Endogenous ACTH Concentration Research Articles

Utility of a corticotropin-releasing hormone test to differentiate pituitary-dependent hyperadrenocorticism from cortisol-producing adrenal tumors in dogs.

BackgroundHyperadrenocorticism (HAC) is a common endocrine disorder in dogs; however, there are no reports on the use of the corticotropin‐releasing hormone test (CRHT) to differentiate between pituitary‐dependent hyperadrenocorticism (PDH) and cortisol‐producing adrenal tumors (CPATs), both causative of HAC.ObjectivesTo evaluate the usefulness of CRHT as a tool to differentiate between PDH and CPAT in dogs and to determine the reference intervals for CRHT in healthy, PDH, and CPAT dogs.AnimalsDogs diagnosed with PDH (n = 21), CPAT (n = 6), and healthy beagle dogs (n = 33).MethodsThis prospective study included dogs with a definitive diagnosis of PDH and CPAT and healthy beagle dogs, in which CRHT was performed, were prospectively evaluated. We investigated the correlations of CRHT (endogenous adrenocorticotropic hormone [ACTH] concentration, endogenous ACTH concentration [EAC], and poststimulation ACTH concentration [PAC]) with pituitary‐to‐brain ratio (PBR) (in PDH) and with indices of adrenal ultrasonography (smaller and larger adrenal gland dorsoventral thickness in PDH and CPAT).ResultsFor EAC, the area under the curve (AUC) was 0.95, with a cutoff value of 26.3 pg/mL (sensitivity: 90.62%, specificity: 87.50%). The AUC for PAC was 0.96 with a cutoff value of 54.5 pg/mL (sensitivity: 100.00%, specificity: 66.67%). The 95% reference interval for CRHT in healthy (control) dogs ranged 5.00 to 79.8 pg/mL (1.10‐17.57 pmol/L) for EAC, and 1.92 to 153.42 pg/mL (0.42‐33.78 pmol/L) for PAC. There was no significant correlation between PBR and CRHT, nor adrenal size and CRHT.Conclusions and Clinical ImportanceCRHT appears to be a rapid and reliable test for differentiating PDH from CPAT in dogs.

Comparison of methods to monitor dogs with hypercortisolism treated with trilostane.

BackgroundThe use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned.ObjectivesTo evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC.AnimalsForty‐five client‐owned dogs with HC treated with trilostane q12h.MethodsProspective cross‐sectional observational study. The dogs were categorized as well‐controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane‐treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before‐ACTH serum cortisol, post‐ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma‐glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol : creatinine ratio.ResultsNinety‐four re‐evaluations of 44 dogs were included; 5 re‐evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P < .001) and in the receiver operating characteristic analysis, Hp cutoff of 151 mg/dL correctly identified 90.0% of well‐controlled dogs (specificity) and 65.6% of undercontrolled dogs (sensitivity). Alanine aminotransferase (P = .01) and γGT (P = .009) were significantly higher in undercontrolled dogs. Cutoff of ALT and γGT greater than or equal to 86 U/L and 5.8 U/L, respectively, were significantly associated with poor control of HC by trilostane.Conclusions and Clinical ImportanceOf all the 12 variables, Hp, and to a lesser degree ALT and γGT, could be considered additional tools to the clinical picture to identify well‐controlled and undercontrolled trilostane‐treated dogs.

Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares.

