Cortisol response to two different doses of intravenous synthetic ACTH (tetracosactrin) in overweight cats

Fifteen middle-aged to older, overweight cats attending a first-opinion clinic were investigated to rule out hyperadrenocorticism as a cause of their weight problem, using two different protocols for the adrenocorticotropic hormone (ACTH) stimulation test. The cats received intravenous synthetic ACTH (tetracosactrin) at an initial dose of 125 microg; a second test was performed between two and three weeks later, using a dose of 250 microg intravenously. The mean basal serum cortisol concentration was 203 nmol/litre (range 81 to 354 nmol/litre). The highest mean serum cortisol concentration occurred at 60 minutes following the 125 microg dose and at 120 minutes following the 250 microg dose. There was, however, no statistically significant difference between these peak cortisol concentrations attained using either dose of tetracosactrin. A significantly higher mean serum cortisol concentration was attained after the higher dose at the 180 minutes time point, indicating a more prolonged response when compared with the lower dose. The cats were followed up for one year after the initial investigations and none were found to develop hyperadrenocorticism during this time.     

Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats

Plasma cortisol responses of 19 healthy cats to synthetic ACTH and dexamethasone sodium phosphate (DSP) were evaluated. After administration of 0.125 mg (n = 5) or 0.25 mg (n = 6) of synthetic ACTH, IM, mean plasma cortisol concentrations increased significantly (P less than 0.05) at 15 minutes, reached a peak at 30 minutes, and decreased progressively to base-line values by 120 minutes. There was no significant difference (P greater than 0.05) between responses resulting from the 2 dosage rates. After administration of 1 mg of DSP/kg of body weight, IV (n = 7), mean plasma cortisol concentrations decreased at postadministration hour (PAH) 1, and were significantly lower than control cortisol concentrations at PAH 4, 6, 8, 10, and 12 (P less than 0.01). Administration of 0.1 mg of DSP/kg, IV (n = 8) or 0.01 mg of DSP/kg, IV (n = 14) induced results that were similar, but less consistent than those after the 1 mg of DSP/kg dosage. Mean plasma cortisol concentrations returned to base-line values by PAH 24. There was not a significant difference between the 3 doses (P greater than 0.05) at most times. Measurement of endogenous ACTH in 16 healthy cats revealed plasma ACTH of less than 20 to 61 pg/ml. Seemingly, administration of synthetic ACTH consistently induced a significant (P less than 0.05) adrenocortical response in healthy cats. On the basis of time-response studies, post-ACTH stimulation cortisol samples should be collected at 30 minutes after ACTH administration to ensure detection of peak adrenocortical response.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 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.     

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 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.     

Effects of single intravenous doses of dexamethasone on baseline plasma cortisol concentrations and responses to synthetic ACTH in healthy dogs

The duration of adrenocortical suppression resulting from a single IV dose of dexamethasone or dexamethasone sodium phosphate was determined in dogs. At 0800 hours, 5 groups of dogs (n = 4/group) were treated with 0.01 or 0.1 mg of either agent/kg of body weight or saline solution (controls). Plasma cortisol concentrations were significantly (P less than 0.01) depressed in dogs given either dose of dexamethasone or dexamethasone sodium phosphate by posttreatment hour (PTH) 2 and concentrations remained suppressed for at least 16 hours. However, by PTH 24, plasma cortisol concentrations in all dogs, except those given 0.1 mg of dexamethasone/kg, returned to control values. Adrenocortical suppression was evident in dogs given 0.1 mg of dexamethasone/kg for up to 32 hours. The effect of dexamethasone pretreatment on the adrenocortical response to ACTH was studied in the same dogs 2 weeks later. Two groups of dogs (n = 10/group) were tested with 1 microgram of synthetic ACTH/kg given at 1000 hours or 1400 hours. One week later, half of the dogs in each group were given 0.01 mg of dexamethasone/kg at 0600 hours, whereas the remaining dogs were given 0.1 mg of dexamethasone/kg. The ACTH response test was then repeated so that the interval between dexamethasone treatment and ACTH injection was 4 hours (ACTH given at 1000 hours) or 8 hours (ACTH given at 1400 hours). Base-line plasma cortisol concentrations were reduced in all dogs given dexamethasone 4 or 8 hours previously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parasites as stressors: plasma cortisol responses of goats infected with the stomach worm Haemonchus contortus to exogenous corticotropin (ACTH)

