cortodoxone and Adrenal-Insufficiency

A cortisol response to adrenocorticotropin injection is the standard test for diagnosing adrenal insufficiency. Multiple steroid hormones can now be accurately measured by tandem mass spectrometry in a single sample. The study objective was to determine whether a steroid profile, created by simultaneous measurement of 10 steroid hormones by tandem mass spectrometry, would help determine the cause of adrenal insufficiency.. A 10-steroid profile was measured by tandem mass spectrometry during the performance of a standard high dose cortrosyn stimulation test. The steroids were measured at baseline, 30, and 60min following synthetic adrenocorticotropin injection. Adrenal insufficiency was defined as a peak cortisol level of less than 20microg/dL. Testing was conducted in the general clinical research center of a university medical center. Normal volunteers, patients suspected of having adrenal insufficiency, and patients with known adrenal insufficiency participated.. Our results showed that adrenal insufficiency of any cause was adequately diagnosed using the response of 11-deoxycortisol, dehydroepiandrosterone, or these analytes combined in a two-steroid profile. A three-steroid profile yielded a test with 100% accuracy for discriminating primary adrenal insufficiency from normal status. Primary adrenal insufficiency was well separated from secondary adrenal insufficiency using only a single aldosterone value. 11-Deoxycortisol, dehydroepiandrosterone, and a two-steroid profile each provided fair discrimination between secondary adrenal insufficiency and normal status.. We conclude that stimulated levels of aldosterone, 11-deoxycortisol, dehydroepiandrosterone, and a two- or three-steroid profile provided additional discrimination between states of adrenal sufficiency and insufficiency. It is proposed that a steroid profile measuring cortisol, aldosterone, 11-deoxycortisol, and dehydroepiandrosterone would potentially improve the ability to determine the cause of adrenal insufficiency.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Chromatography, High Pressure Liquid; Cortodoxone; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Stimulation, Chemical; Tandem Mass Spectrometry

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.

Topics: Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Cortodoxone; Female; Fibromyalgia; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Matched-Pair Analysis; Metyrapone; Pituitary-Adrenal System; Reference Values; Stimulation, Chemical

The glucagon stimulation test (GST) is used for the simultaneous assessment of central adrenal insufficiency (CAI) and growth hormone deficiency. The new Roche cortisol II (C II) assay was recently introduced, confounding interpretation of the GST. The performance of the GST in diagnosing central adrenal insufficiency (CAI), utilising the C II assay, was therefore compared with that of the overnight metyrapone test (ONMTPT).. A diagnostic accuracy study was performed by retrospectively analysing folders and laboratory records of 25 children and adolescents investigated for hypopituitarism with the GST and the ONMTPT between September 2016 and December 2019. The peak serum cortisol (C) of the GST, the post-metyrapone serum 11-deoxycortisol and adrenocorticotropin levels of the ONMTPT were recorded. Diagnostic performance of the GST at a previously suggested cut-off of 374 nmol/L was evaluated.. Seventeen boys and 8 girls, aged 1.7-16.3 years (median 7.3 years) were identified. The sensitivity of the post-GST C-level at 374 nmol/L was 0.40 (95% confidence interval [CI] 0.17-0.69), specificity 0.64 (95% CI 0.39-0.84), positive predictive value 0.44 (95% CI 0.19-0.73), negative predictive value 0.60 (95% CI 0.36-0.80), accuracy 0.54 (95% CI 0.35-0.72), positive likelihood ratio (+LR) 0.93 (95% CI 0.49-1.77) and negative LR 1.12 (95% CI 0.40-3.15). The area under the receiver of operating characteristics (ROC) curve was 0.379 (95% CI 0.142-0.615).. This study suggests that the GST at any C II cut-off cannot replace the ONMTPT as a diagnostic test for CAI in children. Findings should be confirmed in a larger study.

