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

OBJECTIVE: 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. ANIMALS: 10 healthy dogs. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Aldosterone-to-renin and cortisol-to-adrenocorticotropic hormone ratios in healthy dogs and dogs with primary hypoadrenocorticism.

In dogs with primary hypoadrenocorticism, hypocortisolism and hypoaldosteronism usually are present, but these deficiencies also may occur in isolated forms. The diagnosis is commonly made by measuring plasma cortisol concentration before and after stimulation with ACTH, thereby ignoring aldosterone. In search of an alternative approach that would include assessment of glucocorticoid and mineralocorticoid production, 2 pairs of endocrine variables were measured: (1) plasma concentration of cortisol and ACTH, and (2) plasma aldosterone concentration and plasma renin activity. In addition, the cortisol-to-ACTH ratio (CAR) and the aldosterone-to-renin ratio (ARR) were calculated. Reference intervals were established in a population of 60 healthy dogs. In these dogs, CAR ranged from 1.1 to 26.1 and ARR ranged from 0.1 to 1.5. The variables were compared with those of 22 dogs with spontaneous primary hypoadrenocorticism. Plasma concentration of cortisol and ACTH in both groups of dogs overlapped, whereas CAR did not. Similarly, plasma aldosterone concentration and plasma renin activity overlapped, whereas ARR did not. These observations indicate that measurement of these endogenous variables (in one blood sample) allows the specific diagnoses of primary hypocortisolism and primary hypoaldosteronism.

Clinical effects of short-term oral budesonide on the hypothalamic-pituitary-adrenal axis in dogs with inflammatory bowel disease.

Six dogs were entered into a 30-day, prospective, nonrandomized, uncontrolled clinical trial evaluating the effects of an oral preparation of budesonide on the hypothalamic-pituitary-adrenal (HPA) axis during therapeutic management of active inflammatory bowel disease. Oral budesonide, at a dose of 3 mg/m(2), was administered once daily. Upon entry and completion of the trial, serum basal cortisol, adrenocorticotropic (ACTH)-stimulated cortisol, endogenous ACTH concentration, serum alkaline phosphatase (SAP) activity, and urine specific gravity were evaluated, as well as owner assessment of glucocorticoid-associated side effects. Significant suppression of the HPA axis occurred. No significant differences in SAP activity, urine specific gravity, or owner-subjective assessments were detected.

Effects of anaesthesia and manual restraint on the plasma concentrations of pituitary and adrenocortical hormones in ferrets.

Two experiments were carried out to investigate the effect of sampling techniques on the plasma concentrations of pituitary and adrenocortical hormones in ferrets (Mustela putorius furo). In the first experiment blood was collected on two occasions from 29 ferrets which were either manually restrained or anaesthetised with isoflurane. In the second experiment eight intact ferrets were fitted with jugular catheters and blood was collected on four occasions, just before and as soon as possible after they had been manually restrained or anaesthetised with medetomidine or isoflurane; blood was also collected 10 and 30 minutes after the induction of anaesthesia. Medetomidine anaesthesia had no effect on the plasma concentrations of pituitary and adrenocortical hormones. Isoflurane anaesthesia resulted in a significant increase in the plasma concentration of alpha-melanocyte-stimulating hormone (alpha-MSH) directly after the induction of anaesthesia. Manual restraint resulted in a significant increase in the plasma concentrations of cortisol and adrenocorticotrophic hormone (ACTH) and a decrease in the plasma concentration of alpha-MSH.

Use of the urine cortisol-to-creatinine ratio for monitoring dogs with pituitary-dependent hyperadrenocorticism during induction treatment with mitotane (o,p'-DDD).

