Non-dexamethasone-suppressible, pituitary-dependent hyperadrenocorticism in a dog

A 5-year-old female dog with hyperadrenocorticism was determined to have pituitary-dependent hyperadrenocorticism even though plasma cortisol concentrations were not suppressed after high-dosage dexamethasone administration. The diagnosis was based on a supranormal response of plasma cortisol to ACTH administration and a lack of suppression of plasma cortisol concentration after administration of 0.1 mg of dexamethasone/kg. Although a higher dosage of dexamethasone (1 mg/kg) did not cause suppression of plasma cortisol, plasma ACTH concentrations in the dog were increased above those in clinically normal dogs, supporting a diagnosis of pituitary-dependent hyperadrenocorticism. During treatment with mitotane, the dog became unconscious and died. Necropsy revealed a pituitary tumor that had compressed and displaced the hypothalamus. Although high-dosage dexamethasone suppression tests often are useful in the differential diagnosis of hyperadrenocorticism, a lack of suppression of plasma cortisol does not necessarily exclude pituitary-dependent hyperadrenocorticism.     

Comparison of mitotane treatment for adrenal tumor versus pituitary-dependent hyperadrenocorticism in dogs.

The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ATH) vs those with pituitary-dependent hyperadrenocorticism (PDH). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocortical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ATH (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with PDH. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment. Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (+/- SD) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 +/- 9.4 for dogs with ATH vs 45.7 +/- 11.9 for dogs with PDH. The mean plasma cortisol concentrations 1 hour after ACTH administration at the 7-day recheck were significantly higher in dogs with ATH (502 +/- 386 nmol/L) than in dogs with PDH (88 +/- 94 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Hyperadrenocorticism in a cat

A diabetic cat with hyperadrenocorticism had polydipsia, polyuria, ventral abdominal alopecia, thin dry skin, and a pendulous abdomen. Results of laboratory testing indicated persistent resting hypercortisolemia, hyperresponsiveness of the adrenal glands (increased cortisol concentration) to ACTH gel, and no suppression of cortisol concentrations after administration of dexamethasone at 0.01 or 1.0 mg/kg of body weight. Necropsy revealed a pituitary gland tumor, bilateral adrenal hyperplasia, hepatic neoplasia, and demodicosis. Adrenal gland function was concurrently assessed in 2 cats with diabetes mellitus. One cat had resting hypercortisolemia, and both had hyperresponsiveness to ACTH gel (increased cortisol concentration) at one hour. After administration of dexamethasone (0.01 and 1.0 mg/kg), the diabetic cats appeared to have normal suppression of cortisol concentrations. The effects of mitotane were investigated in 4 clinically normal cats. Adrenocortical suppression of cortisol production occurred in 2 of 4 cats after dosages of 25, 37, and 50 mg/kg. Three cats remained clinically normal throughout the study. One cat experienced vomiting, diarrhea, and anorexia.     

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).     

Evaluation of a low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism.

OBJECTIVE: To determine whether low doses of synthetic ACTH could induce a maximal cortisol response in clinically normal dogs and to compare a low-dose ACTH stimulation protocol to a standard high-dose ACTH stimulation protocol in dogs with hyperadrenocorticism. DESIGN: Cohort study. ANIMALS: 6 clinically normal dogs and 7 dogs with hyperadrenocorticism. PROCEDURE: Each clinically normal dog was given 1 of 3 doses of cosyntropin (1, 5, or 10 micrograms/kg [0.45, 2.3, or 4.5 micrograms/lb] of body weight, i.v.) in random order at 2-week intervals. Samples for determination of plasma cortisol and ACTH concentrations were obtained before and 30, 60, 90, and 120 minutes after ACTH administration. Each dog with hyperadrenocorticism was given 2 doses of cosyntropin (5 micrograms/kg or 250 micrograms/dog) in random order at 2-week intervals. In these dogs, samples for determination of plasma cortisol concentrations were obtained before and 60 minutes after ACTH administration. RESULTS: In the clinically normal dogs, peak cortisol concentration and area under the plasma cortisol response curve did not differ significantly among the 3 doses. However, mean plasma cortisol concentration in dogs given 1 microgram/kg peaked at 60 minutes, whereas dogs given doses of 5 or 10 micrograms/kg had peak cortisol values at 90 minutes. In dogs with hyperadrenocorticism, significant differences were not detected between cortisol concentrations after administration of the low or high dose of cosyntropin. CLINICAL IMPLICATIONS: Administration of cosyntropin at a rate of 5 micrograms/kg resulted in maximal stimulation of the adrenal cortex in clinically normal dogs and dogs with hyperadrenocorticism.     

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.     