Topics: Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Cortodoxone; Female; Glucagon; Growth Hormone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Pilot Projects; Pituitary-Adrenal System; Retrospective Studies; Sensitivity and Specificity

To determine whether a single measurement of ACTH instead of less available in daily practice 11-deoxycortisol assay is sufficient to rule out or confirm secondary adrenal insufficiency (SAI) in the short Metyrapone test.. A retrospective analysis of diagnostic tests (Metyrapone and Synacthen tests) performed at our Center between 2016 and 2018 in patients with suspicion of secondary adrenal insufficiency.. In 103 patients short metyrapone test was performed with assessment of 11-deoxycortisol and ACTH concentration after Metyrapone administered at midnight. In 89 of them short Synacthen (SST) test was also done (1 or/and 250 mcg 1-24ACTH). ROC curves have been performed to evaluate the diagnostic performance of ACTH level in metyrapone test as the predictor of secondary adrenal insufficiency (SAI) analysing sensitivity and specificity for various possible thresholds proposed in literature.. 40 (39%) of examined subjects were diagnosed as SAI, basing on post-Metyrapone 11-deoxycortisol concentration below 70 μg/l. In this group ACTH concentration was 128.1 ng/l (95% CI 96.8-159.4) versus 289.9 ng/l (95% CI 249.1-330.9) in patients with proper adrenal response. There was only a moderate positive correlation between ACTH and 11-deoxycortisol concentrations (r=0.5; p<0.05). The best cut off value of ACTH in relation to 11-deoxycortisol serum concentrations was 147 ng/l - with sensitivity of 73.2% and specificity 83.9%. However, plasma ACTH was>200ng/ml (the highest threshold proposed in literature) in 8 cases (20%) with positive diagnosis of SAI made on the basis of low 11-deoxycortisole and confirmed in short Synacthen test.. Our results indicate that for a valuable evaluation of the results of the metyrapone test, the more readily available plasma ACTH assay cannot replace the measurement of 11-deoxycortisol concentrations.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cortodoxone; Humans; Hydrocortisone; Metyrapone; Retrospective Studies

Hypothalamic-pituitary-adrenal axis suppression (HPAS) when treating children with corticosteroids is thought to be rare. Our objective was to determine the prevalence of and predictive factors for various degrees of HPAS.. Clinical features of HPAS, doses, adherence, asthma score, and lung functions were recorded in 143 asthmatic children. The overnight metyrapone test was performed if morning cortisol was >83 nmol/L. Spearman correlations coefficients (r) were calculated between 3 postmetyrapone outcomes and each continuous variable. A multiple linear regression model of √postmetyrapone adrenocorticotropic hormone (ACTH) and a logistic regression model for HPAS were developed.. Hypocortisolemia was seen in 6.1% (1.8-10.5), hypothalamic-pituitary suppression (HPS) in 22.2% (14.5-29.9), adrenal suppression in 32.3% (23.7-40.9), HPAS in 16.3% (9.3-23.3), and any hypothalamic-pituitary-adrenal axis dysfunction in 65.1% (56.5-72.9). Log daily nasal steroid (NS) dose/m(2) was associated with HPAS in the logistic regression model (odds ratio = 3.7 [95% confidence interval: 1.1-13.6]). Daily inhaled corticosteroids (ICSs) + NS dose/m(2) predicted HPAS in the univariate logistic regression model (P = .038). Forced expiratory volume in 1 second/forced vital capacity <80% was associated with HPAS (odds ratio = 4.1 [95% confidence interval: 1.0-14.8]). Daily ICS + NS/m(2) dose was correlated with the postmetyrapone ACTH (r = -0.29, P < .001). BMI (P = .048) and percent adherence to ICS (P < .001) and NS (P = .002) were predictive of √postmetyrapone ACTH (R(2) = .176).. Two-thirds of children on corticosteroids may have hypothalamic-pituitary-adrenal axis dysfunction. In one-third, central function had recovered but adrenal suppression persisted. Predictive factors for HPAS are NS use, BMI, and adherence to ICS and NS.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Cortodoxone; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Hypopituitarism; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Linear Models; Male; Medication Adherence; Metered Dose Inhalers; Metyrapone; Pilot Projects; Pituitary-Adrenal System; Predictive Value of Tests

Adequate adrenal function is pivotal to survive meningococcal sepsis.. The objective of the study was to evaluate adrenocortical function in meningococcal disease.. This was an observational cohort study.. The study was conducted at a university-affiliated pediatric intensive care unit.. Sixty children with meningococcal sepsis or septic shock participated in the study.. The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured.. Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ.. Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Biological Availability; Child; Child, Preschool; Cortodoxone; Etomidate; Female; Humans; Hydrocortisone; Hypnotics and Sedatives; Infant; Interleukin-6; Male; Meningococcal Infections; Renin; Respiration, Artificial; Shock, Septic; Transcortin

