M. Wenger

Histological evaluation of the adrenal glands of seven dogs with hyperadrenocorticism treated with trilostane

The lesions in the adrenal glands of seven dogs with hyperadrenocorticism that had been treated with trilostane were studied histologically. The glands of the six dogs with pituitary-dependent hyperadrenocorticism had moderate to severe cortical hyperplasia that was either diffuse or nodular. The lesions were more pronounced in the zona fasciculata than in the zona reticularis, and the zona glomerulosa was normal. In the dog with a functional adrenal tumour the non-tumour bearing adrenal gland showed mild nodular hyperplasia. Five of the seven dogs had variable degrees of adrenal necrosis, which was severe in two of them. The terminal deoxynucleotidyl transferase-mediated dutp nick-end labelling (tunel) reaction specified areas of cell death as apoptosis in three of the dogs, and was positive in one of the dogs without visible areas of cell death. There were variable degrees of cortical haemorrhage in three of the dogs. In some of the dogs the lesions were severe enough to lead to hypoadrenocorticism.

Endocrine hypertension in small animals.

Hypertension is classified as idiopathic or secondary. In animals with idiopathic hypertension, persistently elevated blood pressure is not caused by an identifiable underlying or predisposing disease. Until recently, more than 95% of cases of hypertension in humans were diagnosed as idiopathic. New studies have shown, however, a much higher prevalence of secondary causes, such as primary hyperaldosteronism. In dogs and cats, secondary hypertension is the most prevalent form and is subclassified into renal and endocrine hypertension. This review focuses on the most common causes of endocrine hypertension in dogs and cats.

Ultrasonographic evaluation of adrenal glands in dogs with primary hypoadrenocorticism or mimicking diseases

The adrenal glands of 30 dogs with primary adrenal insufficiency (hypoadrenocorticism) were measured ultrasonographically and compared with those of 14 healthy dogs and those of 10 dogs with diseases mimicking hypoadrenocorticism. Thickness and length of the adrenals were measured on abdominal ultrasonography and the results for each group were compared. Dogs with primary hypoadrenocorticism had significantly thinner adrenals compared with the other two groups, and their left adrenal glands were also significantly shorter than those of healthy dogs. Adrenal ultrasonography may be of diagnostic value in dogs with clinical signs suggestive of primary hypoadrenocorticism, as a left adrenal gland measuring less than 3.2 mm in thickness is strongly suggestive of the disease.

Evaluation of Aldosterone Concentrations in Dogs with Hypoadrenocorticism

Background Some dogs with primary hypoadrenocorticism (HA) have normal sodium and potassium concentrations, a phenomenon called atypical Addisons disease. The assumption that the zona glomerulosa and aldosterone secretion in these dogs are normal seems widely accepted; however, aldosterone measurements are missing in most published cases. Objectives To measure aldosterone in dogs with HA with and without electrolyte abnormalities and to determine the time point of aldosterone peak concentrations during ACTH stimulation. Animals Seventy dogs with HA, 22 dogs with diseases mimicking HA, and 19 healthy dogs. Methods Prospective study. Blood samples were taken before and 60 minutes after injection of 250 μg ACTH in all dogs. Additional blood samples were taken 15, 30, and 45 minutes after ACTH in 7 dogs with HA and in 22 with diseases mimicking HA. Results Baseline and ACTH‐stimulated aldosterone was significantly lower in dogs with HA than in the other groups. Aldosterone was low or undetectable in 67/70 dogs with HA independently of sodium and potassium levels. In 3 dogs, sodium/potassium concentrations were normal; in 1 dog, sodium was normal and potassium decreased. In all 4, ACTH‐stimulated aldosterone concentrations were below the detection limit of the assay. Aldosterone concentrations were not different at 30, 45, or 60 minutes after ACTH administration. Conclusion and Clinical Importance Cortisol and aldosterone secretion is compromised in dogs with HA with and without electrolyte abnormalities. The term atypical Addisons disease, used for dogs with primary HA and normal electrolytes, must be reconsidered; other mechanisms allowing normal electrolyte balance without aldosterone should be evaluated in these dogs.

Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test

BACKGROUND Cats with diabetes mellitus frequently achieve clinical remission, suggesting residual β-cell function. Responsiveness of β-cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. HYPOTHESIS Diabetic cats with and without remission will have different arginine-induced insulin or glucagon response. ANIMALS Seventeen cats with diabetes, 7 healthy cats. METHODS Blood samples collected on admission and during subsequent IVAST. Glucose, insulin, and glucagon were measured. Response to IVAST was assessed by calculating the insulin and glucagon area under the curve (AUC) and the AUC glucagon-to-insulin ratio. Diabetic cats were treated with insulin and were followed for 18 weeks. Remission was defined as normoglycemia and disappearance of clinical signs of diabetes for ≥4 weeks, without requiring insulin. RESULTS Seven diabetic cats (41%) achieved remission. On admission, blood glucose concentration was significantly lower in cats with remission (median, 389 mg/dL; range, 342-536 mg/dL) than in those without remission (median, 506 mg/dL; range, 266-738 mg/dL). After IVAST, diabetic cats with remission had higher AUC glucagon-to-insulin ratios (median, 61; range, 34-852) than did cats without remission (median, 26; range, 20-498); glucose, insulin, and glucagon AUCs were not different. Diabetic cats had lower insulin AUC than did healthy cats but comparable glucagon AUC. CONCLUSIONS AND CLINICAL IMPORTANCE Diabetic cats with and without remission have similar arginine-stimulated insulin secretion on admission. Although cats with remission had lower blood glucose concentrations and higher AUC glucagon-to-insulin ratios, large overlap between groups prevents use of these parameters in clinical practice.

Evaluation of four methods used to measure plasma insulin-like growth factor 1 concentrations in healthy cats and cats with diabetes mellitus or other diseases

OBJECTIVE To evaluate 4 methods used to measure plasma insulin-like growth factor (IGF) 1 concentrations in healthy cats and cats with diabetes mellitus or other diseases. ANIMALS 39 healthy cats, 7 cats with diabetes mellitus, and 33 cats with other diseases. PROCEDURES 4 assays preceded by different sample preparation methods were evaluated, including acid chromatography followed by radioimmunoassay (AC-RIA), acid-ethanol extraction followed by immunoradiometry assay (AEE-IRMA), acidification followed by immunochemiluminescence assay (A-ICMA), and IGF-2 excess followed by RIA (IE-RIA). Validation of the methods included determination of precision, accuracy, and recovery. The concentration of IGF-1 was measured with all methods, and results were compared among cat groups. RESULTS The intra-assay coefficient of variation was < 10% for AC-RIA, A-ICMA, and AEE-IRMA and 14% to 22% for IE-RIA. The linearity of dilution was close to 1 for each method. Recovery rates ranged from 69% to 119%. Five healthy cats had IGF-1 concentrations > 1,000 ng/mL with the AEE-IRMA, but < 1,000 ng/mL with the other methods. Compared with healthy cats, hyperthyroid cats had significantly higher concentrations of IGF-1 with the A-ICMA method, but lower concentrations with the IE-RIA method. Cats with lymphoma had lower IGF-1 concentrations than did healthy cats regardless of the method used. CONCLUSIONS AND CLINICAL RELEVANCE Differences in the methodologies of assays for IGF-1 may explain, at least in part, the conflicting results previously reported in diabetic cats. Disorders such as hyperthyroidism and lymphoma affected IGF-1 concentrations, making interpretation of results more difficult if these conditions are present in cats with diabetes mellitus.

Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane

The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (pdh) before and one hour after an injection of synthetic adrenocorticotropic hormone (acth). In the dogs with pdh, the cortisol and cortisone concentrations were measured before and after one to two weeks and three to seven weeks of treatment with trilostane. The dogs with pdh had significantly higher baseline and poststimulation concentrations of cortisol and cortisone, and higher baseline cortisol:cortisone ratios than the healthy dogs. During the treatment with trilostane, the poststimulation cortisol, the baseline and poststimulation cortisone concentrations, and the baseline and poststimulation cortisol:cortisone ratios decreased significantly. The decrease in poststimulation cortisone was significantly smaller than the decrease in cortisol.

Low-dose dexamethasone test with "inverse" results: a possible new pattern of cortisol response.

HYPERADRENOCORTICISM (HAC) is a common endocrine disorder in dogs. About 80 to 85 per cent of affected dogs have pituitary-dependent hyperadrenocorticism (PDH) and the remainder have functioning adrenocortical tumours (FAT). In dogs suspected of having HAC, screening tests are run to confirm the diagnosis, followed by testing to differentiate between PDH and FAT. The low-dose dexamethasone suppression (LDDS) test was first described in dogs in 1978 (Meijer and others 1978, 1979); it is one of the most commonly used screening tests. An elevated cortisol concentration eight hours after the administration of dexamethasone is considered consistent with the diagnosis of HAC. In most testing protocols, cortisol concentrations are also measured after four hours (Reusch and Hähnle 2001, Feldman and Nelson 2004). In dogs with a positive LDDS, for example, elevated eight-hour cortisol, further evaluation of the fourand eight-hour cortisol concentrations can be used to determine adrenal suppression or dexamethasone resistance, which may help to distinguish between PDH and FAT (Feldman and others 1996, Feldman and Nelson 2004). False-negative test results are known to occur in some dogs with HAC. In various studies, sensitivity levels between 85 and 99 per cent have been described (Rijnberk and others 1988, Feldman and others 1996, Van Liew and others 1997). The authors had noticed that in a few dogs with HAC, the four-hour cortisol concentration was elevated but the eighthour cortisol results were within the reference range. To the authors’ knowledge such test results have not been described previously and their relevance is unknown. A retrospective study was therefore undertaken to examine all dogs with HAC in which the LDDS test was negative (that is, a normal eighthour cortisol concentration). The objective was to evaluate the frequency of ‘inverse’ test results (that is, normal eighthour and elevated four-hour cortisol concentrations) within this group of dogs. The hospital database was searched for dogs diagnosed with HAC between 1998 and 2003, in which the diagnostic work-up included the LDDS test. Diagnosis was based on parameters such as clinical features consistent with HAC, results of the adrenocorticotrophic hormone (ACTH) stimulation test, results of the LDDS test, measurement of urine cortisol:creatinine ratio (UC:C), histological examination after adrenalectomy, findings at postmortem examination and recovery after treatment with o`p-DDD or trilostane. To differentiate between PDH and FAT, the adrenal glands were examined ultrasonographically (Hörauf and Reusch 1995, Hörauf and Reusch 1999). Some dogs underwent preand postcontrast computed tomography (CT) of the hypophyseal fossa. For the LDDS test, blood samples were collected before, and four and eight hours after administration of 0·01 mg/kg intravenous dexamethasone (Dexadreson; Virbac). Cortisol concentrations less than or equal to 27·6 nmol/l eight hours after dexamethasone application were considered normal (Feldman and Nelson 2004). For the purpose of this study, test results were classified as ‘inverse’ when the eight-hour cortisol concentration was normal (27·6 nmol/l or less), but the four-hour cortisol concentration was greater than 27·6 nmol/l. The ACTH stimulation test and UC:C were performed as described previously (Ruckstuhl and others 2002). A cortisol concentration of 550 nmol/l or more one hour after intramuscular injection of synthetic ACTH (Synacthen; Novartis), and a UC:C greater than 10 x 10–6 were considered abnormal and consistent with HAC. Cortisol concentrations were determined by use of a chemiluminescence assay (ADVIA Centaur System; Bayer), with a detection limit of 5·5 nmol/l. Eighty dogs with HAC met the inclusion criteria. In 10 of them (12·5 per cent) the eight-hour cortisol concentration was 27·6 nmol/l or less and had been recorded as a false negative. In five of these 10 dogs the four-hour cortisol concentration was also 27·6 nmol/l or less. Three of them suffered from PDH and two of them from FAT (Table 1). Another five dogs had ‘inverse’ LDDS test results. All five were diagnosed as having PDH. Three of them had positive ACTH stimulation test results and three had elevated UC:C. In two of the five dogs, large pituitary tumours (tumour heights of 0·9 cm and 2·3 cm) were diagnosed by CT and both underwent radiation therapy. Four dogs received medical treatment: three received trilostane (Modrenal: Wanskerne) and one received mitotane (Lysodren; Bristol Laboratories). All four of these dogs showed marked clinical improvement. One of the dogs with a large pituitary tumour did not receive oral treatment

