Introduction: In total of 5α-reductase 2 is vital in sexual development of male foetus; its deficiency causes impaired virilisation due to defective conversion of testosterone to dihydrotestosterone and is an important cause of Disorders of Sexual Development (DSD). We report 3 cases of severe primary acquired auto-immune hypothyroidism, which show a similar picture of 5α-reductase deficiency (5ARD) on urine steroid profile (USP) and reversible following adequate thyroxine replacement therapy.
Case Reports: Case 1: 13 year old boy with poor growth was finally diagnosed as primary hypothyroidism (TSH >100 mu/l; FT4 4 pmol/l). USP performed due to small penile size and lack of pubertal development showed 5ARD with hypothyroidism reversing when euthyroid, prompting USP review in subsequent cases.
Case 2: 11 year old girl with short stature was confirmed as auto-immune hypothyroidism (TSH >100 mu/l; FT4 0.9 pmol/l). USP showed 5ARD during untreated stage, which reversed completely on thyroxine replacement therapy.
Case 3: 11 year old boy with poor growth was diagnosed as profound hypothyroidism (TSH >100 mu/l; FT4 undetectable). USP showed 5ARD; awaiting repeat USP following treatment.
Results: In total of 3 patients with severe hypothyroidism showed 5ARD and normalisation of 5α reductase steroid markers with thyroxine replacement. The ratios of 5α/5β-reduced tetrahydrocortisol were 0.02, 0.08 and 0.10 in Case 1, 2 and 3 respectively (Normal: Mean 1.04; SD 0.89). Ratios for Case 2 after 2 & 4 months of treatment were 0.36 & 1.69. Ratios for the 5α/5β-reduced androstenedione metabolites were less abnormal, indicating a specific impairment of the 5α-reductase 2 isoform in hypothyroidism.
Conclusion: In total of 5α reductase-2 deficiency is a rare disorder leading to incomplete male genitalia development in patients with 46XY DSD. Untreated or undiagnosed hypothyroidism is a potential cause of reversible 5α reductase-2 deficiency. Altered steroid metabolism in hypothyroidism, if undetected may lead to erroneous results and interpretation of USP; thus excluding hypothyroidism in diagnostic work ups for DSD, especially patients with late presentations is extremely important.
Novel insight: We have demonstrated altered steroid metabolism in hypothyroidism a completely reversible picture of 5ARD with adequate thyroxine replacement therapy; if undetected, may lead to errors in interpreting USP results whilst investigating DSD.
23 - 25 Nov 2016
British Society for Paediatric Endocrinology and Diabetes