Late onset congenital adrenal hyperplasia masquerading as subclinical Cushings syndrome
V Loh1, B Krishnan1, M Prentice2, A Panahloo1 & L Seal1
A 54-year-old AfroCarribean woman developed worsening obesity, hypertension, and proximal muscle weakness. Clinical examination revealed cushingoid facies, truncal obesity (BMI 34.8), abdominal striae and a BP of 150/90, FerrimanGallway score 12.
Investigations:- FBG 10.7 mmol/l, 24 urine cortisols 147 mmol/l, 207 mmol/l (NR 25280 nmol/24 h), normal short synacthen test (cortisol 471 rising to 1002 nmol/l). Subsequent testing revealed a normal overnight 1 mg dexamethasone suppression test (0900 a.m. cortisol <50 nmol/l), TSH 1.83 mu/l, LH 22.3 u/l, 25.1 u/l, prolactin 273 mu/l, testosterone 2.3 nmol/l, ACTH 117 ng/l (1050), 17-OH progesterone 3.0 nmol/l (110), 24 urinary sex steroid collection borderline androsterone 22 (116), 24 urine metanephrines normal.
Abdominal CT scanning demonstrated symmetrical bilateral micronodular adrenal hyperplasia. A pituitary MRI did not reveal any obvious adenoma.
Subsequent investigations 5 months later:- Testosterone 3.5 nmol/l, 24 urinary cortisol was high at 349 nmol. Low dose dexamethasone suppression test cortisol 361 suppressing to 9 nmol/l after 72 h, but with CRH testing at the same time, ACTH increased from 35 to 40. Testosterone was elevated at 3.31 nmol/l. A short synacthen test confirmed normal cortisol response to synacthen 250 mcg (480 mmol/l1207 nmol/l at 60 min) but an exaggerated 17-OH Progesterone response, (3.634.8 nmol/l after 60 min) consistent with a diagnosis of late-onset 21-hydroxlase deficiency. Genetic testing did not reveal a common mutation to the CYP-21 gene. Treatment has been commenced with dexamethasone suppression.
This case demonstrates that CAH is an important differential diagnosis in the assessment of Cushings syndrome. We postulate that the altered steroidogenesis mechanisms in the adrenals as a response to ACTH is responsible for the clinical features of hypercortisolaemia and this may be ACTH dependent. Also synacthen testing may be warranted even if baseline 17OH-progesterone is normal.