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
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.
Differential Diagnosis
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 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 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 among 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 ambigous 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.
Echocardiography or 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 ambigous genitalia in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is surgical correction.
Prevention
Prenatal diagnosis of 11-beta-hydroxylase deficiency is conducted to prevent 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.