11β-hydroxylase deficiency pathophysiology

Congenital adrenal hyperplasia main page
11β-hydroxylase deficiency Microchapters
Home
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating 11β-hydroxylase deficiency from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
11β-hydroxylase deficiency pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of 11β-hydroxylase deficiency pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on 11β-hydroxylase deficiency pathophysiology
CDC on 11β-hydroxylase deficiency pathophysiology
11β-hydroxylase deficiency pathophysiology in the news
Blogs on 11β-hydroxylase deficiency pathophysiology
Directions to Hospitals Treating Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
Risk calculators and risk factors for 11β-hydroxylase deficiency pathophysiology

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 fasciculate, 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.

Adrenal steroid synthesis pathways in adrenal cortex and related enzymes

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.

Associated Conditions

• Hirsutism
• Hypertension
• Testicular tumor

Gross Pathology

Gross pathology findings in patients with 11β-hydroxylase deficiency are:

• 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.

Adrenal gland, Cortex - Hyperplasia in a female rat from a chronic study. There is a hyperplastic lesion (H) in which cortical cells are increased in number but are smaller in size than adjacent normal cortical cells (NC)

Adrenal gland, Cortex - Hyperplasia in a male rat from a chronic study. There are two adjacent foci of hyperplasia (H) in the zona fasciculata.