Lipoid congenital adrenal hyperplasia: Difference between revisions

	WikiDoc Resources for Lipoid congenital adrenal hyperplasia
Articles
Most recent articles on Lipoid congenital adrenal hyperplasia Most cited articles on Lipoid congenital adrenal hyperplasia Review articles on Lipoid congenital adrenal hyperplasia Articles on Lipoid congenital adrenal hyperplasia in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Lipoid congenital adrenal hyperplasia Images of Lipoid congenital adrenal hyperplasia Photos of Lipoid congenital adrenal hyperplasia Podcasts & MP3s on Lipoid congenital adrenal hyperplasia Videos on Lipoid congenital adrenal hyperplasia
Evidence Based Medicine
Cochrane Collaboration on Lipoid congenital adrenal hyperplasia Bandolier on Lipoid congenital adrenal hyperplasia TRIP on Lipoid congenital adrenal hyperplasia
Clinical Trials
Ongoing Trials on Lipoid congenital adrenal hyperplasia at Clinical Trials.gov Trial results on Lipoid congenital adrenal hyperplasia Clinical Trials on Lipoid congenital adrenal hyperplasia at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Lipoid congenital adrenal hyperplasia NICE Guidance on Lipoid congenital adrenal hyperplasia NHS PRODIGY Guidance FDA on Lipoid congenital adrenal hyperplasia CDC on Lipoid congenital adrenal hyperplasia
Books
Books on Lipoid congenital adrenal hyperplasia
News
Lipoid congenital adrenal hyperplasia in the news Be alerted to news on Lipoid congenital adrenal hyperplasia News trends on Lipoid congenital adrenal hyperplasia
Commentary
Blogs on Lipoid congenital adrenal hyperplasia
Definitions
Definitions of Lipoid congenital adrenal hyperplasia
Patient Resources / Community
Patient resources on Lipoid congenital adrenal hyperplasia Discussion groups on Lipoid congenital adrenal hyperplasia Patient Handouts on Lipoid congenital adrenal hyperplasia Directions to Hospitals Treating Lipoid congenital adrenal hyperplasia Risk calculators and risk factors for Lipoid congenital adrenal hyperplasia
Healthcare Provider Resources
Symptoms of Lipoid congenital adrenal hyperplasia Causes & Risk Factors for Lipoid congenital adrenal hyperplasia Diagnostic studies for Lipoid congenital adrenal hyperplasia Treatment of Lipoid congenital adrenal hyperplasia
Continuing Medical Education (CME)
CME Programs on Lipoid congenital adrenal hyperplasia
International
Lipoid congenital adrenal hyperplasia en Espanol Lipoid congenital adrenal hyperplasia en Francais
Business
Lipoid congenital adrenal hyperplasia in the Marketplace Patents on Lipoid congenital adrenal hyperplasia
Experimental / Informatics
List of terms related to Lipoid congenital adrenal hyperplasia

VisualWikitext

Latest revision as of 19:28, 18 October 2017

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 lipoid adrenal hyperplasia, Congenital lipoid adrenal hyperplasia due to STAR deficiency, CLAH.

Overview

Lipoid congenital adrenal hyperplasia is a rare autosomal recessive and usually the most severe form of congenital adrenal hyperplasia. In 1865, Luigi De Crecchio, an Italian pathologist was the first who described Congenital adrenal hyperplasia. Lipoid congenital adrenal is characterized by deficiency of all adrenal hormones and increased corticotropin (ACTH) secretion. This disease is caused by gene mutation that codes a protein called steroid acute regulatory protein (StAR) and helps cholesterol transport from the outer to the inner mitochondrial membrane. On microscopic histopathological analysis, progressive accumulation of cholesterol esters are characteristic findings of lipoid congenital adrenal hyperplasia. Lipoid congenital adrenal hyperplasia must be differentiated from diseases with primary amenorrhea. Some of these causes include androgen insensitivity syndrome, 3 beta-hydroxysteroid dehydrogenase deficiency, 17 alpha-hydroxylase deficiency, gonadal dysgenesis, testicular regression syndrome, LH receptor defects, 5-alpha-reductase type 2 deficiency, mullerian agenesis, primary ovarian insufficiency, hypogonadotropic hypogonadism and turner syndrome. Symptoms can be sever hypotension due to adrenal crisis. Because of lack of androgen production male infants usually have female external genitalia, presenting with primary amenorrhea. Female infants have normal genitalia normally developed at birth and occasional patients undergo spontaneous puberty. Symptoms can be sever hypotension due to adrenal crisis. Laboratory findings in lipoid congenital adrenal hyperplasia are: low cortisol levels, low aldosterone levels, high plasma ACTH concentrations, and high plasma renin activity. High serum gonadotropin levels are seen due to gonadal steroid synthesis impairment. On abdominal CT scan, Lipoid congenital adrenal hyperplasia is characterized by bilateral symmetric enlargement of the adrenal glands. Lipoid congenital adrenal hyperplasia is fatal in infancy period in two-thirds of reported patients. Replacement therapy with glucocorticoids and mineralocorticoids has been reported in a few cases. The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.

