Endocrine Abstracts

Patients with acute intermittent porphyria (AIP) but not those with porphyria cutanea tarda (PCT) have a reported predominance in urine of 5 beta-reduced androgen metabolites over 5 alpha epimers. Steroids of 5 beta- androstane and pregnane types induce delta-aminolevulinic acid (ALA) synthase in chick embryos in vitro, so altered 5-reduction may predispose to attacks. We have comprehensively examined urine androgen and cortisol metabolites by gas-liquid chromatography and urine porphyrin and porphyrin precursor levels by spectrophotometry in 33 patients (7 males) with AIP, 26 (14 males) with PCT and 6 men treated with the 5 alpha-reductase inhibitor finasteride. Ratios of 5 beta/5 alpha reduced steroids for androgen metabolites were (Control, AIP, PCT, finasteride) for males, 0.85, 1.75 (p=0.001) 1.35 (p=0.015), 6.04 (p=<0.001) and for females, 1.22, 1.53 (p=0.594), 1.31 (p=1) Equivalent data for cortisol metabolites were for males, 1.14, 2.35 (p=0.047), 3.00 (p=<0.001), 24.86 (p=<0.001) and for females, 1.84, 3.49 (p=0.014), 4.16 (p=0.011). Androgen and cortisol metabolite ratios were positively correlated in these groups except AIP males. There was a positive correlation between cortisol metabolite ratios and ALA in AIP females; there were no other correlations between porphyrin and porphyrin precursor levels and steroid ratios in other groups. Finasteride treatment was not accompanied by changes in porphyrin and porphyrin precursor levels. There were apparent alterations in this group in 11 beta-hydroxysteroid dehydrogenase activity (as judged by 11-OH/11-oxo cortisol metabolites) but these could be explained by a very diminished excretion of 5 alpha reduced metabolites. No changes in this activity were seen in porphyrics but PCT patients had lower total cortisol metabolites. The ratio of 20-OH/20-oxo cortisol metabolites was unchanged in all patient groups. We conclude that 5 beta-reduction predominates in both AIP and PCT. The 5 beta/5 alpha ratio is more sensitively indicated by the cortisol than the androgen metabolite ratio.