cosyntropin and Pituitary-Diseases

The diagnostic value of tests for detecting hypothalamic-pituitary adrenal insufficiency (HPAI) is controversial.. Our objective was to compare standard-dose and low-dose corticotropin tests for diagnosing HPAI.. We searched the PubMed database from 1966-2006 for studies reporting diagnostic value of standard-dose or low-dose corticotropin tests, with patient-level data obtained from original investigators.. Eligible studies had more than 10 patients. All subjects were evaluated because of suspicion for chronic HPAI, and patient-level data were available. We excluded studies with no accepted reference standard for HPAI (insulin hypoglycemia or metyrapone test) if test subjects were in the intensive care unit or if only normal healthy subjects were used as controls.. We constructed receiver operator characteristic (ROC) curves using patient-level data from each study and then merged results to create summary ROC curves, adjusting for study size and cortisol assay method. Diagnostic value of tests was measured by calculating area under the ROC curve (AUC) and likelihood ratios.. Patient-level data from 13 of 23 studies (57%; 679 subjects) were included in the metaanalysis. The AUC were as follows: low-dose corticotropin test, 0.92 (95% confidence interval 0.89-0.94), and standard-dose corticotropin test, 0.79 (95% confidence interval 0.74-0.84). Among patients with paired data (seven studies, 254 subjects), diagnostic value of low-dose corticotropin test was superior to standard-dose test (AUC 0.94 and 0.85, respectively; P<0.001).. Low-dose corticotropin test was superior to standard-dose test for diagnosing chronic HPAI, although it has technical limitations.

Topics: Adrenal Gland Diseases; Adrenocorticotropic Hormone; Adult; Child; Cosyntropin; Fasting; Glucocorticoids; Humans; Hydrocortisone; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Pituitary Diseases; Reproducibility of Results; ROC Curve

The first half of this manuscript is devoted to a review of the methods used and the results obtained in the published measurements of the normal responses to tests of the three main types of hypothalamic-pituitary-adrenocortical (HPA) activity in man. These are, I, basal, unstressed activity leading to appropriate levels of total daily production of cortisol in the characteristic circadian pattern; II, responses to feedback stimulation of HPA activity by metyrapone administration; and III, responses to tests of the effects of stress on the HPA system including the effects of hypoglycemia, induced fever, vasopressin administration, and ACTH injections and infusions. The advantages and shortcomings of each type of procedure are discussed. The second half of this paper describes the authors' attempts to establish the limits of normality of standard and modified methods of evaluating the HPA system. The defined limits of normality have been used to assess the HPA function in 158 patients with known or suspected disorders of the HPA system. In normal controls, halfhourly plasma cortisol determinations established the normality of circadian and postprandial fluctuations and of mean plasma cortisol concentration, 6.2 +/- 0.3 (SEM) micrograms/dl, which were closely approximated by determinations every 6 h. Metyrapone, given in a dose of 500 mg every 2 h for 24 h increased urinary 17-OHCS excretion to 10.5-32.6 mg/day or to 1.7-7.8 times basal excretion rate. Increasing rates of insulin infusion disclosed significant relationships between resulting plasma glucose and cortisol concentrations. The slopes of the delta cortisol/delta glucose responses were similar after insulin infusions (0.46 +/- 0.05) and after insulin injections, 0.15 U/kg (0.43 +/- 0.09), and were always greater than 0.20 micrograms/mg. This index provides a useful objective measure of the normality of responses to hypoglycemic stress, 0.20-0.87 micrograms/mg. Adrenocortical responses to iv infusions of ACTH (cosyntropin 0.25 mg) may be equivocal at 2 h but are clear cut at 4, 6 and 8 h. Of 158 patients in whom hypopituitarism was known or suspected because of the presence of a pituitary tumor, acromegaly, hyperprolactinemia, or clinical features, HPA function was found to be entirely normal in 88 patients and partially or severely abnormal in the remaining 70 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: 17-Hydroxycorticosteroids; Acromegaly; Adenoma, Chromophobe; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Blood Glucose; Child; Circadian Rhythm; Cosyntropin; Cushing Syndrome; Feedback; Female; Glucocorticoids; Humans; Hydrocortisone; Hypophysectomy; Hypothalamic Neoplasms; Hypothalamo-Hypophyseal System; Infusions, Parenteral; Injections, Intravenous; Insulin; Lypressin; Male; Metyrapone; Middle Aged; Pituitary Diseases; Pituitary Neoplasms; Pituitary-Adrenal System; Prolactin; Pyrogens; Stress, Physiological