Ten male, juvenile pigmy goats of similar age and weight were allocated randomly to two groups. Goats in one group were each inoculated with 20,000 infective larvae of Haemonchus contortus. The other group served as uninfected controls. Goats were housed together, and precautions were taken to avoid the creation of differential, between group, stressogenic circumstances. Body weights, nematode egg production, hematocrits, and clinical signs were monitored over a 61-day period following inoculation of larvae. On Days 59 and 61, adrenal response tests (ART) were conducted by measuring the levels of plasma cortisol before and 2 h after administration of porcine ACTH at the rate of 0.35 I.U. kg-1 body weight on Day 59 and 2.2 I.U. kg-1 on Day 61. Although the infections did not reduce body weights, they were 'heavy' on the basis of egg production, and led to significant reductions in packed erythrocyte volumes. There was no significant difference between the groups of goats in the responses to ART, indicating that the infections did not produce sufficient stress to reduce the ability of the adrenal cortex to respond to exogenous ACTH.     

Comparative effects of proligestone and megestrol acetate on basal plasma glucose concentrations and cortisol responses to exogenous adrenocorticotrophic hormone in cats

Cats were given megestrol acetate (MA, 5 mg once daily for 14 days), subcutaneous proligestone (PRG, 100 mg on two occasions one week apart) or subcutaneous saline (1 ml as for PRG). In cats given saline (n = 6) basal cortical concentrations, cortisol concentrations after adrenocorticotrophic hormone (ACTH) administration and fasting blood glucose concentrations did not change significantly during the following seven weeks. Cats given MA (n = 7) developed suppression of basal and ACTH-stimulated cortisol concentrations and fasting hyperglycaemia during treatment. Effects on cortisol persisted for two weeks after MA dosage ceased. In cats given PRG (n = 7), basal cortisol concentrations were reduced overall, but only three cats had persistently suppressed post-ACTH cortisol concentrations. Adrenal suppression continued for 14 weeks in one of these and for at least 22 weeks in two cats. Fasting blood glucose concentrations were unchanged in PRG-treated cats.     

Measurements of plasma endothelin immunoreactivity in healthy cats and cats with cardiomyopathy

Plasma concentrations of endothelin-1 (ET-1), the most potent endogenous pressor substance discovered to date, are abnormally high in humans with congestive heart failure (CHF), and they correlate with the degree of functional impairment. We sought first to validate a human sandwich ELISA kit that targets that portion of the amino acid sequence that is identical in cats. The assay demonstrated linearity (R2 = .9968) and parallelism (P = .5339), recovery of spiked human ET-1 in cat plasma averaged 98.7%, and intraassay precision had a coefficient of variation <10%. We subsequently determined ET-1 immunoreactivity in healthy cats and in cats with myocardial disease with and without CHF, systemic thromboembolism (STE), or both. Plasma ET-1 immunoreactivity was measured in 12 healthy cats and in 28 cats with primary myocardial disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive or unclassified cardiomyopathy (RCM and UCM), respectively. Plasma ET mean (95% CI) concentrations were 0.777 (0.6536-0.924) fmol/mL in the control cats, 1.427 (0.922-2.209) fmol/mL in 12 cats with cardiomyopathy (HCM = 11, RCM/UCM = 1) but without CHF or evidence of STE, and 2.360 (1.666-3.343) fmol/mL in 16 cats with cardiomyopathy (HCM = 8, RCM/UCM = 7, DCM = 1) and CHF (n = 15) or STE (n = 4). Plasma immunoreactivity of ET-1 was significantly higher in cats with myocardial disease without CHF/STE versus normal cats (P < .05) and in cats with myocardial disease with CHF/STE versus normal cats (P < .001).     

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.     