Historical Perspective

In 1865, Luigi De Crecchio, an Italian pathologist was the first who described Congenital adrenal hyperplasia.^[1]

Classification

There is no established classification system for lipoid congenital adrenal hyperplasia.

Pathophysiology

Lipoid congenital adrenal hyperplasia is an autosomal recessive disease; characterized by deficiency of all adrenal hormones and increased corticotropin (ACTH) secretion.

This disease is caused by gene mutation on chromosome 8. This gene mutation codes for a protein called steroid acute regulatory protein (StAR). StAR protein helps cholesterol transport from the outer to the inner mitochondrial membrane.
On microscopic histopathological analysis, progressive accumulation of cholesterol esters are characteristic findings of lipoid congenital adrenal hyperplasia.^[2]^[3]

Causes

Lipoid congenital adrenal hyperplasia is caused by gene mutation which on chromosome 8. This gene mutation codes for a protein called steroid acute regulatory protein (StAR).

Differentiating congenital lipoid adrenal hyperplasia from other Diseases

Lipoid congenital adrenal hyperplasia must be differentiated from diseases with primary amenorrhea. Some of these causes include androgen insensitivity syndrome, 3 beta-hydroxysteroid dehydrogenase deficiency, 17 alpha-hydroxylase deficiency, gonadal dysgenesis, testicular regression syndrome, LH receptor defects, 5-alpha-reductase type 2 deficiency, mullerian agenesis, primary ovarian insufficiency, hypogonadotropic hypogonadism and turner syndrome.^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]

Differential diagnosis for primary amenorrhea:

Disease name	Cause	Differentiating
Disease name	Cause	Findings	Uterus	Breast development	Testosterone	LH	FSH	Karyotyping
3 beta-hydroxysteroid dehydrogenase deficiency	HSD3B2 gene mutation	Undervirilization in 46,XY individuals due to a block in testosterone biosynthesis. Mild virilization in 46,XX individuals	Yes in female	Yes in female	↓	Normal	Normal	XY and XX
17-alpha-hydroxylase deficiency	CYP17A1 gene mutation	Female external genitalia Primary amenorrhea Hypertension Absence of secondary sexual characteristics Minimal body hair	No	No	↓	Normal	Normal	XY
Gonadal dysgenesis	Mutations in SRY, FOG2/ZFPM2, and WNT1	Female external genitalia Intact Mullerian ducts Streak gonads	Yes	Yes	↓	↑	↑	XY
Testicular regression syndrome	Loss of testicular function and tissue early in development	Female phenotype with atrophic Mullerian ducts.	No	No	↓	↑	↑	XY
LH receptor defects	LH receptor gene mutation on chromosome 2	Female external genitalia Lack a uterus and fallopian tubes Epididymis and vas deferens may be present Laboratory: Unresponsiveness to hCG Normal levels of testosterone precursors (produced in the adrenal glands).	No	No	↓	↑	↑	XY
5-alpha-reductase type 2 deficiency	Autosomal recessive	Female external genitalia or ambiguous Bilateral testes and normal testosterone formation Impaired external virilization during embryogenesis Defective conversion of testosterone to DHT. Testosterone:DHT ratio is >10:1	No	No	Normal male range	High to normal	High to normal	XY
Androgen insensitivity syndrome	Androgen receptor defect	Female external genitalia Resistant to testosterone	No	Yes	Normal male range	Normal	Normal	XY
Mullerian agenesis	Mutations in WNT4	Normal female genitalia Normal breast development	No	Yes	Normal female range	Normal	Normal	XX
Primary ovarian insufficiency	Genetic defects such as turner syndrome, fragile X syndrome, some other chromosomal defects	Normal female genitalia	Yes	Yes	Normal female range	↑	↑	XX
Hypogonadotropic hypogonadism	Functional, sellar masses	Normal female genitalia, Delayed puberty	Yes	No	Normal female range	Low	Normal	XX
Turner syndrome	Chromosomal	Normal female external genitalia	Yes	Yes	Normal female range	↑	↑	45 XO

Epidemiology and Demographics

This disease is a rare disease with unknown prevalence.

Diagnosis

Symptoms

Symptoms can be sever hypotension due to adrenal crisis. Because of lack of androgen production male infants usually have female external genitalia, presenting with primary amenorrhea. Female infants have normal genitalia normally developed at birth and occasional patients undergo spontaneous puberty.^[12]

Physical Examination

Physical examination is remarkable for hypotension and primary amenorrhea (due to lack of androgen in male infants).

