Clinical Use
1 Diagnosis of, and monitoring therapeutic response in, congenital adrenal hyperplasia due to 11b-hydroxylase deficiency.
2 Assessment of adrenal response in the metyrapone test.
Applications
1 Congenital adrenal hyperplasia.
11-Deoxycortisol, the immediate precursor of cortisol, accumulates in the peripheral circulation when there is a deficiency of adrenal 11b-hydroxylase activity. The assay should be requested when congenital adrenal hyperplasia is suspected on clinical grounds, but serum 17a-hydroxyprogesterone values are equivocal (14 – 100 nmol/L).
2 Long metyrapone test.
In the differential diagnosis of Cushing’s syndrome, metyrapone is given to inhibit 11b-hydroxylation. Subsequent changes in serum concentrations of 11-deoxycortisol and cortisol provide strong (but not absolute) indicators of the site of the primary lesion.
3 Overnight metyrapone test.
This, by assessing the 11-deoxycortisol response to the metyrapone-induced decrease in cortisol, provides an assessment of pituitary response.
Patient Preparation
1 Diagnosis of congenital adrenal hyperplasia.
Take blood (5 mL) at 09.00h.
2 Long metyrapone test
The drug (750 mg orally 6-hourly for 2 days) is usually given combined with a snack to minimise epigastric discomfort. Glucocorticoid insufficiency may be precipitated, especially in patients with adrenal tumours. Take blood (5 mL) before administration of the first metyrapone dose (baseline sample) and 48h later.
3 Overnight metapyrone test
Metyrapone (30 mg/kg) is given orally with a snack at midnight. At 09.00h the next morning take 5 mL blood for the measurement of 11-deoxycortisol and cortisol.
Sample Preparation
1 Diagnosis of congenital adrenal hyperplasia.
Send serum (2 mL) to the SAS laboratory.
2 Long metyrapone test.
Send a portion (0.5 mL) of each serum sample to the local laboratory for measurement of cortisol. Send the remaining sample to the SAS laboratory. Record on the SAS request form the time of sampling and the serum cortisol concentration.
3 Overnight metyrapone test.
Send a portion (0.5 mL) of the serum sample to the local laboratory for the measurement of cortisol. Send the remaining sample to the SAS laboratory. Record on the SAS request form the time of sampling and the serum cortisol concentration.
Reference Ranges
1 Diagnosis of 11b-hydroxylase deficiency.
Unaffected adults (09.00h): 7-18 nmol/L;
Unaffected neonates (>48h after birth): <20 nmol/L;
Patients with untreated 11b-hydroxylase deficiency: >100 nmol/L.
2 Long metyrapone test.
(a) Serum 11-deoxycortisol concentration >300 nmol/L at 48h, associated with a normal serum cortisol concentration, is strongly suggestive of Cushing’s disease (pituitary lesion).
(b) Serum 11-deoxycortisol concentration <150 nmol/L at 48h, associated with a subnormal cortisol value, suggests an adrenal adenoma.
(c) Serum 11-deoxycortisol concentration >300 nmol/L at 48h, associated with subnormal or normal serum cortisol concentration, suggests that an ectopic source of ACTH exists. There is an overlap in the results of this test with those from patients with Cushing’s disease.
3 Overnight metyrapone test.
A normal response of 11-deoxycortisol is regarded as >200 nmol/L. For the test to be valid the corresponding cortisol concentration should be <200 nmol/L. A subnormal response is suggestive of inadequate pituitary/ adrenal function.
Centre offering this assay
Reference
Fiad TM, Kirby JM, Cunningham SK, McKenna TJ. The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis. Clin Endocrinol 1994; 40: 603-609.