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Serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates in healthy dogs following stimulation with two doses of cosyntropin.

OBJECTIVE: To compare the effects of 2 doses of cosyntropin (5 microg/kg vs 250 microg, IV) on serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates and determine the optimal sample collection time after adrenal stimulation with cosyntropin. ANIMALS: 10 healthy, privately owned, neutered dogs. PROCEDURE: Dogs were randomly assigned to initially receive cosyntropin at 5 microg/kg or as a total dose of 250 microg, IV. Dogs received the alternate dose 1 to 2 weeks later. Serum was obtained from blood samples collected before (0 minutes) and 30, 60, 90, and 120 minutes after cosyntropin administration. RESULTS: Maximum stimulation of cortisol, androstenedione, progesterone, and 17-hydroxyprogesterone production was achieved at 60 minutes following IV administration of cosyntropin at 5 microg/kg or as a total dose of 250 microg. Serum estradiol concentration did not increase in response to either cosyntropin dose. For all hormones, no significant difference in serum hormone concentrations was found among sample collection times of 0, 30, 60, and 90 minutes when comparing the 2 doses of cosyntropin. CONCLUSIONS AND CLINICAL RELEVANCE: Cosyntropin, when administered at 5 microg/kg, IV, effectively stimulated maximum production of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates at 1 hour after administration.

17-alpha-Hydroxyprogesterone↗

The rapid low-dose (1 microgram) cosyntropin test in the immediate postoperative period: results in elderly subjects after major abdominal surgery.

BACKGROUND: Recently the rapid low-dose (1 microgram) cosyntropin test has been found to be superior to the standard (250 micrograms) rapid cosyntropin test for evaluating the hypothalamic-pituitary-adrenal axis. Because the 1-microgram test has not been studied in postoperative patients, we evaluated the test after major abdominal surgery. METHODS: We performed rapid 1-microgram cosyntropin tests in 20 patients aged 65 years or older immediately and 24 hours after uncomplicated elective abdominal surgery (group A) and in 10 patients who were suspected of having adrenal insufficiency after abdominal surgery (group B). Subsequently, 250 micrograms of cosyntropin was infused over 8 hours on 2 successive days in group B patients. RESULTS: Ninety-five percent of group A patients had normal rapid 1-microgram cosyntropin test results immediately after surgery and 90% had normal test results 24 hours postoperatively. Six group B patients had abnormal rapid 1-microgram cosyntropin test results. Additional testing indicated primary adrenal insufficiency in 2 patients and central adrenal insufficiency in 1 patient; another patient probably had primary adrenal insufficiency and 2 patients appeared to be euadrenal. Four group B patients had normal rapid 1-microgram cosyntropin test results. After additional testing, 3 of these patients appeared to have normal adrenal function; 1 probably had primary adrenal insufficiency. CONCLUSION: The rapid 1-microgram cosyntropin test accurately evaluated adrenal gland function in selected patients after uncomplicated surgery. The test, however, was difficult to interpret in unselected seriously ill postoperative patients. Therefore we recommend that postoperative patients with unexplained hypotension or other features suggestive of adrenal insufficiency who have random plasma cortisol levels less than 20 micrograms/dL be treated with glucocorticoids and the hypothalamic-pituitary-adrenal axis be studied by standard tests after recovery.

Abdominal Neoplasms↗

Comparison of intravenous and intramuscular routes of administering cosyntropin for corticotropin stimulation testing in cats.

