Diagnosis of 5a-reductase deficiency.
Patients presenting with 46 XY karyotype and female or ambiguous genitalia may lack the enzyme testosterone 5a-reductase. This enzyme activity is required for full masculinization of the external genitalia during intrauterine life. At puberty, virilization of affected subjects (often brought up as girls) may occur. 5a-Reductase deficiency can be diagnosed after puberty by measurement of testosterone and 5a-dihydrotestosterone (5a-DHT) concentrations in the same serum sample. Before puberty stimulation of androgen production with human chorionic gonadotrophin (hCG) is usually required to achieve androgen concentrations which can be measured with the precision necessary for accurate diagnosis.
Test combined with hCG stimulation.*
- Day 1 09.00h: Take blood (5 mL) into plain tube for (baseline) testosterone and 5a-DHT assay. 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 (5 mL) into a plain tube for testosterone and 5a-DHT measurements.
* 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.
Send serum samples (2 mL) to the SAS laboratory. Request the assay of testosterone and 5a-DHT.
Serum concentrations of testosterone and 5a-DHT are very variable within the first 6 months of life and through puberty. Baseline values may be at the limit of sensitivity and the testosterone/5a-DHT ratio may be difficult to establish with confidence. In pre-pubertal patients values should be assessed before and after treatment with hCG.
Testosterone/5a-Dihydrotestosterone ratio following a stimulation test:
Less than 6 months of age: <17 >14
Less than 6 months of age (after hCG): <10 >20
6 months – puberty: <20 <20
6 months – puberty (after hCG): <27 >27
Adult males: <17 >25
Adult males (after hCG): <17 >20
The SAS laboratory will undertake assay of both testosterone and dihydrotestosterone in order to be able to advise on the interpretation of the testosterone/5a-DHT ratio.
Centres offering this assay
Pang S, Levine LS, Chow D et al. Dihydrotestosterone and its relationship to testosterone in infancy and childhood. J Clin Endocrinol Metab 1979; 48: 821-826.
Wilson JD, Griffin JE, George JW, Lestin M. The role of gonadal steroids in sexual differentiation. Rec Progr Hormone Res 1981; 37: