Effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism

OBJECTIVE: To evaluate the effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism (PDH), compare the degree of reduction of aldosterone with that of cortisol, and compare aldosterone concentrations of healthy dogs with those of dogs with PDH. ANIMALS: 17 dogs with PDH and 12 healthy dogs. PROCEDURE: For dogs with PDH, the initial dose of trilostane was selected in accordance with body weight. A CBC count, serum biochemical analyses, and ACTH stimulation tests were performed in each dog. Dogs were evaluated 1, 3 to 4, 6 to 8, and 10 to 12 weeks after initiation of treatment. Healthy dogs were evaluated only once. RESULTS: Serum aldosterone concentrations before ACTH stimulation did not change significantly after initiation of treatment with trilostane. At each evaluation after initiation of treatment, serum aldosterone concentrations after ACTH stimulation were significantly lower than corresponding concentrations before initiation of treatment. The overall effect of trilostane on serum aldosterone concentration was less pronounced than the effect on serum cortisol concentration. Median potassium concentrations increased slightly after initiation of treatment with trilostane. Dogs with PDH had significantly higher serum aldo sterone concentrations before and after ACTH stimulation than healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with trilostane resulted in a reduction in serum cortisol and aldosterone concentrations in dogs with PDH, although the decrease for serum aldosterone concentration was smaller than that for serum cortisol concentration. There was no correlation between serum concentrations of aldosterone and potassium during treatment.     

Effect of alternate-day prednisolone administration on hypophyseal-adrenocortical activity in dogs.

OBJECTIVE: To evaluate effect of alternate-day oral administration of prednisolone on endogenous plasma ACTH concentration and adrenocortical response to exogenous ACTH in dogs. ANIMALS: 12 Beagles. PROCEDURE: Dogs were allotted to 2 groups (group 1, 8 dogs treated with 1 mg of prednisolone/kg of body weight; group 2, 4 dogs given excipient only). During a 30-day period, blood samples were collected for determination of plasma ACTH and cortisol concentrations before, during, and after treatment with prednisolone. From day 7 to 23, prednisolone or excipient was given on alternate days. Sample collection (48-hour period with 6-hour intervals) was performed on days 1, 7, 15, 21, and 28; on other days, sample collection was performed at 24-hour intervals. Pre- and post-ACTH plasma cortisol concentrations were determined on days 3, 9, 17, 23, and 30. RESULTS: A significant difference was detected between treatment and time for group 1. Plasma ACTH concentrations significantly decreased for 18 to 24 hours after prednisolone treatment in group-1 dogs. At 24 to 48 hours, ACTH concentrations were numerically higher but not significantly different in group-1 dogs. Post-ACTH plasma cortisol concentration significantly decreased after 1 dose of prednisolone and became more profound during the treatment period. However, post-ACTH cortisol concentration returned to the reference range 1 week after prednisolone administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Single oral administration of 1 mg of prednisolone/kg significantly suppressed plasma ACTH concentration in dogs for 18 to 24 hours after treatment. Alternate-day treatment did not prevent suppression, as documented by the response to ACTH.     

Mitotane (o, p''-DDD) Treatment of 200 Dogs with Pituitary-Dependent Hyperadrenocorticism