Intramuscular administration of a low dose of ACTH for ACTH stimulation testing in dogs

OBJECTIVE: To compare adrenal gland stimulation achieved following administration of cosyntropin (5 microg/kg [2.3 microg/lb]) IM versus IV in healthy dogs and dogs with hyperadrenocorticism. DESIGN: Clinical trial. Animals-9 healthy dogs and 9 dogs with hyperadrenocorticism. PROCEDURES: In both groups, ACTH stimulation was performed twice. Healthy dogs were randomly assigned to receive cosyntropin IM or IV first, but all dogs with hyperadrenocorticism received cosyntropin IV first. In healthy dogs, serum cortisol concentration was measured before (baseline) and 30, 60, 90, and 120 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was measured before and 60 minutes after cosyntropin administration. RESULTS: In the healthy dogs, serum cortisol concentration increased significantly after administration of cosyntropin, regardless of route of administration, and serum cortisol concentrations after IM administration were not significantly different from concentrations after IV administration. For both routes of administration, serum cortisol concentration peaked 60 or 90 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was significantly increased 60 minutes after cosyntropin administration, compared with baseline concentration, and concentrations after IM administration were not significantly different from concentrations after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in healthy dogs and dogs with hyperadrenocorticism, administration of cosyntropin at a dose of 5 microg/kg, IV or IM, resulted in equivalent adrenal gland stimulation.     

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.     

Plasma cortisol concentrations following cortisone infusion in dogs before and after treatment with cortisone acetate

OBJECTIVE: To evaluate effects of iatrogenic hyperadrenocorticism on plasma cortisol concentrations produced by an infusion of hydrocortisone in dogs. PROCEDURE: Plasma cortisol concentrations were measured regularly during a 6 h infusion of hydrocortisone sodium succinate at two dose rates. The infusions were performed before and after treatment for 30 d with oral cortisone acetate at 10 mg/kg/24 h, divided thrice daily. Adrenal activity during the experimental period was assessed by weekly ACTH stimulation tests. RESULTS: Both infusion rates produced lower plasma cortisol concentrations after treatment for 30 d with cortisone. CONCLUSION: Prior exposure to high concentrations of glucocorticoids may result in accelerated metabolism of glucocorticoids administered subsequently. This may necessitate increased dosages when using glucocorticoids to support inadequate adrenal function.     

Perianal adenomas and hypertestosteronemia in a spayed bitch with pituitary-dependent hyperadrenocorticism

Hypertestosteronemia was diagnosed in a spayed bitch with pituitary-dependent hyperadrenocorticism and perianal adenomas. Serum concentrations of cortisol and testosterone decreased after treatment with mitotane was instituted. Excessive testosterone in this dog was thought to have been produced by the adrenal cortex, possibly in response to excessive ACTH concentrations. Development of androgen- or estrogen-responsive tumors in castrated dogs may be an early indication of adrenocortical hyperfunction.     

Use of aminoglutethimide in the treatment of pituitary-dependent hyperadrenocorticism in the dog

The aim of this study was to evaluate the efficacy and safety of aminoglutethimide in the treatment of dogs with pituitary-dependent hyperadrenocorticism (PDH). Ten dogs were diagnosed with PDH based on clinical and laboratory data, adrenal function tests (adrenocorticotropic hormone [ACTH] stimulation test and urinary cortisol/creatinine ratio [UCCR] combined with a high dose oral dexamethasone suppression test) and ultrasonographic evaluation of the adrenal glands. Aminoglutethimide was administered daily at a dose of 15 mg/kg bodyweight for one month. Median basal cortisol concentration and post-ACTH cortisol concentration one month after treatment were significantly lower than pretreatment values. Complete response was achieved in one dog, and partial response was obtained in three dogs. Severe side effects of anorexia, vomiting and weakness occurred in one dog and medication was withdrawn. Two further dogs developed decompensations of concurrent diseases and medication was stopped in these animals as well. Mild toxicity occurred in four dogs. Moderate to severe elevations in liver enzymes occurred in all dogs. The efficacy of this drug is lower than that observed using mitotane and ketoconazole, and adverse effects limit its use. Aminoglutethimide, using the protocol described, cannot be recommended for long-term management of PDH in the dog.     

Diseases of the adrenal cortex of dogs and cats

The most common cause of hypoadrenocorticism in dogs is idiopathic immune-mediated destruction of the adrenal cortex. Other causes include anterior pituitary insufficiency, pituitary or adrenal neoplasia, acute withdrawal of exogenous corticosteroids, and mitotane toxicity. Females are affected more often than males; only 1 feline case has been documented. Animals 2-5 years old are most commonly affected. Clinical signs include lethargy, weakness, weight loss, anorexia, vomiting, diarrhea and bradycardia. Hematologic and biochemical changes can include eosinophilia, lymphocytosis, anemia, hyperkalemia, hyponatremia and hypercalcemia. Diagnosis is by finding negligible resting levels of plasma cortisol and no response to ACTH administration, and a serum Na:K ratio of 20:1 or less. Treatment involves restoring fluid volume, correcting acidosis, and supplementing salt and glucocorticoids. Daily oral use of prednisone at 0.05 mg/kg can safely maintain most affected dogs. Some dogs only require glucocorticoids in stressful situations. Iatrogenic secondary adrenocortical insufficiency (iatrogenic Cushing's disease) may result from a single injection of long-acting glucocorticoids or from long-term use. Clinical signs are the same as for natural hyperadrenocorticism, but endogenous cortisol release is suppressed. Treatment is gradual withdrawal of the offending glucocorticoid and elimination of the cause that initially prompted glucocorticoid therapy.     

