Effects of etomidate on adrenocortical function in canine surgical patients

Adrenocortical function in canine surgical patients given etomidate at 1 of 2 dosages (1.5 mg/kg of body weight or 3 mg/kg, IV) was evaluated and compared with that of dogs given thiopental (12 mg/kg, IV). The adrenocortical function was evaluated by use of adrenocorticotropic hormone (ACTH) stimulation tests and determination of plasma cortisol concentrations at 0 minute (base line) and 60 minutes after ACTH administration. At 24 hours before administration of either drug (ie, induction of anesthesia), each dog had an increase in plasma cortisol concentration when given ACTH. The ACTH stimulation tests were repeated 2 hours after induction of anesthesia. Dogs given thiopental had base-line plasma cortisol concentrations greater than preinduction base-line values, but did not increase plasma cortisol in response to ACTH stimulation. Postinduction ACTH stimulation tests in dogs given etomidate at either dose indicated base-line and 60-minute plasma cortisol concentrations that were not different from preinduction base-line values. Therefore, adrenocortical function was suppressed 2 and 3 hours after the administration of etomidate in canine surgical patients.     

Evaluation of plasma aldosterone concentrations before and after ACTH administration in clinically normal dogs and in dogs with various diseases

Plasma aldosterone concentrations were measured in response to adrenocorticotropic hormone (ACTH) gel administration in clinically normal dogs, in dogs with hypoadrenocorticism, and in dogs (with electrolyte abnormalities) that did not have hypoadrenocorticism. Baseline plasma aldosterone concentrations were determined from specimens obtained every 10 minutes for 3 hours from 2 dogs and every 30 minutes for 7.5 hours from 2 other dogs. During the evaluation period, plasma aldosterone concentrations varied by at least 50% in each dog. A randomized crossover design was used to compare changes in plasma aldosterone concentrations after administration of ACTH gel and physiologic NaCl solution. Dogs had significantly (P = 0.002) higher plasma aldosterone concentrations after administration of ACTH gel than after administration of NaCl solution. Plasma cortisol concentrations increased as expected after ACTH gel administration. Analysis of cortisol and aldosterone concentrations in the same specimens obtained at 7 sample collection times did not reveal significant linear correlation, and scatterplots did not indicate a nonlinear association. In addition, plasma aldosterone concentrations were determined in response to ACTH administration alone and to ACTH combined with a high dose of dexamethasone (0.1 mg/kg, IV). The plasma aldosterone response to ACTH alone was not significantly different from the response to ACTH combined with dexamethasone. For both tests, plasma aldosterone concentrations at 60 and 120 minutes after ACTH administration were significantly (P less than 0.0005 and P = 0.0001, respectively, increased, compared with base-line values. Six dogs with adrenocortical hypofunction, as determined by plasma cortisol concentrations before and after ACTH administration, had plasma aldosterone concentrations that were diminished or did not increase after ACTH administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Use of a low dose synthetic ACTH challenge test in normal and prednisone-treated dogs

The utility of a low dose (1 microgram/kg) synthetic ACTH challenge test in detecting moderate reductions in adrenocortical sensitivity in dogs was examined. First, the adrenocortical responses to an intravenous bolus of either 1 microgram/kg or 0.25 mg per dog of synthetic ACTH were compared in two groups of normal dogs. While plasma cortisol concentrations were similar in both groups 60 minutes after ACTH injection, dogs given 0.25 mg ACTH showed continued elevations in plasma cortisol concentrations at 90 and 120 minutes after ACTH injection. Later, the dogs previously tested with the 1 microgram/kg ACTH challenge were given a single intramuscular dose of prednisone (2.2 mg/kg) and retested with 1 microgram/kg of ACTH one week later. Plasma cortisol levels were significantly reduced after ACTH injection in dogs previously given prednisone demonstrating that a single intramuscular prednisone dose causes detectable adrenocortical suppression one week after administration. The 1 microgram/kg synthetic ACTH challenge test provides a sensitive means for evaluating adrenocortical suppression in dogs.     

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 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.     

Effect of nonadrenal illness on adrenal function in the cat

Adrenal function was assessed by a combined dexamethasone suppression-ACTH stimulation test in 18 healthy cats, 17 diabetic cats, and 19 sick nondiabetic cats. In all groups, plasma cortisol concentrations decreased after dexamethasone was administered and increased after ACTH was administered. There were no significant (P greater than 0.05) differences among groups in time trend changes in cortisol concentration. There was considerable variation in adrenal response between cats in each group. Diabetic cats had more variation in base-line and postdexamethasone plasma cortisol concentrations (P less than 0.05) than did other groups. In sick, nondiabetic cats, cortisol concentrations tended to be higher in cats with hyperthyroidism (P = 0.06) than in cats with other diseases.     

