Effect of low doses of cosyntropin on serum cortisol concentrations in clinically normal dogs

OBJECTIVE: To determine the lowest of 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, or 0.01 microg/kg) administered IV that stimulates maximal cortisol secretion in clinically normal dogs. ANIMALS: 10 clinically normal dogs. PROCEDURES: 5 dose-response experiments were performed in each of the dogs. Each dog received 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, and 0.01 microg/kg) IV in random order (2-week interval between each dose). Serum samples for determination of cortisol concentrations were obtained before (baseline) and at 10, 20, 30, 40, 50, 60, 120, and 240 minutes after cosyntropin administration. RESULTS: Compared with baseline values, mean serum cortisol concentration in the study dogs increased significantly after administration of each of the 5 cosyntropin doses. Mean peak serum cortisol concentration was significantly lower after administration of 0.01, 0.05, and 0.1 microg of cosyntropin/kg, compared with findings after administration of 0.5 and 1.0 microg of cosyntropin/kg. After administration of 0.5 and 1.0 microg of cosyntropin/kg, mean peak serum cortisol concentration did not differ significantly; higher doses of cosyntropin resulted in more sustained increases in serum cortisol concentration, and peak response developed after a longer interval. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of cosyntropin IV at a dose of 0.5 microg/kg induced maximal cortisol secretion in healthy dogs. Serum cortisol concentration was reliably increased in all dogs after the administration of each of the 5 doses of cosyntropin. These data should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill dogs.     

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)     

Effects of a mock ultrasonographic procedure on cortisol concentrations during low-dose dexamethasone suppression testing in clinically normal adult dogs

OBJECTIVE: To determine whether the stress of an ultrasonographic procedure would interfere with the suppressive effect of dexamethasone during a low-dose dexamethasone suppression test (LDDST) in healthy dogs. ANIMALS: 6 clinically normal adult dogs. PROCEDURE: In phase 1, an LDDST was performed 5 times at weekly intervals in each dog. Serum samples were obtained 0, 2, 4, 6, and 8 hours after dexamethasone injection. A mock 20-minute abdominal ultrasonographic examination was performed on all dogs at each time point during the LDDST on weeks 2 through 5. In phase 2, serum cortisol concentrations were measured before and immediately after a 20-minute mock abdominal ultrasonographic examination, as described for phase 1. RESULTS: We did not detect significant differences after dexamethasone injection when comparing median cortisol concentrations for weeks 2 to 5 (mock ultrasonographic procedure) with median concentration for week 1 (no mock ultrasonographic procedure). For 5 of the 6 dogs, cortisol concentrations after dexamethasone injection decreased to < 35.9 nmol/L after each mock ultrasonographic procedure and remained low for the duration of the LDDST. In phase 2, all dogs had significant increases in cortisol concentrations immediately after the mock ultrasonographic procedure. CONCLUSIONS AND CLINICAL RELEVANCE: A 20-minute mock abdominal ultrasonographic examination performed during LDDST did not alter results of the LDDST in most dogs. Cortisol concentrations measured immediately after a mock ultrasonographic examination were significantly increased. Ultrasonographic procedures should be performed a minimum of 2 hours before collection of samples that will be used to measure cortisol concentrations.     

Adrenal function testing in the cat: the effect of low dose intravenous dexamethasone administration

The plasma cortisol responses of 11 normal cats to intravenous dexamethasone at a dose rate of 0.01 mg kg-1 whole bodyweight, were evaluated. Mean plasma cortisol concentrations decreased significantly (P less than 0.01) at three hours and eight hours following dexamethasone administration. Results of this study indicate that plasma cortisol levels are significantly decreased for at least eight hours following low dose intravenous dexamethasone administration in normal cats.     