Laboratory Findings

Laboratory findings in lipoid congenital adrenal hyperplasia are: low cortisol levels, low aldosterone levels, and high plasma ACTH concentrations and high plasma renin activity. High serum gonadotropin levels are seen due to gonadal steroid synthesis impairment.

Imaging Findings

On abdominal CT scan, Lipoid congenital adrenal hyperplasia is characterized by bilateral symmetric enlargement of the adrenal glands.

Treatment

Medical Therapy

Lipoid congenital adrenal hyperplasia is fatal in infancy period in two-thirds of reported patients. Replacement therapy with glucocorticoids and mineralocorticoids has been reported in a few cases.^[13]

Surgery

The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.

References

↑ Delle Piane L, Rinaudo PF, Miller WL (2015). "150 years of congenital adrenal hyperplasia: translation and commentary of De Crecchio's classic paper from 1865". Endocrinology. 156 (4): 1210–7. doi:10.1210/en.2014-1879. PMID 25635623.
↑ Lin D, Sugawara T, Strauss JF, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL (1995). "Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis". Science. 267 (5205): 1828–31. PMID 7892608.
↑ Bose HS, Sugawara T, Strauss JF, Miller WL (1996). "The pathophysiology and genetics of congenital lipoid adrenal hyperplasia". N. Engl. J. Med. 335 (25): 1870–8. doi:10.1056/NEJM199612193352503. PMID 8948562.
↑ Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Grüters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nuñez CJ, Servant N, Lumbroso S, Paris F, Sultan C (2011). "Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients". J. Clin. Endocrinol. Metab. 96 (2): 296–307. doi:10.1210/jc.2010-1024. PMID 21147889.
↑ Moreira AC, Leal AM, Castro M (1990). "Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 71 (1): 86–91. doi:10.1210/jcem-71-1-86. PMID 2164530.
↑ Heremans GF, Moolenaar AJ, van Gelderen HH (1976). "Female phenotype in a male child due to 17-alpha-hydroxylase deficiency". Arch. Dis. Child. 51 (9): 721–3. PMC 1546244. PMID 999330.
↑ Biglieri EG (1979). "Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome". J. Steroid Biochem. 11 (1B): 653–7. PMID 226795.
↑ Saenger P (1996). "Turner's syndrome". N. Engl. J. Med. 335 (23): 1749–54. doi:10.1056/NEJM199612053352307. PMID 8929268.
↑ Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fékété C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R (2015). "Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis". Fertil. Steril. 103 (5): 1297–304. doi:10.1016/j.fertnstert.2015.01.043. PMID 25813279.
↑ Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (1974). "Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism". Science. 186 (4170): 1213–5. PMID 4432067.
↑ Schnitzer JJ, Donahoe PK (2001). "Surgical treatment of congenital adrenal hyperplasia". Endocrinol. Metab. Clin. North Am. 30 (1): 137–54. PMID 11344932.
↑ Fujieda K, Tajima T, Nakae J, Sageshima S, Tachibana K, Suwa S, Sugawara T, Strauss JF (1997). "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. 99 (6): 1265–71. doi:10.1172/JCI119284. PMC 507941. PMID 9077535.
↑ Hauffa BP, Miller WL, Grumbach MM, Conte FA, Kaplan SL (1985). "Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years". Clin. Endocrinol. (Oxf). 23 (5): 481–93. PMID 3841304.

Template:WS Template:WH

[pmid25635623-1] Delle Piane L, Rinaudo PF, Miller WL (2015). "150 years of congenital adrenal hyperplasia: translation and commentary of De Crecchio's classic paper from 1865". Endocrinology. 156 (4): 1210–7. doi:10.1210/en.2014-1879. PMID 25635623.

[pmid7892608-2] Lin D, Sugawara T, Strauss JF, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL (1995). "Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis". Science. 267 (5205): 1828–31. PMID 7892608.

[pmid8948562-3] Bose HS, Sugawara T, Strauss JF, Miller WL (1996). "The pathophysiology and genetics of congenital lipoid adrenal hyperplasia". N. Engl. J. Med. 335 (25): 1870–8. doi:10.1056/NEJM199612193352503. PMID 8948562.

[pmid21147889-4] Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Grüters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nuñez CJ, Servant N, Lumbroso S, Paris F, Sultan C (2011). "Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients". J. Clin. Endocrinol. Metab. 96 (2): 296–307. doi:10.1210/jc.2010-1024. PMID 21147889.

[pmid2164530-5] Moreira AC, Leal AM, Castro M (1990). "Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 71 (1): 86–91. doi:10.1210/jcem-71-1-86. PMID 2164530.

[pmid999330-6] Heremans GF, Moolenaar AJ, van Gelderen HH (1976). "Female phenotype in a male child due to 17-alpha-hydroxylase deficiency". Arch. Dis. Child. 51 (9): 721–3. PMC 1546244. PMID 999330.

