11β-hydroxylase deficiency pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
11β-Hydroxylase deficiency is a type of congenital adrenal hyperplasia resulting from a defect in CYP11B1 on chromosome 8. CYP11B1 gene encodes an enzyme called 11β-hydroxylase in the path of steroid biosynthesis. This enzyme is located in the zona fasciculate, and converts 11-deoxycortisol to cortisol and 11-deoxycorticosterone. Lack of 11β-hydroxylase enzyme in different amounts results in accumulation of 11-deoxycortisol, and decrease amounts of cortisol and 11-deoxycorticosterone. There is an elevation of adrenocorticotropic hormone results in overproduction of 11-deoxycorticosterone (DOC) by mid-childhood. 11-deoxycorticosterone is a weak mineralocorticoid, but because of high amounts in this disease can cause mineralocorticoid excess effects such as salt retention, volume expansion, and hypertension. Non-classic forms mostly doesn't have verifiable mutations and mild 11β-hydroxylase deficiency is currently considered a very rare cause of hirsutism and infertility.
Pathogenesis
- 11β-hydroxylase deficiency is a type of congenital adrenal hyperplasia resulting from a defect in CYP11B1 on chromosome 8.
- CYP11B1 gene encodes an enzyme called 11β-hydroxylase in the path of steroid biosynthesis. This enzyme is located in the zona fasciculata, and converts 11-deoxycortisol to cortisol and 11-deoxycorticosterone.
- Cortisol production reduction has a negative feedback on the pituitary and increases corticotropin (ACTH) secretion. This leads to of 11-deoxycortisol precursors and then adrenocortical hyperplasia.
- With intact amount of other pathways, as a result of high ACTH concentrations, some amount of the 11-deoxycortisol precursors are metabolized to adrenal androgens and can cause virilization in a genetically female fetus or a child of either sex.
- Severity of disease depends on the amount of functional 11β-hydroxylase enzyme that an individual produces.
- Aldosterone production is decreased in this disease but there is an elevation of adrenocorticotropic hormone results in overproduction of 11-deoxycorticosterone (DOC) by mid-childhood. 11-deoxycorticosterone is a weak mineralocorticoid, but because of high amounts in this disease can cause mineralocorticoid excess effects such as salt retention, volume expansion, and hypertension.
- Non-classic forms mostly doesn't have verifiable mutations and mild 11β-hydroxylase deficiency is currently considered a very rare cause of hirsutism and infertility.
Genetics
- 11β-hydroxylase deficiency is an inherited disease with an autosomal recessive pattern, which means both copies of the gene in each cell have gene mutations.
- Commonly, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
- Most CYP11B1 mutations correspond to minimal or absent enzyme activity, resulting in the classic 11β-hydroxylase deficiency phenotype.
- A non-classic form of enzyme deficiency caused by CYP11B1 mutations exists but is very rare.[2][3][4]
Associated Conditions
Gross Pathology
Gross pathology findings in patients with 11β-hydroxylase deficiency are:[5][6]
- Enlarged adrenal glands
- Wrinkled surface adrenal glands
- Cerebriform pattern adrenal glands (pathognomonic sign)
- Normal ultrasound appearances may also be seen
- Testicular masses may be identified representing adrenal rest tissue
Microscopic Pathology
In 11β-hydroxylase deficiency microscopic findings may include:
- Diffuse cortical hyperplasia with smaller cells
- The cell cytoplasm can be vacuolated, and often more basophilic
- Rare mitotic figures may be present
- The hyperplastic cells typically lack features of cellular atypia.[7]
References
- ↑ "File:Adrenal Steroids Pathways.svg - Wikimedia Commons".
- ↑ El-Maouche D, Arlt W, Merke DP (2017). "Congenital adrenal hyperplasia". Lancet. doi:10.1016/S0140-6736(17)31431-9. PMID 28576284.
- ↑ Zachmann M, Tassinari D, Prader A (1983). "Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients". J. Clin. Endocrinol. Metab. 56 (2): 222–9. doi:10.1210/jcem-56-2-222. PMID 6296182.
- ↑ Hannah-Shmouni F, Chen W, Merke DP (2017). "Genetics of Congenital Adrenal Hyperplasia". Endocrinol. Metab. Clin. North Am. 46 (2): 435–458. doi:10.1016/j.ecl.2017.01.008. PMID 28476231.
- ↑ Congenital adrenal hyperplasia. Dr Henry Knipe and Dr M Venkatesh . Radiopaedia.org 2015.http://radiopaedia.org/articles/congenital-adrenal-hyperplasia
- ↑ Teixeira SR, Elias PC, Andrade MT, Melo AF, Elias Junior J (2014). "The role of imaging in congenital adrenal hyperplasia". Arq Bras Endocrinol Metabol. 58 (7): 701–8. PMID 25372578.
- ↑ 7.0 7.1 7.2 "Adrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas".
