Qualitative Alterations in Urinary 17-Ketosteroid Excretion During Aminoglutethimide Administration

Horký, K; Kuchel, O; Gregorvá, I; Stárka, L.

doi:10.1210/jcem-29-2-297

Cited by 20 publications

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“…"11 Nevertheless, controlled trials of corticoid therapy have shown little true antitumor effect.5 T h e non-steroidal adrenocortical inhibitor o,p,DDD induced one objective response among eight patients treated, but androgen suppression was the only endocrine effect notec1. 10 .4minoglutetliiniide+* is derived from the hypnotic glutethimider*r from which it differs only by the presence of an amino group on the benzene ring ( Fig. 1).…”

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confidence: 99%

Preliminary trial of aminoglutethimide in breast cancer

Griffiths¹,

Hall²,

Saba³

et al. 1973

Cancer

103

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Adrenalectomy has been effective in the treatment of metastatic breast cancer, but many patients are poor operative risks. A medical ablation of adrenal function would have wider application. Aminoglutethimide blocks adrenal steroidogenesis high in the biosynthetic pathway. Nine patients with absent ovarian function and enlarging metastases received the drug in daily oral doses of 1.0 to 2.5 g. Corticosteroid replacement consisted of dexamethasone 0.75 mg daily and fludrocortisone acetate 0.1 mg every other day. Regression of osseous disease and disappearance of skin metastases were observed in three patients for 7, 9, and 2 months, respectively. Tumor growth ceased for 4 and 7 months in two patients. Suppression of urinary 17‐ketosteroids and 17‐hydroxycorticoids was only transient in eight patients, presumably because of compensatory increase in ACTH secretion. Estrogen secretion rates were similarly affected. The patient with a 9‐month remission on 2.5 g daily has demonstrated permanent hypoadrenocorticism. Dose‐related CNS toxicity, ranging from drowsiness to semi‐coma, predominated but relative hypoadrenocorticism may have contributed. Anticancer action may result from a peripheral effect of the drug or from suppression of an unidentified steroid. Concurrent pharmacologic doses of glucocorticoids may reduce toxicity and inhibit compensatory ACTH secretion.

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confidence: 99%

Preliminary trial of aminoglutethimide in breast cancer

Griffiths¹,

Hall²,

Saba³

et al. 1973

Cancer

103

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“…Epinephrine, however, stimulates salt and water absorption in the intestine (14,31), and, therefore would be expected to cause an effect opposite of that observed. (d) AG, like the closely related sedative glutethimide, can cause hyperplasia of hepatic smooth endoplasmic reticulum after chronic administration (32), causing accelerated metabolism of glucocorticoids (13), androgens (33), and aminoglutethimide itself (34 (27). cyclic nucleotide in rabbits treated with either NIP or AG, and this may account for the differences between our study and these prior in vitro observations in the rat.…”

Section: Discussionmentioning

confidence: 99%

Physiologic and Pharmacologic Effects of Glucocorticoids on Ion Transport across Rabbit Ileal Mucosa In Vitro

Sellin¹,

Field²

1981

J. Clin. Invest.

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“…(2) In earlier studies, where individual 17-ketosteroids under AG-treatment were determined with colorimetric methods, it has been stated that, while the Porter-Silber chromogens decrease markedly, the 17-ketosteroids may remain unchanged or may even increase paradoxically (Horky et al, 1969). We cannot confirm this observation from our gas chromatographic analysis, but we found a marked reduction of the sum of the individual 17-ketosteroids under AG in all cases from 13.8 k 3.2 mg/24 h t o values below 0.04 mg/24 h after 1-3 months.…”

Section: Discussionmentioning

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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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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Qualitative Alterations in Urinary 17-Ketosteroid Excretion During Aminoglutethimide Administration

Cited by 20 publications

References 0 publications

Preliminary trial of aminoglutethimide in breast cancer

Preliminary trial of aminoglutethimide in breast cancer

Physiologic and Pharmacologic Effects of Glucocorticoids on Ion Transport across Rabbit Ileal Mucosa In Vitro

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

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