Influence of environment on adrenal cortical response to ACTH stimulation in clinically normal dogs.

Effect of testing environment on adrenal cortical responses to an injection of ACTH in clinically normal dogs was examined in three locations, presumably of increasing order of stress elicitation: in a home; veterinary hospital (VH), 4 hours in a cage; and VH, overnight in a cage. Basal cortisol (hydrocortisone) values for plasma were significantly lower (P less than 0.001) for the home group (1.8 microgram/dl) when compared with values for the VH, 4-hour cage (3.8 microgram/dl) or the VH, overnight cage (3.9 microgram/dl) groups. However, significant differences (P greater than 0.05) were not observed 2 hours after ACTH admininstration for the home group (13.7 microgram/dl); VH, 4-hour cage group (14.8 microgram/dl); or VH, overnight cage group (16.0 microgram/dl). Responses of individual dogs were consistent (P less than 0.005). The testing environment did not markedly affect results of adrenal cortical function tests for dogs when ACTH stimulation was utilized. The response of dogs to ACTH, as monitored by immunologic assay techniques (competitive protein-binding assay or radioimmunoassay), was consistent and was useful as a diagnostic aid for adrenal malfunction.     

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

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

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.     

Use of computed tomography adrenal gland measurement for differentiating ACTH dependence from ACTH independence in 64 dogs with hyperadenocorticism

Background: The measurement of adrenal gland size on computed tomography (CT) scan has been proposed for the etiological diagnosis of hyperadrenocorticism (HAC) in dogs. Symmetric adrenal glands are considered to provide evidence for ACTH‐dependent hyperadrenocorticism (ADHAC), whereas asymmetry suggests ACTH‐independent hyperadrenocorticism (AIHAC). However, there are currently no validated criteria for such differentiation. Objective: The aim of this retrospective study was to compare various adrenal CT scan measurements and the derived ratios in ADHAC and AIHAC cases, and to validate criteria for distinguishing between these conditions in a large cohort of dogs. Animals: Sixty‐four dogs with HAC (46 ADHAC, 18 AIHAC). Methods: Dogs with confirmed HAC and unequivocal characterization of its origin were included. Linear measurements of adrenal glands were made on both cross‐sectional and reformatted images. Results: An overlap was systematically observed between the AIHAC and ADHAC groups for all measurements tested. Overlaps also were observed for ratios tested. For the maximum adrenal diameter ratio derived from reformatted images (rADR), only 1/18 AIHAC dogs had a rADR within the range for ADHAC. For a threshold of 2.08, the 95% confidence intervals for estimated sensitivity and specificity extended from 0.815 to 1.000 and from 0.885 to 0.999, respectively, for AIHAC diagnosis. Conclusion and Clinical Importance: Measurements from cross‐sectional or reformatted CT scans are of little use for determining the origin of HAC. However, rADR appears to distinguish accurately between ADHAC and AIHAC, with a rADR > 2.08 highly suggestive of AIHAC.     

Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia

OBJECTIVE: To evaluate adrenal sex hormone concentrations in neutered dogs with hypercortisolemia. DESIGN: Case series. ANIMALS: 11 neutered dogs with hypercortisolemia. PROCEDURE: Serum samples obtained before and 1 hour after administration of ACTH were evaluated for concentrations of cortisol, progesterone, testosterone, dehydroepiandrosterone sulfate or androstenedione or both, and 17-hydroxyprogesterone. RESULTS: For all dogs, concentrations of 1 or more adrenal sex hormones were substantially greater than reference range values before or after administration of ACTH. Testosterone concentration was not greater than reference range values in any of the dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results emphasize the importance of ruling out hypercortisolemia before measuring adrenal sex hormone concentrations as a means of diagnosing adrenal hyperplasia syndrome (alopecia X) in dogs.     

Pituitary–adrenal axis function in dogs with neoplasia*

Adrenocorticotropic hormone (ACTH) stimulation tests were done in healthy and tumour‐bearing dogs. In the tumour‐bearing dogs, plasma endogenous ACTH (eACTH) concentration was measured and adrenal gland size was assessed ultrasonographically. Measurements in the tumour‐bearing dogs were taken prior to therapy. No difference existed in basal or ACTH‐stimulated cortisol concentration between tumour‐bearing and healthy dogs. No difference existed in eACTH concentration between dogs with non‐haematopoietic neoplasia (NHN) and lymphoma. However, of 20 dogs with lymphoma, 15% had increased basal serum cortisol concentration, 5% had an exaggerated response to ACTH and 5% had an increased eACTH concentration. Of 15 dogs with NHN, 20% had increased basal cortisol concentration, 7% had an exaggerated ACTH response and no dogs had an increased eACTH concentration. Of the dogs with lymphoma and NHN, 5 and 13%, respectively, had decreased basal cortisol concentrations; 20% of dogs with lymphoma and 13% with NHN had a subnormal ACTH response. eACTH levels were below the reference range in 10% of dogs with lymphoma and 7% with NHN. Overall, 10 adrenal glands were enlarged in seven dogs, five with lymphoma and two with NHN. The clinical significance of these findings remains to be determined.     