Effects of intravenous infusion of lipopolysaccharide on plasma micromineral, magnesium, and cytokine concentrations and serum cortisol concentrations in lactating goats

OBJECTIVE: To assess the effects of various doses of lipopolysaccharide (LPS) administered IV on plasma microminerals, magnesium, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 concentrations and serum cortisol concentrations in lactating goats. ANIMALS: 6 lactating goats. PROCEDURES: Goats were allotted to 3 LPS-treatment groups: control (0 microg/kg), low LPS (10 microg/kg), and high LPS (50 microg/kg). Rectal temperatures and behaviors of goats were recorded immediately before a 10-minute IV infusion of LPS and at 0.5, 1, 2, 4, 6, 8, and 24 hours after infusion. Blood samples were obtained before IV infusion and at 0.5, 1, 2, 4, 6, 8, and 24 hours after infusion. Plasma zinc, copper, iron, and magnesium concentrations were determined by atomic absorption spectrometry; plasma TNF-alpha and IL-6 concentrations were measured by use of an ELISA; and serum cortisol concentrations were determined by use of a radioimmunoassay. RESULTS: A monophasic fever developed in low-LPS and high-LPS groups. In the low-LPS and high-LPS group, plasma zinc concentrations decreased at 6 hours after infusion; compared with control groups. Plasma iron concentrations were lower at 24 hours after infusion in low-LPS and high-LPS groups than in the control group. Plasma TNF-alpha and IL-6 concentrations were higher in low-LPS and high-LPS groups than in the control group at 1, 2, and 4 hours after infusion. In low-LPS and high-LPS groups, serum cortisol concentrations increased from 0.5 hours onward and peaked at 1 (high-LPS group) and 2 (low-LPS group) hours after infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Following IV infusion of LPS, the immune system is activated, which might affect micromineral homeostatic regulation and, subsequently, the metabolic health of lactating goats.     

Effects of dermal dexamethasone application on ACTH and both basal and ACTH-stimulated cortisol concentration in normal horses

There are no data available regarding the systemic (adverse) effects which might be induced by topical/dermal glucocorticoids (GCs) application in the horse. Besides their widespread use for the treatment of a variety of peripheral inflammatory disorders such as atopic dermatitis, eczemas or arthritis in the horse, their surreptitious application has become a concern in doping cases in competition/performance horses. Assessing both basal and ACTH‐stimulated plasma cortisol as well as basal ACTH concentrations following application of dexamethsone‐containing dermal ointment is necessary to determine influences on hypothalamus‐pituitary‐adrenal (HPA) axis. Ten clinically healthy adult standardbred horses (6 mares, 4 geldings) were rubbed twice daily each with 50 g dexamethasone‐containing ointment on a defined skin area (30 × 50 cm) for 10 days. RIA and chemiluminescent enzyme immuno‐metric assay were used to determine resting and ACTH‐stimulated plasma cortisol and basal ACTH concentrations, respectively. HPA feedback sensitivity and adrenal function were measured by a standard ACTH stimulation test. Dermal dexamethasone suppressed significantly the resting plasma cortisol level (to 75–98%) below baseline (P < 0.001) within the first 2 days and decreased further until day 10. ACTH stimulation test showed a markedly reduced rise in plasma cortisol concentrations (P < 0.001 vs. baseline). Plasma ACTH level decreased also during topical dexamethasone application. The number of total lymphocytes and eosinophil granulocytes was reduced, whereas the number of neutrophils increased. No significant change of serum biochemical parameters was noted. Dermal dexamethasone application has the potential to cause an almost complete and transient HPA axis suppression and altered leukocyte distribution in normal horses. The effects on HPA axis function should be considered in relation to the inability of animals to resist stress situations. The data further implicate that percutaneously absorbed dexamethasone (GCs) may cause systemic effects relevant to ‘doping’.     