Measurement of plasma cortisol by immunoassay after ACTH₁₋₂₄ stimulation is used to assess the hypothalamic-pituitary-adrenal (HPA) axis. Liquid chromatography-tandem mass spectrometry (LCMS) has greater analytical specificity than immunoassay and equilibrium dialysis allows measurement of free plasma cortisol.. We investigated the use of measuring total and free plasma cortisol by LCMS and total cortisol by immunoassay during an ACTH₁₋₂₄ stimulation test to define HPA status in pituitary patients.. This was a case control study conducted in a clinical research facility.. We studied 60 controls and 21 patients with pituitary disease in whom HPA sufficiency (n = 8) or deficiency (n = 13) had been previously defined.. Participants underwent 1 μg ACTH(1-24) intravenous and 250 μg ACTH₁₋₂₄ intramuscular ACTH₁₋₂₄ stimulation tests.. Concordance of ACTH₁₋₂₄-stimulated total and free plasma cortisol with previous HPA assessment.. Total cortisol was 12% lower when measured by immunoassay than by LCMS. Female sex and older age were positively correlated with ACTH₁₋₂₄-stimulated total and free cortisol, respectively. Measurements of total cortisol by immunoassay and LCMS and free cortisol 30 minutes after 1 μg and 30 and 60 minutes after 250 μg ACTH₁₋₂₄ were concordant with previous HPA axis assessment in most pituitary patients. However, free cortisol had greater separation from the diagnostic cutoff than total cortisol.. Categorization of HPA status by immunoassay and LCMS after ACTH₁₋₂₄ stimulation was concordant with previous assessment in most pituitary patients. Free cortisol may have greater clinical use in patients near the diagnostic threshold.

Topics: Adult; Age Factors; Aged; Case-Control Studies; Chromatography, High Pressure Liquid; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunoassay; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Pituitary Diseases; Pituitary-Adrenal System; Sex Characteristics; Tandem Mass Spectrometry

The GHRH/arginine test and short synacthen test (SST) have been validated as safe alternatives to the insulin tolerance test for the assessment of the GH reserve and hypothalamic-pituitary-adrenal axis integrity, respectively. However, these two tests are usually performed separately. The objective was to see whether the synacthen and GHRH/arginine tests could be combined to save time and blood samples and minimize inconvenience to patients.. Twenty-four consecutive patients with adult onset pituitary disease requiring pituitary function testing were randomized to receive sequentially and in random order a SST, a GHRH/arginine test, and a combined SST and GHRH/arginine test on three different visits separated by at least 1 wk.. There was no difference in basal cortisol or ACTH values for the SST done alone or during the combined test. However, when GHRH/arginine was given with synacthen, patients had a lower peak cortisol response with a mean difference of 116 nmol/liter (95% confidence interval, 52.54 to 179.37; P < 0.001), and one patient with a normal response on the SST had a subnormal cortisol response in the combined test. Similar lower peak cortisol responses were observed in males and females with combined test. The difference between the peak cortisol responses showed no significant correlation with age (r = 0.123; P = 0.58) or with the body mass index (r = -0.376; P = 0.09). There was no difference in GH measurements between the GHRH/arginine test done alone or in combination with the SST.. Combining the SST and GHRH/arginine test results in a lower cortisol response to synacthen. For this reason, the combined test cannot be recommended to assess the integrity of cortisol and GH reserve using current diagnostic criteria.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Arginine; Cosyntropin; Drug Combinations; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Diseases; Pituitary-Adrenal Function Tests