A comparison of the adrenal cortical response to ACTH stimulation in Angora and non-Angora goats

The adrenal cortex is believed to be implicated in the high incidence of abortion in the Angora goat. Stimulation testing with adrenocorticotrophic hormone (ACTH) was used to assess the adrenal cortical function in 5 Angora does from herds with a history of abortion and 5 non-Angora does. An acute test involving a single intramuscular (i.m.) injection of 0.25 mg of synthetic ACTH was given during anoestrus, at mid-oestrus, on day 90 and on day 120 of gestation. Blood samples were collected from the jugular vein at 30 min intervals for 1 h before and 5 h after injection. Cortisol concentrations rose within 30 min and returned to baseline values within 3.5 h. Cortisol production was lower (p<0.01) in the pregnant state compared to the non-pregnant state in both groups. Production of cortisol was consistently lower (p<0.05) in the Angora does compared to the non-Angora does during anoestrus and pregnancy and marginally so at mid-oestrus. A chronic stimulation test involving once daily injections of 0.5 mg of a depot form of ACTH i.m. for 7 days commencing on day 90 of pregnancy was also conducted. Cortisol concentrations rose to reach a peak on the third day of treatment in both groups. The values then declined in the Angora does despite continued ACTH treatment, while those for the non-Angora does exhibited a second peak. During and following this treatment, two non-Angora does delivered live kids (day 95, day 120). Out of 7 Angora pregnancies, one Angora doe aborted two dead fetuses at day 116. No significant difference in the cortisol response in the acute test was detected between the animals that aborted and their respective cohorts, but the two non-Angora does that aborted had significantly lower cortisol concentrations during depot ACTH administration. Progesterone and oestradiol levels did not differ between Angora and non-Angora animals during pregnancy or on the test days. The results suggest that the steroidogenic response of the adrenal cortex to ACTH stimulation is significantly less in Angora does with a history of abortion than it is in non-Angora does and support the view that the Angora goat would make a more limited adrenal cortical response to a stressful occurrence during pregnancy.     

Assessment of adrenal function in cats: Response to intravenous synthetic ACTH

The serum cortisol response to intravenous synthetic ACTH (tetracosactrin) was assessed in 15 healthy adult cats. Mean cortisol levels showed a significant (P<0.001) rise at 60 minutes and peaked at 180 minutes. At 120 and 180 min- utes mean cortisol levels were significantly (P<0.001) higher than at 60 minutes. The time of peak cortisol response in individual cats varied between 120 and 240 minutes, but nine (60 per cent) peaked at 180 minutes. In response to the ACTH the cats showed a rise in cortisol levels of between 160 and 1360 per cent. No significant rise in cortisol levels was seen in five cats following administration of sterile saline.     

Evaluation of adrenal function in small-breed dogs receiving otic glucocorticoids

The objectives of this study were to evaluate adrenal function after otic glucocorticoid [Tresaderm (dexamethasone) and Otomax (betamethasone)] therapy in small-breed dogs without evidence of otitis and to evaluate the length of time needed for resolution of adrenal suppression after discontinuation of treatment. Fourteen clinically healthy, privately owned, small-breed dogs with normal ears and normal adrenocorticotropin (ACTH) stimulation tests were assigned to one of two treatment groups, receiving one of the medications at the manufacturer's recommended dosage twice daily for 2 weeks. All of the dogs in the betamethasone treatment group had normal ACTH stimulation tests after 2 weeks of treatment. In contrast, 5/7 (71.43%) in the dexamethasone group, had suppressed adrenocortical responses to exogenous ACTH. Three of these five dogs (42%) returned to normal values 1 week after ceasing the medication and two (28.57%) returned to normal values 2 weeks after ceasing the medication. In conclusion, it appears that adrenal function can be suppressed for up to 2 weeks in dogs receiving otic dexamethasone. A follow-up study repeating this work in dogs with inflamed ears is needed before further clinical recommendations can be made.     

