Congenital adrenal hyperplasia Overview

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.

Historical Perspective

• Congenital adrenal hyperplasia first time seen in 1865 by Luigi De Crecchio, an Italian pathologist, in a man at autopsy, who had large adrenal glands and female internal organs.

• Important aspects of discovering adrenal hormones:
  • In 1563, Eustachius described the adrenals and then published by Lancisi in 1714.
  • In 1849, Thomas Addison, found on a bronzed appearance associated with the adrenal glands called melasma suprarenale while searching for the cause of pernicious anemia.
  • In 1855, Thomas Addison defined the clinical features and autopsy findings in 11 cases of diseases of the suprarenal capsules, and half of them were tuberculous in origin.
  • In 1856, In adrenalectomy experiments, Brown-Séquard found that the adrenal glands are nessesary for life.
  • In 1896, William Osler prepared an oral glycerin extract 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, defined the isolation and structural characterization 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 1981, Vale defined characterization and synthesis of corticotropin-releasing hormone.
  • From 1980-present called the molecular era; highlights in this section are:
    • Cloning and functional characterization of steroid hormone receptors discovered.
    • Steroidogenic enzymes described.
    • Adrenal transcription factors were reported.
    • Molecular basis for human adrenal diseases described.

Pathophisiology

Classification

Congenital adrenal hyperplasia is classified into seven types based on the genetic causes that lead to hyperplasia and hormonal imbalance.

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	Deoxycorticosterone 11-Deoxy-cortisol 17-hydroxyprogesterone, mild elevation	Cortisol Corticosterone Aldosterone	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	17-hydroxyprogesterone Exaggerated Androstenedione, DHEA, and 17-hydroxyprogesterone response to ACTH		Normal	CYP21A1 and CYP21A2 gene
17-α hydroxylase deficiency		Hypertension	Female: normal Male: ambiguous	Deoxycorticosterone Corticosterone Progesterone	Cortisol Aldosterone	Low	CYP17A1
11-β hydroxylase deficiency		Hypertension	Female: ambiguous Male: normal or scrotal pigmentation and large phallus	Deoxycorticosterone 11-Deoxy-cortisol 17-hydroxyprogesterone, mild elevation	Cortisol Corticosterone Aldosterone	Low	CYP11B1
3β-Hydroxysteroid Dehydrogenase				Dehydroepiandrosterone 17-hydroxypregnenolone Pregnenolone	Cortisol Aldosterone	High
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Congenital lipoid adrenal hyperplasia
Cholesterol side-chain cleavage enzyme deficiency