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At least 73 records · Page 4Linked to original sources
PubMed1985

Effects of etomidate on cortisol biosynthesis in isolated guinea-pig adrenal cells: comparison with metyrapone.

The effects of the iv hypnotic etomidate on cortisol biosynthesis have been investigated in short term incubations of dispersed guinea-pig adrenal cells and were compared with those produced by metyrapone. Fifty percent inhibition of cortisol output was obtained at a final medium concentration of 3.5 10(-8) M (basal), 2.8 10(-8) M (ACTH-stimulated) for etomidate and of 5.10(-7) M (stimulated) for metyrapone. In the presence of etomidate, 11-deoxycortisol at 5.10(-8) M reached a peak value of 244 +/- 11% of control (mean +/- SE, n = 7). 17 alpha-Hydroxyprogesterone and progesterone were not significantly affected up to 10(-7) M, but at higher concentrations, all three precursors fell under their control values. Metyrapone induced a progressive rise of 11-deoxycortisol, from 10(-7) M upwards, to a maximum level at 10(-5) M (210 +/- 15% of control, mean +/- SE, n = 5). 17-Hydroxyprogesterone and progesterone concentrations were not significantly modified by metyrapone. The less active hypnotic L-enantiomer of etomidate had almost no inhibitory effect on cortisol production. The results obtained so far suggest that etomidate is a potent inhibitor of the mitochondrial cytochrome P-450 enzymes of the adrenal cortex, mainly the 11 beta-hydroxylase. At higher dose the cholesterol side-chain cleavage enzyme system seemed also to be affected.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Adrenocortical carcinoma with Cushing's syndrome presenting unusual urinary 17-ketosteroid fractionation.

A case of adrenal carcinoma with Cushing's syndrome was presented. Endocrinological and morphological investigations disclosed the presence of a functional adrenal carcinoma. This case was characterized by its unusual urinary 17-ketosteroid (17-KS) fractionation, i.e. a marked elevation of 17-KS was accompanied by the increments of etiocholanolone, but not of dehydroepiandrosterone (DHEA) or androsterone. Measurements of the plasma adrenocorticosteroids revealed normal DHEA and DHEA-S (sulfate) levels, moderately increased 17-OH-pregnenolone, and markedly increased (less than 100 times the normal) 11-deoxycortisol (cpd S). Therefore, it seems plausible that the normal urinary DHEA level in this patient would have occurred as a result of remarkably low C17-20 lyase activity sufficient to hamper DHEA production, and that markedly increased etiocholanolone might possibly have been converted from cpd S as well as from DHEA and androstenedione through 5 beta-reduction.

17-Ketosteroids↗
PubMed1993

Metyrapone induced increase in plasma corticotropin is not associated with changes in peripheral venous arginine vasopressin or corticotropin releasing factor.

The responses of the "stress hormones" cortisol, 11-deoxycortisol, ACTH, vasopressin (AVP), and corticotropin releasing factor (CRF) were studied in 6 normal males in response to acute cortisol deficiency induced by the 11-beta-hydroxylase inhibitor, metyrapone. A 750 mg dose was administered orally at 08:00 h on day 1 and at 4 hourly intervals over a 24-h period. A 20 mg tablet of hydrocortisone or placebo was then given at 08:00 h on day 2, according to a randomized cross-over design. Each subject was restudied after an interval of at least one month. Blood samples were taken for all hormones at 08:00 h on day 1 and at 04:00 h on day 2. Thereafter ACTH and AVP were sampled at 10-min intervals, CRF at 20-min intervals, and cortisol and 11-deoxycortisol at hourly intervals until 12:00 h on day 2. Cortisol (mean +/- SE) fell from 628 +/- 218 nmol/l at 08:00 h (day 1) to a minimum of 230 +/- 78 nmol/l at 05:00 h on day 2. Plasma 11-deoxycortisol rose from 14.0 +/- 0.8 nmol/l to a maximum of 622 +/- 36 nmol/l and plasma ACTH rose from 8.71 +/- 1.64 pmol/l to a maximum of 166.2 +/- 57.5 pmol/l. Diurnal rhythmicity of plasma ACTH was maintained. There was no detectable change in plasma levels of AVP or CRF from baseline (AVP 2.5 +/- 0.8 pmol/l, CRF 3.4 +/- 0.5 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1990

A pilot study for neonatal screening of congenital adrenal hyperplasia due to 21-hydroxylase and 11-beta-hydroxylase deficiency in Campania region.