Evaluation of adrenal function in psittacine birds, using the ACTH stimulation test

The effect of ACTH (16 units) on plasma cortisol and corticosterone concentrations in healthy psittacine birds was evaluated. Plasma corticosterone significantly increased (P less than 0.01) from a mean (+/- SD) basal concentration of 3.25 +/ 3.6 ng/ml to 26.47 +/- 9.25 (one hour after ACTH administration) and 25.69 +/- 13.23 ng/ml (2 hours after ACTH administration). For maximal increase in plasma corticosterone as measured by radioimmunoassay (RIA), heat denaturation was necessary to release corticosteroids from steroid-binding proteins. As measured by RIA, plasma cortisol concentrations did not increase, whether or not the heat denaturation step was included. Addition of cortisol to avian plasma did not prevent accurate quantification of cortisol as measured by RIA. Plasma corticosterone concentrations in cockatoos, macaws, Amazon parrots, conures, and lorikeets before and after ACTH administration indicated that the ACTH stimulation test could be used to evaluate adrenal secretory capacity in psittacine birds.     

Relative adrenal insufficiency in dogs with sepsis

BACKGROUND: A syndrome of relative adrenal insufficiency has been identified in septic humans, and is associated with hypotension and death. Relative adrenal insufficiency is generally associated with basal serum cortisol concentration within or above the reference range and a blunted cortisol response to adrenocorticotropic hormone administration. It is unknown whether relative adrenal insufficiency occurs in septic dogs. HYPOTHESIS: That relative adrenal insufficiency occurs in septic dogs, and that relative adrenal insufficiency is associated with hypotension and mortality. ANIMALS: Thirty-three septic dogs admitted to a small animal intensive care unit. METHODS: Dogs were included in the study if they had a known or suspected infectious disease and had systemic inflammatory response syndrome. Dogs were excluded if they had disease or medication history expected to affect the hypothalamic-pituitary-adrenal axis. Serum cortisol and endogenous plasma adrenocorticotropic hormone concentrations were measured before, and serum cortisol concentration measured 1 hour after, intramuscular administration of 250 microg of cosyntropin/dog. The change in cortisol concentration (delta-cortisol) before and after cosyntropin administration was determined in each dog. RESULTS: Hypotension was associated with lower delta-cortisol values (OR 1.3; CI 1.0-1.9; P = .029). delta-Cortisol cutoff of 3.0 microg/dL was most accurate for predicting hypotension, survival to discharge, and 28-day survival. The rate of death in dogs with delta-cortisol < or = 3 microg/dL was 4.1 times that of dogs with delta-cortisol > 3 microg/dL (RR 4.1; CI 1.5-12.3; P = .01). CONCLUSIONS AND CLINICAL RELEVANCE: Delta-cortisol < or = 3 microg/dL after adrenocorticotropic hormone administration is associated with systemic hypotension and decreased survival in septic dogs.     

Comparison of aqueous porcine ACTH with synthetic ACTH in adrenal stimulation tests of the female dog

The adrenocortical (plasma corticosteroid) responses in female dogs given porcine ACTH in gelatin (1-39 amino acid sequence) and synthetic ACTH (1-24 amino acid sequence) were compared. Sixteen dogs were used. Each dog underwent 4 different ACTH stimulation studies, these being done with a 4- to 8-week interval. The studies in each dog included injections of 2 doses of porcine ACTH--2.2 IU and 4.4 IU/kg of body weight--and of 2 doses of synthetic ACTH--0.25 mg/dog and 0.50 mg/dog. The dogs were arbitrarily allotted to 4 groups, each group being subjected to a given sequence of stimulation studies. The purpose in this project was to determine whether the established methods for synthetic and porcine ACTH stimulation tests had similar results. Statistical analysis of the 4 stimulation methods revealed no significance (P greater than 0.05) in the resting or poststimulation plasma corticosteroid concentrations. Thus, it was concluded that either recommended method using ACTH (porcine ACTH at 2.2 IU/kg or synthetic ACTH at 0.25 mg/dog) causes maximal secretion of adrenocortical reserve. Either ACTH preparation, using the established method, can be used interchangeably.     

Ultrasonographic evaluation of the adrenal glands in six dogs with hypoadrenocorticism.

The purpose of this study was to determine the value of ultrasonographic characterization of the adrenal glands in dogs with hypoadrenocorticism. Measurements of adrenal glands were obtained in six dogs with hypoadrenocorticism. The adrenal glands on both sides were shorter (range: left adrenal gland length, 10.0 to 19.7 mm; right adrenal gland length, 9.5 to 18.8 mm) and thinner (range: left adrenal gland thickness, 2.2 to 3.0 mm; right adrenal gland thickness, 2.2 to 3.4 mm) than in normal dogs (range: left adrenal gland length, 13.2 to 26.3 mm; right adrenal gland length, 12.4 to 22.6 mm; left adrenal gland thickness, 3.0 to 5.2 mm; right adrenal gland thickness, 3.1 to 6.0 mm). Statistical analysis revealed a significant reduction in size of the left adrenal gland (p less than 0.05) in dogs with hypoadrenocorticism compared to the left adrenal gland in normal dogs. The results of this study show that atrophy of the adrenal glands in dogs with hypoadrenocorticism seems to lead to an ultrasonographic-measurable reduction in size of the adrenal glands.     

