Urine steroid profile in the diagnosis of partial androgen insensitivity – a case presentation

Abstract

Case presentation 36-year-old Eritrean immigrant with undescended inguinal testes and hypospadias during a routine health assessment. Biochemistry Total testosterone, DHT and SHBG were normal while LH, FSH and cortisol were elevated. Normal androgen receptor genetic studies excluded an androgen receptor defect. A defect in the androgen metabolic pathway was suspected. A urine steroid profile showed a very low androsterone, DHEA and high etiocholanolone, pregnenediol, pregenetriol, cortisone and cortisol. Low androsterone to etiocholanolone ratio suggests a defect in the 5 alpha reductase enzyme. Due to the block in the alpha pathway, metabolites undergo beta reduction leading to higher levels of etiocholanolone. Precursors also undergo 21 and 11 beta hydroxylase activity leading to high cortisol and cortisone. This diagnosis was confirmed by SRD5A2 gene analysis which demonstrated a homozygous mutation (c.682G > A), which has previously been reported in an Eritrean patient. Discussion The defect in 5 alpha reductase activity lead to the production of beta metabolites and the accumulation of precursors. This pattern is also seen with the use of 5 alpha reductase inhibitors (e.g., finesteride). In contrast to complete androgen insufficiency due to receptor defects, the effects of 5 alpha reductase deficiency are partial because testosterone as well as DHT bind to the androgen receptor. USP is a valuable and inexpensive tool in the diagnosis of steroid metabolic defects in patients with unusual presentations.