Evaluation of cortisol precursors for the diagnosis of pituitary-dependent hypercortisolism in dogs

The serum concentrations of cortisol, 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, 21-deoxycortisol and 11-deoxycortisol were measured in 19 healthy dogs, 15 dogs with pituitary-dependent hypercortisolism (pdh) and eight dogs with other diseases before and one hour after an injection of synthetic adrenocorticotrophic hormone (acth). At both times the dogs with pdh had significantly higher concentrations of cortisol, 17α-hydroxypregnenolone, 17α-hydroxyprogesterone and 21-deoxycortisol than the healthy dogs. Basal 11-deoxycortisol concentrations were also significantly higher in dogs with pdh compared with healthy dogs. When compared with the dogs with other diseases, the dogs with pdh had significantly higher basal and post-acth cortisol and basal 21-deoxycortisol, and significantly lower post-acth 11-deoxycortisol concentrations. The dogs with other diseases had significantly higher post-acth cortisol, 17α-hydroxyprogesterone and 11-deoxycortisol concentrations than the healthy dogs. In general, the post-acth concentrations of 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, 11-deoxycortisol and 21-deoxycortisol were more variable than the post-acth concentrations of cortisol, resulting in large overlaps of the concentrations of these hormones between the three groups. A two-graph receiver operating characteristic (roc) analysis was used to maximise the sensitivity and specificity of each hormone for diagnosing hypercortisolism; it showed that the post-acth concentration of cortisol had the highest sensitivity and specificity. The overlaps between the healthy dogs, the dogs with pdh and the dogs with other diseases suggested that the individual precursor hormones would not be useful as a screening test for hypercortisolism.

Unexplained bleeding as primary clinical complaint in dogs infected with Angiostrongylus vasorum.

INTRODUCTION Unexplained bleeding was the primary clinical complaint in 15 dogs diagnosed with A. vasorum and was observed in the mouth, as external bleeding, as large subcutaneous hematoma, as hemoptysis, in the brain, post ovariectomy, as epistaxis, in the anterior ocular chamber and on a tracheal intubation tube. In 8 dogs the cause of bleeding initially was suspected to be a minor trauma or a surgical complication, and various surgical approaches had been undertaken to eliminate the problem. In only 3 dogs respiratory signs were observed before the bleeding prompted referral. The median time elapsed between the first recognized clinical signs attributed to A. vasorum until diagnosis was 2 weeks (range1 day to 4 months). Four dogs died, 3 on the day of admission and 1 dog 4 days after admission. Suspected causes of death were respiratory failure and cerebral hemorrhage in 2 dogs each. Four dogs had been pre-treated with NSAIDs; of these, 2 dogs developed severe hemoptysis (1 died), 1 dog developed brain hemorrhage (and died), and 1 dog developed a large subcutaneous hematoma with marked anemia. Bleeding at various sites may be the only recognized abnormality in A. vasorum infection. Without a high index of suspicion, the diagnosis and appropriate therapy may be delayed to the point of a fatal outcome. Tests of coagulation were quite variable and the cause of bleeding likely multifactorial.