BackgroundPituitary pars intermedia dysfunction (PPID) is an endocrine disorder the clinical signs of which include infertility, but few reports have examined the relationship between PPID and reproductive performance in broodmares.Hypothesis/ObjectiveBroodmares with infertility of unknown etiology were screened for PPID using baseline endogenous plasma ACTH concentrations, and its relationship with subsequent reproductive performance was analyzed.AnimalsSixty‐seven Thoroughbred broodmares.MethodsAdrenocorticotropic hormone concentrations were measured in autumn. The broodmares were divided into 3 groups based on endogenous plasma ACTH concentration (low, <50 pg/mL; intermediate 50‐100 pg/mL; and high >100 pg/mL) as recommended by the Equine Endocrinology Group. We compared these results with those of other blood tests, clinical examinations, subsequent conception, and frequency of normal delivery.ResultsThe numbers of horses per group (percentage) were 22 (32.8%), 20 (29.9%), and 25 (37.3%). The mean ± SD ages (years) were 11.1 ± 3.4, 12.1 ± 4.5, and 13.0 ± 4.3, with no significant difference among groups. Mean ± SD plasma cortisol concentrations (μg/dL) were 4.0 ± 1.6, 7.1 ± 1.4, and 7.6 ± 1.9, with the intermediate and high ACTH groups having significantly higher results than the low ACTH group (P < .001). Conception rates were 77.3%, 89.5%, and 56.5% and normal delivery rates were 77.2%, 84.2%, and 43.5% with the percentage of each significantly lower in the high ACTH group (P = .02, P = .008, respectively).Conclusions and Clinical ImportanceThe study group of infertile broodmares may include horses with PPID. The reproductive performance of the high ACTH group was significantly lower than the other groups. Early diagnosis and treatment of infertile broodmares by screening plasma ACTH concentrations could help improve reproductive performance.

Reversible megaoesophagus in a dog with isolated glucocorticoid-deficient hypoadrenocorticism

An eight-year-old, female, neutered labradoodle was presented for investigation of a three-week history of lethargy and regurgitation. Two sets of conscious thoracic radiographs, performed approximately two weeks apart, revealed the...

Effects of Trilostane on urinary Catecholamines and their metabolites in dogs with Hypercortisolism

BackgroundGlucocorticoids influence the synthesis and metabolism of catecholamines (epinephrine and norepinephrine) and metanephrines (metanephrine and normetanephrine). The aim of this study was to measure urinary catecholamines and metanephrines in dogs with hypercortisolism before and during trilostane therapy.Urine samples were collected during initial work up and during therapy with trilostane in 14 dogs with hypercortisolism and in 25 healthy dogs. Epinephrine, norepinephrine, metanephrine and normetanephrine were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration.ResultsUntreated dogs with hypercortisolism had significantly higher epinephrine, norepinephrine, and normetanephrine:creatinine ratios compared to healthy dogs. During trilostane therapy, urinary catecholamines and their metabolites did not decrease significantly. However, dogs with low post-ACTH cortisol concentrations during trilostane therapy had less increased epinephrine, norepinephrine and normetanephrine:creatinine ratios compared to healthy dogs. There was no correlation of urinary catecholamines and their metabolites with baseline or post-ACTH cortisol or endogenous ACTH concentrations during trilostane therapy.ConclusionInfluences between steroid hormones and catecholamines seem to occur, as dogs with hypercortisolism have significantly higher urinary epinephrine, norepinephrine, and normetanephrine:creatinine ratios. Once-daily trilostane therapy does not lead to a significant decrease in catecholamines and their metabolites. Trilostane-treated dogs still have increased urinary epinephrine, norepinephrine and normetanephrine:creatinine ratios during trilostane therapy.

The Effect of Geographic Location on Circannual Adrenocorticotropic Hormone Plasma Concentrations in Horses in Australia.