Low doses of ACTH [1-24] (0.1, 0.5 and 1.0 microg per 1.73 m2) may provide a more physiological level of adrenal stimulation than the standard 250 microg test, but not all studies have concluded that the 1.0 microg is a more sensitive screening test for central hypoadrenalism. Eight-hour infusions of high dose ACTH [1-24] have also been suggested as a means of assessing the adrenals' capacity for sustained cortisol secretion. In this study, we compared the diagnostic accuracy of three low dose ACTH tests (LDTs) and the 8-h infusion with the standard 250 microg test (HDT) and the insulin hypoglycaemia test (IHT) in patients with hypothalamic-pituitary disease.. Three groups of subjects were studied. A healthy control group (group 1, n = 9) and 33 patients with known hypothalamic or pituitary disease who were divided into group 2 (n = 12, underwent IHT) and group 3 (n = 21, IHT contraindicated). Six different tests were performed: a standard IHT (0.15 U/kg soluble insulin); a 60-minute 250 microg HDT; three different LDTs using 0.1 microg, 0.5 microg and 1.0 microg (all per 1.73 m2); and an 8-h infusion test (250 microg ACTH [1-24] at a constant rate over 8 h).. Nine out of the 12 patients in group 2 failed the IHT. Three out of 12 patients from group 2 who clearly passed the IHT, also passed all the ACTH [1-24] stimulation tests. Seven of the 9 patients who failed the IHT, failed by a clear margin (peak cortisol < 85% of the lowest normal). Two of the 7 also failed all the ACTH [1-24] tests. Five of the 7 patients had discordant results, four passed the 0.1 LDT, one (out of four) passed the 0.5 LDT, none (out of three) passed the 1.0 LDT, two passed the HDT and three passed the 8-h test. Two patients were regarded as borderline fails in the IHT. Both passed the ACTH [1-24] tests, although one was a borderline pass in the 8-h test. Only five out of the 21 patients in group 3 showed discordance between the HDT and the LDTs. One patient passed the HDT and failed the 0.1 LDT, four patients failed the HDT but passed some of the different LDTS.. We conclude that in the diagnosis of central hypoadrenalism, ACTH [1-24] stimulation tests may give misleading results compared to the IHT. The use of low bolus doses of ACTH [1-24] (1.0, 0.5 or 0.1 microg) or a high dose prolonged infusion does not greatly improve the sensitivity of ACTH [1-24] testing. Dynamic tests that provide a central stimulus remain preferable in the assessment of patients with suspected ACTH deficiency.

Topics: Adrenal Glands; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cosyntropin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Hypothalamic Diseases; Infusions, Intravenous; Injections, Intravenous; Insulin; Male; Middle Aged; Pituitary Diseases; Predictive Value of Tests; Single-Blind Method; Stimulation, Chemical

There is still uncertainty about what is the most appropriate test for assessment of the integrity of the hypothalamo-pituitary-adrenal (HPA) axis. Many advocate the insulin tolerance test (ITT), but this is unpleasant and resource intensive, and may occasionally give misleading results. The conventional [250 microg tetracosactrin, ACTH-(1-24)] short synacthen test (SST) has been used as a simple alternative to the ITT, but it has produced some falsely reassuring results with potentially serious consequences. A low dose [1 microg tetracosactrin, ACTH-(1-24)] short synacthen test (LDSST) has recently been advocated as a more reliable and safer alternative to ITT. Some studies, however, have failed to demonstrate any difference between SST and LDSST. The purpose of this study was to assess the clinical usefulness of LDSST compared to SST and ITT in patients with pituitary disease. We studied 64 patients with suspected or proven pituitary disease. All patients underwent SST and LDSST. Forty-two patients underwent ITT. There was a high correlation between the ITT and LDSST peak cortisol responses (r = 0.89; P < 0.0001), the ITT and SST 30 min cortisol levels (r = 0.83; P < 0.0001), and the LDSST peak cortisol response and the SST 30 min cortisol level (r = 0.85; P < 0.0001). In the LDSST, all but six patients achieved maximal cortisol response by 30 min. A plasma cortisol cut-off of 600 nmol/L is more helpful than 500 nmol/L for clinical decision-making using either the SST 30 min cortisol level or the LDSST peak cortisol response. The sensitivity of the LDSST was 100% (cortisol response of >600 nmol/L indicates intact HPA axis), with no falsely reassuring results. SST (pass cortisol level, >600 nmol/L) was less sensitive than LDSST, it produced 2 of 64 (3%) falsely reassuring results. Even the ITT (pass cortisol level, >500 nmol/L) failed to identify one patient with clinically evident cortisol deficiency. The results of this study indicate that both SST and LDSST, at a cortisol cut-off of 600 nmol/L, are safe for the purpose of clinical decision-making with regard to steroid replacement therapy in patients with pituitary disease. As the LDSST produced no falsely reassuring decisions, we suggest that this could replace the SST and ITT for initial evaluation of the HPA axis in patients with pituitary disease. We suggest administering 1 microg tetracosactrin, i.v., with sampling at 0, 20, and 30 min.