OBJECTIVE: To determine whether the urine cortisol-to-creatinine ratio (UCCR) could replace the ACTH stimulation test in monitoring effectiveness of mitotane induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). ANIMALS: 15 dogs with PDH. PROCEDURE: All 15 dogs were given an induction dose of mitotane (o,p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the induction period, free-catch morning urine samples were collected for determination of UCCR, followed by ACTH stimulation testing, every other day. Treatment response was divided into 3 categories: well-controlled PDH (post-ACTH serum cortisol concentration > or = 28 nmol/L but < or = 138 nmol/L), deficient cortisol secretion (post-ACTH serum cortisol concentration < 28 nmol/L), and excess cortisol secretion (post-ACTH serum cortisol concentration > 138 nmol/L). RESULTS: The linear relation between UCCR and post-ACTH serum cortisol concentration was significant (P < 0.001); however, the prediction intervals surrounding the line were too broad to be clinically useful. The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR > 79 x 10(-6) were always classified as having excess cortisol secretion. CONCLUSION AND CLINICAL RELEVANCE: The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR > 79 x 10(-6) obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR < or = 79 x 10(-6) would be inconclusive.

Thyroid and adrenal function tests in adult male ferrets.

Effects of thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) on plasma concentrations of thyroid hormones, and effects of ACTH and dexamethasone on plasma concentrations of cortisol, were studied in adult male ferrets. Thirteen ferrets were randomly assigned to test or control groups of eight and five animals, respectively. Combined (test + control groups) mean basal plasma thyroxine (T4) values were different between the TRH (1.81 +/- 0.41 micrograms/dl, mean +/- SD) and TSH (2.69 +/- 0.87 micrograms/dl) experiments, which were performed 2 months apart. Plasma T4 values significantly (P less than 0.05) increased as early as 2 hours (3.37 +/- 1.10 micrograms/dl) and remained high until 6 hours (3.45 +/- 0.86 micrograms/dl) after IV injection of 1 IU of TSH/ferret. In contrast, IV injection of 500 micrograms of TRH/ferret did not induce a significant increase until 6 hours (2.75 +/- 0.79) after injection, and induced side effects of hyperventilation, salivation, vomiting, and sedation. There was no significant increase in triiodothyronine (T3) values following TSH or TRH administration. Combined mean basal plasma cortisol values were not significantly different between ACTH stimulation (1.29 +/- 0.84 micrograms/dl) and dexamethasone suppression test (0.74 +/- 0.56 micrograms/dl) experiments. Intravenous injection of 0.5 IU of ACTH/ferret induced a significant increase in plasma cortisol concentrations by 30 minutes (5.26 +/- 1.21 micrograms/dl), which persisted until 60 minutes (5.17 +/- 1.99 micrograms/dl) after injection. Plasma cortisol values significantly decreased as early as 1 hour (0.41 +/- 0.13 micrograms/dl), and had further decreased by 5 hours (0.26 +/- 0.15 micrograms/dl) following IV injection of 0.2 mg of dexamethasone/ferret.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal function in 15 dogs with insulin-dependent diabetes mellitus.

Pituitary-adrenal function was assessed by a combined dexamethasone suppression-ACTH stimulation test in 15 diabetic and 9 healthy dogs. In both groups, plasma cortisol concentrations decreased (P less than 0.001) after dexamethasone administration and increased (P less than 0.001) after ACTH administration. Differences between groups (P greater than 0.05) and group-by-time interactions were not significant (P greater than 0.05). Seemingly, adrenal function was not altered in well-regulated diabetic dogs.

Computed tomography in the diagnosis of canine hyperadrenocorticism not suppressible by dexamethasone.

Computed tomography (CT) was performed in 10 dogs with hyperadrenocorticism not suppressible by dexamethasone. In 6 of these dogs, a unilateral adrenal mass was found on CT images. Specimens of the masses were obtained via retroperitoneal laparotomy; histologic examination revealed 4 carcinomas, 1 adenoma, and 1 nodular hyperplasia. In the 4 other dogs, CT revealed symmetric bilateral adrenal gland enlargement. In 2 of these dogs, contrast-enhanced CT revealed a mass in the pituitary fossa, which could be identified at necropsy as a pituitary tumor. The other 2 dogs were successfully treated with mitotane.

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.

Evaluation of a combined dexamethasone suppression/ACTH stimulation test in dogs with hyperadrenocorticism.

