107: Effect of aminoglutethimide (AG) on urinary cortisol and metabolites in patients with Cushing's syndrome (CS)

Abstract

The effect of AG (4×250 mg, 670 mg/m² daily) on the excretion of cortisol (RIA) and its metabolites (gas chromatography on capillary column) was studied monthly during 2 to 5 months in 4 patients with CS not due to an adenoma. Basal cortisol metabolites were moderately (total 10.9 ± 1.3 (SEM), THE 5.2 ± 0.8, THF-alloTHF 3.5 ± 0.6, cortolone 1.5 ± 0.5, β-cortolone 0.7 ± 0.2 mg/m²/day) and free cortisol was markedly (803 ± 282 μg/m²/day) increased. Under AG, all compounds were reduced (minimum total 1.45 ± 0.7, THE 0.73 ±0.3, THF-alloTHF 0.41 ± 0.3, cortolone 0.13 ±0.05, β-cortolone 0.07 ± 0.06 mg/m²/day, free cortisol 267 ± 38 μg/m²/day) and a non-steroidal peak appeared on the chromatogram. The reduction was most significant for the total metabolites (p<0.001), followed by THE, THF-alloTHF (<0.01), cortolone and β-cortolone (< 0.05) but not significant for free cortisol. With continued Treatment, a rebound was noted after 3 to 5 months (total 4.62 ± 1.6, THE 2.82 ± 0.2, THF-alloTHF 2.45 ± 0.8, cortolone 0.63 ± 0.02, β-cortolone 0.28 ± 0.05). It is concluded that 1) AG reduces cortisol synthesis in man only temporarily as in animals, 2) paradoxic steroid increments in the early phase of treatment as reported from colorimetric analysis are non-specific, and 3) AG possibly modifies steroid catabolizing liver enzymes (inhibition of 5β-reductase and stimulation of 20α- and 20β-dehydrogenase).

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