BackgroundLongitudinal evaluation of plasma endogenous ACTH concentration in clinically normal horses has not been investigated in the Southern Hemisphere.ObjectivesTo longitudinally determine monthly upper reference limits for plasma ACTH in 2 disparate Australian geographic locations and to examine whether location affected the circannual rhythm of endogenous ACTH in the 2 groups of horses over a 12‐month period.AnimalsClinically normal horses <20 years of age from 4 properties (institutional herd and client owned animals) in Perth (n = 40) and Townsville (n = 41) were included in the study.MethodsA prospective longitudinal descriptive study to determine the upper reference limit and confidence intervals for plasma ACTH in each geographic location using the ASVCP reference interval (RI) guidelines, for individual months and monthly groupings for 12 consecutive months.ResultsPlasma endogenous ACTH concentrations demonstrated a circannual rhythm. The increase in endogenous ACTH was not confined to the autumnal months but was associated with changes in photoperiod. During the quiescent period, plasma ACTH concentrations were lower, ≤43 pg/mL (upper limit of the 90% confidence interval (CI)) in horses from Perth and ≤67 pg/mL (upper limit of the 90% CI) in horses from Townsville, than at the acrophase, ≤94 pg/mL (upper limit of the 90% CI) in horses from Perth, ≤101 pg/mL (upper limit of the 90% CI) in horses from Townsville.Conclusions and Clinical ImportanceCircannual rhythms of endogenous ACTH concentrations vary between geographic locations, this could be due to changes in photoperiod or other unknown factors, and upper reference limits should be determined for specific locations.

Extended low-dose dexamethasone suppression test for diagnosis of atypical Cushing's syndrome in dogs

The purpose of this study was to evaluate extension of the low-dose dexamethasone suppression (LDDS) test from 8 h to 12 h to detect possible hypercortisolemia associated with atypical hyperadrenocorticism (AHAC). Twelve client-owned dogs were enrolled in the study: 6 healthy dogs (group 1) and 6 dogs with suspected AHAC (group 2). Baseline EDTA plasma samples were collected for endogenous ACTH determination using an immunoradiometric assay. Serum samples were collected before and at 4, 8, 10, and 12 h post-administration of 0.01 mg/kg dexamethasone IV for cortisol concentration determination via chemiluminescent assay. Mean endogenous ACTH concentration did not differ between groups (group 1: 22.4 pg/mL, group 2: 20.0 pg/mL; P > 0.2). Mean baseline cortisol concentration also did not differ significantly between groups (group 1: 3.03 μg/dL, group 2: 4.95 μg/dL; P > 0.2) nor was there any difference in mean cortisol concentration between the groups at any other time point (P > 0.2). The cortisol concentration from 1 dog in group 2 suppressed to 0.7 μg/dL at 8 h but increased to 1.5 μg/dL at 10 h and 3.7 μg/dL at 12 h post-dexamethasone. Based on results of this study, use of an extended LDDS test could not differentiate between healthy dogs and dogs with AHAC. Diagnosis of AHAC should continue to be based on prior established criteria until new testing has been identified.

Use of the cortisol-to-ACTH ratio for diagnosis of primary hypoadrenocorticism in dogs.

BackgroundThe ACTH stimulation test is currently required for definitive diagnosis of hypoadrenocorticism. Increased cost of synthetic ACTH (cosyntropin) has prompted a search for alternative diagnostic methods.ObjectiveThe purpose of this study was to determine whether a cortisol‐to‐ACTH ratio (CAR) can be used to differentiate dogs with hypoadrenocorticism from normal dogs and those with nonadrenal illness.AnimalsEight healthy dogs (H), 19 dogs with nonadrenal illness (NAI), and 15 dogs with hypoadrenocorticism (HAD).MethodsDogs in the HAD group were retrospectively identified from PUVTH medical records. The NAI group consisted of hospitalized dogs with clinical signs, clinicopathologic findings, or both, consistent with a diagnosis of hypoadrenocorticism, but in which hypoadrenocorticism was ruled out based on ACTH stimulation test results. Healthy dogs were recruited from hospital staff and students. Endogenous ACTH concentrations and cortisol concentrations before and after ACTH stimulation were measured in all dogs.ResultsBaseline cortisol concentration was significantly lower, and ACTH concentration was significantly higher, in the HAD group versus the H and NAI group (P < .001). However, there was overlap among groups. Cortisol‐to‐ACTH ratio was significantly lower in the HAD group versus the H and NAI groups (P < .001), and there was no overlap between the HAD group and the other 2 groups.Conclusions and Clinical Importance CAR can be used for definitive diagnosis of primary hypoadrenocorticism.

