The pitfalls associated with urinary steroid metabolite ratios in children undergoing investigations for suspected disorders of steroid synthesis

BACKGROUND: Urinary steroid metabolite ratios may improve the diagnostic yield of potential disorders of steroid hormone synthesis. OBJECTIVES: To investigate the range of ratios and their predictive value in children with suspected disorders of steroid synthesis. DESIGN AND METHODS: Twelve ratios were calculated on steroid metabolite data analysed by gas chromatography–mass spectrometry in urine samples collected between 2008–2010 from 93 children. Urine samples were also analysed in 252 children with no known endocrine concerns. RESULTS: Of the 252 controls, 115 (46%) were male with a median age of 10 yr (range 1 month,18.5 years). Of the 93 cases, 38 (41%) were male with a median age of 6.5 yr (1 day,18.5 yrs). Of these, 41 (44%) had at least one ratio greater than the 95% percentile for controls. The most frequently abnormal ratio, found in 18/93 (19%) cases was (THS/(THE + THF + 5αTHF)) suggestive of 11β-hydroxylase deficiency. Over this period, 8 (9%) children were subsequently diagnosed with a steroid hormone disorder; 4 with 21-hydroxylase deficiency, 2 with11β-hydroxylase deficiency and 2 with 5α-reductase deficiency. All except one of these children had at least 1 raised ratio. CONCLUSIONS: Urinary steroid metabolite ratios in suspected disorders of hormone synthesis often exceed the reference range for normal children. The predictive value of steroid metabolite ratios in identifying a genetic abnormality may be condition specific and needs further study to improve its clinical utility.