URINARY STEROID HORMONE METABOLITES IN PATIENTS WITH PORPHYRIAS

Christakoudi S, Taylor Nf, Deacon Ac, Peters Tj

 

King's College, London, UK

 

 

Patients with acute intermittent porphyria (AIP) but not those with porphyria cutanea tarda (PCT) are reported to show predominance in urine of 5β-reduced androgen metabolites compared to the 5α-epimers. Steroids of 5β-androstane and pregnane types induce δ-aminolevulinic acid synthase in vitro, so altered 5-reduction may predispose to acute porphyric attacks. Urinary metabolites of both androgens and cortisol were quantified by gas-liquid chromatography and the urinary porphyrin and porphyrin precursor levels by spectrophotometry in 33 patients with AIP, 26 with PCT and in six with benign prostatic hyperplasia treated with the 5α-reductase inhibitor Finasteride. Ratios of 5β/5α reduced steroids for both androgen and cortisol metabolites showed increase vs. controls in both patient groups but that for androgens was only significant in males. In Finasteride-treated patients, a marked decrease of 5α-reduced metabolites was not accompanied by changes in porphyrin and porphyrin precursor levels. Apparent alterations in 11β-hydroxysteroid dehydrogenase activity were explained by the very diminished excretion of 5α-reduced metabolites. No changes in this activity were seen in acute porphyrics, but PCT patients had lower total cortisol metabolites. 5β-reduction predominates in both AIP and PCT. The 5β/5α ratio is more sensitively indicated by the cortisol than the androgen metabolite ratio.