Plasma cortisol and immunoreactive (IR)-ACTH responses to 125 micrograms of synthetic ACTH (cosyntropin) administered IV or IM were compared in 10 clinically normal cats. After IM administration of cosyntropin, mean plasma cortisol concentration increased significantly (P less than 0.05) within 15 minutes, reached maximal concentration at 45 minutes, and decreased to values not significantly different from baseline concentration by 2 hours. After IV administration of cosyntropin, mean plasma cortisol concentration also increased significantly (P less than 0.05) at 15 minutes, but in contrast to IM administration, the maximal cortisol response took longer (75 minutes) and cortisol concentration remained significantly (P less than 0.05) higher than baseline cortisol concentration for 4 hours. Mean peak cortisol concentration (298 nmol/L) after IV administration of cosyntropin was significantly (P less than 0.05) higher than the peak value (248 nmol/L) after IM administration. All individual peak plasma cortisol concentrations and areas under the plasma cortisol response curve were significantly (P less than 0.05) higher after IV administration of cosyntropin than after IM administration. Mean plasma IR-ACTH concentration returned to values not statistically different from baseline by 60 minutes after IM administration of cosyntropin, whereas IR-ACTH concentration still was higher than baseline concentration 6 hours after IV administration. Peak plasma IR-ACTH concentration and area under the plasma IR-ACTH response curve also were significantly (P less than 0.05) higher after IV administration of cosyntropin. Results of the study confirmed that IV administration of cosyntropin induces significantly (P less than 0.05) greater and more prolonged adrenocortical stimulation than does IM administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Can 1 microg of cosyntropin be used to evaluate adrenal insufficiency in critically ill patients?

OBJECTIVE: To evaluate the utility of cosyntropin 1 microg in assessing adrenal function in critically ill patients. DATA SOURCES: A computerized literature search using MEDLINE, EMBASE, International Pharmaceutical Abstracts, and the Cochrane Database (1966-August 2004) was undertaken for trials evaluating cosyntropin 1 mug using the following search terms: adrenocorticotropin-releasing hormone (ACTH), cosyntropin, adrenal insufficiency, cortisol, corticosteroids, glucocorticoids, sepsis, septic shock, diagnosis, critically ill, intensive care, and critical care. STUDY SELECTION AND DATA SYNTHESIS: Identifying patients with sepsis with relative adrenal insufficiency (AI) using cosyntropin testing may identify those likely to benefit from corticosteroids. The results of 5 heterogeneous studies in non-intensive care unit (ICU) patients suggest that both 1 microg and 250 microg of cosyntropin stimulate similar cortisol responses and that testing using both doses correlates well with results from insulin tolerance testing. Some data from non-ICU patients suggest that the 1-microg test may be more sensitive to detect AI; 3 heterogeneous studies in ICU patients confirmed the improved sensitivity of the 1-microg test. CONCLUSIONS: Use of cosyntropin 1 microg should detect AI in all patients who would have been diagnosed using 250 microg. Unfortunately, all of the clinical trials evaluating the role of corticosteroids in septic shock that used the cosyntropin stimulation test administered 250 microg. Extrapolation of the existing guidelines to treat patients with septic shock testing positive for relative AI using the 1-microg test may provide effective therapy to appropriate patients not diagnosed by the 250-microg testing or may introduce additional adverse effects in patients who should not receive corticosteroids. Large-scale, head-to-head comparison data of steroid effectiveness after 1- and 250-microg ACTH stimulation tests are needed to expand upon these promising results.

Adrenal Insufficiency↗

Comparison of serum cortisol concentrations in clinically normal dogs after administration of freshly reconstituted versus reconstituted and stored frozen cosyntropin.

OBJECTIVE: To evaluate the biological stability of reconstituted cosyntropin after storage at -20 C for 2, 4, and 6 months. DESIGN: Prospective study. ANIMALS: 10 clinically normal dogs. PROCEDURE: Serum cortisol concentrations in dogs were determined before and 1 hour after administration of freshly reconstituted cosyntropin (synthetic ACTH) or cosyntropin that had been reconstituted and stored frozen at -20 C in plastic syringes for 2, 4, and 6 months. Cosyntropin was administered at 5 micrograms/kg (2.3 micrograms/lb) of body weight, i.v. RESULTS: Baseline serum cortisol concentrations were similar at each sampling time. Compared with the effects of freshly reconstituted cosyntropin, administration of cosyntropin that had been frozen did not have a significantly different effect on serum cortisol concentrations. CLINICAL IMPLICATIONS: Cosyntropin can be reconstituted and stored frozen at -20 C in plastic syringes for 6 months with no adverse effects on bioactivity of the polypeptide.

Animals↗

A high-sensitivity test in the assessment of adrenocortical insufficiency: 10 microg vs 250 microg cosyntropin dose assessment of adrenocortical insufficiency.