Two hundred dogs with pituitary dependent hyperadrenocorticism (PDH) were treated with mitotane at an initial daily dosage of 21 to 69 mg/kg (mean = 45.2 mg/kg) for 5 to 14 days. During the induction period, 194 of the dogs also were given daily maintenance dosages of a glucocorticoid. Fifty of the dogs exhibited one or more adverse effects during initial induction, including weakness, vomiting, anorexia, diarrhea, and ataxia. After completion of the induction period, repeat ACTH stimulation testing revealed significant decreases in mean serum cortisol concentrations when compared with initial values. Twenty-five dogs, however, still responded to exogenous ACTH with serum cortisol concentrations above normal resting range, necessitating daily treatment for an additional 5 to 55 days. In contrast, 70 of the 200 dogs had low post-ACTH serum cortisol concentrations after the induction period. These subnormal serum cortisol concentrations generally increased spontaneously to within normal resting range 2 to 6 weeks after cessation of mitotane. In 184 dogs, mitotane was continued at an initial mean maintenance dosage of 49 mg/kg administered weekly in two to three divided doses. Of these dogs, 107 had one or more relapses of hyperadrenocorticism during treatment. In the 75 dogs that had one relapse, the median maintenance dosage was increased by approximately 35%, whereas the median maintenance dosage in the 32 dogs having two or more relapses was eventually increased by 225% over the initial dosage. After a mean maintenance treatment time of 2.0 years, the final maintenance dosage required in the 184 dogs ranged from 26.8 to 330 mg/kg/week.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum 17-alpha-hydroxyprogesterone and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs with suspected hyperadrenocorticism

OBJECTIVE: To assess serum 17-alpha-hydroxyprogesterone (17OHP) and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs being screened for hyperadrenocorticism. DESIGN: Prospective study. ANIMALS: 16 clinically normal dogs, 35 dogs with nonadrenal neoplasia, and 127 dogs with suspected hyperadrenocorticism. PROCEDURE: ACTH stimulation tests were performed in all dogs. Baseline serum cortisol and corticosterone concentrations were measured in the healthy dogs; baseline serum cortisol concentration and ACTH-stimulated cortisol, corticosterone, and 17OHP concentrations were measured in all dogs. Endogenous plasma ACTH concentration was also measured before administration of ACTH in dogs with neoplasia. RESULTS: In 35 dogs with neoplasia, 31.4% had high serum 17OHP concentration and 22.9% had high serum corticosterone concentration. Of the 127 dogs with suspected hyperadrenocorticism, 59 (46.5%) had high ACTH-stimulated cortisol concentrations; of those, 42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum 17OHP and corticosterone concentrations, respectively. Of dogs with serum cortisol concentration within reference range after ACTH administration, 9 of 68 (13.2%) and 7 of 67 (10.4%) had high serum 17OHP and corticosterone concentrations, respectively. In the dogs with neoplasia and dogs suspected of having hyperadrenocorticism, post-ACTH serum hormone concentrations were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Serum concentrations of 17OHP or corticosterone after administration of ACTH may be high in dogs with nonadrenal neoplasia and no evidence of hyperadrenocorticism. Changes in serum 17OHP or corticosterone concentrations after administration of ACTH are proportionate with changes in cortisol concentration.     

Use of compounded adrenocorticotropic hormone (ACTH) for adrenal function testing in dogs

Serum cortisol concentrations were measured in five healthy dogs in response to five adrenocorticotropic hormone (ACTH) preparations. Cortisol concentrations were similar at time 0 (pre-ACTH) and at 30 and 60 minutes after injection of all forms of ACTH. However, at 90 and 120 minutes post-ACTH, serum cortisol concentrations were significantly lower following injection of two compounded forms of ACTH. The data showed that injection of four compounded forms of ACTH caused elevations in serum cortisol concentrations of a similar magnitude as cosyntropin in samples collected 60 minutes after administration; but concentrations at later times varied, depending on the type of ACTH used.     

Adrenal gland function in dogs given methylprednisolone

Serum cortisol (hydrocortisone) was measured by radioimmunoassay in dogs given methylprednisolone (MP) orally or methylprednisolone acetate (MPA) IM. The MP was given on a daily and on an alternate-day basis to different treatment groups and the MPA was administered weekly. Samples of blood were obtained twice a week over a 9-week treatment period for serum cortisol determination, and the adrenal gland response to ACTH was assessed on posttreatment days 1, 3, 5, and 7. Administration of MP on an alternate or daily basis caused a slight but significant (P < 0.05) depression in mean resting cortisol values over time. The MPA administration caused a severe depression of resting serum cortisol values. In response to ACTH, cortisol values invariably increased sharply in nontreated control dogs and in those dogs given MP on an alternate-day basis. Dogs given MP daily had a depressed response to ACTH. The MPA treatment resulted in adrenal cortices that were unresponsive to ACTH. Dogs given MPA, but not challenge exposed with ACTH, had markedly lowered cortisol values for at least 2 weeks after cessation of treatment. Consequently, a difference between daily- and alternate-day MP administration was detected after ACTH challenge exposure; MPA administration inhibited adrenal cortisol secretion for at least the duration of the experiment.     