Topics: Adult; Aged; Cosyntropin; Dose-Response Relationship, Drug; Evaluation Studies as Topic; Humans; Hypothalamo-Hypophyseal System; Insulin; Insulin Resistance; Middle Aged; Pituitary Diseases; Pituitary-Adrenal System

The short synacthen test (SST) is an effective method of assessing the hypothalamo-pituitary-adrenal (HPA) axis in patients with pituitary disease. Chronic glucocorticoid therapy may result in suppression of the HPA axis, and use of the SST has not been evaluated in these patients. This study compares the SST with the insulin tolerance test (ITT) in patients on long-term corticosteroid therapy. Both tests were done on 22 patients on long-term, stable-dose prednisolone (< 10 mg/day). A pass was defined as a 30 minute plasma cortisol > 550 nmol/l for the SST and a maximal cortisol of > 500 nmol/l for the ITT. Five patients passed both tests; nine failed both. Eight patients had discrepant results; all passed the ITT but failed the SST. There was a significant correlation (p < 0.001) between the maximum cortisol level achieved during the ITT and the 30 min SST value and the incremental rise. There was an inverse correlation between the dose and duration of use of steroids and the cortisol response during both tests. The SST is a reliable, safe and easily performed initial assessment of the HPA axis in patients on long-term corticosteroids. The ITT remains a valuable test for those who fail the SST.

Topics: Adult; Aged; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary Diseases; Pituitary-Adrenal System; Prednisolone; Time Factors

Accurate assessment of adrenal function is essential in patients with hypothalamic-pituitary-adrenal (HPA) disease. The measurement of salivary cortisol (SaC) instead of serum cortisol (SeC) offers several advantages, such as the determination of the free hormone. We evaluated the diagnostic value of SeC and SaC both unstimulated and during a high-dose short synacthen test (HDT) in comparison to the insulin tolerance test (ITT).. Comparative study between 2005 and 2007.. Fifty-five patients with HPA impairment and 21 healthy controls were enrolled. Samples were collected in the early morning and over 120 min during the HDT. Receiver operating characteristic analysis revealed individual thresholds for four HDT periods (0-30, 0-60, 0-90, and 0-120 min).. The ITT identified 30 subjects as adrenal insufficient. With respect to the four HDT periods, sensitivity and specificity were 67-79% and 71-88% for SeC, compared with 63-72% and 72-86% for SaC. If upper and lower thresholds (with specificities >95%) were applied, patients were diagnosed in 40-45% by SeC and in 25-31% by SaC. The combination of basal cortisol and HDT allowed a diagnosis in 47-49% (SeC) and in 42-45% (SaC) respectively.. We suggest the determination of basal SeC or SaC as first-line test. In comparison to the ITT, the HDT has only limited value in screening for alterations of the HPA axis. If the HDT is performed, sampling may be limited to 30 min post-synacthen, using either SeC or SaC. Due to the ease of collection and the independence of binding proteins, SaC may be preferable.

