11β-hydroxylase deficiency overview
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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
- ↑ 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.
- ↑ 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.