[pmid226795-7] Biglieri EG (1979). "Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome". J. Steroid Biochem. 11 (1B): 653–7. PMID 226795.

[pmid8929268-8] Saenger P (1996). "Turner's syndrome". N. Engl. J. Med. 335 (23): 1749–54. doi:10.1056/NEJM199612053352307. PMID 8929268.

[pmid25813279-9] Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fékété C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R (2015). "Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis". Fertil. Steril. 103 (5): 1297–304. doi:10.1016/j.fertnstert.2015.01.043. PMID 25813279.

[pmid4432067-10] Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (1974). "Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism". Science. 186 (4170): 1213–5. PMID 4432067.

[pmid11344932-11] Schnitzer JJ, Donahoe PK (2001). "Surgical treatment of congenital adrenal hyperplasia". Endocrinol. Metab. Clin. North Am. 30 (1): 137–54. PMID 11344932.

[pmid9077535-12] Fujieda K, Tajima T, Nakae J, Sageshima S, Tachibana K, Suwa S, Sugawara T, Strauss JF (1997). "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. 99 (6): 1265–71. doi:10.1172/JCI119284. PMC 507941. PMID 9077535.

[pmid3841304-13] Hauffa BP, Miller WL, Grumbach MM, Conte FA, Kaplan SL (1985). "Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years". Clin. Endocrinol. (Oxf). 23 (5): 481–93. PMID 3841304.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

