11β-hydroxylase deficiency overview: Difference between revisions

Jump to navigation Jump to search
(No difference)

Revision as of 15:27, 19 July 2017

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Congenital adrenal hyperplasia due to 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 overview 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 overview

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 overview

CDC on 11β-hydroxylase deficiency overview

11β-hydroxylase deficiency overview in the news

Blogs on 11β-hydroxylase deficiency overview

Directions to Hospitals Treating Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Risk calculators and risk factors for 11β-hydroxylase deficiency overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Overview

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency arises due to a defect in the gene encoding the enzyme steroid 11β-hydroxylase which mediates the final step of cortisol synthesis in the adrenal. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency was first described by Dr. Walter Eberlein and Dr. Alfred M. Bongiovanni, American physicians, in 1956 based on the study they conducted on accumulated steroids. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may be classified according to clinical presentation into 2 subtypes: classic form and the non-classic form. Mutations in the CYP11B1 gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as adrenal crisis, conn syndrome, gastric outlet obstruction, congenital adrenal hyperplasia due to 17-hydroxylase deficiency, congenital adrenal hyperplasia due to 21-hydroxylase deficiency, hypertension, hypokalemia, hypomagnesemia, infertility, polycystic ovarian syndrome, malignant hypertension, Stein-Leventhal syndrome, and viral gastroenteritis. The prevalence of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is approximately 1 per 100,000 individuals the United States. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency affects male and female equally. The most potent risk factor in the development of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the presence of family history of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Prenatal screening for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency by injection a dose of 11-deoxycortisol into the amniotic fluid is recommended for patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. If left untreated, patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include muscle weakness, metabolic alkalosis, and azoospermia. Prognosis is generally good with treatment. On abdominal CT scan, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands. On abdominal MRI, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands. Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates hyperplasia, poorly defined zonation, and intermingling of the chromaffin and cortical cells. The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy. The predominant therapy for ambiguous genitalia in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the surgical correction.

Historical Perspective

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency was first described by Dr. Walter Eberlein and Dr. Alfred M. Bongiovanni, American physicians, in 1956 based on the study they conducted on accumulated steroids.[1] In 1999, White was the first to discover the association between homozygous mutation in the CYP11B1 gene and development of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.[2]

Classification

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may be classified according to clinical presentation into 2 subtypes: classic form and the non-classic form.

Pathophysiology

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency arises due to a defect in the gene encoding the enzyme steroid 11β-hydroxylase which mediates the final step of cortisol synthesis in the adrenal. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is transmitted in autosomal recessive pattern. On gross pathology, thickening of adrenal gland and cerebriform appearance are characteristic findings of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. On microscopic histopathological analysis, diffuse cortical hyperplasia and lipid-depleted cortical cells are characteristic findings of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Causes

Mutations in the CYP11B1 gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Differentiating Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency from other Diseases

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as adrenal crisis, conn syndrome, gastric outlet obstruction, congenital adrenal hyperplasia due to 17-hydroxylase deficiency, congenital adrenal hyperplasia due to 21-hydroxylase deficiency, hypertension, hypokalemia, hypomagnesemia, infertility, polycystic ovarian syndrome, malignant hypertension, Stein-Leventhal syndrome, and viral gastroenteritis.

Epidemiology and Demographics

The prevalence of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is approximately 1 per 100,000 individuals the United States. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency affects male and female equally. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency usually affects individuals of the Jewish race.

Risk Factors

The most potent risk factor in the development of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the presence of family history of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Screening

Prenatal screening for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency by injection a dose of 11-deoxycortisol into the amniotic fluid is recommended for patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Natural history, Complications and Prognosis

If left untreated, patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include muscle weakness, metabolic alkalosis, and azoospermia. Prognosis is generally good with treatment.

History and Symptoms

Symptoms of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include acne, oligomenorrhea, and aggressive behavior.

Physical Examination

Patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency usually appear healthy. Physical examination of patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is usually remarkable for gynaecomastia, hyperpigmentation, hypertension, and ambiguous genitalia.

Laboratory Findings

Laboratory findings consistent with the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include elevated 17α-hydroxyprogesterone, elevated androstenedione, elevated urinary 17-ketosteroids and decreased renin.

CT

On abdominal CT scan, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands.

MRI

On abdominal MRI, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands.

Ultrasound

Ultrasound may be helpful in the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Findings on ultrasound suggestive of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include testicular masses, adnexal structures, and gonadal abnormalities.

Other Imaging Findings

Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates hyperplasia, poorly defined zonation, and intermingling of the chromaffin and cortical cells.

Other Diagnostic Studies

Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates hyperplasia, poorly defined zonation, and intermingling of the chromaffin and cortical cells.

Medical Therapy

The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy.

Surgery

The predominant therapy for ambiguous genitalia in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the surgical correction.

Prevention

Prenatal diagnosis of 11-beta-hydroxylase deficiency is conducted to prevent the complication of the disease in future life and treated with prenatal dexamethasone treatment.

Reference

  1. BONGIOVANNI AM, EBERLEIN WR (1956). "Plasma and urinary corticosteroids in the hypertensive form of congenital adrenal hyperplasia". J Biol Chem. 223 (1): 85–94. PMID 13376579.
  2. White PC, Dupont J, New MI, Leiberman E, Hochberg Z, Rösler A (1991). "A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin". J Clin Invest. 87 (5): 1664–7. doi:10.1172/JCI115182. PMC 295260. PMID 2022736.