Diagnostic efficacy of the leukogram and the chemiluminometric ACTH measurement to diagnose canine hypoadrenocorticism

The gold standard in the diagnosis of canine hypoadrenocorticism (HA) is the adrenocorticotropin (ACTH) response test. As synthetic ACTH (tetracosactide [Synacthen®]) is currently not available in the European Union, the evaluation of other diagnostic tests seemed warranted. The diagnostic efficacy of electrolytes, the leukogram and endogenous ACTH concentrations to diagnose HA was investigated. The medical records of 145 dogs with clinical signs suspect for spontaneous HA were included in a retrospective study. HA was diagnosed (n=38) or ruled out (n=84) by using an ACTH response test. In 23 patients HA was excluded by basal cortisol measurement. The diagnostic performance of various variables was assessed based on receiver operating characteristic (ROC) curves and by calculating differential positive rates. A decision tree (IBM SPSS Decision Trees 20, IBM Corporation) was constructed with the variables neutrophil to lymphocyte ratio (N/LR) and sodium to potassium ratio (Na/KR) to illustrate the diagnostic efficacy of the respective test results. The best single variables to diagnose HA were the endogenous ACTH concentration (area under the ROC curve [ROC AUC] 0.97; cutoff >50pmol/l: sensitivity 96%, specificity 100%) and the Na/KR (ROC AUC 0.905; cutoff ≤22: sensitivity 92%, specificity 91%). The diagnostic performance of various variables of the leukogram was poor to moderate (ROC AUC 0.625-0.828). 68% of dogs with HA had a Na/KR ≤22 and a N/LR ≤2.3, a combination not observed in dogs with non-adrenal diseases. As secondary HA is very rare, endogenous ACTH measurement is a very good alternative to the traditional ACTH response test. Data also suggest that the combination of a Na/KR ≤22 and a N/LR ≤2.3 is highly specific and can be used to rule in HA.

Effect of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs

To determine the effects of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs. 10 healthy neutered dogs. Each dog received dexamethasone (0.01 mg/kg), synthetic ACTH (5 μg/kg), or saline (0.9% NaCl) solution (0.5 mL) IV at intervals of ≥ 30 days. Plasma endogenous ACTH concentrations were measured before (baseline; time 0) and 1, 8, 12, and 24 hours after drug administration; serum cortisol concentrations were measured before and 1 hour after synthetic ACTH and saline solution administration and 8 hours after dexamethasone administration. Analysis of serum cortisol concentrations confirmed effects of drug administration. Dexamethasone significantly decreased the endogenous ACTH concentration from the baseline value at both 8 and 12 hours. Synthetic ACTH administration significantly decreased the endogenous ACTH concentration from the baseline value at 8 hours. Saline solution administration had no significant effect on endogenous ACTH concentration. Dexamethasone and synthetic ACTH administered IV at doses used routinely during testing for hyperadrenocorticism caused significant but transient reductions of endogenous ACTH concentrations in healthy dogs. Thus, a 2-hour washout period following ACTH stimulation testing before collection of samples for measurement of the endogenous ACTH concentration may be insufficient. Although this effect has not been verified in dogs with hyperadrenocorticism, these data suggested that samples for measurement of endogenous ACTH concentrations should be obtained before or > 8 hours after initiation of an ACTH stimulation test or before or > 12 hours after the start of a low-dose dexamethasone suppression test.

