Metyrapone In Patients Research Articles

PREOPERATIVE TREATMENT WITH METYRAPONE IN PATIENTS WITH CUSHING'S SYNDROME DUE TO ADRENAL ADENOMA.

ObjectiveMetyrapone has been approved for the treatment of patients with Cushing’s syndrome (CS), but only few retrospective clinical studies are available. The aim of our study was the prospective assessment of metyrapone as pre-operative treatment.Design and methodsBefore adrenalectomy, seven patients with ACTH-independent CS due to adrenal adenoma were prospectively treated with metyrapone for 3 months in three tertiary academic centers, with endocrine work-up and clinical evaluation at screening and at predefined evaluation time points (Days 14, 31, 48, 65, 82).ResultsIn all patients, UFC levels decreased up to normal range from baseline to Day 82 (609 (188–1476) vs 69 (28–152) nmol/24 h, P < 0.02), with a reduction of serum and salivary cortisol levels, and no significant increase of plasma ACTH and serum DHEAS levels. Clinical improvement was reported on quality of life (+16.7 (+4.2; +52.00) points, P < 0.04) and pressure control (systolic pressure, −25 (−52; −10) mmHg, P < 0.01; diastolic pressure, −16 (−50; +2 mmHg), P < 0.03). No significant change in weight, electrolytes, glycemic and lipid profile was reported. Although in women a significant increase of testosterone and androstenedione was reported, no worsening of clinical hyperandrogenism was observed. All drug-related adverse events (nausea, fatigue, low grade fever, edema of lower limbs and facial rash) were grade 1 or 2 and generally transient.ConclusionsThis prospective pilot study demonstrated that metyrapone is effective in normalizing biochemical and clinical parameters in patients with CS due to adrenal adenoma before surgical intervention, with minimal side effects.

A polymorphism in the CYP17A1 gene influences the therapeutic response to steroidogenesis inhibitors in Cushing's syndrome.

Steroidogenesis inhibitors, such as ketoconazole (KTZ) and metyrapone (MTP), are used to lower hypercortisolism in patients with Cushing's syndrome (CS). Cortisol normalization is not reached in all patients taking these medications. To test the hypothesis that variants in genes affecting steroidogenesis contribute to different responses to KTZ and/or MTP in patients with CS. Fifty-four CS patients (46 women; mean [±SD] age, 39.7±12.7; 83% with Cushing's disease [CD] and 17% with an adrenal adenoma) preoperatively treated with KTZ (20%), MTP (37%) or a combination of both (43%). Thirty-nine of these (72%) were described in a previous study investigating the outcome of preoperative treatment with KTZ or MTP in CS patients. Following single-nucleotide polymorphisms (SNPs) were analysed: rs6410 (CYP11B1 gene), rs1799998 and rs4546 (CYP11B2 gene), and rs6163 (CYP17A1 gene). The associations between SNPs and cortisol levels at the end of medical treatment were evaluated. Normalization of urinary free cortisol (UFC) was achieved in 50% of patients after 5months of treatment. Patients carrying the CC genotype of SNP rs6163 were more likely to be controlled than AC/AA (OR 0.25 [95%CI, 0.075-0.88]; P=.031). When only patients reaching eucortisolism after medical treatment were analysed, median interquartile range (IQR) duration of treatment was shorter in patients carrying the CC genotype of SNP rs6163 as compared to AA/AC carriers (4 [4.57]months vs 5.2 [6.1]months; P=.026). A polymorphism in the CYP17A1 gene was associated with the response to steroidogenesis inhibitors in CS. Genetic differences in the steroidogenic enzymes might account for inter-individual variations in the responsiveness to adrenal-blocking agents.

Restoring the circadian cortisol rhythm with metyrapone in patients with adrenal incidentalomas and subclinical hypercortisolism reduces IL6 levels

Restoring the circadian cortisol rhythm with metyrapone in patients with adrenal incidentalomas and subclinical hypercortisolism reduces IL6 levels

P.1.065 Effect of combined treatment with imipramine and metyrapone in patients with drug-resistant ular depression - clinical and pharmacokinetic studies

P.1.065 Effect of combined treatment with imipramine and metyrapone in patients with drug-resistant ular depression - clinical and pharmacokinetic studies

Plasma corticotropin and cortisol responses to ovine corticotropin- releasing hormone (CRH), arginine vasopressin (AVP), CRH plus AVP, and CRH plus metyrapone in patients with Cushing's disease

Plasma corticotropin and cortisol responses to ovine corticotropin- releasing hormone (CRH), arginine vasopressin (AVP), CRH plus AVP, and CRH plus metyrapone in patients with Cushing's disease

Part 2. Response of Corticotropin to Insulin-induced Hypoglycemia and Metyrapone in Patients with Hypothalamic-Pituitary Disorders

Pediatrics InternationalVolume 23, Issue 2 p. 264-265 Part 2. Response of Corticotropin to Insulin-induced Hypoglycemia and Metyrapone in Patients with Hypothalamic-Pituitary Disorders First published: November 1981 https://doi.org/10.1111/j.1442-200X.1981.tb00458.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume23, Issue2November 1981Pages 264-265 RelatedInformation

Inhibitory effect of diphenylhydantoin on the feedback control of corticotrophin release.