Comparison of aqueous porcine ACTH with synthetic ACTH in adrenal stimulation tests of the female dog

The adrenocortical (plasma corticosteroid) responses in female dogs given porcine ACTH in gelatin (1-39 amino acid sequence) and synthetic ACTH (1-24 amino acid sequence) were compared. Sixteen dogs were used. Each dog underwent 4 different ACTH stimulation studies, these being done with a 4- to 8-week interval. The studies in each dog included injections of 2 doses of porcine ACTH--2.2 IU and 4.4 IU/kg of body weight--and of 2 doses of synthetic ACTH--0.25 mg/dog and 0.50 mg/dog. The dogs were arbitrarily allotted to 4 groups, each group being subjected to a given sequence of stimulation studies. The purpose in this project was to determine whether the established methods for synthetic and porcine ACTH stimulation tests had similar results. Statistical analysis of the 4 stimulation methods revealed no significance (P greater than 0.05) in the resting or poststimulation plasma corticosteroid concentrations. Thus, it was concluded that either recommended method using ACTH (porcine ACTH at 2.2 IU/kg or synthetic ACTH at 0.25 mg/dog) causes maximal secretion of adrenocortical reserve. Either ACTH preparation, using the established method, can be used interchangeably.     

Effects of single intravenously administered doses of dexamethasone on response to the adrenocorticotropic hormone stimulation test in dogs

The effects of single IV administered doses of dexamethasone on response to the adrenocorticotropic hormone (ACTH) stimulation test (baseline plasma ACTH, pre-ACTH cortisol, and post-ACTH cortisol concentrations) performed 1, 2, and 3 days (experiment 1) or 3, 7, 10, and 14 days (experiment 2) after dexamethasone treatment were evaluated in healthy Beagles. In experiment 1, ACTH stimulation tests were carried out after administration of 0, 0.01, 0.1, 1, and 5 mg of dexamethasone/kg of body weight. Dosages greater than or equal to 0.1 mg of dexamethasone/kg decreased pre-ACTH plasma cortisol concentration on subsequent days, whereas dosages greater than or equal to 1 mg/kg also decreased plasma ACTH concentration. Treatment with 1 or 5 mg of dexamethasone/kg suppressed (P less than 0.05) post-ACTH plasma cortisol concentration (on day 3 after 1 mg of dexamethasone/kg; on days 1, 2, and 3 after 5 mg of dexamethasone/kg). In experiment 2, IV administration of 1 mg of dexamethasone/kg was associated only with low (P less than 0.05) post-ACTH plasma cortisol concentration in dogs on day 3. In experiment 2, pre-ACTH plasma cortisol and ACTH concentrations in dogs on days 3, 7, 10, and 14 and post-ACTH plasma cortisol concentration on days 7, 10, and 14 were not affected by dexamethasone administration. The results suggest that, in dogs, a single IV administered dosage of greater than or equal to 0.1 mg of dexamethasone/kg can alter the results of the ACTH stimulation test for at least 3 days. The suppressive effect of dexamethasone is dose dependent and is not apparent 7 days after treatment with 1 mg of dexamethasone/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of multiple intramuscular injections and doses of dexamethasone on plasma cortisol concentrations and adrenal responses to ACTH in horses

Adrenocortical function was assessed in horses given multiple IM doses of dexamethasone to determine the duration of adrenocortical suppression and insufficiency caused by 2 commonly used dosages of dexamethasone (0.044 and 0.088 mg/kg of body weight). Dexamethasone was administered at 5-day intervals for a total of 6 injections. Daily blood samples were collected. The plasma was frozen and later assayed for cortisol. An ACTH response test was determined 2 days before the first injection of dexamethasone and again 8 days after the last dexamethasone injection. Maximum suppression of plasma cortisol was observed in horses given both dosages of dexamethasone (0.044 and 0.088 mg/kg). Plasma cortisol concentrations returned to base-line values in all horses by 4 days after dexamethasone injection. Normal ACTH responses observed after 6 dexamethasone injections given at 5-day intervals indicated that measurable adrenal atrophy did not develop under the conditions of this study.     

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.     

