Clinical Use
1 Management of congenital adrenal hyperplasia due to 11b- or 21-hydroxylase deficiency.
2 Diagnosis of 17b-hydroxysteroid dehydrogenase deficiency.
Applications
1 Congenital adrenal hyperplasia.
Although androstenedione concentrations are increased in CAH due to an 11b- or 21-hydroxylase deficiency, 11-deoxycortisol and 17a-hydroxyprogesterone, respectively, are better diagnostic hormones. The measurement of androstenedione is particularly helpful in the management of such patients since suppression of the diagnostic steroids into the normal range is usually associated with symptoms of glucocorticoid excess. In addition, it is the androgens in particular which must be controlled to avoid virilisation.
2 17b-Hydroxysteroid dehydrogenase deficiency.
Male (46 XY) babies born with this enzyme deficiency have female or ambiguous genitalia. At puberty, marked virilization occurs. Early diagnosis and selection of gender for rearing are important. The condition is characterised by an increased serum concentration of androstenedione relative to that of testosterone. In infants, where androgen levels are normally low, androstenedione and testosterone should be measured after stimulation with human chorionic gonadotrophin (hCG).
Patient Preparation
1 Diagnosis and monitoring of congenital adrenal hyperplasia.
None. Take blood (2 mL). It is advisable to avoid stress.
2 Diagnosis of 17b-hydroxysteroid dehydrogenase deficiency.
For postpubertal children and adults, none. Take blood (2 mL).
For infants, stimulation with hCG is usually required to achieve serum androgen concentrations which can be measured with the precision necessary for accurate diagnosis.
Test combined with hCG stimulation. *
- *Day 1, 09.00h: Take blood (2 mL) into plain tube for (baseline) androstenedione and testosterone assays. Give hCG, (i.m., 1500 IU for infants, 3000 IU for adults);*Day 2, 09.00h: Give hCG (i.m., as above);*Day 3, 09.00h: Give hCG (i.m., as above);*Day 4, 09.00h: Take blood (2 mL) into plain tube for androstenedione and testosterone assays.
*Different protocols are used by different Centres. It is important to use the protocol of the Centre to which you send your samples, so that the Centre can interpret the results. Therefore contact the SAS Centre before carrying out this test.
Sample Preparation
Send serum samples (1 mL) to the SAS laboratory. Record on the SAS request form the time of sampling, details of any recent steroid therapy and, where appropriate, the time of hCG injection.
Reference Ranges
Adult males: 2-10 nmol/L;
Adult females: 3-12 nmol/L;
Prepubertal children: <3.5 nmol/L.
Androstenedione/testosterone ratio:
Unaffected males, all ages: <1.0;
Affected adults: >3.0;
Affected prepubertal children after hCG: >2.0.
Of particular diagnostic importance in 17b-hydroxysteroid dehydrogenase deficiency is an exaggerated rise in serum androstenedione concentration relative to the small increase in testosterone concentration in response to hCG. This is in marked contrast to the response in boys without the deficiency in whom testosterone concentrations increase much more than those of androstenedione.
In patients where 17b-hydroxysteroid dehydrogenase deficiency is suspected the SAS laboratory will undertake assay of both testosterone and androstenedione in order to advise on the interpretation of the androstenedione/testosterone ratio.
Centres offering this assay
Leeds General Infirmary Steroid Centre
References
Korth-Schutz et al. Serum androgens as a continuing index of adequacy of treatment of congenital adrenal hyperplasia. J Clin Endocrinol Metab 1978; 46: 452-458.
Rosler A. Steroid 17b-hydroxysteroid dehydrogenase deficiency in man: an inherited form of male pseudohermaphroditism. J Steroid Biochem Molec Biol 1992; 43: 989-1002.