Diagnostic ambiguity in classical CAH is unusual. We present two patients who were referred to us following longterm adrenal suppression in whom IV ACTH testing did not initially confirm the diagnosis. Pt#1 (7 y. o. F) was adopted at 4.5 y. Pregnancy was complicated by attempted termination using a synthetic progestin. Clitoromegaly at birth and dehydration at 10 d lead to a diagnosis of salt-losing 21-hydroxylase deficiency in Russia and she was treated with prednisone (2.5 mg b.i.d., 28 mg/M2 cortisol equiv.) and DOCA (3.5 mg q.d.). No laboratory data are available. At adoption, height was at -2.6 S.D. and weight was at 50th percentile for height. She was placed on 20 mg/M2 per day of cortisol (t.i.d. dosing) and 0.05 mg 9-alpha-fludrocortisone b.i.d. At 7 yr, height was at 15th%ile, but more than 6 morning 17OHP measurements were <5 ng/dL. Because of the Hx of progestin exposure, an IV bolus ACTH test was performed. At 60 min, cortisol was <1μg/dL and 17OHP was 9.4 ng/dL. One month after reduction in cortisol dose by 40%, repeat ACTH stim (17OHP 0= 380, 60 min = 456 ng/dL), confirmed neonatal diagnosis. Pt #2 (8 y.o. M) was diagnosed with CAH in Brazil at 4.5 y because of adrenarche, advanced bone age and one 17OHP of 800 ng/dL. He was treated with prednisone 2.5 mg b.i.d.(20 mg/M2 cortisol equiv.), but growth failure was noted. Several 17OHP levels were <10 ng/dL, and rose to 40 ng/dL 48 h off glucocorticoid. At 60 min after bolus IV ACTH (1-24), 17OHP was only 170 ng/dL. However, 17OHP with bolus IV ACTH (1-24) 12 h after ACTH gel IM X2 was 2140 ng/dL.

There is now a cohort of neonatally screened children with CAH who have been treated before they are symptomatic. Late confirmation of diagnosis in these children may require repeated ACTH stimulation, or prolonged observation after reduction in glucocorticoid dose.