Congenital adrenal hyperplasia Overview

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Congenital adrenal hyperplasia main page

Overview

Classification

21-hydroxylase deficiency
11β-hydroxylase deficiency
17 alpha-hydroxylase deficiency
3 beta-hydroxysteroid dehydrogenase deficiency
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Lipoid congenital adrenal hyperplasia

Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]

Synonyms and Keywords: Congenital adrenal hyperplasia, CAH, Adrenal hyperplasia

Overview

Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive conditions resulting from biochemical paths of the steroidogenesis of cortisol from cholesterol by the adrenal glands. Most of these conditions involve greater or lesser production of sex steroids and can alter development of primary or secondary sex characteristics in affected infants, children, and adults. Only a small minority of people with CAH can be said to have an intersex condition, but this attracted American public attention in the late 1990s and many accounts of varying accuracy have appeared in the popular media. Approximately 95% of cases of CAH are due to 21-hydroxylase deficiency. Prenatal diagnosis can be made in both of these disorders by chorionic villous sampling, but this can only be done at 8-10 weeks. In order to prevent the deleterious effect of excess androgens on genital (and brain!) development, therapy must be started earlier. This is most often considered if there is an affected sibling. Treatment is dexamethasone, which is not degraded by the placenta, but is associated with significant maternal weight gain, hypertension, and edema.

Classification

Congenital adrenal hyperplasia is classified into seven types based on the genetic causes that lead to hyperplasia and hormonal imbalance. There are three zones of hormonal synthesis in adrenal cortex that are shown below, and impairment of each pathway may lead to a specific subtype of congenital adrenal hyperplasia.

Adrenal Steroids.png

Disease History and symptoms Laboratory findings Defective gene
Blood pressure Genitalia Increased Decreased K levels
21-hydroxylase deficiency Classic type
  • Low in salt-wasting
  • Normal in non-salt-wasting
  • Female: ambiguous
  • Male: normal or scrotal pigmentation and large phallus
  • High in salt wasting type
  • Normal in non salt wasting
  • CYP21A1 and CYP21A2 gene
Non-classic type
  • Normal
  • Female: virilization after puberty
  • Male: normal appearance

response to ACTH

  • Normal
  • CYP21A1 and CYP21A2 gene
17-α hydroxylase deficiency
  • Hypertension
  • Female: normal
  • Male: ambiguous
  • Low
  • CYP17A1
11-β hydroxylase deficiency
  • Hypertension
  • Female: ambiguous
  • Male: normal or scrotal pigmentation and large phallus
  • Low
  • CYP11B1
3β-Hydroxysteroid Dehydrogenase
  • High
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Congenital lipoid adrenal hyperplasia
Cholesterol side-chain cleavage enzyme deficiency

Differential Diagnosis

Congenital adrenal hyperplasia must be differentiated from diseases that cause ambiguous genitalia:[1][2]

Disease name Laboratory tests Important clinical findings
Increased Decreased
Classic type of 21-hydroxylase deficiency
11-β hydroxylase deficiency
17-α hydroxylase deficiency
3β-Hydroxysteroid Dehydrogenase
Gestational hyperandrogenism

congenital adrenal hyperplasia must be differentiated from diseases that cause virilization and hirsutism in female:[3][2][4]

Disease name Steroid status Other laboratory Important clinical findings
Non-classic type of 21-hydroxylase deficiency Increased:

response to ACTH

  • No symptoms in infancy and male
11-β hydroxylase deficiency Increased:

Decreased:

3β-Hydroxysteroid Dehydrogenase Increased:

Decreased:

Polycystic ovary syndrome
Adrenal tumors
  • Variable levels depends on tumor type
  • Older age
  • Rapidly progressive symptoms
Ovarian virilizing tumor
  • Variable levels depends on tumor type
  • Older age
  • Rapidly progressive symptoms
Cushing's syndrome
Hyperprolactinemia

Screening

According to Endocrine Society Clinical Practice Guideline, screening for 21-hydroxylase deficiency by measuring 17a-hydroxyprogesterone is recommended for all newborns.

  • Blood sample on filter paper should be obtained from heel puncture preferably between two and four days after birth.
  • Screening programs should be done using a two-tier protocol (initial immunoassay with further evaluation of positive tests by liquid chromatography/tandem mass spectrometry.
  • Most affected neonates have concentrations greater than 3500 ng/dL (105 nmol/L).[5][6]

Genetic counseling

The Endocrine Society's Clinical Practice Guideline recommends that genetic counseling be provided for individuals who are planning to conceive, and there is a family history of 21-hydroxylase deficiency.[6]

References

  1. Hughes IA, Nihoul-Fékété C, Thomas B, Cohen-Kettenis PT (2007). "Consequences of the ESPE/LWPES guidelines for diagnosis and treatment of disorders of sex development". Best Pract. Res. Clin. Endocrinol. Metab. 21 (3): 351–65. doi:10.1016/j.beem.2007.06.003. PMID 17875484.
  2. 2.0 2.1 White PC, Speiser PW (2000). "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Endocr. Rev. 21 (3): 245–91. doi:10.1210/edrv.21.3.0398. PMID 10857554.
  3. Hohl A, Ronsoni MF, Oliveira M (2014). "Hirsutism: diagnosis and treatment". Arq Bras Endocrinol Metabol. 58 (2): 97–107. PMID 24830586. Vancouver style error: initials (help)
  4. Melmed, Shlomo (2016). Williams textbook of endocrinology. Philadelphia, PA: Elsevier. ISBN 978-0323297387.=
  5. Gonzalez RR, Mäentausta O, Solyom J, Vihko R (1990). "Direct solid-phase time-resolved fluoroimmunoassay of 17 alpha-hydroxyprogesterone in serum and dried blood spots on filter paper". Clin. Chem. 36 (9): 1667–72. PMID 2208708.
  6. 6.0 6.1 Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC (2010). "Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline". J. Clin. Endocrinol. Metab. 95 (9): 4133–60. doi:10.1210/jc.2009-2631. PMC 2936060. PMID 20823466.

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