Evaluation of Baseline Cortisol, Endogenous ACTH, and Cortisol/ACTH Ratio to Monitor Trilostane Treatment in Dogs with Pituitary‐Dependent Hypercortisolism

The effectiveness of trilostane treatment is currently monitored by regular ACTH stimulation tests, which are time-consuming and expensive. Therefore, a monitoring system without a stimulation protocol and with less client expense would be preferable. The aim of our study was to evaluate if baseline cortisol, endogenous ACTH (ACTH) concentration or the baseline cortisol to ACTH ratio (cortisol/ACTH ratio) could replace the ACTH stimulation test. Forty trilostane-treated dogs with pituitary-dependent hypercortisolism (PDH) were included in this prospective study. A total of 148 ACTH stimulation tests and 77 ACTH concentrations and cortisol/ACTH ratios were analyzed. Control of cortisol release was classified according to cortisol concentration after ACTH administration as excessive (<1.5 μg/dL; group 1), adequate (1.5-5.4 μg/dL; group 2), or inadequate (>5.4 μg/dL; group 3). Baseline cortisol concentrations had considerable overlap between excessively, adequately, and inadequately controlled dogs. Only baseline cortisol >4.4 μg/dL (in 12% of tests) was a reliable diagnosis of inadequate control. Endogenous ACTH concentrations did not differ between groups. The overlap of the cortisol/ACTH ratio between groups was large. Correct classification was only possible if the cortisol/ACTH ratio was >15, which occurred in 4% of tests. To monitor trilostane treatment the ACTH stimulation test cannot be replaced by baseline cortisol, ACTH concentration, or the cortisol/ACTH ratio.

The Effect of Starvation on Blood Stream Cancer Cell Metastasis to the Liver in Rat after Laparotomy

Preoperative malnutrition worsens the prognosis of cancer patients. However, it is not certain how preoperative malnutrition affects postoperative hematogenous metastasis. We examined the influence of preoperative starvation on liver metastasis in rats using intra-vascular injection of AH109A hepatoma cells. Male donryu rats were divided into Fasting and Control groups. Rats received laparotomy and (125)I-iodo-deoxyuridine labeled AH109A hepatoma cells were inoculated via superior mesenteric vein. Radioactivity in the organs, macroscopic liver metastasis, white blood cell count, leukocyte count, NK cell activity, endogenous serum corticosterone and ACTH concentration and mRNA expression of cytokine in the liver and brain were evaluated at certain time points. 48hours preoperative starvation reduced body weight and induced a state of malnutrition. Accumulation of radioactivity in the liver was more than 4 times higher, and the number of liver metastases was 3.5 times higher in the Fasting than in the Control group. Preoperative starvation caused an almost 2 fold increase in plasma endogenous corticosterone levels and a 66% reduction in white blood cell and lymphocyte counts. Postoperative hypothalamus pituitary adrenal axis response was preserved. In addition, inflammatory cytokine expression in the liver was suppressed in the starved animals, suggesting that preoperative starvation led to a state of cellular immunosuppression, which would be an important factor for liver metastasis. Preoperative malnutrition by 48 hours starvation reduced inflammatory cytokine response and cellular immunity, resulting in an increase in hematogenous liver metastasis.

Highlights of recent clinically relevant papers

Highlights of recent clinically relevant papers

Seasonal variation in results of diagnostic tests for pituitary pars intermedia dysfunction in older, clinically normal geldings

To determine whether seasonal variations exist in endogenous plasma ACTH, plasma α-melanocyte-stimulating hormone (α-MSH), serum cortisol, and serum insulin concentrations and in the results of a dexamethasone suppression test for older, clinically normal geldings in Alabama. Cohort study. 15 healthy mixed-breed geldings (median age, 14 years). Sample collection was repeated monthly for 12 months. Dexamethasone (0.04 mg/kg [0.02 mg/lb], IM) was administered and cortisol concentrations were determined at 15 and 19 hours. Radioimmunoassays were used to measure ACTH, α-MSH, cortisol, and insulin concentrations at each testing time. Hormone concentrations were compared between months via repeated-measures ANOVA and correlated with age within each month. A significant time effect was found between months for α-MSH and insulin concentrations. Endogenous cortisol and ACTH concentrations remained within existing reference ranges. Significant correlations were detected between age and ACTH concentration for several fall and winter months and between age and insulin concentration for September. Older horses have higher ACTH concentrations in several fall and winter months and higher insulin concentrations in September than do younger horses. Seasonally specific reference ranges are required for α-MSH and insulin concentrations, with significantly higher concentrations detected in the fall. Practitioners should be advised to submit samples only to local laboratories that can provide such reference ranges for their local geographic region.