Plasma cortisol response to exogenous ACTH in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia

The plasma cortisol response to exogenous ACTH (ACTH stimulation test) was evaluated in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia. The mean basal cortisol concentration (6.3 microgram/dl) was high, but 7 dogs had basal cortisol concentrations that were within normal range. Administration of exogenous ACTH increased the plasma cortisol concentrations in each dog. Normal post-ACTH cortisol concentrations were found in 9 (41%) of the 22 dogs; 13 (59%) had an exaggerated increase in cortisol concentrations after ACTH administration. In 9 of 13 dogs with carcinoma and in 4 of 9 with adenoma, the cortisol response was exaggerated. The mean post-ACTH cortisol concentration in the dogs with carcinoma was approximately 4 times that of the dogs with adenoma; the 7 dogs with the highest concentrations had carcinoma. Repeat studies were performed in 6 dogs 2 to 8 weeks after initial testing. In 5 of the 6 dogs, repeat testing yielded data of similar diagnostic significance. One dog, however, had an abnormally high post-ACTH cortisol concentration at initial evaluation, but had only a minimal response to ACTH administration, with a normal post-ACTH cortisol concentration, at time of resting. Although ACTH stimulation testing is useful in diagnosing hyperadrenocorticism, it can not reliably separate dogs with hyperfunction adrenocortical tumors from clinically normal dogs or from dogs with pituitary-dependent hyperadrenocorticism (bilateral adrenocortical hyperplasia).     

Effects of delmadinone acetate on pituitary-adrenal function, glucose tolerance and growth hormone in male dogs

Objective To characterise the effects of delmadinone acetate on the pituitary-adrenal axis, glucose tolerance and growth hormone concentration in normal male dogs and dogs with benign prostatic hyperplasia.
Design A prospective study involving nine normal male dogs and seven with prostatic hyperplasia.
Procedure Delmadinone acetate was administered to six normal male dogs and seven dogs with benign prostatic hyperplasia at recommended dose rates (1.5 mg/kg subcuta-neously at 0, 1 and 4 weeks). Three normal controls received saline at the same intervals. Blood concentrations of ACTH, cortisol, glucose, insulin and growth hormone were measured over 50 days. Intravenous glucose tolerance and ACTH response tests were performed before and after treatment in the nine normal animals.
Results A substantial suppression of basal and 2 h post-ACTH plasma cortisol secretion was demonstrated after one dose in all dogs given delmadinone acetate. Individual responses after the second and third administration varied between recovery in adrenal responsiveness to continued suppression. Plasma ACTH concentration was also diminished after one treatment. No effects were evident on glucose tolerance or serum growth hormone concentrations.
Conclusion Delmadinone acetate causes adrenal suppression from inhibition of release of ACTH from the pituitary gland. Treated dogs may be at risk of developing signs of glucocorticoid insufficiency if subjected to stressful events during or after therapy. Neither glucose intolerance nor hyper-somatotropism seems likely in male dogs given delmadinone acetate at the recommended dose rate, but the potential for excessive growth hormone secretion in treated bitches remains undetermined.     

