congenital adrenal hyperplasia (21-hydroxylase deficiency)
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Introduction
Adrenal hyperplasia syndromes are examples of mixed hypo- & hyperadrenocorticism.
Etiology
- deficient activity of one of the following is associated with various subtypes:
- p450c21 (21-hydroxylase), CYP21A2 (type 3), CYP21
- p450c11 (11-beta-hydroxylase), CYP11B1
- p450c17 (17-hydroxylase/17,20-lyase), CYP17A1
- p450scc (cholesterol desmolase)
- 3-beta-hydroxysteroid dehydrogenase
- cyt P450 reductase deficiency results in apparent combined P450C17 & P450C21 deficiency
Pathology
- synthesis of cortisol or aldosterone or both are disrupted
- inadequate production of glucocorticoids leads to further stimulation by ACTH from the pituitary resulting in large adrenal glands with characteristic cerebriform appearance
- over-production of cortisol precursors
- androgen excess
- microscopic pathology: cortical cells are lipid depleted
Genetics
Clinical manifestations
- abnormal sexual development
- ambiguous genitalia in affected females
- hypertrophy of the clitoris & labia majora[3]
- presence of a urogenital sinus[3]
- rapid somatic growth during childhood in both sexes with premature closure of the epiphyses & short adult stature
- salt wasting
- hypertension (may be absent)[3]
- acute adrenal insufficiency
- signs of androgen excess (virilization)
- sinus tachycardia (case report of 179 beats/min in neoate)[3]
- four clinical types:
- 'salt wasting' (SW, the most severe type)
- 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis
- 'non-classic form' or late onset (NC or LOAH)
- 'cryptic' (asymptomatic)
Laboratory
- CYP21 genotyping
- serum potassium high (case report of 7.4 mmol/L)[3]
- serum sodium low (case report of 125 mmol/L[3]
- serum 17-hydroxyprogesterone level high (case report of 196.0 ug/L {reference interval 0.5-.4 ug/L}[3]
- serum testosterone high (case report of 15.0 ng/L (reference interval 0.1- 0.8 ng/mL in neonate)[3]
- karytyping (46 XX females)[3]
- see ARUP consult[2]
Radiology
- ultrasonography of the abdomen: bilateral adrenal hypertrophy without visible testes (case report[3])
Differential diagnosis
- hypospadias with cryptorchidism in males
Management
- see adrenal insufficiency
- management of electrolyte abnormalities, intravenous fluids, & glucocorticoid & mineralocorticoid replacement
- surgical reconstruction
More general terms
- adrenal cortical hyperplasia; hyperadrenocorticism
- gonadal disorder
- lipid metabolism, inborn error; lipid storage disease; lipidosis
More specific terms
- adrenal hyperplasia 1; congenital lipoid adrenal hyperplasia (CLAH)
- adrenal hyperplasia type 2
- adrenal hyperplasia type 5
References
- ↑ Diagnostic Surgical Pathology. Sternberg ed. Lippincott, Williams & Wilkins, 3rd ed. 1999
- ↑ 2.0 2.1 ARUP Consult: Congenital Adrenal Hyperplasia - CAH The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/congenital-adrenal-hyperplasia
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 Ko PJ,Yeh ML Congenital Adrenal Hyperplasia. N Engl J Med 2015; 372:e32. June 11, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26061858 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMicm1403201
Patient information
congenital adrenal hyperplasia patient information