17 alpha-hydroxylase deficiency pathophysiology
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17 alpha-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene CYP17A1, which encodes for the enzyme 17 alpha-hydroxylase and 17,20-lyase. 17 alpha-hydroxylase deficiency is transmitted in an autosomal recessive pattern. Mineralocorticoid excess and lack of androgens are two main features in this disease.
- CYP17A1 gene defects can cause two type of enzyme deficiencies: 17α-hydroxylase enzyme deficiency and 17,20-lyase deficiency. The dual activities mediate key transformations in cortisol and sex steroid synthesis:
- Mineralocorticoid excess is the major clinical clue distinguishing the 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids.
- In 17 alpha-hydroxylase deficiency, steroid biosynthesis will be limited to progesterone, 11-deoxycorticosterone (DOC), and corticosterone.
- 11-deoxycorticosterone (DOC) binds to the mineralocorticoid receptor and its excess amounts in 17 alpha-hydroxylase deficiency causes aldosterone effects such as volume expansion, hypertension, and hypokalemia. Also, 11-deoxycorticosterone (DOC) effects will suppress renin and aldosterone production.
- The most important features of 17 alpha-hydroxylase deficiency include hypertension, hypokalemia and sexual infantilism.
- 17 alpha-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.
- 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
In 17 alpha-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
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