The short cosyntropin (synthetic ACTH) test is recognized as the best screening manoeuvre in the assessment of adrenocortical insufficiency. Recent data, however, suggest that i.v. administration of 250 microg cosyntropin could be a pharmacological rather than a physiological stimulus, losing sensitivity for detecting adrenocortical failure. Our objective was to compare 10 vs 250 microg cosyntropin in order to find differences in serum cortisol peaks in healthy individuals, the adrenocortical response in a variety of hypothalamic-pituitary-adrenal axis disorders and the highest sensitivity and specificity serum cortisol cut-off point values. The subjects were 83 healthy people and 37 patients, the latter having Addison's disease (11), pituitary adenomas (7), Sheehan's syndrome (9) and recent use of glucocorticoid therapy (10). Forty-six healthy subjects and all patients underwent low- and standard-dose cosyntropin testing. In addition, 37 controls underwent the low-dose test. On comparing low- and standard-dose cosyntropin testing in healthy subjects there were no statistical differences in baseline and peaks of serum cortisol. In the group of patients, 2 out of 11 cases of Addison's disease showed normal cortisol criterion values during the standard test but abnormal during the low-dose test. In our group of patients and controls, the statistical analysis displayed a better sensitivity of the low-dose vs standard-dose ACTH test at 30 and 60 min. In conclusion, these results suggest that the use of 10 microg rather than 250 microg cosyntropin i.v. in the assessment of suspicious adrenocortical dysfunction gives better results.

Addison Disease↗

Adrenal function in the cat: comparison of the effects of cosyntropin (synthetic ACTH) and corticotropin gel stimulation.

The serum cortisol responses of 10 normal cats to natural adrenocorticotrophic hormone (ACTH) gel and synthetic ACTH (cosyntropin) were evaluated and compared. Following administration of either ACTH gel or cosyntropin, mean serum cortisol concentrations increased significantly (P less than 0.05) within 30 minutes and reached a maximal response (2.5 to 10 times basal values) at 90 minutes. The time to reach peak serum cortisol concentrations was variable, however, and occurred sooner after cosyntropin (30 to 60 minutes) than after ACTH gel administration (90 to 180 minutes). While ACTH gel tended to produce a prolonged cortisol response, the effects of cosyntropin were more transient, with serum cortisol concentrations returning to normal range within three hours after injection. Results of this study indicate that the administration of either ACTH gel or cosyntropin consistently produces an adequate adrenocortical response in the cat. Based on the time response studies, post ACTH cortisol samples should be collected 60 to 90 minutes after cosyntropin or 90 to 120 minutes after ACTH gel injection to ensure detection of peak adrenocortical response with either ACTH preparation.

Adrenal Cortex↗

Effects of dexamethasone infusion on the plasma cortisol response to cosyntropin (synthetic ACTH) injection in normal dogs.

Graded dosages of cosyntropin (synthetic corticotropin) were injected into groups of normal dogs on consecutive days. On the first day, cosyntropin was administered alone and, on the second, dogs were infused with dexamethasone three hours before cosyntropin injection. Adrenocortical function was assessed by sequential measurement of plasma cortisol (hydrocortisone) concentration. While no response differences were noted to the various amounts of cosyntropin injected with or without dexamethasone pretreatment, the magnitude of adrenocortical response was significantly greater in dogs infused with dexamethasone. It is concluded that dexamethasone pretreatment renders the canine adrenal cortex more responsive to a subsequent injection of cosyntropin. The combined dexamethasone infusion-cosyntropin injection test produces consistent adrenocortical responses in normal dogs, and has potential value in evaluation of adrenopathic dogs.

Adrenal Glands↗

Enhanced adrenocortical sensitivity to submaximal doses of cosyntropin (alpha1-24-corticotropin) in depressed patients.