Topics: Adrenal Insufficiency; Adult; Algorithms; Area Under Curve; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamic Diseases; Insulin; Male; Middle Aged; Pituitary Diseases; Random Allocation; ROC Curve; Saliva; Sensitivity and Specificity

Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic-pituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences.. In this study we evaluated the integrity of the HPA in 24 patients (age 4.2-31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency.. At a cortisol cut-off for a normal response of 550 nmol/l (20 microg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2-135.2 nmol/l (2.4-4.9 microg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST.. We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re-assessment of adrenal function.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Child, Preschool; Corticotropin-Releasing Hormone; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Human Growth Hormone; Humans; Hypoglycemia; Hypoglycemic Agents; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary Diseases; Pituitary-Adrenal System; Reproducibility of Results

The 1 microgram ACTH stimulation test has been advocated as a sensitive indicator of the integrity of the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism. The aim of our study was to define the normal response to 1 microgram ACTH stimulation in a control population and to study the sensitivity and specificity of the test in a group of patients with suspected pituitary disease.. A prospective analysis of the performance of the 1 microgram ACTH stimulation test in a group of patients with pituitary disease.. The cortisol response to 1 microgram ACTH was evaluated in 21 normal subjects and 65 patients with pituitary disease. The patients with pituitary disease were divided into two groups according to the 11-deoxycortisol response to overnight metyrapone: normal (11-deoxycortisol > 200 nmol/l) and subnormal ACTH secretory status (11-deoxycortisol < 200 nmol/l).. In both controls and patients, blood was sampled for cortisol at - 15, 0, + 20, + 30, + 40 and + 60 minutes after intravenous administration of 1 microgram synthetic ACTH (Synacthen(R)). The overnight metyrapone test was performed only in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered orally at 2300 h and blood was sampled at 0830 h the following morning for 11-deoxycortisol.. The 65 patients with pituitary disease were categorized according to the 11-deoxycortisol response to metyrapone as follows: 53 normal (11-deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients who failed the metyrapone test had a significantly impaired cortisol response to low dose ACTH stimulation at all time points when compared with both the control group and the pituitary patients with a normal response to metyrapone (P < 0.001). Comparing the pituitary patients who had a normal response to metyrapone and the control subjects, there was no significant difference in the cortisol response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the 21 control subjects was 414 nmol/l and this was defined as the minimum normal cortisol response to 1 microg ACTH. Using this criterion, six of the 12 patients with a subnormal response to metyrapone had a normal cortisol response to low dose ACTH stimulation. Empirically increasing the cortisol cut-off to 600 nmol/l increased the sensitivity of the low dose ACTH test to 83%, although the specificity was reduced from 100% to only 58%.. The normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 microgram ACTH stimulation test, like the 250 microgram-test, lacks sensitivity for the diagnosis of ACTH deficiency.

Topics: Adult; Case-Control Studies; Cortodoxone; Cosyntropin; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Pituitary Diseases; Reference Values; ROC Curve; Sensitivity and Specificity; Stimulation, Chemical

Topics: Cosyntropin; Humans; Hydrocortisone; Pituitary Diseases; Pituitary Function Tests; Predictive Value of Tests

Tetracosactin [corticotropin-(1-24)] is used for clinical testing of adrenocortical responsiveness. The usual dose [high dose test (HDT)] is 250 micrograms. With this test, patients with mild secondary adrenal insufficiency are usually not identified, thus putting them at risk of an adrenal crisis in stressful situations. It was recently reported that a tetracosactin test with approximately 1 micrograms [low dose test (LDT)] identifies patients with mild forms of pituitary-adrenal insufficiency. We performed both the HDT and the LDT in 35 control subjects and in 44 patients with pituitary disease, mostly pituitary tumors. In these patients, more sensitive reference tests for evaluating the pituitary-adrenal axis (insulin-induced hypoglycemia, metyrapone, and CRH tests) were also performed. In the HDT, plasma cortisol was measured 30 and 60 min after tetracosactin injection; in the LDT (0.5 microgram/m2 body surface area), plasma cortisol was measured 20, 30, 40, 50, and 60 min postinjection. In 6 control subjects, tetracosactin plasma levels were also measured after injection. In the HDT, the correlation between 30 and 60 min cortisol levels was extremely high (r = 0.991; P < 0.0001), but the correlation of the LDT with the HDT at 30 min was also highly significant (r = 0.948; P < 0.0001). The lower normal limit of cortisol responses (means of controls minus 2 SD) at 30 min was lower in the LDT by 3.1 micrograms/dL (85 nmol/L) than in the HDT. Compared with the reference tests, the diagnostic sensitivities of the HDT and the LDT were almost identical. Both tests identified patients with moderately to severely pathological insulin and metyrapone tests, but not those with slightly pathological reference tests. In the HDT, plasma tetracosactin rose to more than 60,000 pg/mL shortly after injection. In the LDT, it rose to 1,900 pg/mL. Both concentrations stimulate cortisol (supra-) maximally. Together, these data show that in pituitary disorders the results of the LDT and the HDT are almost identical. Plasma tetracosactin levels in the LDT still rise to levels that maximally stimulate the adrenal. Tetracosactin testing with low or high doses cannot generally replace the more expensive and cumbersome insulin or metyrapone tests.