Evaluation of serum 17-hydroxyprogesterone concentration after administration of ACTH in dogs with hyperadrenocorticism

OBJECTIVE: To evaluate serum 17-hydroxyprogesterone (17-OHP) concentration measurement after administration of ACTH for use in the diagnosis of hyperadrenocorticism in dogs. DESIGN: Prospective study. ANIMALS: 110 dogs. PROCEDURE: Serum 17-OHP concentrations were measured before and after ACTH stimulation in 53 healthy dogs to establish reference values for this study. Affected dogs had pituitary-dependent (n = 40) or adrenal tumor-associated (12) hyperadrenocorticism or potentially had atypical hyperadrenocorticism (5; diagnosis confirmed in 1 dog). In affected dogs, frequency interval and borderline and abnormal serum 17-OHP concentrations after ACTH stimulation were determined. Serum cortisol concentrations were assessed via low-dose dexamethasone suppression and ACTH stimulation tests. RESULTS: In healthy dogs, serum 17-OHP concentration frequency intervals were grouped by sex and reproductive status (defined as < 95th percentile). Frequency intervals of serum 17-OHP concentrations after ACTH stimulation were < 77, < 2.0, < 3.2, and < 3.4 ng/mL (< 23.3, < 6.1, < 9.7, and < 10.3 nmol/L) for sexually intact and neutered females and sexually intact and neutered males, respectively. In 53 dogs with confirmed hyperadrenocorticism, serum cortisol concentrations after ACTH stimulation and 8 hours after administration of dexamethasone and serum 17-OHP concentrations after ACTH stimulation were considered borderline or abnormal in 79%, 93%, and 69% of dogs, respectively. Two of 5 dogs considered to have atypical hyperadrenocorticism had abnormal serum 17-OHP concentrations after ACTH stimulation. CONCLUSIONS AND CLINICAL RELEVANCE: Serum 17-OHP concentration measurement after ACTH stimulation may be useful in the diagnosis of hyperadrenocorticism in dogs when other test results are equivocal.     

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)     

Pituitary-adrenal function in dogs with acute critical illness

OBJECTIVE: To evaluate pituitary-adrenal function in critically ill dogs with sepsis, severe trauma, and gastric dilatation-volvulus (GDV). DESIGN: Cohort study. ANIMALS: 31 ill dogs admitted to an intensive care unit (ICU) at Washington State University or the University of Pennsylvania; all dogs had acute critical illness for < 48 hours prior to admission. PROCEDURES: Baseline and ACTH-stimulated serum cortisol concentrations and baseline plasma ACTH concentrations were assayed for each dog within 24 hours after admission to the ICU. The change in cortisol concentrations (Delta-cortisol) was calculated for each dog. Morbidity and mortality data were recorded for each patient. RESULTS: Overall, 17 of 31 (55%) acutely critically ill dogs had at least 1 biochemical abnormality suggestive of adrenal gland or pituitary gland insufficiency. Only 1 (3%) dog had an exaggerated response to ACTH stimulation. Dogs with Delta-cortisol < or = 83 nmol/L were 5.7 times as likely to be receiving vasopressors as were dogs with Delta-cortisol > 83 nmol/L. No differences were detected among dogs with sepsis, severe trauma, or GDV with respect to mean baseline and ACTH-stimulated serum cortisol concentrations, Delta-cortisol, and baseline plasma ACTH concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Biochemical abnormalities of the hypothalamic-pituitary-adrenal axis indicative of adrenal gland or pituitary gland insufficiency were common in critically ill dogs, whereas exaggerated responses to ACTH administration were uncommon. Acutely ill dogs with Delta-cortisol < or = 83 nmol/L may be more likely to require vasopressors as part of the treatment plan.     

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)     

Adrenal response to adrenocorticotropic hormone in dogs before and after surgical attenuation of a single congenital portosystemic shunt