Endocrine responses of healthy parrots to ACTH and thyroid stimulating hormone

Effects of exogenous ACTH on plasma corticosterone and cortisol concentrations and the effects of thyroid stimulating hormone (TSH) on plasma triiodothyronine (T3) and thyroxine (T4) were determined in the following 3 species of parrots: red-lored Amazon (group 1), blue-fronted Amazon (group 2), and African gray (group 3). Each bird was given ACTH (0.125 mg/bird) IM, except for 3 to 4 birds in each group, which were given saline solution (controls). Blood samples were collected before and 90 minutes after ACTH stimulation. In group 1 (n = 12), mean plasma corticosterone concentrations increased significantly (P less than 0.001) from 1.06 microgram/dl (before ACTH) to 4.89 micrograms/dl (after ACTH); mean corticosterone concentrations increased in the control birds from 1.06 microgram/dl to 1.84 microgram/dl; and mean cortisol concentrations increased only slightly from 0.228 microgram/dl to 0.266 microgram/dl. In group 2 (n = 12), mean corticosterone concentrations increased significantly (P less than 0.001) from 2.09 micrograms/dl to 10.58 micrograms/dl; control mean corticosterone concentrations decreased slightly from 2.09 micrograms/dl to 1.77 microgram/dl; and mean cortisol concentrations increased from less than or equal to 0.16 microgram/dl to 0.266 microgram/dl. In group 3 (n = 12), mean plasma corticosterone concentrations increased significantly (P less than or equal to 0.001) from 2.33 micrograms/dl to 4.67 micrograms/dl; mean control plasma corticosterone concentrations decreased from 2.33 micrograms/dl to 1.68 microgram/dl; and plasma corticol concentrations were not detectable. Each bird was given TSH, IM (1 U/bird). Blood samples were collected before and 6 hours after TSH administration. Saline solution was not administered as controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Consistent capacity for adrenocortical response to ACTH administration in pigs

The effect of ACTH administration on plasma cortisol concentrations in purebred and crossbred pigs was investigated. Pigs were given either 25 IU of ACTH or physiologic saline solution IM. Blood samples were collected immediately before and 1 hour after ACTH or saline solution administration. Administration of ACTH resulted in a significant (P less than 0.01) increase in plasma cortisol concentration compared with that resulting from administration of saline solution; mean values after ACTH administration were similar in both breed groups. In contrast, a fivefold range of differences was observed among individual pigs of the same age, sex, and body weight, irrespective of breed group. The type and magnitude of the adrenocortical response was consistent and repeatable in pigs over a 3-month period, suggesting that pigs have a consistent capacity for adrenocortical response to ACTH administration. Development of a dynamic test allowed the high and low responding extremes in a population to be detected. The most suitable dose of synthetic ACTH was established to be 50 IU, and the best time for blood sample collection was 60 minutes after ACTH administration. The classification of individual pigs as high or low responders was repeatable and was not affected by prior short-term exposure to ACTH.     

Effects of phenylbutazone and anabolic steroids on adrenal and thyroid gland function tests in healthy horses

Adrenal and/or thyroid gland function tests were evaluated in horses at various times during short-term therapy with phenylbutazone, stanozolol, and boldenone undecylenate. There were no significant treatment or time effects on mean basal plasma cortisol concentrations in horses during treatment with the following: phenylbutazone, given twice daily (4 to 5 mg/kg, IV) for 5 days; stanozolol, given twice weekly (0.55 mg/kg, IM) for 12 days; boldenone undecylenate, given twice weekly (1.1 mg/kg, IM) for 12 days; or nothing. There was no significant effect of phenylbutazone treatment on the changes in plasma cortisol concentration during the combined dexamethasone-suppression adrenocorticotropic hormone (ACTH)-stimulation test. Plasma cortisol concentration was significantly decreased from base line at 3 hours after dexamethasone administration and was significantly increased from base line at 2 hours after ACTH in all horses (P less than 0.05). Likewise, the stimulation of basal plasma cortisol concentrations at 2 hours after administration of ACTH (P less than 0.05) was not affected by treatment with stanozolol or boldenone undecylenate. There were no significant treatment effects on mean basal plasma concentrations of thyroxine (T4) or triiodothyronine (T3) among horses during the following treatments: stanozolol, given twice weekly (0.55 mg/kg, IM) for 12 days; boldenone undecylenate, given twice weekly (1.1 mg/kg, IM) for 12 days; or nothing. There was a significant time effect on overall mean basal plasma T4 and T3 concentrations (P less than 0.05): plasma T4 was lower on day 8 than on days 1, 10, and 12; plasma T3 was higher on day 8 than on days 4 and 12.(ABSTRACT TRUNCATED AT 250 WORDS)     