@@ Line 1: / Line 1: @@
 __NOTOC__
-{{Lipoid congential adrenal hyperplasia}}
+{{SI}}
-{{CMG}}
+{{CMG}}; {{AE}} {{MJ}}
-==What is CAH?==
-''Congenital adrenal hyperplasia'' (CAH) refers to any of several [[autosomal recessive]] diseases resulting from defects in steps of the [[synthesis]] of [[cortisol]] from [[cholesterol]] by the [[adrenal gland]]s. All of the forms of CAH involve excessive or defective production of [[sex steroid]]s and can pervert or impair development of [[primary sex characteristic|primary]] or [[secondary sex characteristic]]s in affected infants, children, and adults. Many also involve excessive or defective production of [[mineralocorticoid]]s, which can cause [[hypertension]] or salt-wasting.
-The most common type of CAH is due to [[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency|deficiency of 21-hydroxylase]]. Lipoid CAH is one of the less common types of CAH due to deficiencies of other proteins and enzymes involved in cortisol synthesis.
+{{SK}} Congenital lipoid adrenal hyperplasia, Congenital lipoid adrenal hyperplasia due to STAR deficiency, CLAH.
-==Lipoid congenital adrenal hyperplasia==
-Lipoid congenital adrenal hyperplasia results from defects in the steps from cholesterol to pregnenolone. The adrenals are large and filled with [[lipid]] globules derived from [[cholesterol]]. Life-threatening [[mineralocorticoid]] and [[glucocorticoid]] deficiency becomes apparent in infancy or early childhood. [[Sex steroid]] production is greatly impaired. XY infants (genetic males) are severely undervirilized so that the external genitalia at birth are female (normal or slightly virilized). XX infants have normal female anatomy and if their mineralocorticoid and glucocorticoid deficiencies are treated will often undergo spontaneous puberty. Lipid storage damages the adrenals and eventually the [[gonad]]s as well, so that all persons with this condition have so far been [[infertility|infertile]].
-==Pathophysiology and genetics of lipoid CAH==
-Understanding of the molecular basis for this disease has been advanced in the last decade by better understanding of adrenal steroidogenesis as well as genetic studies of affected patients. It used to be assumed that lipoid CAH resulted from a defect of the enzymes that converted cholesterol to pregnenolone. The conversion reactions are mediated by a single enzyme, formerly referred to as 20,22-desmolase, but now identified as [[P450scc]] ([[side chain]] cleavage enzyme). However, as of 2003, only a single case of lipoid CAH due to a mutation and defect of P450scc has been identified.
-All other cases of lipoid adrenal hyperplasia that have been studied have been found to be due to mutations of the [[gene]] for a protein which transports cholesterol into the mitochondria. This [[steroidogenic acute regulatory protein]] (StAR) is coded by a gene on 8p11.2. Inheritance is autosomal recessive. The [[OMIM]] number is 20170 for the deficiency.
+==Overview==
+Lipoid congenital adrenal hyperplasia is a rare [[autosomal recessive]] and usually the most severe form of [[congenital adrenal hyperplasia]]. In 1865, Luigi De Crecchio, an Italian [[pathologist]] was the first who described [[Congenital adrenal hyperplasia]]. Lipoid congenital adrenal is characterized by deficiency of all [[adrenal]] hormones and increased [[corticotropin]] ([[ACTH]]) secretion. This disease is caused by [[gene mutation]] that codes a [[protein]] called steroid acute regulatory protein (StAR) and helps [[cholesterol]] transport from the outer to the inner [[mitochondrial membrane]]. On [[microscopic]] [[histopathological]] analysis, progressive accumulation of [[cholesterol]] esters are characteristic findings of lipoid congenital adrenal hyperplasia. Lipoid congenital adrenal hyperplasia must be differentiated from diseases with [[primary amenorrhea]]. Some of these causes include [[androgen insensitivity syndrome]], [[3 beta-hydroxysteroid dehydrogenase deficiency]], [[17 alpha-hydroxylase deficiency]],  [[gonadal dysgenesis]], [[testicular regression syndrome]], [[LH receptor|LH receptor defects]], [[5-alpha-reductase deficiency|5-alpha-reductase type 2 deficiency]], [[mullerian agenesis]], [[Ovarian insufficiency|primary ovarian insufficiency]], [[hypogonadotropic hypogonadism]] and [[turner syndrome]]. Symptoms can be sever [[hypotension]] due to [[adrenal crisis]]. Because of lack of [[androgen]] production male [[infants]] usually have female [[external genitalia]], presenting with [[primary amenorrhea]]. Female infants have normal [[genitalia]] normally developed at birth and occasional patients undergo spontaneous [[puberty]]. Symptoms can be sever [[hypotension]] due to [[adrenal crisis]]. Laboratory findings in lipoid congenital adrenal hyperplasia are: low [[cortisol]] levels, low [[aldosterone]] levels, high plasma [[ACTH]] concentrations, and high [[Renin|plasma renin]] activity. High serum [[gonadotropin]] levels are seen due to [[gonadal]] [[steroid]] synthesis impairment. On abdominal [[CT scan]], Lipoid congenital adrenal hyperplasia is characterized by bilateral symmetric enlargement of the [[adrenal glands]]. Lipoid congenital adrenal hyperplasia is fatal in [[infancy]] period in two-thirds of reported patients. Replacement therapy with [[glucocorticoids]] and [[mineralocorticoids]] has been reported in a few cases. The reconstruction surgery for [[ambiguous genitalia]] in [[genetically]] male patients may be applied.
+==Historical Perspective==
+In 1865, Luigi De Crecchio, an Italian [[pathologist]] was the first who described [[Congenital adrenal hyperplasia]].<ref name="pmid25635623">{{cite journal |vauthors=Delle Piane L, Rinaudo PF, Miller WL |title=150 years of congenital adrenal hyperplasia: translation and commentary of De Crecchio's classic paper from 1865 |journal=Endocrinology |volume=156 |issue=4 |pages=1210–7 |year=2015 |pmid=25635623 |doi=10.1210/en.2014-1879 |url=}}</ref>
