EFFECT OF AMINOGLUTETHIMIDE ON URINARY CORTISOL AND CORTISOL METABOLITES IN ADOLESCENTS WITH CUSHING'S SYNDROME

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Abstract
The effect of aminoglutethimide (AG) 4 × 250 mg (670 mg/m2 daily by mouth) on the excretion of free cortisol (radio‐immunoassay) and of its metabolites THE, THF‐alloTHF, cortolone and β‐cortolone (gas chromatography on capillary column) was studied monthly during 3 – 5 months in four adolescents (one girl, three boys) aged 15.9 – 18 years with Cushing's syndrome due to bilateral adrenal hyperplasia, but without evidence of a pituitary tumour. Under AG, all compounds decreased to a minimum after 1 – 2 months. The decrease of THE‐ THF‐allo THF was most marked, followed by cortolone‐β‐cortolone and free cortisol. The sum of the conjugated metabolites was normalized, but free cortisol remained high. A rebound was noted after 3 – 5 months of continued treatment. This was associated with clinical relapse (weight gain, increasing blood pressure). With AG, a non‐steroidal peak appeared on the chromatograms. It is concluded that: (1) AG is only temporarily effective in diminishing the excretion of cortisol and its metabolities; (2) paradoxical increments of 17‐ketosteroids as reported from colorimetric analysis are non‐specific and are probably due to the non‐steroidal peak; and (3) AG appears to modify steroid catabolizing liver enzymes (inhibition of 5β‐reductases and/or 3a‐dehydrogenase, possibly stimulation of 20a‐ and 20β‐dehydrogenases). This could increase the biological half‐life of cortisol and contribute to the clinical rebound, which is due to increased ACTH‐secretion. Because of its excellent short‐term effects, AG appears to be useful to prepare patients for bilateral adrenalectomy.