Extraadrenal Effects of Metyrapone in Man*

Levin, Joseph; Zumoff, Barnett; Fukushima, David K.

doi:10.1210/jcem-47-4-845

Cited by 14 publications

(5 citation statements)

References 14 publications

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“…The present fmdings on steroid excretion rates principally reflect the time course of plasma cortisol. An activating effect of metyrapone on 20-oxidoreductase, äs described by Levin et al (18), could not be confirmed by the present data.…”

Section: Discussioncontrasting

confidence: 88%

20-Dihydroisomers of Cortisol and Cortisone in Human Urine: Excretion Rates under Different Physiological Conditions

Eisenschmid¹,

Heilmann²,

Oelkers³

et al. 1987

Clinical Chemistry and Laboratory Medicine

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The urinary excretion rates of free cortisol and cortisone äs well äs of their 20-dihydroisomers have been studied in normal subjects under different physiological or pharmacological conditions. For the estimation of steroid excretion rates, a fully automated, liquid-chromatographic method was used.In normal subjects, the median steroid excretion rates of free cortisol, cortisone, 20-a-dihydrocortisol, 20-ß-dihydrocortisol, 20-a-dihydrocortisone and 20-ß-dihydrocortisone were 6.7, 8.0, 9.8, 5.2, 5.7 and 1.3 / mpl creatinine.The excretion rates measured at three different intervals of the day followed a circadian rhythm similar to that known for the cortisol secreting activity of the adrenal gland.After adrenal Stimulation by i. v. application of 250 g of tetracosactide hexaacetate, (Synacthen®, corticotro-) excretion of urinary cortisol was sigiiificantly higher than those of the other steroids.During a 24 h infusion of corticotropiii^..^, the excretion rates of cortisol and its C-20 reduced isomers increased to a significantly greater extent than those of cortisone and its C-20 reduced isomers.During a fourJiour infusion of hydrocortisone, the relative increase of cortisol excretion was greater than that of the other steroids.During a five-hour infusion of metyrapone at different dosages, the excretion of all steroids decreased in a ;dose-deperident manner.The present data indicate that the 20^dihydroisomers of cortisol and cortisone in human urine primarily originate from the peripheral metabolism of cortisol rather than from adrenal secretion. A partial secretion of the C-20-reduced isomers of cortisol by the adrenal gland and an Inhibition of 11-oxidoreductase by corticotropin^ >24 can not be excluded. A 24 h Stimulation by corticotropin^.24 is not sufficiently chronic to significantly induce the 20-oxidoreductase. -i J. Clin. Chem. Clin. Biochem. / Vol. 25,1987 / No. 6 JL Brought to you by | University of Manchester Authenticated Download Date | 5/25/15 10:43 PM346 Eisensohmid el al.: 20-Dihydroisomcrs of cortisol and cortisone in human urine

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Section: Discussioncontrasting

confidence: 88%

20-Dihydroisomers of Cortisol and Cortisone in Human Urine: Excretion Rates under Different Physiological Conditions

Eisenschmid¹,

Heilmann²,

Oelkers³

et al. 1987

Clinical Chemistry and Laboratory Medicine

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“…However, by the present data it cannot be ex¬ cluded that lowering of the sum of adrenal steroids at least partially is caused by a metyrapone induced acceleration of the metabolic clearance of plasma S and DOC as is the case for cortisol (Levin et al 1978).…”

Section: Discussioncontrasting

confidence: 61%

“…Acceler¬ ating effects of metyrapone on the metabolic clear¬ ance rate of adrenal steroids are known only for cortisol so far (Levin et al 1978). To our know¬ ledge, detailed data on the influence of metyra¬ pone on the metabolic behavior of other steroids are lacking.…”

Section: Discussionmentioning

confidence: 99%

Multiple-sites of inhibition by intravenous metyrapone of human adrenal steroidogenesis

Schöneshöfer¹,

Claus²

1985

Acta Endocrinologica

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“…Metyrapone has also demonstrated extra-adrenal effects by influencing peripheral glucocorticoid metabolism [46], that contribute to the reduction of plasma cortisol levels [47,48]. Following oral administration of metyrapone (40mg/kg) in healthy volunteers, the levels of cortisol begin to decrease within 15-30 min, with maximal reduction in cortisol levels obtained in ≈ 2 h and maintained for ≈ 7 h post-dose [49];…”

Section: How Does Metyrapone Work In Cushing's Syndrome?mentioning

confidence: 99%

“…b Median daily dose of 750 mg (3 capsules) at days 14, 31, 65 and 82; and 1000 mg (4 capsules) at day48 …”

mentioning

confidence: 99%

Metyrapone in Cushing’s syndrome: a profile of its use

Al-Salama

2021

Drugs Ther Perspect

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Metyrapone (Metopirone ® ), a pyridine derivative, is a useful treatment option for the management of patients with endogenous Cushing's syndrome, based on evidence from more than six decades of its use in clinical practice, prospective and retrospective studies, as well as case reports. Metyrapone is associated with a rapid onset of action and is effective in reducing cortisol levels and improving clinical and/or biochemical features and cortisol-related comorbidities of Cushing's syndrome. The efficacy of metyrapone was demonstrated in all aetiologies of the condition, when used in a range of clinical settings (including presurgery treatment and when used in combination with other drugs) and in the short and long term. Metyrapone is generally well tolerated when used in the treatment of patients with endogenous Cushing's syndrome, with gastrointestinal adverse events being the most commonly reported. Plain Language SummaryEndogenous Cushing's syndrome is a rare disease, resulting from cortisol hypersecretion, and is associated with substantial morbidity and mortality. Surgery is the mainstay treatment for the majority of patients with Cushing's syndrome; however, medical therapy is increasingly being used, particularly when surgery is not indicated or is unsuccessful, or while waiting for radiotherapy to be effective. Oral metyrapone (Metopirone ® ), a pyridine derivative, is approved for the management of endogenous Cushing's syndrome in the EU. Evidence for the efficacy of metyrapone in the treatment of Cushing's syndrome has been demonstrated in prospective and retrospective studies. Metyrapone has a rapid onset of action (≈ 2 h), reduces cortisol levels, improves the clinical and/or biochemical features and cortisol-related comorbidities of the disease, and demonstrates sustained efficacy in the long term; the efficacy of metyrapone is evident in a range of clinical settings. Metyrapone is generally well tolerated in patients with endogenous Cushing's syndrome. Given its efficacy and tolerability profile, metyrapone is a useful treatment option for the management of patients with endogenous Cushing's syndrome.

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Extraadrenal Effects of Metyrapone in Man*

Cited by 14 publications

References 14 publications

20-Dihydroisomers of Cortisol and Cortisone in Human Urine: Excretion Rates under Different Physiological Conditions

20-Dihydroisomers of Cortisol and Cortisone in Human Urine: Excretion Rates under Different Physiological Conditions

Multiple-sites of inhibition by intravenous metyrapone of human adrenal steroidogenesis

Metyrapone in Cushing’s syndrome: a profile of its use

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