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congenital adrenal hyperplasia (21-hydroxylase deficiency)
Adrenal hyperplasia syndromes are examples of mixed hypo- & hyperadrenocorticism.
Etiology:
-> deficient activity of one of the following is associated with various subtypes:
1) p450c21 (21-hydroxylase), CYP21A2 (type 3), CYP21
2) p450c11 (11-beta-hydroxylase), CYP11B1
3) p450c17 (17-hydroxylase/17,20-lyase), CYP17A1
4) p450scc (cholesterol desmolase)
5) 3-beta-hydroxysteroid dehydrogenase
6) cyt P450 reductase deficiency results in apparent combined P450C17 & P450C21 deficiency
Pathology:
1) synthesis of cortisol or aldosterone or both are disrupted
2) inadequate production of glucocorticoids leads to further stimulation by ACTH from the pituitary resulting in large adrenal glands with characteristic cerebriform appearance
3) over-production of cortisol precursors
4) androgen excess
5) microscopic pathology: cortical cells are lipid depleted
Genetics:
- associated with defects in CYP21 gene
- implicated genes: TNXB
Clinical manifestations:
1) abnormal sexual development
- ambiguous genitalia in affected females
- hypertrophy of the clitoris & labia majora [3]
- presence of a urogenital sinus [3]
2) rapid somatic growth during childhood in both sexes with premature closure of the epiphyses & short adult stature
3) salt wasting
4) hypertension (may be absent) [3]
5) acute adrenal insufficiency
6) signs of androgen excess (virilization)
7) sinus tachycardia (case report of 179 beats/min in neoate) [3]
7) four clinical types:
a) 'salt wasting' (SW, the most severe type)
b) 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis
c) 'non-classic form' or late onset (NC or LOAH)
d) '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
Specific
adrenal hyperplasia 1; congenital lipoid adrenal hyperplasia (CLAH)
adrenal hyperplasia type 2
adrenal hyperplasia type 5
General
adrenal cortical hyperplasia; hyperadrenocorticism
gonadal disorder
lipid metabolism, inborn error; lipid storage disease; lipidosis
Database Correlations
OMIM correlations
References
- Diagnostic Surgical Pathology. Sternberg ed.
Lippincott, Williams & Wilkins, 3rd ed. 1999
- ARUP Consult: Congenital Adrenal Hyperplasia - CAH
The Physician's Guide to Laboratory Test Selection & Interpretation
https://www.arupconsult.com/content/congenital-adrenal-hyperplasia
- Ko PJ,Yeh ML
Congenital Adrenal Hyperplasia.
N Engl J Med 2015; 372:e32. June 11, 2015
PMID: 26061858
http://www.nejm.org/doi/full/10.1056/NEJMicm1403201