The short Synacthen test, the overnight metyrapone test and the insulin tolerance test are frequently used in the evaluation of patients suspected of adrenal insufficiency. in the present study, we established reference values for these diagnostic tests, as well as for baseline morning plasma cortisol and adrenocorticotrophic hormone (ACTH).. We studied 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. A short ACTH stimulation test (250 microg Synacthen iv), an overnight metyrapone test (2.0, 2.5, or 3.0 g given orally depending on body weight at 23.30 hours) and an insulin tolerance test (0.15 U/kg actrapid iv) were performed. Reference intervals are given as the means +/- 2SD of observed hormone concentrations after logarithmic transformation.. The following reference values were established: 09.00 hr plasma cortisol 150 to 802 nmol/l, 09.00 hr plasma ACTH 8 to 93 ng/l, peak plasma cortisol after Synacthen 591 to 1,113 nmol/l, peak plasma cortisol after insulin-induced hypoglycaemia 557 to 1,015 nmol/l, and plasma 11-deoxycortisol after metyrapone 197 to 759 nmol/l.. We established reference values for diagnostic tests that are useful in the evaluation of patients suspected of primary or secondary/tertiary adrenal insufficiency.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Anti-Inflammatory Agents; Biomarkers; Cortodoxone; Enzyme Inhibitors; Female; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Male; Metyrapone; Middle Aged

DAX-1 is an orphan nuclear receptor that plays a key role in the development and function of the adrenal gland and hypothalamic-pituitary gonadal axis. Mutations in the gene encoding DAX-1 result in X-linked adrenal hypoplasia congenita (AHC). Affected boys typically present with primary adrenal failure in infancy or childhood and hypogonadotropic hypogonadism at the time of puberty. The majority of DAX1 mutations described to date are nonsense or frameshift mutations that result in premature truncation of the DAX-1 protein and loss of DAX-1 repressor function. Relatively few missense mutations in DAX1 have been reported. Here, we describe missense mutations in three additional families with X-linked AHC. When combined with previous reports, the DAX1 missense mutations appear to cluster within restricted regions of the putative ligand-binding domain of DAX-1 and affect amino acids that are evolutionarily conserved, suggesting that these regions correspond to critical functional domains. Transcription assays, using a variety of artificial and native target genes, were performed to assess the effects of these mutations on the function of DAX-1. All DAX-1 missense mutant constructs showed marked loss of repressor function, with the exception of I439S, a mutation previously shown to be associated with delayed-onset adrenal failure and incomplete hypogonadotropic hypogonadism. These data indicate that most DAX1 missense mutations associated with classic AHC exhibit marked loss of function. The locations of these mutations thereby identify important functional domains in the carboxyl-terminus of the protein.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Cell Line; Cortodoxone; DAX-1 Orphan Nuclear Receptor; DNA-Binding Proteins; Embryo, Mammalian; Genetic Linkage; Humans; Hydrocortisone; Hyperkalemia; Hyponatremia; Infant; Infant, Newborn; Kidney; Male; Mutation, Missense; Receptors, Retinoic Acid; Renin; Repressor Proteins; Transcription Factors; Transcription, Genetic; X Chromosome

The ACTH stimulation test examines adrenal responsiveness but may not examine the entire hypothalamic-pituitary-adrenal (HPA) axis and requires parenteral administration. The cortisol response to hypoglycaemia provides an index of activity of the entire HPA axis but is demanding for patients and medical staff. The aim of the present study was to examine the performance of the overnight single-dose metyrapone test as it provides a simple alternative test for HPA axis function.. Audit of the overnight metyrapone test performed in one centre between 1979 and 1991.. Three hundred and ninety-eight patients underwent 576 tests. Comparisons between the responses to metyrapone and the ACTH stimulation test and of the responses to metyrapone and insulin induced hypoglycaemia test were possible in 87 and 17 patients respectively.. Following the midnight administration of metyrapone tablets, 30 mg/kg orally, blood samples were obtained between 0800 and 0930 h for radioimmunoassay of both 11-deoxycortisol and cortisol.. Five hundred and seventy-six metyrapone tests were performed on 398 patients with no serious side-effects encountered. Adrenal insufficiency was diagnosed in 105 patients. Of these, 18 had a primary adrenal disorder and 87 had a disorder of the hypothalamic-pituitary unit. One hundred per cent concordance between the metyrapone, the ACTH and the hypoglycaemia test was seen in patients with primary adrenal insufficiency. In 19 patients with secondary adrenal insufficiency, who underwent both the metyrapone and the ACTH tests, discord between these two tests was observed in 10 patients (53%). Nine of these patients demonstrated a normal response to ACTH and a subnormal response to metyrapone. In only one patient was an abnormal cortisol response to ACTH associated with a normal response to metyrapone. In contrast, in 17 patients discord between the metyrapone and the hypoglycaemia test was seen in only 1 patient who demonstrated a normal response to the metyrapone test and a subnormal response to hypoglycaemia.. Since the metyrapone test gives similar information about hypothalamic-pituitary axis function as does the hypoglycaemia test, we recommend the use of the overnight metyrapone test as a safe, simple and reliable index of the hypothalamic-pituitary axis integrity. The ACTH stimulation test should not be used for patients suspected of having secondary adrenal insufficiency.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cortodoxone; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Medical Audit; Metyrapone; Pituitary-Adrenal System