Comparison of plasma, liver, and skeletal muscle carnitine concentrations in cats with idiopathic hepatic lipidosis and in healthy cats

Concentrations of total, free, and esterified carnitine were determined in plasma, liver, and skeletal muscle from cats with idiopathic hepatic lipidosis and compared with values from healthy cats. The mean concentrations of plasma, liver, and skeletal muscle total carnitine; plasma and skeletal muscle free carnitine; and plasma and liver esterified carnitine were greater (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. The mean for the ratio of free/total carnitine in plasma and liver was lower (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. These data suggest that carnitine deficiency does not contribute to the pathogenesis of feline idiopathic hepatic lipidosis.     

Plasma renin activity and plasma concentrations of aldosterone, cortisol, adrenocorticotropic hormone, and alpha-melanocyte-stimulating hormone in healthy cats

A pathogenetic role of the renin-angiotensin-aldosterone system has been implicated in cats in both systemic arterial hypertension and hypokalemic myopathy. Yet, measurement of plasma aldosterone concentrations (PACs) and plasma renin activity (PRA) has not unequivocally pointed to hyperaldosteronism as a cause of these conditions. To obtain appropriate reference ranges, this study included a large number (130) of healthy house cats of different breeds without a history of recent illness and plasma concentrations of urea and creatinine below the upper limit of the respective reference ranges. In addition, the pituitary-adrenocortical axis was studied by measuring plasma concentrations of adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), and cortisol. Reference ranges for PACs (110-540 pmol/L; 40-195 pg/mL), PRA (60-630 fmol/L/s; 0.3-3 ng/mL/h), and the aldosterone to renin ratio (ARR) (0.3-3.8) were very similar to those established in the same laboratory for humans in a supine position. No breed differences were found. The ARRs in neutered cats were significantly higher than in intact cats, primarily because of low PRA in neutered cats. The ARRs of cats > or = 5 years of age were significantly higher than those of cats < 5 years of age. The plasma concentrations of ACTH, alpha-MSH, and cortisol did not correlate significantly with PAC. Thus, although blood sampling was performed in cats in nonstandardized positions and was associated with a wide variation of stress responses, the references ranges of PAC, PRA, and ARR were similar to the relatively narrow limits established for humans under standardized conditions. The effects of neutering and aging on PRA and ARR warrant further investigation.     

Insulin responses to administrations of amino acids and fatty acids in healthy cats

In order to compare the stimulation ability of insulin secretion, we determined changes in plasma glucose and insulin concentrations after intravenous administration of various amino acids and essential fatty acids in clinically healthy adult cats. Plasma glucose concentrations were within the normal ranges after injection of amino acids and fatty acids. Plasma insulin concentrations increased rapidly 2 to 4 min after injection of arginine, then decreased to the basal levels at 20 min in all five cats. Insulin peak responses were significantly greater in arginine injections than in normal saline (P<0.01). Areas under the curve (AUC) of plasma insulin concentrations from 0 to 10 min after injection of arginine were significantly larger than after injection of normal saline (P<0.01) and glucose (P<0.05). Increases in AUC of plasma insulin concentration from 0 to 60 min were observed after injection of arginine, leucine, alanine, and fat emulsion. Arginine had a strong insulinotropic effect, and leucine, alanine, and fatty acids had weak ones. Besides, valine, methionine, taurine and glutamine had no stimulant activity of insulin. Given the risk of glucose toxication and required time for testing, the intravenous arginine tolerance test may be useful for estimation of insulin responses in cats.     

Effects of synthetic ovine corticotropin-releasing hormone on plasma concentrations of immunoreactive adrenocorticotropin, alpha-melanocyte-stimulating hormone, and cortisol in dogs with naturally acquired adrenocortical insufficiency.

