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Lipoid congenital adrenal hyperplasia
Introduction
Synonyms and keywords: Congenital lipoid adrenal hyperplasia, Congenital lipoid adrenal hyperplasia due to STAR deficiency, CLAH.
Overview
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
Historical Perspective
In 1865, Luigi De Crecchio, an Italian pathologist was the first who described Congenital adrenal hyperplasia.[1]
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References
Classification
Classification
There is no established classification system for lipoid congenital adrenal hyperplasia.
Pathophysiology
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
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
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 | ||||||
|---|---|---|---|---|---|---|---|---|
| Findings | Uterus | Breast development | Testosterone | LH | FSH | Karyotyping | ||
| 3 beta-hydroxysteroid dehydrogenase deficiency |
|
Yes in female |
Yes in female |
β |
Normal |
Normal |
||
| 17-alpha-hydroxylase deficiency |
|
No |
No |
β |
Normal |
Normal |
||
| Gonadal dysgenesis |
|
|
Yes |
Yes |
β |
β |
β |
|
| Testicular regression syndrome |
|
|
No |
No |
β |
β |
β |
|
| LH receptor defects |
|
No |
No |
β |
β |
β |
||
| 5-alpha-reductase type 2 deficiency |
|
No |
No |
Normal male range |
High to normal |
High to normal |
||
| Androgen insensitivity syndromeΒ |
|
|
No |
Yes |
Normal male range |
Normal |
Normal |
|
| Mullerian agenesis |
|
No |
Yes |
Normal female range |
Normal |
Normal |
||
| Primary ovarian insufficiency |
|
|
Yes |
Yes |
Normal female range |
β |
β |
|
| Hypogonadotropic hypogonadism |
|
|
Yes |
No |
Normal female range |
Low |
Normal |
|
|
Yes |
Yes |
Normal female range |
β |
β |
|||
Epidemiology and Demographics
Epidemiology and Demographics
This disease is a rare disease with unknown prevalence.
Overview
Epidemiology and Demographics
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
References
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Diagnosis
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
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
References
- β 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): 1210β7. doi:10.1210/en.2014-1879. PMIDΒ 25635623.
- β 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): 1828β31. PMIDΒ 7892608.
- β Bose HS, Sugawara T, Strauss JF, Miller WL (1996). “The pathophysiology and genetics of congenital lipoid adrenal hyperplasia”. N. Engl. J. Med. 335 (25): 1870β8. doi:10.1056/NEJM199612193352503. PMIDΒ 8948562.
- β 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, GrΓΌters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, NuΓ±ez CJ, Servant N, Lumbroso S, Paris F, Sultan C (2011). “Phenotypical, biological, and molecular heterogeneity of 5Ξ±-reductase deficiency: an extensive international experience of 55 patients”. J. Clin. Endocrinol. Metab. 96 (2): 296β307. doi:10.1210/jc.2010-1024. PMIDΒ 21147889.
- β 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): 86β91. doi:10.1210/jcem-71-1-86. PMIDΒ 2164530.
- β 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): 721β3. PMCΒ 1546244. PMIDΒ 999330.
- β Biglieri EG (1979). “Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome”. J. Steroid Biochem. 11 (1B): 653β7. PMIDΒ 226795.
- β Saenger P (1996). “Turner’s syndrome”. N. Engl. J. Med. 335 (23): 1749β54. doi:10.1056/NEJM199612053352307. PMIDΒ 8929268.
- β Bastian C, Muller JB, Lortat-Jacob S, Nihoul-FΓ©kΓ©tΓ© 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): 1297β304. doi:10.1016/j.fertnstert.2015.01.043. PMIDΒ 25813279.
- β 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): 1213β5. PMIDΒ 4432067.
- β Schnitzer JJ, Donahoe PK (2001). “Surgical treatment of congenital adrenal hyperplasia”. Endocrinol. Metab. Clin. North Am. 30 (1): 137β54. PMIDΒ 11344932.
- β 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): 1265β71. doi:10.1172/JCI119284. PMCΒ 507941. PMIDΒ 9077535.
- β 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): 481β93. PMIDΒ 3841304.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]