BACKGROUND: Dogs with single congenital portosystemic shunts (CPSS) often develop postoperative hypoglycemia and prolonged anesthetic recovery. These abnormalities could be attributable to inadequate adrenal response. However, adequacy of adrenal response after CPSS surgery is unexplored. HYPOTHESIS: Dogs with CPSS have inadequate postoperative adrenal response. ANIMALS: Eight nonoperated, 8 ovariohysterectomy (OHE), and 16 CPSS dogs. METHODS: Consecutive day ACTH stimulation tests were performed on nonoperated healthy dogs, healthy dogs before and after OHE, and CPSS dogs before and after surgery. Adequate response was defined as >50% or >30 ng/mL increase in cortisol after ACTH administration. Blood glucose (BG) was monitored before and after surgery. Prolonged anesthetic recovery and refractory hypoglycemia episodes were recorded. RESULTS: Results of consecutive day ACTH stimulation tests did not vary in normal dogs. Results of preoperative ACTH stimulation tests of CPSS and OHE dogs were not significantly different. Dogs with CPSS had higher postoperative baseline cortisol concentrations (median, 329 ng/mL) than OHE dogs (median, 153 ng/mL). Postoperative cortisol increase after ACTH in CPSS was < or =50% in 10/16 and < or =30 ng/mL in 6/16. After surgery, BG was < or =60 mg/dL in 7/16 CPSS dogs. Cortisol concentrations were not correlated with BG. Two CPSS dogs had refractory hypoglycemia and 4 had delayed recovery; all improved with dexamethasone administration (0.1-0.2 mg/kg/IV). CONCLUSIONS AND CLINICAL IMPORTANCE: Contrary to previous reports, baseline cortisol concentrations in CPSS and healthy dogs are similar. Many CPSS dogs have postoperative hypercortisolemia. Response to ACTH does not correlate with postoperative hypoglycemia or prolonged anesthetic recovery.     

Adrenal response to the low dose ACTH stimulation test and the cortisol-to-adrenocorticotrophic hormone ratio in canine babesiosis

This prospective, interventional, case-controlled study sought to determine the association between adrenocortical function and mortality in dogs with naturally occurring Babesia rossi babesiosis. Sixty-eight dogs with canine babesiosis were studied and fifteen normal dogs were used as controls. Blood samples were obtained from the jugular vein in each dog prior to treatment, at admission to hospital, for the measurement of basal plasma ACTH (adrenocorticotrophic hormone) and serum cortisol concentrations. Immediately thereafter, each dog was injected intravenously with 5 microg/kg of ACTH (tetracosactrin). A second blood sample was taken 1h later for serum ACTH-stimulated cortisol measurement and the resultant calculation of delta cortisol by subtracting basal from ACTH-stimulated cortisol. Diagnosis of babesiosis was confirmed by polymerase chain reaction (PCR) and reverse line blot (RLB). Three outcomes were defined: hospitalization with subsequent death (n=4); hospitalization followed by recovery (n=48); and treatment as an outpatient (n=16). Basal cortisol, but not ACTH-stimulated cortisol, was significantly higher in patients compared to control dogs. Basal- and ACTH-stimulated serum cortisol concentrations were significantly higher in the dogs that died, compared to hospitalized dogs that survived and compared to dogs treated as outpatients. There was no significant difference in delta cortisol concentrations or cortisol to ACTH ratios across outcome groups in dogs suffering from B. rossi babesiosis However, dogs with delta cortisol concentrations below 83 nmol/l had significantly higher cortisol to ACTH ratios compared to dogs with delta cortisol concentrations above 83 nmol/l. These findings of increased basal- and ACTH-stimulated cortisol and increased cortisol to ACTH ratios confirm the absence of adrenal insufficiency and concur with those in human malaria.     

Duration of pituitary and adrenocortical suppression after long-term administration of anti-inflammatory doses of prednisone in dogs.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P less than 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P less than 0.05) reduced and reserve function was markedly (P less than 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.     

