Suppression of tumorous adrenal hyperfunction by aminoglutethimide

Smilo, Renata P.; Earll, Jerry M.; Forsham, Peter H.

doi:10.1016/0026-0495(67)90048-0

Cited by 28 publications

(9 citation statements)

References 7 publications

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“…Our results concerning the total cortisol metabolites and free cortisol are similar to the observations made with steroid group determinations (Smilo et al, 1967;Fishman et al, 1967;Cash et al, 1967). They confirm that in ACTHdependent cases of CS, where the feedback system is at least partially intact (suppressibility with high doses of dexamethasone), the effectiveness of AG is only of short duration.…”

Section: Discussionsupporting

confidence: 89%

“…Among these drugs, AG has been evaluated most extensively (Philbert et al, 1966;Cash et al, 1967;Dexter et al, 1967;Fishman et al, 1967;Schteingart & Conn, 1967;Smilo et al, 1967;Horky et al, 1968;ThCvenet et al, 1968;Boyer et a/., 1973;Motlik et al, 1973). In general, good temporary results were obtained, but in hypothalamus-or pituitarydependent cases of CS, rising ACTH-levels with continued treatment induced a reboundphenomenon.…”

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confidence: 99%

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Effect of Aminoglutethimide on Urinary Cortisol and Cortisol Metabolites in Adolescents With Cushing's Syndrome

Zachmann

Gitzelmann

Zagalak

et al. 1977

Clinical Endocrinology

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The effect of aminoglutethimide (AG) 4 X 250 mg (670 mg/m2 daily by mouth) on the excretion of the free cortisol (radio-immunoassay) and of its metabolites THE, THF-allo THF, cortolone and beta-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-beta-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 metabolites; (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 5beta-reductase and/or 3alpha-dehydrogenase, possibly stimulation of 20alpha- and 20beta-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.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Effect of Aminoglutethimide on Urinary Cortisol and Cortisol Metabolites in Adolescents With Cushing's Syndrome

Zachmann

Gitzelmann

Zagalak

et al. 1977

Clinical Endocrinology

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“…Also the aminoglutethimide, as well as exerting a prompt adrenal blocking effect, decreased the rate of cortisol turnover which was not observed with op'-DDD. Similar therapeutic results have subsequently been described by Philbert et al (1966); Smilo, Earll & Forsham, (1967);Horky et al (1968) and Bochner et al (1969). The latter authors have carefully compared the effects of aminoglutethimide and op'-DDD.…”

Section: Peripheral Metabolism Of Steroidssupporting

confidence: 65%

“…In contrast to the cases with adrenal neoplasm, those with bilateral adrenal hyperplasia have responded less well to aminoglutethimide, presumably as a result of compensatory increases in ACTH secretion (Smilo et al 1967). , measuring plasma ACTH in normal subjects on aminoglutethimide found a consistent rise in plasma ACTH values.…”

Section: Peripheral Metabolism Of Steroidsmentioning

confidence: 99%

Aminoglutethimide: a ‘side-effect’ turned to therapeutic advantage

Hughes¹,

Burley²

1970

Postgraduate Medical Journal

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SummaryAminoglutethimide was introduced as an anticonvulsant drug in the U.S. A. in 1960. The occurrence of a number of side-effects, including several endocrine effects such as goitrogenesis, sexual precocity and virilization, led to its withdrawal.Further investigation indicated that the drug inhibited adrenal biosynthesis, particularly of aldosterone, cortisol and androgens, probably by interfering with the conversion of cholesterol to delta-5-pregnenolone.Aminoglutethimide has also been shown to modify the extra-adrenal metabolism of cortisol.The possible clinical applications of these 'sideeffects' are discussed.

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“…Recommended daily doses range from 0.5 to 2 g [154][155][156][157][158][159]. The agent is begun at a dose of 500 mg daily, in divided doses, and can be increased by 250 to 500 mg every three to four days.…”

Section: Aminoglutethimide Pharmacological Propertiesmentioning

confidence: 99%