Like the other forms of CAH, suspicion of severe 3β-HSD CAH is usually raised by the appearance of the genitalia at birth or by development of a salt-wasting crisis in the first month of life. The diagnosis is usually confirmed by the distinctive pattern of adrenal steroids: elevated pregnenolone, 17-hydroxypregnenolone, DHEA, and renin. In clinical circumstances this form of CAH has sometimes been difficult to distinguish from the more common 21-hydroxylase deficient CAH because of the 17OHP elevation, or from simple premature adrenarche because of the DHEA elevation.
In cases of ambiguous genitalia it is important to obtain a karyotype. If the patient has hypertension, plasma renin activity and plasma aldosterone concentrations should be checked before considering steroid profile analysis.
A 24h urine collection with no preservative is ideal. Random samples may be acceptable for the identification of inborn errors of steroid metabolism.
Endogenous cortisol production cannot usefully be examined if hydrocortisone or cortisone acetate is being given. If glucocorticoid treatment is essential, dexamethasone is preferred since dexamethasone metabolites do not interfere in the assay. A depot Synacthen test can be used to assess adrenal function during dexamethasone treatment.
For diagnosis of the cause (other than 21-hydroxylase deficiency) of salt-loss in a neonate, salt intake and mineralocorticoid treatment should be reduced as much as possible.