There is evidence that excessive cortisol secretion in depressed patients might result, in part, from an enhanced adrenocortical sensitivity to corticotropin. This phenomenon has been examined using the cosyntropin (alpha1-24-corticotropin) stimulation test. Most studies have used supramaximal doses of cosyntropin administered in the morning, when adrenal sensitivity to corticotropin is at its maximum. This could partially obscure subtle differences in adrenocortical sensitivity in depression that might otherwise be evident at lower cosyntropin doses given later in the day. To test this hypothesis, we administered two consecutive cosyntropin tests on separate occasions employing a submaximal 0.05-microgram/kg dose and a maximal 0.2-microgram/kg dose. The cortisol centered cumulative response over 240 minutes was measured after each test in 12 depressed patients (7 melancholic, 5 nonmelancholic) and 6 healthy volunteers. When the difference in mean cortisol centered cumulative response values was determined, healthy controls demonstrated a significant increase in cortisol centered cumulative response, while the nonmelancholic patients had a less robust increase in cortisol centered cumulative response. In contrast, the melancholic patients demonstrated cortisol responses similar to those of the healthy subjects after each cosyntropin dose, suggesting an enhanced adrenocortical sensitivity to corticotropin. These data support the hypothesis that increased glucocorticoid secretion in depression may result from abnormalities at several sites within the hypothalamic-pituitary-adrenocortical axis.

Adrenal Cortex↗

Prevalence of abnormal adrenocortical function in human immunodeficiency virus infection by low-dose cosyntropin test.

Recent evidence suggests that 10 microg cosyntropin test has higher sensitivity for detecting hypothalamus-hypophysis-adrenal axis (HHA-A) dysfunction. Our objective was to determine prevalence of glucocorticoid insufficiency with the 10 microg cosyntropin test and the level of the HHA-A defect. One hundred and four HIV-infected patients underwent the 10 microg cosyntropin test. In abnormal and borderline respondents, insulin-induced hypoglycaemia test and human corticotropin releasing hormone test were used to confirm and localize the level of the HHA-A defect. Thirty-two patients with HIV infection and 72 with AIDS were identified. Prevalence of glucocorticoid insufficiency by the 10 microg cosyntropin test was 21.2%. By clinical categories, the frequency in AIDS and HIV infection patients was 26.4% and 9.4%, respectively. Confirmed glucocorticoid insufficiency by insulin-induced hypoglycaemia test was found in 16 out of 19 cases. Twelve cases had primary glucocorticoid insufficiency, 7 had secondary glucocorticoid insufficiency and 3 were false positive. In conclusion, adrenocortical dysfunction occurs in approximately 20% of the cases with HIV disease. Clinical findings commonly occurring in HIV disease as well as adrenocortical insufficiency are not reliable indicators for performing adrenocortical laboratory assessment. Our results suggest screening all AIDS patients with the 10 microg cosyntropin test.

Acquired Immunodeficiency Syndrome↗

Comparison of the immunoreactive plasma corticotropin and cortisol responses to two synthetic corticotropin preparations (tetracosactrin and cosyntropin) in healthy cats.

Plasma cortisol and immunoreactive (IR)-ACTH responses to 125 micrograms of tetracosactrin and cosyntropin--the formulation of synthetic ACTH available in Europe and the United States, respectively--were compared in 10 clinically normal cats. After administration of tetracosactrin or cosyntropin, mean plasma cortisol concentration reached a peak and plateaued between 60 and 120 minutes, then gradually decreased to values not significantly different from baseline concentration by 5 hours. Mean plasma IR-ACTH concentration reached a maximal value at 15 minutes after administration of tetracosactrin or cosyntropin and was still higher than baseline concentration at 6 hours. Difference between mean plasma cortisol and IR-ACTH concentrations for the tetracosactrin or cosyntropin trials was not significant at any of the sample collection times. Individual cats had some variation in the time of peak cortisol response after administration of either ACTH preparation. About half the cats had peak cortisol concentration at 60 to 90 minutes, whereas the remainder had the peak response at 2 to 4 hours. In general, however, peak cortisol concentration in the cats with delayed response was not much higher than the cortisol concentration at 60 to 90 minutes. Overall, these results indicate that tetracosactrin or cosyntropin induce a comparable, if not identical, pattern of adrenocortical responses when administered to healthy cats.

Adrenocorticotropic Hormone↗

Adrenal gland function in the horse: effects of cosyntropin (synthetic) and corticotropin (natural) stimulation.