Cortisol and luteinizing hormone after adrenocorticotropic hormone administration to postpartum beef cows

Cortisol and luteinizing hormone (LH) were measured in serum after the administration of adrenocorticotropic hormone (ACTH) to suckled (S) and nonsuckled (NS) beef cows. Blood was sampled on 2 consecutive days every 2 weeks for four bleeding periods starting 14 days after calving. Cows were injected with 200 IU ACTH or saline in a 2-day switchback design. Serum was collected before ACTH or saline injection and at 30-min intervals thereafter for 8 hours. Average cortisol concentrations in serum were similar in S and NS cows (6.4 +/- .6 and 6.1 +/- .8 ng/ml, respectively) after saline. Average cortisol concentrations in serum collected during an 8-hr period after ACTH on days 14, 28, 42 and 56 postpartum were 24.7 +/- 2.4, 31.8 +/- 3.5, 36.4 +/- 4.2 and 40.7 +/- .5 ng/ml, respectively, for S cows, and 31.1 +/- 2.9, 44.7 +/- 5.2, 45.0 +/- 5.7 and 46.0 +/- 5.4 ng/ml, respectively, for NS cows. Cortisol response to ACTH, measured as area under the response curve, was greater (P less than .05) in NS than in S cows. Amount of cortisol released by 200 IU ACTH was maximal by days 28 to 29 postpartum in NS cows, but the response increased gradually between days 14 to 15 and days 56 to 57 in S cows. overall, LH in serum averaged .55 +/- .08 ng/ml for S cows and .92 +/- .06 ng/ml for NS cows after saline, and .49 +/- .07 ng/ml for S cows and .94 +/- .06 ng/ml for NS cows after ACth. Although mean and peak serum LH concentrations did not differ between cows given ACTH and those given saline, the number of LH peaks and the number of cows having LH after saline. Mean serum LH concentrations were lower (P less than. 05) in S than in NS cows at 28 days postpartum. The number of LH peaks was lower (P less than .05) and the magnitude of the largest LH peak tended to be lower (P less than .06) in S cows at all sampling periods.     

Adrenocortical suppression by topically applied corticosteroids in healthy dogs

Three corticosteroid products (triamcinolone acetonide, fluocinonide, betamethasone valerate) and a control product composed of water, petrolatum, mineral oil, cetyl alcohol, steryl alcohol, sodium lauryl sulfate, cholesterol, and methylparaben each were applied topically to healthy dogs (5 dogs/product) once daily for 5 consecutive days. Plasma concentrations of immunoreactive adrenocorticotropic hormone (iACTH) and cortisol were determined before 1 microgram of ACTH/kg of body weight was given intravenously (pre-ACTH values) and cortisol was again measured 60 minutes after ACTH was given (post-ACTH values). Cortisol and iACTH concentrations were determined in each dog before, during, and after administration of the corticosteroid products. All 3 corticosteroids caused prompt and sustained pituitary-adrenocortical suppression. Compared with control applications, the application of corticosteroids resulted in significant reduction of plasma cortisol and iACTH concentrations by day 2 of treatment, and the lower concentrations continued to day 5. One week after the last application of the corticosteroids, plasma iACTH concentrations in the corticosteroid-treated dogs had returned to the range of values for the control dogs; however, pre- and post-ACTH cortisol concentrations remained suppressed in all corticosteroid-treated dogs. Two weeks after the last treatment, the pre-ACTH plasma cortisol concentrations of corticosteroid-treated dogs returned to those of the control dogs, but the post-ACTH plasma cortisol concentrations remained suppressed. By 3 weeks after the last treatment, post-ACTH plasma cortisol concentrations of dogs treated with triamcinolone acetonide had returned to the range of values for the control dogs, but remained suppressed in the other 2 groups of dogs. All indices of pituitary-adrenocortical activity were within the control range by 4 weeks after the last treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane

The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and one hour after an injection of synthetic adrenocorticotropic hormone (ACTH). In the dogs with pdh, the cortisol and cortisone concentrations were measured before and after one to two weeks and three to seven weeks of treatment with trilostane. The dogs with PDH had significantly higher baseline and poststimulation concentrations of cortisol and cortisone, and higher baseline cortisol:cortisone ratios than the healthy dogs. During the treatment with trilostane, the poststimulation cortisol, the baseline and poststimulation cortisone concentrations, and the baseline and poststimulation cortisol:cortisone ratios decreased significantly. The decrease in poststimulation cortisone was significantly smaller than the decrease in cortisol.     

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 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)