Assessment of adrenal reserve and the diagnosis of adrenal insufficiency by acute adrenocortical stimulation with ACTH-(1-24) has been well established. Alternatively, estimation of adrenocortical enzymatic activities by this method for the detection of inherited or acquired biosynthetic abnormalities has been less well characterized. Some of the discrepancies between studies estimating adrenocortical enzymatic activities in different pathological conditions (e.g. hyperandrogenism) may result from the different stimulation protocols used. The objective of this prospective study was to establish the inherent variability of the adrenal response to acute ACTH-(1-24) stimulation and to determine the effect of sampling time, stimulation dose, and subject weight on the same. Forty-one normal female volunteers were recruited (mean age, 29.1 yr), 30 within 90-110% ideal body weight and 11 weighing more than 120% ideal body weight. Three protocols were designed to study 1) the effects of sampling time, ACTH-(1-24) dose, and subject weight on adrenal response; 2) the effect of time of the day on the variability of basal steroid levels and the adrenal response to stimulation; and 3) the long term reproducibility of the adrenal response to ACTH-(1-24). Androstenedione, 17-hydroxyprogesterone, 11-deoxycortisol, dehydroepiandrosterone, and cortisol were measured in serum under basal and stimulated conditions. All subjects had normal basal levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and PRL. The acute iv administration of 0.10, 0.25, and 1.0 mg ACTH-(1-24) elicited similar and maximal steroid responses, with all steroid levels reaching a plateau 60-90 min poststimulation regardless of subject weight. Sampling of basal steroid levels every 5 min in the morning (AM; beginning 0700-0900 h) or evening (PM; 1500-1700 h) did not reveal any difference in steroid variability. Only the mean basal cortisol level was higher in AM than PM testing (P less than 0.03). Although the mean levels of dehydroepiandrosterone and 17-hydroxyprogesterone 60 min after stimulation were significantly higher in AM than PM studies, these differences were minimal. Ten volunteers underwent an average of four (range, 2-6) adrenal stimulation studies using 1.0 mg ACTH-(1-24) over a 1-yr period. The long term coefficient of variation (CV) for basal steroid levels ranged from 15-28%. Calculations of net adrenal response (delta steroid O-T and area delta steroid O-T) were less

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Glands; Adrenal Insufficiency; Adult; Analysis of Variance; Androstenedione; Body Weight; Circadian Rhythm; Cortodoxone; Cosyntropin; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Menstrual Cycle; Prospective Studies; Reproducibility of Results; Time Factors

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Chromatography, High Pressure Liquid; Cortodoxone; Dexamethasone; Gas Chromatography-Mass Spectrometry; Humans; Metyrapone; Radioimmunoassay

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Chromatography, High Pressure Liquid; Cortodoxone; Humans; Metyrapone; Radioimmunoassay; Reference Values

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)

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Aldosterone; Blood Glucose; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Hypothalamic Diseases; Insulin; Male; Metyrapone; Middle Aged; Pituitary Diseases; Prednisone

A 71-year-old man presented with clinical and common biological features of secondary adrenal insufficiency. Basal ACTH level was in the normal range. As it has been previously reported in ACTH deficiency, cortisol response to ACTH-test was normal. A single-dose metyrapone test, performed to confirm the diagnosis of adrenal insufficiency, gave unexpectedly normal results. However 11-desoxycortisol (compound S) response to standard-metyrapone test was subnormal ascertaining the diagnosis of ACTH-deficiency. Thus normal responses to single-dose metyrapone test do not imperatively exclude secondary adrenal failure.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Cortodoxone; False Negative Reactions; Humans; Male; Metyrapone

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Anesthesia, Intravenous; Cortodoxone; Etomidate; Female; Humans; Hydrocortisone; Male; Middle Aged