The plasma concentration of hydrocortisone was determined in mares given either cosyntropin (100 IU, given IV) or corticotropin (200 IU, given IM). Plasma hydrocortisone concentrations of the mares treated with cosyntropin increased by 46%, 57% and 80% at 30, 60, and 120 minutes, respectively, when compared with base-line values; these values returned to base line at 240 minutes. In mares treated with corticotropin, mean plasma hydrocortisone concentrations increased by 42%, 143%, 101% and 155% at 30, 60, 120, and 240 minutes, respectively, when compared with base-line values. Differences in total leukocyte count, total eosinophil count, and plasma concentrations of electrolytes (calcium, sodium, magnesium, potassium) of cosyntropin- and corticotropin-treated mares, and these values in control animals were not significant. Results of the present study indicated that the horse responds to small dosages of cosyntropin (IV) in a prompt and reproducible manner as determined by plasma hydrocortisone values. Response to corticotropin was slow and less consistent. Thus, administration of cosyntropin to the horse, according to test results with paired samples collected (before administration and again at 2 hours after injection), was found to be a prompt and meaningful test of adrenal gland function.

Adrenal Glands↗

Dose-response relation between plasma concentrations of corticotropin and cortisol after administration of incremental doses of cosyntropin for corticotropin stimulation testing in cats.

We compared the plasma cortisol and immunoreactive corticotropin (IR-ACTH) responses to incremental doses (1.25, 12.5 and 125 micrograms) of synthetic ACTH (cosyntropin) administered IV to 6 clinically normal cats. Mean plasma cortisol concentration increased significantly (P < 0.0001) after administration of all 3 doses of cosyntropin. After administration of the 1.25- and 12.5-microgram doses, plasma cortisol concentration peaked at 30 minutes, then decreased to values not significantly different from baseline concentration by 90 and 120 minutes, respectively. In contrast, after administration of the 125-micrograms dose, mean cortisol concentration peaked at 60 minutes and remained significantly (P < 0.05) higher than baseline values at 120 minutes. Compared with the 1.25- and 12.5-micrograms doses, administration of the 125-micrograms dose of cosyntropin induced significantly (P < 0.05) higher cortisol responses at 60, 90, and 120 minutes. Although individual cat's peak plasma cortisol concentration after administration of the 125-micrograms dose was higher than the peak value determined after administration of the 2 lower doses of cosyntropin, these differences were not statistically significant. Mean plasma IR-ACTH concentration increased significantly (P < 0.0001) and reached a maximal value at 30 minutes after administration of all 3 doses of cosyntropin. After administration of the 1.25- and 12.5-micrograms doses, plasma IR-ACTH concentration decreased to values not significantly different from baseline concentration by 60 and 120 minutes, respectively, whereas mean IR-ACTH concentration remained significantly (P < 0.05) higher than baseline values 120 minutes after administration of the 125-micrograms dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test in the dog: new approach to testing of adrenal gland function.

A combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test was developed in the dog so that information concerning pituitary gland (hypophysis) and adrenal gland competence could be provided in a single trial, during a short time span. Treatment of dogs with dexamethasone (0.1 mg/kg, IM) resulted in total suppression (below assay sensitivity or < 10 ng/ml) of plasma hydrocortisone (cortisol) at postinjection hour (PIH) 2 in 100% of the dogs, whereas suppression was inconsistent at PIH 1. Cosyntropin (0.5 U/kg, IV) administration to normal or dexamethasone-suppressed dogs increased plasma hydrocortisone concentration 3.5 to 4.5 times base-line values at PIH 1, which was the time of maximal effect. The combined test concept for adrenal gland function is valid, convenient (three sample collections; 3-hour period), and allows testing of adrenal gland response to dexamethasone suppression and ACTH stimulation in a single trial. The following test procedure for dogs is recommended: (i) collect base-line plasma sample (0900 hours) followed by injection of dexamethasone (0.1 mg/kg, IM); (ii) collect second plasma sample 2 hours after dexamethasone (to evaluate suppression of plasma hydrocortisone concentration) followed by the injection of cosyntropin (0.5 U/kg, IV); and (iii) collect a third plasma sample 1 hour later to evaluate plasma hydrocortisone concentration after cosyntropin stimulation.