Topics: Adult; Aged; Aged, 80 and over; Corticotropin-Releasing Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Insulin; Kinetics; Male; Metyrapone; Middle Aged; Pituitary Diseases; Pituitary Neoplasms

Topics: Adult; Cosyntropin; Female; Fluorescence Polarization Immunoassay; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Diseases

To define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic-pituitary disorders.. The cortisol response to 250 micrograms im ACTH1-24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post-ACTH cortisol results were also determined using the four immunoassays.. The distribution of cortisol results at all time points and for all methods were non-Gaussian and significant differences in the absolute values of the 5th-95th percentiles were found between methods (P < 0.01). At 30 min post-Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post-ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min.. The definition of the 'normal' response to Synacthen should be both gender and method related at all time points. The data suggest that up to one-third of untreated patients with pituitary disease may have subtle defects in the hypothalamic-pituitary-adrenal axis.

Topics: Adult; Aged; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Immunoassay; Male; Middle Aged; Pituitary Diseases; Pituitary-Adrenal Function Tests; Reference Values; Sensitivity and Specificity

Topics: Biomarkers; Cosyntropin; Humans; Hydrocortisone; Insulin; Pituitary Diseases; Predictive Value of Tests; Stress, Physiological

Topics: Adrenal Insufficiency; Cosyntropin; Humans; Insulin; Pituitary Diseases

The insulin tolerance test (ITT) has long been used to assess the hypothalamic-pituitary-adrenal axis, but may be hazardous. The standard synthetic ACTH (Synacthen) test has been advocated as a substitute but is sometimes insensitive. In this study the ITT has been compared to a low dose ACTH stimulation test (1 microg) and the standard ACTH stimulation test (250 microg).. Twenty-seven subjects were studied, 24 with verified or suspected hypothalamic-pituitary disorders and three on long-term glucocorticoid therapy.. Insulin tolerance, low dose ACTH and standard ACTH tests were performed in all patients. The ITT was performed less than 48 hours after the ACTH tests. Synacthen was administered as an intravenous bolus.. Serum cortisol values were determined by radioimmunoassay. The peak cortisol value during ITT was compared to the cortisol levels during the ACTH tests.. There was a highly significant correlation between peak cortisol values during ITT and cortisol levels after 20-60 minutes in the low dose ACTH test (r(s) = 0.91-0.93; P < 0.0001) and after 30 and 60 minutes in the standard ACTH test (r(s) = 0.85 and 0.89 respectively; P < 0.0001). Four patients showed discrepancies between the three tests.. The 1-microg ACTH test follows the ITT more closely and may be more sensitive than the standard ACTH test in detecting more subtle insufficiency of the hypothalamic-pituitary-adrenal axis. The standard ACTH test and the insulin tolerance test may thus be replaced by the 1-microg ACTH test in screening for secondary cortisol insufficiency. We recommend that serum cortisol is measured before and 30 and 40 minutes after the ACTH injection.