Effects of dexamethasone infusion on the plasma cortisol response to cosyntropin (synthetic ACTH) injection in normal dogs

Graded dosages of cosyntropin (synthetic corticotropin) were injected into groups of normal dogs on consecutive days. On the first day, cosyntropin was administered alone and, on the second, dogs were infused with dexamethasone three hours before cosyntropin injection. Adrenocortical function was assessed by sequential measurement of plasma cortisol (hydrocortisone) concentration. While no response differences were noted to the various amounts of cosyntropin injected with or without dexamethasone pretreatment, the magnitude of adrenocortical response was significantly greater in dogs infused with dexamethasone. It is concluded that dexamethasone pretreatment renders the canine adrenal cortex more responsive to a subsequent injection of cosyntropin. The combined dexamethasone infusion-cosyntropin injection test produces consistent adrenocortical responses in normal dogs, and has potential value in evaluation of adrenopathic dogs.     

Effects of administration of a low dose of frozen thyrotropin on serum total thyroxine concentrations in clinically normal dogs.

Thyroid function was evaluated in 18 healthy dogs by thyrotropin (TSH) stimulation. Two dose regimens were used in each dog: 0.1 IU/kg body weight of freshly reconstituted lyophilized TSH and 1 IU/dog of previously frozen and stored TSH (up to 200 days), both given intravenously. Blood samples were collected prior to and at four and six hours after TSH administration. Serum was evaluated for total thyroxine concentrations by radioimmunoassay. All dogs were classified as euthyroid on the basis of response to 0.1 IU/kg body weight of freshly reconstituted TSH at four and six hours. The 1 IU dose of TSH, previously frozen for up to 200 days, induced increases in serum total thyroxine concentration over baseline at four and six hours that were not significantly different from those resulting from the use of the higher dose of fresh TSH. In all test groups, there were no statistically significant differences between total thyroxine concentrations at four and six hours post-TSH administration. It was concluded that an adequate TSH response can be achieved with the use of 1 IU of TSH/dog for clinically normal dogs between 29.0 kg and 41.6 kg body weight, even if this TSH has been frozen at -20 degrees C for up to 200 days. Further, blood collection can be performed at any time between four and six hours. Similar studies are needed to evaluate this new protocol in hypothyroid dogs and euthyroid dogs suffering nonthyroidal systemic diseases.     

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

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

Plasma cortisol concentrations in normal dogs given hydrocortisone sodium succinate

OBJECTIVE: To evaluate the effects on plasma cortisol concentration of a continuous infusion of a readily available steroid with equipotent glucocorticoid and mineralocorticoid effects. PROCEDURE: Plasma cortisol concentrations were measured before and regularly after hydrocortisone sodium succinate was administered as a continuous intravenous infusion over 6 h at 0.32 and 0.65 mg kg-1 h-1 to 12 healthy dogs weighing 12 to 22 kg. RESULTS: The infusion at both does rates produced significant and stable increases in plasma cortisol concentrations. The plateau concentrations produced by the large and small doeses were respectively above and below plasma cortisol concentrations likely to provide adequate glucocorticoid and mineralocorticoid activity in stressed dogs with significantly decreased adrenal function. CONCLUSION: This paper presents information regarding the changes in plasma cortisol concentrations in 12 normal dogs given an hydrocortisone sodium succinate infusion at two dose rates. The marked and continuous increase in plasma cortisol concentrations suggests a continuous HSS infusion may be a possible alternative to desoxycorticosterone acetate and dexamethasone in the treatment of acute adrenal dysfunction.     

Monitoring the circadian rhythm of serum and salivary cortisol concentrations in the horse