+==Classification==
+There is no established classification system for lipoid congenital adrenal hyperplasia.
+==Pathophysiology==
+Lipoid congenital adrenal hyperplasia is an [[autosomal recessive]] disease; characterized by deficiency of all adrenal hormones and increased [[corticotropin]] ([[Adrenocorticotropic hormone|ACTH]]) secretion.
+* This disease is caused by [[gene mutation]] on [[chromosome 8]]. This [[gene mutation]] codes for a [[protein]] called steroid acute regulatory protein (StAR). StAR [[protein]] helps [[cholesterol]] transport from the outer to the inner [[mitochondrial membrane]].
+* On [[microscopic]] [[histopathological]] analysis, progressive accumulation of [[cholesterol]] esters are characteristic findings of lipoid congenital adrenal hyperplasia.<ref name="pmid7892608">{{cite journal |vauthors=Lin D, Sugawara T, Strauss JF, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL |title=Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis |journal=Science |volume=267 |issue=5205 |pages=1828–31 |year=1995 |pmid=7892608 |doi= |url=}}</ref><ref name="pmid8948562">{{cite journal |vauthors=Bose HS, Sugawara T, Strauss JF, Miller WL |title=The pathophysiology and genetics of congenital lipoid adrenal hyperplasia |journal=N. Engl. J. Med. |volume=335 |issue=25 |pages=1870–8 |year=1996 |pmid=8948562 |doi=10.1056/NEJM199612193352503 |url=}}</ref>
+==Causes==
+Lipoid congenital adrenal hyperplasia is caused by [[gene mutation]] which on [[chromosome 8]]. This [[gene mutation]] codes for a protein called steroid acute regulatory protein (StAR).
+==Differentiating congenital lipoid adrenal hyperplasia from other Diseases==
+Lipoid congenital adrenal hyperplasia must be differentiated from diseases with [[primary amenorrhea]]. Some of these causes include [[androgen insensitivity syndrome]], [[3 beta-hydroxysteroid dehydrogenase deficiency]], [[17 alpha-hydroxylase deficiency]],  [[gonadal dysgenesis]], [[testicular regression syndrome]], [[LH receptor|LH receptor defects]], [[5-alpha-reductase deficiency|5-alpha-reductase type 2 deficiency]], [[mullerian agenesis]], [[Ovarian insufficiency|primary ovarian insufficiency]], [[hypogonadotropic hypogonadism]] and [[turner syndrome]].<ref name="pmid21147889">{{cite journal |vauthors=Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Grüters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nuñez CJ, Servant N, Lumbroso S, Paris F, Sultan C |title=Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients |journal=J. Clin. Endocrinol. Metab. |volume=96 |issue=2 |pages=296–307 |year=2011 |pmid=21147889 |doi=10.1210/jc.2010-1024 |url=}}</ref><ref name="pmid2164530">{{cite journal |vauthors=Moreira AC, Leal AM, Castro M |title=Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=71 |issue=1 |pages=86–91 |year=1990 |pmid=2164530 |doi=10.1210/jcem-71-1-86 |url=}}</ref><ref name="pmid999330">{{cite journal |vauthors=Heremans GF, Moolenaar AJ, van Gelderen HH |title=Female phenotype in a male child due to 17-alpha-hydroxylase deficiency |journal=Arch. Dis. Child. |volume=51 |issue=9 |pages=721–3 |year=1976 |pmid=999330 |pmc=1546244 |doi= |url=}}</ref><ref name="pmid226795">{{cite journal |vauthors=Biglieri EG |title=Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome |journal=J. Steroid Biochem. |volume=11 |issue=1B |pages=653–7 |year=1979 |pmid=226795 |doi= |url=}}</ref><ref name="pmid8929268">{{cite journal |vauthors=Saenger P |title=Turner's syndrome |journal=N. Engl. J. Med. |volume=335 |issue=23 |pages=1749–54 |year=1996 |pmid=8929268 |doi=10.1056/NEJM199612053352307 |url=}}</ref><ref name="pmid25813279">{{cite journal |vauthors=Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fékété C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R |title=Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis |journal=Fertil. Steril. |volume=103 |issue=5 |pages=1297–304 |year=2015 |pmid=25813279 |doi=10.1016/j.fertnstert.2015.01.043 |url=}}</ref><ref name="pmid4432067">{{cite journal |vauthors=Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE |title=Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism |journal=Science |volume=186 |issue=4170 |pages=1213–5 |year=1974 |pmid=4432067 |doi= |url=}}</ref><ref name="pmid11344932">{{cite journal |vauthors=Schnitzer JJ, Donahoe PK |title=Surgical treatment of congenital adrenal hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=137–54 |year=2001 |pmid=11344932 |doi= |url=}}</ref>
-Deficiency results in impaired synthesis of all three categories of adrenal steroids (cortisol, mineralocorticoids, sex steroids) and high levels of [[adrenocorticotropic hormone]] (ACTH). A low level of steroid synthesis proceeds even without efficient transport, but is rarely enough to prevent the consequences of deficiency.
+=== Differential diagnosis for [[primary amenorrhea]]: ===
+{| class="wikitable"
+|-
+! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + | Disease name
+! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + | Cause
+! colspan="7" style="background:#4479BA; color: #FFFFFF;" + | Differentiating
+|-
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Findings
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Uterus
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Breast development
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Testosterone
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |LH
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |FSH
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Karyotyping
+|-
+|[[3 beta-hydroxysteroid dehydrogenase deficiency]]
+|
+* HSD3B2  [[gene]] [[mutation]]
+|
+* [[Undervirilization]] in 46,XY individuals due to a block in [[testosterone]] biosynthesis.
+* Mild [[virilization]] in 46,XX individuals
+| align="center" style="padding: 5px 5px; background: " |
+Yes in [[female]]
+| align="center" style="padding: 5px 5px; background: " |
+Yes in [[female]]
+| align="center" style="padding: 5px 5px; background: " |
+↓
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+[[XY]] and [[XX]]
+|-
+|[[17-alpha-hydroxylase deficiency]]
+|
+* [[CYP17A1|CYP17A1 gene mutation]]
+|
+* Female [[external genitalia]]
-ACTH stimulates growth of the adrenal cells, and increases [[Low density lipoprotein|LDL]] receptors to amplify transport of cholesterol into the adrenal cells, where it accumulates because little is transferred into the mitochondria. The adrenals become markedly enlarged by the combination of ACTH-induced [[hyperplasia]] and accumulated lipid. Lipid accumulation is thought to damage the cells further (“second hit hypothesis”).
+* [[Primary amenorrhea]]
+* [[Hypertension]]
+* Absence of secondary [[sexual characteristics]]
+* Minimal [[body hair]]
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+↓
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+[[XY]]
+|-
+|[[Gonadal dysgenesis]]
+|
+* Mutations in [[SRY]], FOG2/ZFPM2, and WNT1
+|
+* Female [[external genitalia]]
+* Intact [[Mullerian ducts]]
+* Streak [[gonads]]
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+↓
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+[[XY]]
+|-
+|[[Testicular regression syndrome]]
+|
+* Loss of [[testicular]] function and [[tissue]] early in development
+|
+* Female phenotype with atrophic [[Mullerian ducts]].
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+↓
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+[[XY]]
+|-
+|[[LH receptor|LH receptor defects]]
+|
+* [[LH receptor]] [[gene]] [[mutation]] on [[chromosome 2]]
+|
+* Female [[external genitalia]]
+* Lack a [[uterus]] and [[fallopian tubes]]
+* [[Epididymis]] and [[vas deferens]] may be present
+* Laboratory:
+** Unresponsiveness to [[hCG]]
+** Normal levels of [[testosterone]] precursors (produced in the [[adrenal glands]]).
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+↓
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+[[XY]]
+|-
+|[[5-alpha-reductase deficiency|5-alpha-reductase type 2 deficiency]]
+|
+* [[Autosomal recessive]]
+|
+* Female [[Ambiguous genitalia|external genitalia or ambiguous]]
+* Bilateral [[testes]] and normal [[testosterone]] formation
-Because the StAR protein is also involved in cholesterol transport into testicular and ovarian cells for sex steroid synthesis, [[testis|testicular]] production of [[testosterone]] and [[ovary|ovarian]] production of [[estrogen]] are also impaired. Lipid accumulation damages the [[Leydig cell]]s of the testes more completely than the [[granulosa cell]]s of the ovaries.
+* Impaired external [[virilization]] during [[embryogenesis]]
+* Defective conversion of [[testosterone]] to [[DHT]].
+* [[Testosterone]]:[[DHT]] ratio is >10:1
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+Normal male range
+| align="center" style="padding: 5px 5px; background: " |
+High to normal
+| align="center" style="padding: 5px 5px; background: " |
+High to normal
+| align="center" style="padding: 5px 5px; background: " |
+[[XY]]
+|-
+|[[Androgen insensitivity syndrome]]
+|
+* [[Androgen receptor]] defect
+|
+* Female [[external genitalia]]
+* Resistant to [[testosterone]]
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+Normal male range
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+[[XY]]
+|-
+|[[Mullerian agenesis]]
+|
+* Mutations in ''[[WNT4]]''
+|
+* Normal female [[genitalia]]
+* Normal [[breast]] development
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+Normal [[female]] range
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+[[XX]]
+|-
+|[[Ovarian insufficiency|Primary ovarian insufficiency]]
+|
+* [[Genetic defects]] such as [[turner syndrome]], [[fragile X syndrome]], some other chromosomal defects
+|
+* Normal [[female genitalia]]
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+Normal female range
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+[[XX]]
+|-
+|[[Hypogonadotropic hypogonadism]]
+|
+* Functional, sellar masses
+|
+* Normal [[female genitalia]],
-Lipoid CAH is quite rare in European and North American populations. Most cases have occurred in Japan and Korea (where the incidence is 1 in 300,000 births) and Palestinian Arabs. Despite autosomal recessive inheritance, there has been an unexplained preponderance of genetic females in reported cases.
+* Delayed [[puberty]]
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+No
+| align="center" style="padding: 5px 5px; background: " |
+Normal female range
+| align="center" style="padding: 5px 5px; background: " |
+Low
+| align="center" style="padding: 5px 5px; background: " |
+Normal
+| align="center" style="padding: 5px 5px; background: " |
+[[XX]]
+|-
+| align="center" style="padding: 5px 5px; background: " |
+[[Turner syndrome]]
+|
+* [[Chromosomal]]
+|
+* Normal female [[external genitalia]]
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+Yes
+| align="center" style="padding: 5px 5px; background: " |
+Normal [[female]] range
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+↑
+| align="center" style="padding: 5px 5px; background: " |
+[[Turner syndrome|45 XO]]
+|}
-The pathophysiology of lipoid CAH differs from other forms of CAH in certain aspects. First, the affected enzyme (StAR) is a transport protein rather than a steroidogenic enzyme. Second, because the defect is so proximal, all steroid synthesis is compromised and there are no effects of excessive mineralocorticoids or androgens to be suppressed. Third, lipid accumulation damages the testes and ovaries so that even with appropriate adrenal hormone replacement, gonadal function and fertility cannot be preserved.
+==Epidemiology and Demographics==
+This disease is a rare disease with unknown [[prevalence]].
+== Diagnosis ==
+=== Symptoms ===
+Symptoms can be sever [[hypotension]] due to [[adrenal crisis]]. Because of lack of [[androgen]] production male [[infants]] usually have female [[external genitalia]], presenting with [[primary amenorrhea]]. Female infants have normal [[genitalia]] normally developed at birth and occasional patients undergo spontaneous [[puberty]].<ref name="pmid9077535">{{cite journal |vauthors=Fujieda K, Tajima T, Nakae J, Sageshima S, Tachibana K, Suwa S, Sugawara T, Strauss JF |title=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 |journal=J. Clin. Invest. |volume=99 |issue=6 |pages=1265–71 |year=1997 |pmid=9077535 |pmc=507941 |doi=10.1172/JCI119284 |url=}}</ref>
+=== Physical Examination ===
+Physical examination is remarkable for [[hypotension]] and [[primary amenorrhea]] (due to lack of [[androgen]] in male infants).
+=== Laboratory Findings ===
+Laboratory findings in lipoid congenital adrenal hyperplasia are: low [[cortisol]] levels, low [[aldosterone]] levels, and high plasma [[ACTH]] concentrations and high plasma [[renin]] activity. High serum [[gonadotropin]] levels are seen due to [[gonadal]] [[steroid]] synthesis impairment.
+===Imaging Findings===
+On abdominal [[CT scan]], Lipoid congenital adrenal hyperplasia is characterized by bilateral symmetric enlargement of the [[adrenal glands]].
+== Treatment ==
+=== Medical Therapy ===
+Lipoid congenital adrenal hyperplasia is fatal in [[infancy]] period in two-thirds of reported patients. Replacement therapy with [[glucocorticoids]] and [[mineralocorticoids]] has been reported in a few cases.<ref name="pmid3841304">{{cite journal |vauthors=Hauffa BP, Miller WL, Grumbach MM, Conte FA, Kaplan SL |title=Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years |journal=Clin. Endocrinol. (Oxf) |volume=23 |issue=5 |pages=481–93 |year=1985 |pmid=3841304 |doi= |url=}}</ref>
+=== Surgery ===
+The reconstruction surgery for [[ambiguous genitalia]] in genetically male patients may be applied.
+==References==
+{{Reflist|2}}
-==Clinical manifestations of lipoid CAH==
+{{WS}}
-Problems caused to persons with lipoid CAH can be divided into:
+{{WH}}
-# mineralocorticoid deficiency,
-# glucocorticoid deficiency,
-# sex steroid deficiency, and
-# damage to gonads caused by lipid accumulation.
-===Mineralocorticoid deficiency===
-Most infants born with lipoid CAH have had genitalia female enough that no disease was suspected at birth. Because the adrenal [[zona glomerulosa]] is undifferentiated and inactive before delivery, it is undamaged at birth and can make [[aldosterone]] for a while, so the eventual salt-wasting crisis develops more gradually and variably than with severe [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency|21-hydroxylase-deficient CAH]].
-Most came to medical attention between 2 weeks and 3 months of age, when after a period of poor weight gain and vomiting, they were found to be dehydrated, with severe [[hyponatremia]], [[hyperkalemia]], and [[metabolic acidosis]] (a "salt-wasting crisis"). [[Renin]] but not [[aldosterone]] is elevated. Many infants born with this condition died before a diagnosis was recognized and treatment begun. In a few cases, signs and symptoms of mineralocorticoid and glucocorticoid deficiency have only developed after months or even years.
-===Glucocorticoid deficiency===
-Inefficiency of [[cortisol]] synthesis has several consequences. Elevated ACTH is accompanied by and contributes to marked [[hyperpigmentation]] even in the newborn period. An inadequate cortisol response to stress undoubtedly hastens the deterioration as dehydration develops, can cause [[hypoglycemia]], and contributes to the high mortality rate in infancy.
-==Management of lipoid CAH==
-Management of salt-wasting crises and mineralocorticoid treatment are as for other forms of salt-wasting [[congenital adrenal hyperplasia]]: saline and [[fludrocortisone]].
-Glucocorticoids can be provided at minimal replacement doses because there is no need for suppression of excessive adrenal androgens or mineralocorticoids. As with other forms of adrenal insufficiency, extra glucocorticoid is needed for stress coverage.
-XX females with lipoid CAH may need estrogen replacement at or after puberty. To date, ovulation and pregnancy has not been reported even with early diagnosis and careful glucocorticoid replacement to suppress ACTH-induced lipid damage to the ovaries.
-Nearly all XY children have been so undervirilized that they have been raised as girls. The testes have been uniformly nonfunctional and are removed to prevent long term neoplastic risk.
-==Related Chapters==
-*[[Congenital adrenal hyperplasia]] for an overview of CAH
-*[[Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency|Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency]]
-*[[Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency|Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency]]
-*[[Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency|Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency]]
-*[[Intersex]] and [[ambiguous genitalia]]
-*[[Adrenal insufficiency]]
-[[Category:Pediatrics]]
-[[Category:Endocrinology]]
-[[Category:Genetic disorders]]
-[[Category:Intersexuality]]
-{{WikiDoc Help Menu}}
-{{WikiDoc Sources}}