Adrenal Glands↗

Enhanced adrenal sensitivity to exogenous cosyntropin (ACTH alpha 1-24) stimulation in major depression. Relationship to dexamethasone suppression test results.

ACTH alpha 1-24 (cosyntropin) (250 micrograms by intravenous bolus) was given to 38 medicated patients with major depressive disorder (MDD) and to 34 normal control subjects. Patients with MDD had significantly higher plasma cortisol concentrations and significantly higher increases in plasma cortisol levels 60 minutes after cosyntropin infusion than did control subjects. Patients who were nonsuppressors in the dexamethasone suppression test had significantly higher 60-minute cortisol concentrations and cortisol increases than did normal subjects and patients with MDD who were suppressors. There were significant, strongly positive correlations between cortisol secretory responses to cosyntropin and postdexamethasone cortisol concentrations in patients with MDD. These findings confirm that adrenal sensitivity to corticotropin (ACTH) is enhanced in MDD and suggest that this endocrine abnormality may be related pathophysiologically to the resistance of cortisol secretion to dexamethasone suppression.

Adolescent↗

The use of a cosyntropin stimulation test to predict adrenal suppression in renal transplant patients being withdrawn from prednisone.

Eighteen renal transplant patients were studied to identify predictors of steroid-induced adrenal suppression. A cosyntropin adrenal stimulation test was administered to each patient and the response was correlated with the past transplant course and their subsequent prognosis. Eight (44%) of the 18 patients studied had a suppressed cosyntropin stimulation test. The suppressed adrenal response could not be predicted accurately by any one factor, although a history of a total prednisone dose greater than 25 g or a duration of steroid therapy of more than 12 months occurred more often among the suppressed patients. Four of the five deaths occurred among the suppressed patients. These deaths occurred despite maintenance of steroid administration. The cosyntropin stimulation test can be easily performed to identify renal transplant patients at risk of steroid-induced adrenal suppression when rapid steroid tapering is desired. An unsuppressed response gives assurance that steroid withdrawal is safe.

Adolescent↗

Adrenal response to serial cosyntropin stimulation after repeated high-dose prednisone administration in patients with lymphoma.

To determine if repeated courses of high-dose prednisone given to patients with lymphoma as part of multiple-drug chemotherapy programs would lead to progressive adrenal suppression, serial cosyntropin stimulation tests were performed. Four patients with diffuse histiocytic lymphoma (group 1) received prednisone for 5 days every 3 weeks for five courses, and five patients with Hodgkin's disease (group 2) received prednisone for 14 days every 4 weeks for six courses. Testing was done on Day 1 of each treatment course prior to the administration of therapy and after the final course of chemotherapy. In group 1 patients, there was no evidence of adrenal suppression after any of the courses of prednisone. The plasma cortisol increments after cosyntropin injection were also normal. In the group 2 patients, significant depression of basal plasma cortisol concentrations was observed after the first and fifth courses of prednisone, compared to the pretreatment values. The depression reflected the previous course of prednisone administration only and was not progressive with subsequent courses. The plasma cortisol increments after cosyntropin injection were normal despite depressed basal plasma cortisol levels.

Adrenal Cortex Function Tests↗

Severe hyperkalemia in two patients with diabetes after cosyntropin administration.

Some patients with diabetes mellitus are at increased risk for the development of hyperkalemia. Included in this group are patients with glucose-induced hyperkalemia who may have renal insufficiency, hyporeninemic hypoaldosteronism, or other impediments to the release or action of aldosterone. In an unusual demonstration of this abnormality, two patients with diabetes, who form the basis of our report, became markedly hyperglycemic and hyperkalemic after cosyntropin administration. To our knowledge, this complication of adrenocorticotropic hormone (ACTH) stimulation testing has not been previously reported. It should therefore be emphasized that the use of cosyntropin as a diagnostic agent can provoke severe hyperglycemia and hyperkalemia in a susceptible subgroup of patients with diabetes mellitus.

Aldosterone↗