Adrenal Hypoplasia

Updated: Nov 04, 2016
  • Author: Thomas A Wilson, MD; Chief Editor: Robert P Hoffman, MD  more...
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Overview

Background

Adrenocorticotropic hormone (ACTH) deficiency due to any cause and defects in the ACTH receptor result in hypoplasia of the adrenal cortex. However, this article focuses on primary disorders of adrenal gland formation (ie, primary adrenal hypoplasia). [1, 2, 3]

Four forms of congenital adrenal hypoplasia have been identified, as follows:

  • An X-linked form (OMIM 300200) is caused by a mutation or deletion of the DAX1 gene (dosage-sensitive sex reversal adrenal hypoplasia congenita critical region of the X chromosome, also called the NR0B1 gene) on the X chromosome. [4, 5, 6, 7, 8] This form is usually associated with hypogonadotropic hypogonadism. [9, 10] It may be part of a contiguous chromosome deletion, which may include congenital adrenal hypoplasia, Duchenne muscular dystrophy (OMIM 310200), and glycerol kinase deficiency (OMIM 307030).
  • The autosomal recessive form is due to a mutation or deletion of the gene that codes for steroidogenic factor 1 (SF-1) on chromosome 9q33 (OMIM 184757). [11] This form is also associated with hypogonadotropic hypogonadism.
  • An autosomal recessive form of uncertain etiology (OMIM 240200) has also been identified.
  • A form of adrenal hypoplasia associated with intrauterine growth retardation, metaphysial dysplasia, and genital abnormalities has been identified (ie, intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies [IMAGe] association; OMIM 300290). [12]
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Pathophysiology

The roles of DAX1 and the undefined autosomal recessive gene in development of the adrenal cortex are not understood. [13] DAX1 appears to be necessary for differentiation of the definitive adult adrenal cortex but not the fetal adrenal cortex because the latter is preserved in patients who have deletions of DAX1. The autosomal recessive gene appears to be important in the development of both the fetal adrenal cortex and the definitive adult adrenal cortex because both are hypoplastic in this form of congenital adrenal hypoplasia.

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Epidemiology

Frequency

International

Congenital adrenal hypoplasia is rare. Although the frequency has been estimated in Japan at 1 case per 12,500 births, clinical experience indicates that this disease is not as common as congenital adrenal hyperplasia due to 21-hydroxylase deficiency (incidence is approximately 1 per 10,000-15,000 births worldwide).

Mortality/Morbidity

Congenital adrenal hypoplasia is a lethal disease unless promptly recognized and appropriately treated. With proper medical treatment, patients do well unless they are also affected with Duchenne muscular dystrophy. Glycerol kinase deficiency, if present, does not result in morbidity but results in hyperglycerolemia. This may be recognized by factitiously elevated serum triglyceride concentrations.

Patients with congenital adrenal hypoplasia due to a mutation or deletion of DAX1 or SF1 (gene name NR5A1) develop hypogonadotropic hypogonadism. Some patients with the X-linked form have been found to have sensorineural deafness (OMIM 300200). Patients with IMAGe association also have intrauterine growth retardation and skeletal and genital abnormalities.

Sex

Because one form of congenital adrenal hypoplasia is X-linked, the disease occurs more commonly in males.

Age

Patients with congenital adrenal hypoplasia generally present in infancy with signs of adrenal insufficiency. However, the age of onset widely varies, and some cases are not identified until the patient is an adult. [14]

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