Daily fluctuations of cortisol concentration in the blood or saliva have been repeatedly reported. However, several contradictions in the existing literature appear on this subject. The present study was performed to definitively establish options for testing adrenocortical function. To the best of our knowledge, this is the first study to evaluate parallel circadian rhythms in salivary and serum cortisol concentrations during a 24-h period. Twenty horses were examined under the same conditions. Blood and saliva samples were taken every 2 h for 24 h to determine the daily changes in cortisol concentrations of saliva and serum at rest and to determine the relationship between salivary and serum cortisol levels. Cosinor analysis of group mean data confirmed a significant circadian component for both serum and salivary cortisol concentrations (P < 0.001 in both cases). The serum cortisol circadian rhythm had an acrophase at 10:50 AM (95% CI, 10:00 AM–11:40 AM), a MESOR of 22.67 ng/mL, and an amplitude of 11.93 ng/mL. The salivary cortisol circadian rhythm had an acrophase at 10:00 AM (95% CI, 9:00 AM–11:00 AM), a MESOR of 0.52 ng/mL, and an amplitude of 0.12 ng/mL. We found a significant but weak association between salivary and serum cortisol concentrations; the Pearson correlation coefficient was 0.32 (P < 0.001). The use of salivary cortisol level as an indicator of hypothalamic-pituitary-adrenal axis activity may be warranted. However, the salivary cortisol levels are more likely to be correlated with free plasma cortisol than with the total plasma cortisol concentration.     

Postprandial serum gastrin concentrations in normal foals

Postprandial gastrin concentrations were assayed in serum samples from a group of six foals at one day, one week, one month and three months of age. Before sampling, each foal was prevented from feeding for 2 h and was then allowed to suck for 15 mins. Blood samples were taken at the start of the meal and at 30 min intervals for the next 3 h. Feeding increased serum gastrin concentrations at one day, one week and one month, with the greatest increases detected at one day. Mean pre-feeding gastrin concentrations were 25.2 +/- 2.3 pg/ml at one day, 22.8 +/- 3.9 pg/ml at one week, 15.2 +/- 2.3 pg/ml at one month and 15.6 +/- 7.5 pg/ml at three months. Highest mean post prandial concentrations were at 60 mins on Day one (47.4 +/- 15.2 pg/ml) and one month (25.2 +/- 4.1 pg/ml) old foals. There was no apparent post prandial increase in serum gastrin concentrations in foals at three months of age. Precise reasons for changes in postprandial serum gastrin concentrations remain unknown. Factors that could be important include maturation of G cell function, alterations in gastrin metabolism and excretion, and changes in gastrointestinal motility with increasing age.     

高精料诱导的SARA对泌乳期山羊血液和瘤胃液中皮质醇的影响

选择7只装有永久性瘤胃瘘管的泌乳中期山羊,2×2拉丁方设计,分别饲喂精粗比为6∶4和4∶6的饲料,通过饲喂精粗比6∶4饲料建立泌乳期山羊瘤胃亚急性酸中毒(subacute ruminal acidosis, SARA)模型,研究SARA时山羊血液和瘤胃液中皮质醇浓度、肝脏皮质醇受体(glucocorticoid receptor, GR)mRNA表达及其他相关指标的变化。结果表明,精粗比6∶4日粮饲喂2周后成功诱导SARA状态(SARA组),采食后瘤胃液pH值低于5.8持续时间约6 h,而精粗比为4∶6组山羊瘤胃液pH均高于6.0 (对照组)。高精料日粮处理对瘤胃pH和乳酸以及瘤胃液和血浆内的脂多糖、皮质醇浓度有显著性影响(P<0.05),采食前SARA组山羊瘤胃液中乳酸浓度显著高于对照组(P<0.05),采食后0~4 h乳酸含量下降,6~10 h时逐渐增加并极显著高于对照组(P<0.01);2组间瘤胃液中脂多糖浓度无显著性差异(P>0.05),SARA组血浆脂多糖浓度在采食前和采食后6 h均显著高于对照组(P<0.05);采食前SARA组山羊血液中皮质醇浓度高于对照组(P=0.05),但采食后6 h两组间无显著差异(P>0.05); 2组山羊瘤胃液中皮质醇浓度在采食后2,4和6 h分别显著高于对照组(P<0.05),但在采食前和采食后10 h无显著差异(P>0.05)。Real-time PCR结果显示,SARA组山羊肝脏中GR mRNA表达显著下调(P<0.05)。本研究结果显示,泌乳期山羊发生SARA时糖皮质激素水平升高,负反馈下调肝脏GR的表达水平,提示SARA时机体处于应激状态,可能引起肝脏的物质代谢和营养物质重分配的改变。     