ABSTRACT Suppression of plasma corticosteroids by dexamethasone was studied in 4 control subjects before and during treatment with diphenylhydantoin (DPH), and also in 14 epileptic patients, 13 of whom received DPH while one received primidone. At 8 a. m. the mean value of plasma corticosteroids in 31 normal subjects 9 hours after one mg of dexamethasone given orally was less than 4.4 μg/100 ml, but in the epileptic patients the plasma corticosteroids were not suppressed to this control level. Similar experiments in the control subjects demonstrated that during treatment with DPH an insufficient response to one mg dexamethasone is found. When suppression with 2 mg of dexamethasone given orally was repeated in 4 epileptic patients and in two control subjects receiving DPH, the plasma corticosteroids still did not decrease below 4.4 μg/100 ml. After 4 mg of dexamethasone, however, the plasma corticosteroids were suppressed to values of about 4.4 μg/100 ml in 4 out of 7 epileptic patients and in two control subjects receiving DPH. A normal diurnal rhythm of plasma corticosteroids was found in 7 out of 9 epileptic patients and in 3 control subjects receiving DPH. Krieger (1962) and Rinne (1966) observed a limited response to metyrapone in patients treated with DPH. This observation and the insufficient suppression of plasma corticosteroids by dexamethasone found in patients receiving DPH, is most likely a consequence of a partial inhibition of the feedback control of corticotrophin (ACTH) release. Since DPH does not appear to interfere with diurnal rhythm of ACTH release, it is most unlikely that the diurnal rhythm of ACTH release is dependent solely on a negative feedback mechanism. In patients receiving DPH, the metyrapone test and the one mg dexamethasone test are of no value in the diagnosis of pituitary-adrenal diseases.

The impaired response to metyrapone in patients taking oestrogen.

ABSTRACT The impaired response to metyrapone during ethinyloestradiol administration has been studied in a further seven patients. A two day metyrapone test was done in the control period and then when the patient was receiving ethinyloestradiol 0.1 mg daily. In four of the patients the metyrapone tests were repeated in the control and oestrogen periods, but with the addition of an 8-hour infusion of ACTH on each of the metyrapone days. The 17-hydroxycorticosteroids excreted in the urine were converted to 17-oxosteroids using Few's method, chromatographed, and the 11β-hydroxyaetiocholanolone and aetiocholanolone fractions eluted and measured. Any change in the degree of 11β-hydroxylase inhibition by metyrapone should be reflected in a change in the ratio of 11β-hydroxyaetiocholanolone to aetiocholanolone, as these are derived from the metabolites of cortisol and 11-deoxycortisol respectively. It was found that this ratio was higher when metyrapone was administered during the oestrogen period than when it was administered during the control period. The effect was still seen when the adrenal cortex was maximally stimulated with ACTH during the periods of metyrapone administration. It is concluded that oestrogen administration impairs 11β-hydroxylase inhibition by metyrapone, possibly as a result of increased 11β-hydroxylase activity in the adrenal cortex.

Urinary oestrogen excretion after metyrapone administration to patients with the polycystic ovary syndrome.

SUMMARY The 24 hr. urinary excretion of oestrone, oestradiol and oestriol was measured during metyrapone administration in six normal women, four patients with primary amenorrhoea, six patients with polycystic ovary syndrome (POS) and three patients with secondary amenorrhoea. In the six normal women the oestrogen excretion on the first and second day of metyrapone administration did not differ from the control values except for a slight, probably significant, decrease in the excretion of oestradiol on the first day. In the patients with primary and secondary amenorrhoea the results were similar to those in the normal women. In the POS group the urinary excretion of oestrogens increased by 11–120% on the first day of metyrapone administration and by 63–140% on the second day. Studies with metyrapone in three patients with POS during dexamethasone suppression and/or ACTH administration suggest that the increased oestrogen excretion after metyrapone depended on the usual feedback mechanism between the adrenal and the hypothalamo-hypophysial system. Possible reasons for the absence of this increase in the normal subjects are discussed. It is concluded that the abnormal response to metyrapone in patients with the POS was not due to the amenorrhoea per se and the possibility that this response was related to the underlying disorder of POS is considered.