Topics: Adult; Aged; Cosyntropin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary Diseases; Pituitary-Adrenal System; Predictive Value of Tests; Stimulation, Chemical

Topics: Cosyntropin; Drug Administration Schedule; Humans; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Pituitary Diseases; Pituitary-Adrenal System; Predictive Value of Tests; Sensitivity and Specificity; Stimulation, Chemical

We wished to compare peak and incremental rise in plasma cortisol in response to insulin induced hypoglycaemia (IIH) stress test, i.m. glucagon stimulation test (IMGST) and short Synacthen test (SST) in patients with pituitary disease, using a modern radioimmunoassay for cortisol. We compared the three stimulants using receiver operator characteristic (ROC) plots, assuming a cortisol threshold of 500 nmol/l or 580 nmol/l for the IIH stress test which we used as the standard from which to evaluate the SST and the IMGST.. We prospectively studied 16 patients (8F, 8M mean age 43.69 +/- 3.72 years) admitted to the investigation ward for IIH stress test and who were asked to undergo two additional tests (IMGST and SST) on consecutive days.. We measured serum cortisol at baseline, 30, 45, 60, 90 and 120 minutes during the IIH stress test; baseline, 150 and 180 minutes during GST, and baseline and 30 minutes during the SST.. There was a significant rise in cortisol from baseline in all tests (P < 0.001). There was no significant difference among the peak plasma cortisol responses or the incremental rises in plasma cortisol following IMGST, SST and IIH stress test (repeated measures ANOVA F = 0.704, P = 0.503; F = 0.238, P = 0.79). The ROC plots clearly showed that the SST has poor diagnostic utility at both IIH thresholds, compared with the IMGST.. The peaks and incremental rises in cortisol following all three tests are comparable. Using the insulin induced hypoglycaemia stress test as a reference and peak cortisol thresholds of 500 and 580 nmol/l as discriminating variables, the short Synacthen displayed poor diagnostic utility when compared to the i.m. glucagon stimulation test. The short Synacthen may be misleading if used as a screening test as advocated by a number of authors.

Topics: Adult; Analysis of Variance; Cosyntropin; Female; Glucagon; Humans; Hydrocortisone; Injections, Intramuscular; Insulin; Male; Middle Aged; Pituitary Diseases; Pituitary Function Tests; Pituitary Gland; Predictive Value of Tests; Prospective Studies; Radioimmunoassay

The natural history and pathogenesis of lymphocytic hypophysitis remain poorly understood. We describe a 34-yr-old woman with postpartum thyroiditis and ACTH deficiency, studied at monthly intervals for 18 months after pregnancy. A significant titer of thyroid peroxidase autoantibodies was detected at 16 weeks gestation, and she was recruited into a prospective study of postpartum thyroid function. Four months postpartum she developed mild hyperthyroidism [free T4 (fT4), 27 pmol/L; TSH, less than 0.2 mU/L] and showed a rise in thyroid peroxidase and thyroglobulin autoantibodies. At 9 months postpartum, serum fT4 and fT3 levels were low normal (8.0 and 1.7 pmol/L, respectively), but TSH was not raised (0.4 mU/L). Subsequent investigation showed a low basal plasma cortisol level (28 nmol/L) in association with undetectable ACTH, and subnormal cortisol responses to depot Synacthen (535 nmol/L at 6 h) and hypoglycemia (peak, 145 nmol/L). FSH, LH, GH, and PRL function and computerized tomography of the pituitary were normal. Retrospective analysis of serum samples taken throughout the postpartum year showed developing hypocortisolemia between 3-9 months postpartum. Each sample was also tested for pituitary autoantibodies using a specific indirect immunofluorescent assay; none was detected. The ACTH deficiency recovered spontaneously, with normal cortisol responses to depot Synacthen (greater than 1380 at 6 h) and hypoglycemia (peak, 590) 14 and 18 months postpartum, respectively. This case illustrates that postpartum pituitary deficiencies are potentially reversible. The pattern of pituitary deficit and postpartum thyroiditis supported a diagnosis of autoimmune hypophysitis.

Topics: Adrenocorticotropic Hormone; Adult; Autoantibodies; Autoimmune Diseases; Cosyntropin; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Iodide Peroxidase; Pituitary Diseases; Pregnancy; Pregnancy Complications; Puerperal Disorders; Thyroiditis, Autoimmune; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine