et-al. Ultrasound findings in the adreno-genital syndrome (congenital adrenal hyperplasia). J Ultrasound Med. 1989;7 (12): 675-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3070057">Pubmed citation</a><span class="auto"></span>
5. Carlson AD, Obeid JS, Kanellopoulou N et-al. Congenital adrenal hyperplasia: update on prenatal diagnosis and treatment. J. Steroid Biochem. Mol. Biol. 1999;69 (1-6): 19-29. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10418977">Pubmed citation</a><span class="auto"></span>
6. New MI. An update of congenital adrenal hyperplasia. Ann. N. Y. Acad. Sci. 2004;1038 (1): 14-43. <a href="http://dx.doi.org/10.1196/annals.1315.009">doi:10.1196/annals.1315.009</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/15838095">Pubmed citation</a><span class="auto"></span>
7. Teixeira SR, Elias PC, Andrade MT et-al. The role of imaging in congenital adrenal hyperplasia. Arq Bras Endocrinol Metabol. 2015;58 (7): 701-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25372578">Pubmed citation</a><span class="auto"></span>
10.1016/S0140-6736(17)31431-9
10.1007/s00261-019-02048-6

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