A neonatal screening for both 21-hydroxylase and 11-beta-hydroxylase deficiencies, responsible for congenital adrenal hyperplasia (CAH), has been conducted in Campania Region, Southern Italy. In 4380 neonates, aged 2-10 days, capillary blood from a heel prick was collected on microfilter paper, and 17-alpha-hydroxyprogesterone (17OHP) measured by radioimmunoassay (RIA) using a highly specific antibody (Ab A). In addition, in 295 of these samples, both 17OHP and 11-deoxycortisol (S) were measured using an anti-deoxycortisol antibody (Ab B) cross-reacting with 17OHP 100%. All results were compared with plasma 17OHP and S levels in 21 patients with diagnosed 21-hydroxylase deficiency and in 5 healthy volunteers on metyrapone test used for blocking the 11-beta-hydroxylase activity. CAH due to 21-hydroxylase deficiency was diagnosed in a female newborn. The assay, based on the antibody reacting with both 17OHP and S, is particularly suitable for wide-scale screening programs enabling the simultaneous detection of two congenital enzyme defects.

Adolescent↗
PubMed1988

Plasma pro-opiomelanocortin fragments and adrenal steroids following administration of metyrapone to normal and hirsute women.

The present study was undertaken to characterize further the adrenal abnormalities in the polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH). We have previously reported the close association of elevated estrone levels with amenorrhea in hyperandrogenemic patients. In addition we have suggested that high estrone levels in PCOS occur as a consequence of the provision of excess substrate, androstenedione, for conversion to estrone. In the present study plasma estrone levels rose following endogenous adrenal stimulation induced using metyrapone; the highest plasma estrone levels achieved were seen in patients with PCOS and occurred later than peak androstenedione levels. These findings are consistent with the hypothesis that elevated estrone levels occurring in PCOS may arise as a consequence of increased adrenal androgen secretion. In addition, we have examined ACTH and other pro-opiomelanocortin (POMC) fragments in an attempt to identify a factor responsible for the excessive adrenal androgen secretion occurring in hirsute patients. Plasma levels of ACTH, and of immunoreactive beta-endorphin and h-lipotropin were not elevated when androgen levels were raised prior to therapy, although these POMC fragments, and also the 16K fragment, rose in response to metyrapone treatment as did androgen levels. Following treatment with dexamethasone there was more profound suppression of the 16K, beta-endorphin and h-lipotropin responses to metyrapone stimulation, than of the ACTH response, as indicated by decreased POMC-fragment/ACTH ratios; this parallels the dissociation of cortisol from androgens in hirsute patients under similar conditions. However, we have not identified a POMC fragment which consistently parallels changes in androgen levels in patients with idiopathic hirsutism or PCOS.

Administration, Oral↗
PubMed1988

Assessment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction: comparison of ACTH stimulation, insulin-hypoglycemia and metyrapone.

The response to ACTH stimulation, insulin-hypoglycemia and metyrapone in patients with suspected HPA axis dysfunction due to corticosteroid therapy (Group I, n = 10), or pituitary surgery (Group II, n = 7) and in a control population (Group III, n = 8) was studied. Group I patients had been maintained on a stable low dose of prednisone 5.0-7.5 mg/day for 1 month-16 yr (mean = 31 mos) prior to testing. Basal 08:00 h cortisol levels in this group were not different from control values. However, the mean responses to all three testing procedures were suppressed (Group I vs III, ACTH p less than 0.001, insulin p less than 0.01, metyrapone p less than 0.05). Group II patients had undergone surgery 1-26 months (mean = 10 mo) prior to testing and had been maintained subsequently on a stable dose of prednisone 5.0-7.5 mg/day. In this group basal mean 08:00 h cortisol and the cortisol response to ACTH and insulin-hypoglycemia were not significantly different from control values while the response to metyrapone was suppressed (Group II vs III p less than 0.02). Basal serum DHEA-S levels were suppressed in both Groups I and II when compared to Group III (p less than 0.001). Discordant responses to the three testing procedures were noted in 6 patients with suspected HPA dysfunction with abnormal test results in 1/6 using cortrosyn, 3/6 using insulin-hypoglycemia and 4/6 using metyrapone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1997

Cushing's syndrome due to ACTH-independent bilateral adrenocortical macronodular hyperplasia.

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is a rare cause of Cushing's syndrome in which adrenal glands become very enlarged, occupied and distorted by multiple cortical nodules. We report on such two patients, a 44-year-old man and a 40-year-old woman. Physical examination revealed in both cases a classic cushingoid habit. Laboratory studies showed overt hypercortisolism with high urinary free cortisol excretion and elevated serum cortisol with loss of the circadian rhythm. Serum cortisol levels were not modified after high dose dexamethasone. ACTH levels were undetectable both in baseline conditions and following CRH or metyrapone. In both cases, abdominal CT demonstrated bilaterally enlarged adrenal glands which were distorted by multiple bumps. 131I-Norcholesterol scintiscan showed bilateral uptake of the radionuclide. Pituitary region was normal at neuroradiologic imaging. Bilateral adrenalectomy was performed in both cases. In patient I, adrenal glands weighted 77 and 90 g, respectively, while in patient II they were of 90 and 55 g, respectively. At histological examination, the adrenal cortex was occupied by multiple nodular lesions composed mostly of clear cells. In the internodular regions, no evidence of cortical architecture was observed. At the immunohistochemical evaluation, both cases displayed KI-67 staining comparable with that of ACTH-dependent diffuse hyperplasia. Postoperative course was uneventful and signs of Cushing's syndrome resolved in about three months. At the last follow up, the patients are going well on glucocorticoid and mineralocorticoid supplementation. Plasma ACTH levels are 65 and 107 pg/ml, respectively.

Adrenal Cortex↗
PubMed1985

Female pseudohermaphroditism with adrenal cortical tumor in adulthood.

Data are presented concerning a case of female pseudohermaphroditism of unknown etiology. The child was born with labioscrotal fusion and clitoromegaly. From the age of 5 to the age of 25 there was no clinical evidence of a hormonal abnormality. At the age of 25 the patient presented with masculinization and Cushing's syndrome, and a left adrenal tumor was removed. The patient was restudied at the age of 29, when 21-hydroxylase deficiency was excluded. Other types of congenital adrenal hyperplasia are considered unlikely. The possible relationship between the ambiguous genitalia present at birth and the virilizing tumor diagnosed at the age of 25 is analyzed.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.

Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

Adrenal Glands↗
PubMed2005

A fluorimetric assay for cortisol.

A simple, rapid and sensitive fluorimetric assay for the quantitative determination of cortisol is reported. The assay is based on the formation of a fluorescent dye when cortisol is incubated with a mixture of sulfuric acid and acetic acid. The fluorescence spectrum recorded for the resulting dye shows a maximum extinction at 475 nm and a maximum emission at 525 nm. The solvent 2-methyl-4-pentanone was used for extraction and was found to act as a fluorescence amplifier. A limit of detection of 2.7 muM was achieved, making it possible to forego solvent evaporation. The assay suffers minor interference from 11-deoxycortisol which exhibits low fluorescence at lambda (ex): 460 nm; lambda (em): 505 nm. Typical standard deviations were below 4%. We validated the assay using a biotransformation with recombinant Schizosaccharomyces pombe which regioselectively hydroxylates 11-deoxycortisol to cortisol. The method described herein is suitable for preliminary screening of microorganisms capable of steroid hydroxylation.

Biotransformation↗
PubMed1997

Exhaustive screening of the 21-hydroxylase gene in a population of hyperandrogenic women.

21-hydroxylase (21-OH) deficiency accounts for the vast majority of nonclassic (NC) forms of congenital adrenal hyperplasia (CAH), and is associated with symptoms detectable either in childhood (precocious puberty) or sometimes only later in adulthood (hirsutism, acne, amenorrhea). While the severe forms of the disease responsible for salt wasting or simple virilization have been extensively studied, the NC 21-OH deficiency is less well characterized, especially in adults. We studied the 21-OH gene (CYP21) in a population of 69 unrelated hyperandrogenic subjects suspected to be homozygous or heterozygous for NC 21-OH deficiency, based on basal and adrenocorticotrophin (ACTH)-stimulated plasma 17-hydroxyprogesterone (17-OHP, 17-OHPSI) and 21-desoxycortisol (21-DOF, 21-DOFSI) levels. To identify all mutations involved, determination of the whole gene sequence, including exons, exon-intron junctions, and promoter region, was performed, followed by a study of large rearrangements and identification of compound heterozygotes. Alterations were identified in at least one allele of 55 hyperandrogenic subjects. Two NC alterations, Val282Leu and Pro454Ser, were detected in 68% and 7% of the affected alleles, respectively, whereas mutations involved in severe forms were identified in 21% of them. These results document the utility of a molecular diagnosis in hyperandrogenic women suspected of being either heterozygous or homozygous for NC 21-OH deficiency and clearly indicate the importance of genetic counseling in such a population.

17-alpha-Hydroxyprogesterone↗
PubMed1983

The superiority of the metyrapone test versus the high-dose dexamethasone test in the differential diagnosis of Cushing's syndrome.

Differentiating the cause of Cushing's syndrome traditionally has depended upon measuring the response of 24-hour urine samples of cortisol or glucocorticoid metabolites to the high-dose (8 mg per day) dexamethasone test. The metyrapone test, however, is more convenient because it is a shorter test and requires the obtainment of serum samples, which can be collected more simply and more reliably than 24-hour urine samples. The usefulness of these two tests has not been adequately evaluated in a large series of patients with Cushing's syndrome. This study prospectively evaluated the accuracy of the dexamethasone and metyrapone tests in determining the cause of Cushing's syndrome in a series of 25 unselected patients. The diagnostic accuracy of these tests was calculated as follows: diagnostic accuracy = true positives and true negatives/study population X 100. Results of this study demonstrated that the metyrapone test was more accurate than the dexamethasone test in differentiating Cushing's disease from adrenocortical neoplasm (diagnostic accuracy, 100 percent versus 81 percent). All patients with Cushing's disease had a normal postmetyrapone 11-deoxycortisol concentration (greater than 10 micrograms/dl), while all patients with adrenocortical neoplasm had a suppressed 11-deoxycortisol concentration (less than 10 micrograms/dl). Thus, this study demonstrates that the metyrapone test is superior to the high-dose dexamethasone test in the differential diagnosis of Cushing's syndrome.

Adolescent↗
PubMed1986

Clinically silent congenital adrenal hyperplasia masquerading as ectopic adrenocorticotropic hormone syndrome.

A 64-year-old man with an asymptomatic pulmonary mass discovered on routine chest roentgenography was found to have substantial bilateral adrenal enlargement by abdominal computed tomography. Percutaneous adrenal aspiration biopsy showed cytologically normal adrenal glands. A diagnosis of subclinical 21-hydroxylase deficiency was established by stimulation testing with adrenocorticotropic hormone. The adrenal size and appearance by computed tomographic scanning in congenital adrenal hyperplasia and particularly in its subclinical form have not been well defined. This case demonstrates that marked adrenal enlargement can occur and may provide the only clue to the diagnosis in an asymptomatic patient without other clinical stigmata of adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗
PubMed1980

Cortisol, 11-desoxycortisol, and 21-desoxycortisol concentrations in amniotic fluid during normal pregnancy.

Concentrations of unconjugated cortisol, 11-desoxycortisol, and 21-desoxycortisol were measured by radioimmunoassay in amniotic fluid throughout gestation. Cortisol levels rose from a median of 6.5 nanograms per milliliter prior to 20 weeks to 13.9 ng/ml at 28 to 37 weeks. Median levels of 11-desoxycortisol and 21-desoxycortisol were 2.6 ng/ml and 0.21 ng/ml, respectively, and did not change with advancing gestation. These normal values provide a basis for the application of assays of 11-desoxycortisol and 21-desoxycortisol in amniotic fluid in the prenatal diagnosis of congenital adrenal hyperplasia.

17-Hydroxycorticosteroids↗
PubMed1983

Plasma 11-deoxycortisol in normal and abnormal human pregnancy.

11-Deoxycortisol was assayed in maternal and cord plasma. The concentrations in maternal plasma increased as pregnancy progressed and reached a peak at 39 weeks. The levels decreased very rapidly in the postpartum period. In cases of intrauterine fetal death and anencephalic fetuses, the values were apparently lower than normal. In women who had undergone bilateral adrenalectomy, the maternal plasma levels were almost normal. The maternal levels were high in cases of twin pregnancies. Therefore, it is assumed that the fetus or the fetoplacental unit is the source of the increased 11-deoxycortisol in maternal plasma during late pregnancy.

17-Hydroxycorticosteroids↗
PubMed1987

Stable adrenocorticotropin-stimulated 11-beta-hydroxylase activity but loss of age-related changes in patients with hypercortisolemia.

Eleven-beta-hydroxylase activity was measured before and after acute adrenocorticotrophic hormone (ACTH) stimulation in 28 controls, 25 depressed Dexamethasone Suppression Test (DST) suppressors, 13 DST nonsuppressor patients, and 8 patients with Cushing's syndrome to investigate changes in states of cortisol hypersecretion. Eleven-beta-hydroxylase activity was equivalent among groups both before and after stimulation. Such 11-beta-hydroxylase stability, however, resulted in higher cortisol and 11-deoxycortisol poststimulation levels in both depressed DST nonsuppressors and Cushing's patients than in controls. Basal 11-beta-hydroxylase activity is positively correlated and 11-deoxycortisol is negatively correlated with age in controls and DST suppressors, but not in the patients tested with evidence of cortisol hypersecretion. These findings suggest that in vivo basal 11-beta-hydroxylase activity rises gradually with age, but does not rise after acute administration of exogenous ACTH. The age relationship is lost in states of cortisol hypersecretion, but the lack of response to acute exogenous ACTH is not affected.

Adrenocorticotropic Hormone↗