Effects of long-term phenobarbital treatment on the thyroid and adrenal axis and adrenal function tests in dogs

Phenobarbital can interfere with the thyroid axis in human beings and rats by accelerating hepatic thyroxine metabolism because of enzyme induction. In human beings, it also can interfere with the low-dose dexamethasone suppression test (LDDST) used to assess adrenal function by accelerating dexamethasone metabolism. This effect can cause a lack of suppression of pituitary ACTH and subsequent adrenal cortisol release after dexamethasone administration. The effects of phenobarbital on the thyroid axis, the adrenal axis, and adrenal function tests were prospectively investigated in 12 normal, adult dogs. Phenobarbital was administered at 5 mg per kilogram of body weight (range, 4.8–6.6 mg/kg) PO q12h for 29 weeks, resulting in therapeutic serum concentrations (20–40 μg/mL). Serum total thyroxine (TT4), free thyroxine (FT4) by equilibrium dialysis, total triiodothyronine (TT3), thyrotropin (TSH), and cholesterol were determined before and during phenobarbital treatment. LDDST, ACTH stimulation tests, and ultra-sonographic evaluation of the adrenal glands were performed before and during treatment. TT4 and FT4 decreased significantly ( P ≤ .05), TT3 had minimal fluctuation, TSH had only a delayed compensatory increase, and cholesterol increased during phenobarbital treatment. The delayed increase in TSH, despite persistent hypothyroxinemia, suggests that accelerated hepatic thyroxine elimination may not be the only effect of phenobarbital on the thyroid axis. There was no significant effect of phenobarbital on either of the adrenal function tests. With the methods employed, we did not find any effects of the drug on the hormonal equilibrium of the adrenal axis.     

Neutrophil function in dogs with congenital ciliary dyskinesia.

In vitro neutrophil function was assessed in two English Springer Spaniel dogs, two Bichon Frise dogs, and one Chow Chow dog with congenital ciliary dyskinesia; three clinically normal English Springer Spaniel dogs that were presumed heterozygous for congenital ciliary dyskinesia; and five control dogs. Chemotaxis and random migration in affected and heterozygous dogs were found to be comparable to those of control dogs. Increased (P less than or equal to 0.05) neutrophil adhesion, antibody dependent cell-mediated cytotoxicity, iodination of proteins, and oxygen radical production in neutrophils from affected dogs were probably the result of chronic bacterial infection in vivo. Bacterial ingestion by neutrophils from the three heterozygous English Springer Spaniel dogs was significantly increased compared to control dogs but was not different from affected English Springer Spaniel dogs, suggesting a breed-related phenomenon. Significant decreases in neutrophil function were not seen in any of the dogs with congenital ciliary dyskinesia, indicating that a defective microtubular system is not shared by respiratory cilia and neutrophils and that defective neutrophil function does not contribute to respiratory infection.     

Secretion of sex hormones in dogs with adrenal dysfunction

OBJECTIVE: To evaluate adrenal sex hormone concentrations in response to ACTH stimulation in healthy dogs, dogs with adrenal tumors, and dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Prospective study. ANIMALS: 11 healthy control dogs, 9 dogs with adrenal-dependent hyperadrenocorticism (adenocarcinoma [ACA] or other tumor); 11 dogs with PDH, and 6 dogs with noncortisol-secreting adrenal tumors (ATs). PROCEDURE: Hyperadrenocorticism was diagnosed on the basis of clinical signs; physical examination findings; and results of ACTH stimulation test, low-dose dexamethasone suppression test, or both. Dogs with noncortisol-secreting ATs did not have hyperadrenocorticism but had ultrasonographic evidence of an AT. Concentrations of cortisol, androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone were measured before and 1 hour after i.m. administration of 0.25 mg of synthetic ACTH. RESULTS: All dogs with ACA, 10 dogs with PDH, and 4 dogs with ATs had 1 or more sex hormone concentrations greater than the reference range after ACTH stimulation. The absolute difference for progesterone, 17-hydroxyprogesterone, and testosterone concentrations (value obtained after ACTH administration minus value obtained before ACTH administration) was significantly greater for dogs with ACA, compared with the other 3 groups. The absolute difference for androstenedione was significantly greater for dogs with ACA, compared with dogs with AT and healthy control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with ACA secrete increased concentrations of adrenal sex hormones, compared with dogs with PDH, noncortisol-secreting ATs, and healthy dogs. Dogs with noncortisol-secreting ATs also have increased concentrations of sex hormones. There is great interdog variability in sex hormone concentrations in dogs with ACA after stimulation with ACTH.