11β-hydroxylase deficiency pathophysiology

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.

• 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.

• 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]

• Hirsutism
• Hypertension
• Testicular tumor

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

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]