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24 - Congenital adrenal hyperplasia

from Part III - Management of specific disorders

Published online by Cambridge University Press:  04 May 2010

By
Gerry S. Conway  and
Pierre D. E. Mouriquand
Edited by
Adam H. Balen ,
Sarah M. Creighton ,
Melanie C. Davies ,
Jane MacDougall  and
Richard Stanhope
Gerry S. Conway
Affiliation:
Department of Endocrinology, Middlesex Hospital, London
Pierre D. E. Mouriquand
Affiliation:
Claude-Bernard University-Lyon I and Hospital Debrousse, Lyon, France
Adam H. Balen
Affiliation:
Leeds Teaching Hospitals, University Trust
Sarah M. Creighton
Affiliation:
University College London Hospitals
Melanie C. Davies
Affiliation:
University College London
Jane MacDougall
Affiliation:
Addenbrooke's Hospital, Cambridge
Richard Stanhope
Affiliation:
Great Ormond Street Hospital
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Summary

Characteristics of congenital adrenal hyperplasia and medical treatment

Overview of the adrenal gland

The adrenal glands are triangular in shape, measuring 3 cm × 5 cm × 1 cm, and are sited above each kidney. The central adrenal medulla is responsible for production of adrenaline and noradrenaline. This portion of the adrenal may be dysplastic early in the natural history of congenital adrenal hyperplasia (CAH) and in time the hyperplastic cortex takes over and the medulla becomes atrophic (Merke et al., 2000a). Absence of the adrenal medulla is thought to be of no consequence because catecholamines are also produced throughout the nervous system.

The adrenal cortex is responsible for the production of three types of steroid; glucocorticoids (cortisol), mineralocorticoids (aldosterone) and androgens. CAH refers to defects in one of the enzyme steps in the adrenal steroidogenesis pathways, which mediate the alterations to the basic four carbon rings in the substrate cholesterol.

Cholesterol is the substrate for all steroid hormones (Miller, 1991). It is taken up by adrenal cells via receptors for low and high density lipoprotein (LDL and HDL, respectively), the abundance of which is increased by the action of adrenocorticotrophic hormone (ACTH). The scheme of adrenal steroid production is presented in Fig. 24.1. The conversion of cholesterol to cortisol occurs in five stages.

  1. Cholesterol side-chain cleavage (cholesterol desmolase; gene designation: CYP11A1) is the rate-limiting step in the cortisol pathway. Cholesterol is delivered by StAR protein (steroidogenic acute regulatory protein) to the mitochondria where the side-chain cleavage enzyme is located. The electron transfer process, which results in removal of the side chain at C20, produces the cortisol precursor pregnenolone.

  2. […]

Type
Chapter
Information
Paediatric and Adolescent Gynaecology
A Multidisciplinary Approach
 , pp. 310 - 326
Publisher: Cambridge University Press
Print publication year: 2004

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