Congenital lipoid adrenal hyperplasia
- Lynnette K Nieman, MD
Lynnette K Nieman, MD
- Section Editor — Adrenal Disease
- Senior Investigator
- Bethesda, MD
- Section Editors
- André Lacroix, MD
André Lacroix, MD
- Section Editor — Adrenal Disease
- Professor of Medicine
- University of Montreal, Quebec, Canada
- Mitchell E Geffner, MD
Mitchell E Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
Congenital adrenal hyperplasia (CAH) refers to several disorders characterized by genetic defects in the proteins and enzymes involved in cortisol biosynthesis (figure 1). The decrease in cortisol production releases the feedback inhibition of cortisol on the pituitary and increases the production of corticotropin (ACTH). High ACTH causes adrenal hyperplasia and drives excessive accumulation of cortisol precursors and/or overproduction of ACTH-dependent adrenal steroids along other pathways. The clinical manifestations of the different disorders are due to diminished production of cortisol and, depending upon the site of block, decreased or increased production of mineralocorticoids and/or androgens. (See "Adrenal steroid biosynthesis".)
The most common cause of CAH worldwide, accounting for >90 percent of cases, is 21-hydroxylase deficiency (21OHD). The prevalence of these other forms of CAH varies geographically, largely due to founder mutations that are often isolated to specific regions. Other unusual forms of CAH include:
●CYP17A1 deficiencies (combined 17-hydroxylase/17,20-lyase deficiency [17OHD] and isolated 17,20-lyase deficiency [ILD])
●3-beta-hydroxysteroid dehydrogenase type 2 deficiency
●CYP11B1 deficiency (11-hydroxylase deficiency [11OHD])
- Sugawara T, Holt JA, Driscoll D, et al. Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13. Proc Natl Acad Sci U S A 1995; 92:4778.
- Lin D, Sugawara T, Strauss JF 3rd, et al. Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 1995; 267:1828.
- Clark BJ, Wells J, King SR, Stocco DM. The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J Biol Chem 1994; 269:28314.
- Stocco DM, Ascoli M. The use of genetic manipulation of MA-10 Leydig tumor cells to demonstrate the role of mitochondrial proteins in the acute regulation of steroidogenesis. Endocrinology 1993; 132:959.
- Stocco DM, Sodeman TC. The 30-kDa mitochondrial proteins induced by hormone stimulation in MA-10 mouse Leydig tumor cells are processed from larger precursors. J Biol Chem 1991; 266:19731.
- Rhéaume E, Simard J, Morel Y, et al. Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene. Nat Genet 1992; 1:239.
- Bose HS, Sugawara T, Strauss JF 3rd, et al. The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. N Engl J Med 1996; 335:1870.
- Katsumata N, Kawada Y, Yamamoto Y, et al. A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab 1999; 84:3983.
- González AA, Reyes ML, Carvajal CA, et al. Congenital lipoid adrenal hyperplasia caused by a novel splicing mutation in the gene for the steroidogenic acute regulatory protein. J Clin Endocrinol Metab 2004; 89:946.
- Fujieda K, Okuhara K, Abe S, et al. Molecular pathogenesis of lipoid adrenal hyperplasia and adrenal hypoplasia congenita. J Steroid Biochem Mol Biol 2003; 85:483.
- Bose HS, Pescovitz OH, Miller WL. Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein. J Clin Endocrinol Metab 1997; 82:1511.
- Ishii T, Hasegawa T, Pai CI, et al. The roles of circulating high-density lipoproteins and trophic hormones in the phenotype of knockout mice lacking the steroidogenic acute regulatory protein. Mol Endocrinol 2002; 16:2297.
- Achermann JC, Ito M, Ito M, et al. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet 1999; 22:125.
- Sakai Y, Yanase T, Okabe Y, et al. No mutation in cytochrome P450 side chain cleavage in a patient with congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab 1994; 79:1198.
- Lin D, Gitelman SE, Saenger P, Miller WL. Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia. J Clin Invest 1991; 88:1955.
- Tajima T, Fujieda K, Kouda N, et al. Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency. J Clin Endocrinol Metab 2001; 86:3820.
- Katsumata N, Ohtake M, Hojo T, et al. Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans. J Clin Endocrinol Metab 2002; 87:3808.
- Gassner HL, Toppari J, Quinteiro González S, Miller WL. Near-miss apparent SIDS from adrenal crisis. J Pediatr 2004; 145:178.
- Fujieda K, Tajima T, Nakae J, et al. Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene. J Clin Invest 1997; 99:1265.
- Pang S, Carbunaru G, Haider A, et al. Carriers for type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) deficiency can only be identified by HSD3B2 genotype study and not by hormone test. Clin Endocrinol (Oxf) 2003; 58:323.
- Hauffa BP, Miller WL, Grumbach MM, et al. Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years. Clin Endocrinol (Oxf) 1985; 23:481.
- Nakae J, Tajima T, Sugawara T, et al. Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia. Hum Mol Genet 1997; 6:571.
- Hiort O, Holterhus PM, Werner R, et al. Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure. J Clin Endocrinol Metab 2005; 90:538.