Objective—To evaluate the effects of mitotane administration on the function and morphology of pituitary corticotrophs in clinically normal dogs.
Animals—12 clinically normal adult Beagles.
Procedures—Dogs were randomly assigned to the control group or the mitotane treatment group. In mitotane treatment group dogs, mitotane was administered for 1 month. In both groups, ACTH stimulation testing and corticotrophin-releasing hormone (CRH) stimulation testing were performed. Magnetic resonance imaging (MRI) of the pituitary gland and brain was performed in mitotane treatment group dogs before and after administration of mitotane. After CRH stimulation testing and MRI, dogs were euthanatized and the pituitary gland and adrenal glands were excised for gross and histologic examination.
Results—ACTH concentrations in mitotane treatment group dogs were significantly higher than in the control group dogs following CRH stimulation. Magnetic resonance imaging revealed that pituitary glands were significantly larger in treatment group dogs after administration of mitotane, compared with before administration. On gross and histologic examinations, the adrenal cortex was markedly atrophied. Immunohistochemistry revealed hypertrophy of corticotrophs in pituitary glands of mitotane treatment group dogs.
Conclusions and Clinical Relevance—These findings indicate that inhibition of the adrenal cortex by continuous administration of mitotane leads to functional amplification and morphologic enhancement of corticotrophs in clinically normal dogs. In instances of corticotroph adenoma, hypertrophy of individual corticotrophs induced by mitotane may greatly facilitate enlargement of the pituitary gland and increases in ACTH secretion.
Objective—To evaluate whether use of recombinant human (rh) thyroid-stimulating hormone (TSH) induces equivalent stimulation, compared with bovine TSH (bTSH), and to evaluate activity of rhTSH in dogs of various large breeds.
Animals—18 healthy research Beagles and 20 healthy client-owned dogs of various breeds with body weight > 20 kg.
Procedures—The 18 Beagles were randomly assigned to 3 groups, and each dog received either 75 μg of rhTSH, IM or IV, or 1 unit of bTSH, IM, respectively, in a crossover design. The 20 client-owned dogs received 75 μg of rhTSH, IV. Blood samples were taken before and 6 hours after TSH administration for determination of total serum thyroxine (T4) concentration. Additional blood samples were taken after 2 and 4 hours in Beagles that received rhTSH, IM.
Results—There was a significant increase in T4 concentration in all dogs, but there were no differences between values obtained after administration of bTSH versus rhTSH or IV versus IM administration of rhTSH. Although there was a significant difference in age and body weight between Beagles and non-Beagles, there was no difference in post-TSH simulation T4 concentration between the 2 groups.
Conclusions and Clinical Relevance—Results indicated an equivalent biological activity of rhTSH, compared with bTSH. Use of 75 μg of rhTSH, IV, did not induce a different magnitude of stimulation in large-breed dogs, compared with Beagles. Euthyroidism was confirmed if post-TSH simulation T4 concentration was ≥ 2.5 μg/dL and at least 1.5 times basal T4 concentration.
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 ≥ 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.
Objective—To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3′-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs.
Procedure—Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day −7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days −7 and 28.
Results—Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib.
Conclusions and Clinical Relevance—Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.
Objective—To investigate effects of short- and long- term administration of glucocorticoids, feeding status, and serum concentrations of insulin and cortisol on plasma leptin concentrations in dogs.
Animals—20 nonobese dogs.
Procedure—For experiment 1, plasma leptin concentrations and serum concentrations of insulin and cortisol were monitored for 24 hours in 4 dogs administered dexamethasone (0.1 mg/kg, IV) or saline (0.9% NaCl) solution for fed and nonfed conditions. For experiment 2, 11 dogs were administered prednisolone (1 mg/kg, PO, q 24 h for 56 days [7 dogs] and 2 mg/kg, PO, q 24 h for 28 days [4 dogs]) and 5 dogs served as control dogs. Plasma leptin and serum insulin concentrations were monitored weekly.
Results—For experiment 1, dexamethasone injection with the fed condition drastically increased plasma leptin concentrations. Furthermore, injection of saline solution with the fed condition increased plasma leptin concentrations. These increases in plasma leptin concentrations correlated with increases in serum insulin concentrations. Dexamethasone injection with the nonfed condition increased plasma leptin concentrations slightly but continuously. Injection of saline solution with the nonfed condition did not alter plasma leptin concentrations. For experiment 2, prednisolone administration at either dosage and duration did not alter plasma leptin concentrations in any dogs.
Conclusions and Clinical Relevance—Dexamethasone injection and feeding increased plasma leptin concentrations in dogs. In addition, dexamethasone administration enhanced the effect of feeding on increases in plasma leptin concentrations. Daily oral administration of prednisolone (1 or 2 mg/kg) did not affect plasma leptin concentrations in dogs.
Objective—To compare results obtained from assay of total thyroxine (T4) concentration in serum of dogs and cats by use of 4 methods.
Sample Population—Serum samples obtained from 98 dogs and 100 cats and submitted by veterinarians to an endocrine testing laboratory.
Procedure—Total T4 concentration was determined in each sample by use of 4 assay methods. Assay methods included a radioimmunoassay (RIA) marketed for use in dogs, an RIA for use in humans, a chemiluminescent enzyme immunoassay for use in humans, and an in-house ELISA.
Results—Total T4 concentrations obtained by use of all methods were significantly correlated. Bias-plot comparison revealed similar good overall agreement. Total T4 concentrations determined by use of the RIA marketed for use in dogs were generally lower than concentrations measured by use of the other methods. Clinical comparisons were made by evaluation of the T4 results in the context of the reference range recommended by each laboratory. A difference was found for clinical comparisons on the basis of T4 assay method when used to identify dogs as possible hypothyroid suspects. This difference was related more to the reference range used than to the absolute T4 value. The number of hyperthyroid-suspect cats with T4 values greater than the reference range was the same for each of the 4 assay methods.
Conclusions and Clinical Relevance—Total T4 concentrations determined in dogs and cats by use of 4 commonly used methods provided similar and consistent results.