Duration of etomidate-induced adrenocortical suppression during surgery in dogs

Plasma cortisol concentrations were compared in canine surgical patients given etomidate (2 mg/kg of body weight, IV) or thiopental sodium (12 mg/kg, IV) for anesthetic induction. Blood samples to determine plasma concentrations of etomidate were obtained at 0, 5, 10, 15, and 30 minutes and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours after induction. Adrenocortical function was evaluated before surgery by use of adrenocorticotropic hormone stimulation tests. Dogs in both induction groups had high plasma cortisol concentrations after induction. Dogs given thiopental had a significant increase (P less than 0.05) in plasma cortisol concentration from baseline at 2, 3, 4, 5, 6, 8, and 12 hours after induction. Dogs given etomidate had a significant increase (P less than 0.05) in plasma cortisol concentration from baseline at 5, 6, and 8 hours after induction. A comparison of plasma cortisol concentrations determined at 2, 3, 4, 5, and 6 hours after induction with thiopental or etomidate revealed a higher (P less than 0.05) concentration in dogs given thiopental. The disposition of etomidate was best described by a 2-compartment model, with a redistribution half-life of 0.12 +/- 0.04 minute and a terminal half-life of 1.70 +/- 0.27 minute. Plasma cortisol concentrations did not correlate with plasma etomidate concentrations. We conclude that, compared with thiopental, a single bolus injection of etomidate reduces the adrenocortical response to anesthesia and surgery from 2 to 6 hours after induction. Because cortisol concentrations were significantly higher than baseline, and because cardiopulmonary function is maintained after a single bolus injection of etomidate, it can be considered a safe induction agent in dogs.     

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.     

Feline plasma cortisol (hydrocortisone) measured by radioimmunoassay.

Plasma cortisol (hydrocortisone) was measured by radioimmunoassay in 6 normal cats. Blood was collected from the cats by venipuncture at intervals of 3 hours for 3 days. Resting plasma cortisol concentrations averaged 17.0 +/- 2.8 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 82.8 ng/ml. Of 144 plasma samples, 95% contained less than 40 ng of cortisol/ml. Circadian rhythm of cortisol secretion was not detected, suggesting that adrenal function tests may be started in feline patients at any time of day. Intramuscular injection of 2.2 U of ACTH gel/kg of body weight caused detectable increase in plasma cortisol concentrations at 1 and 2 hours after injection. Maximal response to ACTH in the 6 cats ranged from 41.6 to 178.4 ng/ml. Oral administration of 0.1 mg of dexamethasone/kg suppressed plasma cortisol to nondetectable concentrations for 32 hours in 5 of the 6 cats.     

Assessment of adrenal function in cats: Response to intravenous synthetic ACTH

The serum cortisol response to intravenous synthetic ACTH (tetracosactrin) was assessed in 15 healthy adult cats. Mean cortisol levels showed a significant (P<0.001) rise at 60 minutes and peaked at 180 minutes. At 120 and 180 min- utes mean cortisol levels were significantly (P<0.001) higher than at 60 minutes. The time of peak cortisol response in individual cats varied between 120 and 240 minutes, but nine (60 per cent) peaked at 180 minutes. In response to the ACTH the cats showed a rise in cortisol levels of between 160 and 1360 per cent. No significant rise in cortisol levels was seen in five cats following administration of sterile saline.     

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro study of the function of adrenocortical cells from pigs of differing in vivo response to adrenocorticotropin

A study was conducted to determine whether within-breed differences in adrenocortical response to exogenous adrenocorticotropin (ACTH) might be accounted for by differences in responsiveness of the adrenocortical cells per se. Large White x Landrace male pigs (n = 20) were used; 10 had high adrenocortical response to ACTH administration and 10 had low response. Five high and 5 low responders were euthanatized at 15 weeks of age, and the remaining 5 high and 5 low responders were euthanatized at 21 weeks of age. Adrenal glands were removed and weighed, and adrenocortical cells were dispersed by tryptic digestion and incubated for 2 hours with synthetic ACTH at concentrations ranging from 0.5 to 10,000 pg/ml. Samples were taken at 30-minutes intervals, and cortisol concentration was determined by use of a radioimmunoassay. Results indicate that for pigs of both age groups, high responders had heavier adrenal glands, with higher adrenocortical cell density and higher cell yield than did low responders. Synthetic ACTH had a stimulatory effect on dispersed porcine adrenocortical cells, as indicated by changes in cortisol concentration in vitro. Adrenocortical cells from high responders produced less cortisol, on a per-cell basis, than did those from low responders. However, when corrected for total cell yield, the potential cortisol production by each pair of adrenal glands was significantly (P less than 0.05) higher in the high responders than in the low responders. Thus, high-responding pigs have larger adrenal glands and higher adrenocortical cell density, which may result in higher output of cortisol after ACTH administration or exposure to stressors.(ABSTRACT TRUNCATED AT 250 WORDS)