We evaluated the effect of ovine corticotropin-releasing hormone (CRH) on plasma immunoreactive (IR) concentrations of ACTH, alpha-melanocyte-stimulating hormone, and cortisol in 8 dogs with naturally acquired adrenocortical insufficiency. Of the 7 dogs with primary adrenal insufficiency, 6 had markedly high basal plasma IR-ACTH concentrations and exaggerated ACTH responses to CRH administration, whereas 1 dog that was receiving replacement doses of prednisone at the time of testing had normal basal IR-ACTH concentrations and a nearly normal response to CRH. In contrast, the 1 dog with secondary adrenocortical insufficiency had undetectable basal plasma IR-ACTH concentrations, which failed to increase after administration of CRH. Basal plasma alpha-melanocyte-stimulating hormone concentrations in the dogs with adrenal insufficiency were within normal range and were unaffected by CRH administration. In all 8 dogs with adrenal insufficiency, plasma cortisol concentrations were low and did not increase after administration of CRH. Therefore, stimulation with CRH produced 2 patterns of plasma IR-ACTH response when administered to dogs with naturally acquired adrenal insufficiency. Dogs with primary adrenal insufficiency had high basal plasma IR-ACTH concentrations and exaggerated responses to CRH, whereas the dog with secondary adrenal insufficiency had undetectable basal plasma concentrations of IR-ACTH that did not increase after stimulation with CRH.     

Evaluation of coagulation markers in the plasma of healthy cats and cats with asymptomatic hypertrophic cardiomyopathy

BACKGROUND: Thrombosis and arterial thromboembolism are frequent complications of feline cardiomyopathy, especially when associated with left atrial enlargement. Markers of activated coagulation may be used to evaluate the coagulation status of cats with hypertrophic cardiomyopathy (HCM) in relation to left atrial size. OBJECTIVES: The objective of this study was to compare plasma concentrations of thrombin-antithrombin complex (TAT), D-dimer, and fibrin degradation products (FDP) between clinically healthy cats and cats with HCM. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin activity were also compared and the association between left atrial (LA) size and coagulation results in cats with HCM was evaluated. METHODS: Blood samples from 19 clinically healthy cats and 20 cats with HCM were obtained. All cats with HCM were asymptomatic and had no signs of heart failure. LA diameter and LA to proximal aortic (Ao) diameter ratio (LA:Ao) were determined by echocardiography. RESULTS: Reference intervals for D-dimer and TAT concentrations in plasma of healthy cats were established as 0.09-0.32 microg/mL and 2.0-20.0 microg/L, respectively. TAT, D-dimer, and FDP concentrations were increased in 5, 3, and 2 cats with HCM, respectively. TAT and D-dimer concentrations, and PT and aPTT were not significantly different between groups. Antithrombin activity was significantly decreased in cats with HCM (P=.03) despite marked range overlap. LA and LA:Ao were not correlated with coagulation results. CONCLUSIONS: Laboratory evidence of hypercoagulability was found in 45% of cats with HCM. Left atrial size was not associated with laboratory evidence of hypercoagulability. Association between coagulation markers and risk of thrombosis has yet to be evaluated in cats with HCM.     

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.     

Evaluation of plasma C-terminal atrial natriuretic peptide in healthy cats and cats with heart disease

BACKGROUND: The clinical implications of evaluating C-terminal atrial natriuretic peptide (ANP) concentration in cats are still controversial. HYPOTHESIS: The objective of this study was to investigate the relationship between plasma C-terminal ANP concentration and left atrial pressure (LAP) in healthy cats with volume overload (study 1), and to compare plasma C-terminal ANP in normal cats and cats with cardiomyopathy (study 2). ANIMALS: Five healthy adult cats were used in study 1, and clinically healthy cats (n=8) and cats with cardiomyopathy (n=14) were used in study 2. METHODS: In study 1, cats were anesthetized and given acetated Ringer's solution (100 mL/kg/h for 60 minute) via the cephalic vein. Hemodynamic measurements and blood samples, collected from the jugular vein, were performed at 10-min intervals. In study 2, blood samples from normal cats and cats with cardiomyopathy were collected from the cephalic vein. The plasma C-terminal ANP concentration was determined by radioimmunoassay for human alpha-ANP. RESULTS: In study 1, volume overload significantly increased the C-terminal ANP concentration and LAP from baseline. The C-terminal ANP concentration was strongly correlated with the mean LAP. In study 2, age, E wave velocity, and the ratios of the left atrium to aorta were significantly higher in the cats with cardiomyopathy compared with the normal cats. The C-terminal ANP concentration was significantly higher in the cats with cardiomyopathy compared with the normal cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that the measurement of plasma C-terminal ANP in cats may provide additional information for the diagnosis of heart disease.