Seasonal Changes in Plasma Adrenocorticotropic Hormone and α‐Melanocyte‐Stimulating Hormone in Response to Thyrotropin‐Releasing Hormone in Normal, Aged Horses

Results of diagnostic tests for equine pituitary pars intermedia dysfunction (PPID), including endogenous ACTH concentration and the overnight dexamethasone suppression test (DST), are affected by season. New and potentially more sensitive diagnostic tests for equine PPID, such as thyrotropin-releasing hormone (TRH)-stimulated ACTH response, have been developed, but have had limited evaluation of seasonality. Our purpose was to evaluate seasonal changes in plasma ACTH and alpha-melanocyte-stimulating hormone (α-MSH) responses to TRH administration. Nine, healthy, aged horses with normal DST results. Synthetic TRH (1 mg) was administered IV. Plasma ACTH and α-MSH concentrations were measured at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 180 minutes. Testing was performed in February, July, August, September, October, and November. Mean TRH-stimulated ACTH and α-MSH concentrations were compared across months and time by repeated measures analysis of variance. Significance was set at the P < .05 level. Concentrations of ACTH and α-MSH significantly increased after TRH administration. Endogenous and TRH-stimulated ACTH and α-MSH concentrations were significantly different across months with higher concentrations in the summer and fall compared with February. Plasma ACTH and α-MSH responses to TRH administration experience seasonal variation, with TRH-stimulated ACTH and α-MSH concentrations increasing from summer through fall. These results support previous evidence of a seasonal influence on the equine pituitary-adrenal axis. More research is warranted with a larger number of horses to determine if seasonal reference ranges for TRH stimulation testing need to be defined.

Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia

To compare the effect of thyrotropin-releasing hormone (TRH) administration on endogenous ACTH concentrations in healthy horses and those with pituitary pars inter-media hyperplasia and compare the test with the dexamethasone suppression test (DST). Prospective case series. 15 horses with clinical signs of pituitary pars intermedia dysfunction (PPID), 4 horses with equivocal signs of PPID, and 29 horses without signs of PPID. ACTH concentrations prior to and after administration of TRH were measured 61 times in 48 horses. Results of the DST (cortisol response) were compared with those of the TRH test in 29 horses. Thirty-three horses (24 with no clinical signs of PPID, 5 with clinical signs of PPID, and 4 with equivocal clinical signs of PPID) were euthanized and necropsied and their pituitary glands evaluated. ACTH concentrations increased in all horses, but magnitude and duration of increase were significantly higher in horses with PPID. Endogenous ACTH concentrations were influenced by season. The ACTH baseline concentrations and response to TRH were not correlated with results of the DST. Results of DST were abnormal only in clinically abnormal horses or those with pars intermedia hyperplasia, but were within reference range in 17 of 26 tests in these horses. The ACTH response to TRH is a useful test for diagnosis of pituitary gland hyperplasia, particularly in horses in which baseline ACTH concentrations are within reference range. The DST was specific but not sensitive and was inconsistent for individuals, and results often did not agree with the TRH test response.

Effects of oral administration of controlled-ileal-release budesonide and assessment of pituitary-adrenocortical axis suppression in clinically normal dogs