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.     

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia.

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared with the results from 12 dogs with confirmed pituitary-dependent hyperadrenocorticism (PDH). The post-ACTH cortisol concentration in the dogs with adrenocortical tumours ranged from 61 to 345-6 nmol/litre (median 251.5 nmol/litre) and they were within the reference range (150 to 450 nmol/litre) in five and unexpectedly low (< 150 nmol/litre) in three dogs. Both the basal and post-ACTH cortisol concentrations were significantly lower in the dogs with adrenocortical neoplasia than in the dogs with PDH. Eight hours after the LDDST, only two of six dogs with adrenocortical tumours had a cortisol concentration above 30 nmol/litre, and the median resting, three, and eight-hour cortisol concentrations were 31.5, 23.0, and 22.7 nmol/litre respectively. There was no significant cortisol suppression during the LDDST, although interpretation was complicated by the low cortisol concentrations, but two dogs showed a pattern of apparent suppression. Two dogs with adrenal tumours showed a diagnostically significant increase in 17-OH-progesterone concentration in response to ACTH although their cortisol concentrations did not increase greatly. These results differ from previous reports of the response of functional adrenal tumours to dynamic endocrine tests.     

Study of the effects of once daily doses of trilostane on cortisol concentrations and responsiveness to adrenocorticotrophic hormone in hyperadrenocorticoid dogs

The effects of trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor on basal cortisol concentrations and the results of ACTH stimulation tests in dogs with pituitary-dependent hyperadrenocorticism were investigated. In eight of nine dogs trilostane suppressed the concentration of cortisol below the lower limit of the reference range (<50 nmol/l) for a mean (sd) of 3.5 (2.3) hours during the day, but for no longer than 13 hours. In another 10 dogs, there was a clear difference between the post ACTH cortisol concentrations observed four and 24 hours after the administration of trilostane. Furthermore, in the six dogs whose clinical signs were poorly controlled the post-ACTH concentrations observed four and 24 hours after the administration of trilostane were always higher than the equivalent cortisol concentrations in the four dogs whose clinical signs were controlled. A short duration of drug action may be responsible for the failure of some dogs to respond adequately to once daily trilostane administration.     

Results of surgical treatment for hyperadrenocorticism caused by adrenocortical neoplasia in the dog: 25 cases (1980-1984)

Results of surgical treatment for neoplasia of the adrenal cortex that caused hyperadrenocorticism were evaluated in 25 dogs. Surgical examination of the adrenal glands was performed by use of a ventral midline approach in 24 dogs and a retroperitoneal approach in 1 dog. All 25 dogs had a unilateral, adrenocortical tumor. Histologic examination identified 14 adrenocortical carcinomas and 11 adenomas. Seven dogs with carcinoma had visible metastasis to the liver, 3 had local invasion into the caudal vena cava, and 1 had extension into the adjacent renal vein. Seven of the 9 dogs with metastasis were euthanatized at time of surgery. Of the remaining 18 dogs that survived surgery, 9 (4 with carcinoma and 5 with adenoma) developed serious postoperative complications including acute renal failure, pneumonia, and pulmonary artery thromboembolism; 8 of these dogs died or were euthanatized. Of the remaining 10 dogs, clinical signs associated with hyperadrenocorticism resolved in the 7 dogs that had adrenocortical adenoma and in 1 of the 3 dogs that had carcinoma. The remaining 2 dogs with carcinoma had persistent hyperadrenocorticism and were treated with high doses of mitotane. Although no response was observed in 1 dog with visible hepatic metastasis, a decrease in serum cortisol concentrations and resolution of clinical signs were detected in the other dog during prolonged daily administration of mitotane.     

The use of 17-hydroxyprogesterone in the diagnosis of canine hyperadrenocorticism

A number of dogs are seen with clinical signs consistent with hyperadrenocorticism (HAC), supporting CBC and biochemical findings, but the disease cannot be confirmed with either the ACTH stimulation test or the low-dose dexamethasone suppression test (LDDST). Therefore, another screening test is required to aid diagnosis in these atypical cases of HAC. The aim of this study was to investigate whether measuring 17-hydroxyprogesterone (OHP) concentrations could be used in this role. Plasma cortisol and OHP concentrations were measured in dogs with clinical signs suggestive of HAC before and after administration of exogenous ACTH. In dogs with HAC, plasma OHP showed an exaggerated response to ACTH stimulation. This was seen in both typical cases of HAC with a positive cortisol response to ACTH administration and in atypical cases with negative screening test results. The test can be performed on plasma already taken for a conventional ACTH stimulation test. Post-ACTH OHP concentrations decreased after treatment with mitotane or adrenalectomy. These results suggest that OHP measurements can be used as an aid to diagnose and manage canine HAC.     

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.     

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.