Twenty-one dogs with hyperadrenocorticism were studied. Six dogs had functioning adrenocortical tumors and 15 had pituitary-dependent hyperadrenocorticism. Each dog was evaluated, using endogenous plasma ACTH, ACTH stimulation, dexamethasone screening, dexamethasone suppression, and combined dexamethasone suppression/ACTH stimulation tests. The ACTH stimulation portion of the combined test was less reliable as a screening test in diagnosing hyperadrenocorticism than was the isolated ACTH stimulation test or the dexamethasone screening test. The dexamethasone suppression portion of the combined test was less reliable in distinguishing dogs with adrenocortical tumors from those with pituitary-dependent hyperadrenocorticism than was the endogenous ACTH or isolated dexamethasone suppression test. The combined test is not recommended for use. The ACTH stimulation test is the recommended screening test because of its diagnostic reliability and its subsequent importance as a base line in determining success of mitotane therapy.

Stages of hyperadrenocorticism: response of hyperadrenocorticoid dogs to the combined dexamethasone suppression/ACTH stimulation test.

A study was designed to evaluate the response of blood cortisol content in dogs tentatively diagnosed as having hyperadrenocorticism by using the combined dexamethasone suppression/ACTH stimulation test procedure. Four groups of abnormal responses were identified in 54 dogs. In group I (14.8% of the dogs with abnormal responses), the only abnormality was partial suppression with dexamethasone (clinically normal dogs suppressed to less than 10 ng/ml). In group II (29.6%), 2 abnormalities were found: partial suppression with dexamethasone and hyperreactivity to the ACTH stimulation test. In group III (typical pituitary-dependent hypercortisolism, 48.1%), 3 abnormalities were found: base-line hypercortisolemia, partial suppression with dexamethasone, and hyperreactivity to the ACTH stimulation test. In group IV (7.4%), 2 abnormalities were found: base-line hypercortisolemia and partial suppression with dexamethasone. Base-line blood cortisol content was normal in 44.4% of the adrenopathic dogs. A normal response to ACTH stimulation was seen in 25.9% of the dogs, and 74.1% of the dogs hyperreacted to the ACTH stimulation test. All of the adrenopathic dogs were found to suppress partially with dexamethasone. Failure to suppress the adrenal gland completely (less than 10 ng/ml) with dexamethasone was the most consistent finding in adrenopathic dogs when using the combined dexamethasone suppression/ACTH stimulation test procedure. It was concluded that the test procedure is feasible, flexible, and convenient for clinical situations. Also, these results suggested that there may be several stages in the negative feedback failure associated with hyperadrenocorticism in 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)

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

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

Atypical hypoadrenocorticism in three dogs.

Three dogs with hypoadrenocorticism did not have characteristically abnormal serum concentrations of sodium, potassium, and chloride and had not been treated with glucocorticoids. Diagnosis was based on lack of adrenocortical response to exogenous adrenocorticotropic hormone. Clinical signs included lethargy, weakness, anorexia, vomiting, and weight loss. The case demonstrated that the diagnosis of canine hypoadrenocorticism should not be excluded on the basis of normal serum electrolyte values.

Combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test in the dog: new approach to testing of adrenal gland function.

A combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test was developed in the dog so that information concerning pituitary gland (hypophysis) and adrenal gland competence could be provided in a single trial, during a short time span. Treatment of dogs with dexamethasone (0.1 mg/kg, IM) resulted in total suppression (below assay sensitivity or < 10 ng/ml) of plasma hydrocortisone (cortisol) at postinjection hour (PIH) 2 in 100% of the dogs, whereas suppression was inconsistent at PIH 1. Cosyntropin (0.5 U/kg, IV) administration to normal or dexamethasone-suppressed dogs increased plasma hydrocortisone concentration 3.5 to 4.5 times base-line values at PIH 1, which was the time of maximal effect. The combined test concept for adrenal gland function is valid, convenient (three sample collections; 3-hour period), and allows testing of adrenal gland response to dexamethasone suppression and ACTH stimulation in a single trial. The following test procedure for dogs is recommended: (i) collect base-line plasma sample (0900 hours) followed by injection of dexamethasone (0.1 mg/kg, IM); (ii) collect second plasma sample 2 hours after dexamethasone (to evaluate suppression of plasma hydrocortisone concentration) followed by the injection of cosyntropin (0.5 U/kg, IV); and (iii) collect a third plasma sample 1 hour later to evaluate plasma hydrocortisone concentration after cosyntropin stimulation.