地塞米松对山羊皮质醇分泌和瘤胃生物钟基因表达的影响

为了研究地塞米松对山羊皮质醇分泌和瘤胃生物钟基因表达的影响,试验选用10只装有永久性瘤胃瘘管的波尔杂交山羊,随机分为对照组(n=5)和地塞米松组(n=5),对照组注射生理盐水,地塞米松组注射地塞米松(0.2 mg/kg),每天注射1次,连续注射21 d。试验结束后,采集血液和瘤胃组织;放射免疫分析法(radioimmunoassay,RIA)检测血浆皮质醇含量;Real-time PCR检测瘤胃生物钟基因表达量。结果显示:与对照组相比,地塞米松组血浆皮质醇浓度显著降低(P0.05),瘤胃液中皮质醇浓度无显著变化(P0.05),瘤胃上皮组织中永恒蛋白基因(Tim)和肌肉芳香烃受体核转运样蛋白1(Bmal1)mRNA表达显著上调(P0.05);相关性分析结果显示:血浆皮质醇浓度与瘤胃上皮组织中Tim(R=-0.64,P=0.08)和Bmal1(R=-0.62,P=0.09)mRNA表达呈负相关趋势,瘤胃中皮质醇浓度与瘤胃上皮组织中Bmal1 mRNA表达呈显著负相关(R=-0.84,P0.05)。结果提示,外源性地塞米松降低山羊体内内源性皮质醇的生成,上调瘤胃上皮组织中生物钟基因的表达,且生物钟基因表达水平与血液、瘤胃液中皮质醇浓度呈高度负相关。     

Delayed growth in two German shepherd dog littermates with normal serum concentrations of growth hormone, thyroxine, and cortisol

Four German Shepherd Dogs from a litter of 10 were evaluated because of postnatal onset of proportionate growth stunting that clinically resembled well-documented hypopituitary dwarfism in that breed. Although 2 pups had histologic evidence of hypopituitarism, the remaining 2 pups had normal serum growth hormone concentration and adrenocorticotropin secretory capability, and normal adrenal function test and thyroid function study results. Furthermore, the initially stunted German Shepherd Dogs grew at a steady rate until at 1 year, body weight and shoulder height approximated normal measurements. Seemingly, delayed growth in these pups may represent one end of a clinical spectrum associated with hypopituitarism in German Shepherd Dogs.     

Evaluation of plasma catecholamine and serum cortisol concentrations in horses with colic

OBJECTIVE: To evaluate plasma epinephrine and norepinephrine concentrations and serum cortisol concentration in horses with colic and assess the relationship of these variables with clinical signs, routinely measured clinicopathologic variables, and outcome in affected horses. DESIGN: Prospective observational study. ANIMALS: 35 horses with colic. PROCEDURE: Blood samples were collected within 30 minutes of arrival at the veterinary hospital from horses referred because of colic. Plasma and serum samples were analyzed for cortisol, epinephrine, norepinephrine, lactate, and electrolyte concentrations and acid-base variables. Heart rate at admission and outcome (survival or nonsurvival) were recorded. Univariate logistic regression was used to calculate crude (unadjusted) odds ratios and 95% confidence intervals. RESULTS: Of the 35 horses with colic, 26 survived. Higher plasma epinephrine, plasma lactate, and serum cortisol concentrations were significantly associated with increased risk of nonsurvival, but plasma norepinephrine concentration was not associated with outcome. Plasma epinephrine concentration was significantly correlated with heart rate (r = 0.68), plasma lactate concentration (r = 0.87), blood pH (r = -0.83), anion gap (r = 0.74), and base excess (r = -0.81). CONCLUSIONS AND CLINICAL RELEVANCE: The risk of death appears to be greater in colic-affected horses with high circulating concentrations of epinephrine and cortisol. The correlation of epinephrine with other biochemical markers of illness severity and with heart rate indicates that the degree of sympathetic activation in horses with colic can be inferred from routinely measured variables.