To evaluate the effects of oral administration of controlled-ileal-release (CIR) budesonide on the pituitary-adrenal axis in dogs with a normal gastrointestinal mucosal barrier. 10 healthy dogs. 5 dogs received CIR budesonide orally once daily for days 1 through 28, and 5 dogs received placebo. Treatment group dogs that weighed < 18 kg received 2 mg of CIR budesonide; treatment group dogs that weighed > or = 18 kg received 3 mg of CIR budesonide. In the treatment and placebo groups, there were 3 and 2 dogs, respectively, that weighed > 18 kg. Plasma cortisol concentration before and after ACTH stimulation, basal plasma endogenous ACTH concentration, and body weight were measured on days 0, 7, 14, 21, 28, and 35. Serum biochemical analysis, CBC determination, and urinalysis were performed on days 0, 28, and 35. On days 7, 14, and 21, serum ALP and ALT activities, serum glucose concentration, and urine specific gravity were obtained in lieu of a full hematologic evaluation and urinalysis. Basal and post-ACTH stimulation plasma cortisol concentrations and plasma endogenous ACTH concentration were significantly suppressed by treatment. No other variables were altered over the course of the study. Budesonide suppresses pituitary-adrenal function in dogs with normal gastrointestinal integrity, whereas other variables often affected by glucocorticoids were not altered by a 4-week treatment course. Budesonide may be a good alternative to traditional cortico-steroids if used short-term for acute exacerbations of inflammatory bowel disease.

Pituitary ACTH and adrenocortical secretion in critically ill dogs.

To evaluate pituitary-adrenal function in a population of critically ill dogs by measuring serial plasma concentrations of basal cortisol, ACTH-stimulated cortisol, and endogenous ACTH. Prospective study. 20 critically ill dogs admitted to an intensive care unit (ICU). Basal plasma cortisol, ACTH-stimulated cortisol, and endogenous ACTH concentrations were measured for each dog within 24 hours of admission and daily until death, euthanasia, or discharge from the ICU. Established reference ranges for healthy dogs were used for comparison. Survival prediction index (SPI) scores were calculated for each dog within 24 hours of admission. No significant difference was found between initial concentrations of basal cortisol, ACTH-stimulated cortisol, and endogenous ACTH in 13 dogs that survived and those in 7 dogs that died. High initial basal endogenous ACTH concentrations were correlated with subsequent high values. Low basal ACTH-stimulated cortisol concentrations were predictive of higher subsequent values. All basal and ACTH-stimulated cortisol concentrations were within or above the reference range in the 52 plasma samples collected from the 20 dogs during hospitalization. The SPI scores correlated with outcome (ie, alive or dead), but none of the plasma hormone concentrations correlated with SPI score or outcome. Results indicate that none of the critically ill dogs in our study population developed adrenal insufficiency during hospitalization in the ICU.

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

Abstract 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. (Am J Vet Res 1999;60:698–702)

Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs

Objective To assess the efficacy and determine prognostic factors of megavoltage irradiation for pituitary macrotumors in dogs with neurologic signs. Design Prospective clinical trial. Animals 24 dogs with pituitary macrotumor syndrome; 19 ACTH-secreting and 5 clinically endocrine-inactive tumors. Procedure Dogs were treated with 48 Gy of radiation during 4 weeks on an alternate-day schedule of 4 Gy/fraction. Three (12.5%) dogs did not complete the planned treatment because of progression of neurologic signs. Results A significant correlation was found between relative tumor size (ie, size of tumor relative to calvarium size) and severity of neurologic signs and between relative tumor size and remission of neurologic signs after irradiation. In dogs with pituitary dependent hyperadrenocorticism, a significant correlation was found between relative tumor size and plasma endogenous ACTH concentrations. Prognostic factors that independently affected duration of remission of neurologic signs were relative tumor size and endocrine activity. The prognostic factor that independently affected overall survival time was severity of neurologic signs. Prognostic factors of duration of eucortisolism were not found. Use of a large field of irradiation was associated with substantial damage to brain tissue. Clinical Implications Because radiation therapy was effective for treatment of tumors of small relative size in dogs, early treatment of pituitary tumors should improve prognosis. Further improvements may be obtained, using protocols in which higher total radiation doses and smaller radiation dose fractions are given. Irradiation was effective for long-term control of functional pituitary macrotumors and resulted in acceptably low complication rates when small fields of radiation were used. (J Am Vet Med Assoc 1998;213:225-231)