Clinical Utility of Urinary Steroid Metabolite Ratios in Children Undergoing Investigations for Suspected Disorders of Steroid Synthesis

Background: Calculation of a urinary steroid metabolite ratio (uSMR) may be a useful method of improving diagnostic yield when investigating disorders of steroid hormone synthesis. Our aim was to investigate the range of uSMR in children with suspected disorders of steroid hormone synthesis. Methods: Ten ratios were calculated on steroid metabolite data analysed by GC-MS in urine samples collected between 2008 and 2010 from 94 children who were undergoing investigations. To obtain reference data, urine samples were also analysed in 252 children with no background of endocrine concerns. Results: Of the 94 cases, 38 (40%) were male and the median age at the time of the test was 6.5 years (range 1 day–18 years). The most common indication for urinary steroid analysis was to investigate early puberty (22%). Of the 252 controls, 115 (46%) were male and the median age at the time of the test was 10 years (range 1 month–18 years). 40 (43%) had at least one ratio >2SDS above the mean for the reference range. The number of ratios per case which were >2SDS ranged from 1 to 6 (median 0). A high THS/(THE+THF+5αTHF) was the most commonly abnormal ratio and found to be >2SDS in 18 cases. A total of 9/94 (10%) cases were diagnosed with a steroid hormone disorder (true positives); 4 (44%) with 21-hydroxylase deficiency, 2 (22%) with 11β-hydroxylase CAH, 2 (22%) with 5α-reductase deficiency and 1 (11%) with Cushings disease. All except one of these patients had at least 1 ratio >2SDS. The case with the normal steroid hormone ratios was later diagnosed with 5α-reductase deficiency. Conclusions: Abnormal urinary steroid metabolite ratios are commonly encountered in children undergoing investigations for disorders of steroid synthesis. On the other hand, the use of ratios may not identify all disorders of steroid synthesis, especially 5α-reductase deficiency.