Unstimulated plasma ACTH concentrations remain at or below the detection limit of conventional immunoassays. Grossly elevated ACTH concentrations are diagnostic in suspected adrenal insufficiency, remain elevated well above 200 ng/l during substitution therapy and obviate the need of further tests. For the diagnosis of secondary adrenal failure, plasma ACTH, cortisol and 11-desoxycortisol response to a single midnight dose of metyrapone (1.2 g/m2 = 30 mg/kg) discriminates between a normal (morning ACTH above 100 ng/l), diminished (morning ACTH detectable, but below 100 ng/l), and an absent (ACTH below 20 - 40 ng/l) ACTH reserve. In congenital adrenal hyperplasia, plasma ACTH concentrations mirror, together with 17-alpha-hydroxyprogesterone, the extent of ACTH suppression. Elevated ACTH concentrations were suppressed by prednisolone (25%), dexamethasone (2% of the hydrocortisone dose) or by addition of cyproterone acetate (100 mg/m2/day). Using selective venous catheterisation in clinically and biochemically proven Cushing's syndromes, a pituitary adenoma could be identified and localized in 6 of 8 patients by measuring ACTH concentrations in the left and right petrosal sinus before and after stimulation with corticotrophin releasing hormone.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Gland Diseases; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Child; Cortodoxone; Cushing Syndrome; Humans; Hydrocortisone; Hydroxyprogesterones; Metyrapone; Pituitary Neoplasms

In normal subjects, plasma pregnenolone sulfate (PS) levels high at birth, decreased during the first year of life in relation to the pattern of involution of the fetal adrenal zone. Thereafter, PS levels, in contrast with those of DHAS, did not show the abrupt rise characteristic of the adrenarche, but increased very progressively till adulthood. The response of PS to various provocative tests of adrenal and pituitary function (ACTH and Metyrapone stimulation, dexamethasone suppression), has been established in normal subjects. The measurement of plasma PS levels in basal conditions as well as in response to dynamic tests was very useful in the diagnosis of various adrenal and pituitary diseases in children.

Topics: Adolescent; Adrenal Gland Diseases; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aging; Child; Child, Preschool; Cortodoxone; Dexamethasone; Female; Humans; Hydrocortisone; Infant; Metyrapone; Pituitary Diseases; Pregnenolone

Topics: 17-Hydroxycorticosteroids; Adrenal Insufficiency; Cortodoxone; Cosyntropin; Humans; Hydrocortisone; Ketoconazole; Male; Metyrapone; Middle Aged

The reliability of the beta 1-24 corticotropin test, which is both cheap and safe, in the assessment of the hypothalamic-pituitary-adrenocortical function was re-evaluated by comparing its results with those of the metyrapone test in 71 subjects: 30 controls and 51 patients with suspected pituitary-adrenal dysfunction. Response to a 500 micrograms intramuscular injection of beta 1-24 corticotropin was evaluated by measuring the 60 min plasma cortisol levels; 4.5 g of metyrapone divided into 6 doses were then administered orally and response was evaluated by measuring plasma 11-desoxycortisol levels. A highly significant correlation (r = 0.79; p less than 0.001) was observed between plasma cortisol and plasma 11-desoxycortisol levels. The results were best interpreted by expressing the values obtained as plasma cortisol concentrations which, in normal subjects are at least 21 micrograms/100 ml. The rapid beta 1-24 corticotropin test was found to be very reliable (sensitivity 90%, specificity 100%) to detect adrenal insufficiency, irrespective of the organs affected on the hypothalamic-adrenocortical axis.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Cortodoxone; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Pituitary-Adrenal System; Time Factors

Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations as well as plasma ACTH and 11-deoxycortisol responses to the administration of a single dose of metyrapone were evaluated in 104 patients with intact pituitary-adrenal axis, in 20 patients with secondary adrenal insufficiency, and in seven patients with primary adrenal insufficiency. In patients with primary adrenal insufficiency, baseline ACTH levels were high. Following metyrapone administration, 11-deoxycortisol concentrations were low and ACTH levels did not change. In patients with secondary adrenal insufficiency, baseline plasma ACTH levels were normal, but neither 11-deoxycortisol nor ACTH levels increased in response to metyrapone. The metyrapone test is not only useful to screen for adrenal insufficiency, it is also useful to differentiate a primary from a secondary cause.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cortodoxone; Diagnosis, Differential; Humans; Hydrocortisone; Metyrapone