Nadja S Sieber-Ruckstuhl

Remission of Diabetes Mellitus in Cats with Diabetic Ketoacidosis

BACKGROUND Diabetic ketoacidosis (DKA) has long been considered a key clinical feature of type-1 diabetes mellitus (DM) in humans although. An increasing number of cases of ketoacidosis have been reported in people with type-2 DM. HYPOTHESIS/OBJECTIVES Cats initially diagnosed with DKA can achieve remission from diabetes. Cats with DKA and diabetic remission are more likely to have been administered glucocorticoids before diagnosis. ANIMALS Twelve cats with DKA and 7 cats with uncomplicated DM. METHODS Retrospective case review. Medical records of cats presenting with DKA or DM were evaluated. Diabetic remission was defined as being clinically unremarkable for at least 1 month after insulin withdrawal. The cats were assigned to 1 of 3 groups: (1) cats with DKA and diabetic remission; (2) cats with DKA without diabetic remission; and (3) cats with DM and diabetic remission. RESULTS Seven cats with DKA had remission from diabetes. These cats had significantly higher concentrations of leukocytes and segmented neutrophils, and significantly lower concentrations of eosinophils in blood and had pancreatic disease more often than did cats with uncomplicated DM and diabetic remission. With regard to pretreatment, 3/7 cats in group 1, 1/5 cats in group 2, and 1/7 cats in group 3 had been treated with glucocorticoids. CONCLUSIONS AND CLINICAL IMPORTANCE Remission of DM in cats presenting with DKA is possible. Cats with DKA and remission have more components of a stress leucogram, pancreatic disease, and seemed to be treated more often with glucocorticoids than cats with uncomplicated DM and diabetic remission.

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.

Contrast-enhanced power and color Doppler ultrasonography of the pancreas in healthy and diseased cats

BACKGROUND The diagnosis of feline pancreatic disease is difficult, because clinical abnormalities and routine noninvasive diagnostic tests are unreliable. OBJECTIVE The purpose of this study was to investigate by Doppler ultrasonography if vascularity and blood volume differs in the otherwise ultrasonographically normal and diseased feline pancreas. ANIMALS Thirty-six client owned cats. METHODS The pancreas was examined with B-mode and contrast-enhanced color and power Doppler ultrasonography. Doppler images were analyzed with a computer program: parameter fractional area represents a vascularity index and color-weighted fractional area assesses blood volume. RESULTS Based on the B-mode findings, the pancreas was considered normal in 11 clinically healthy cats and diseased in 25 cats of which 4 were clinically healthy and 21 had clinical signs consistent with pancreatic disease. Histologic or cytologic samples were taken in all diseased pancreata. Fifteen samples were of diagnostic quality: purulent or mixed cellular inflammation (8), nodular hyperplasia (4), and neoplasia (3) were identified. Vascularity and blood volume for all Doppler methods was significantly higher in cats with pancreatic disease. Significantly higher Doppler values were detected with power Doppler than with color Doppler, and with postcontrast color and power Doppler than with precontrast Doppler technologies. CONCLUSION Contrast-enhanced Doppler ultrasonography appears feasible in the feline pancreas. Significant differences were found between normal cats and those with evidence of pancreatic pathology. Further studies are needed to evaluate its use for the differentiation of pancreatic disorders and in cats suspected to have pancreatic disease but without B-mode ultrasonographic changes of the pancreas.

Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs.

BACKGROUND Urinary catecholamines and metanephrines are used for the diagnosis of pheochromocytoma (PHEO) in dogs. Hyperadrenocorticism (HAC) is an important differential diagnosis for PHEO. OBJECTIVES To measure urinary catecholamines and metanephrines in dogs with HAC. ANIMALS Fourteen dogs with HAC, 7 dogs with PHEO, and 10 healthy dogs. METHODS Prospective clinical trial. Urine was collected during initial work-up in the hospital; in dogs with HAC an additional sample was taken at home 1 week after discharge. Parameters were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration. RESULTS Dogs with HAC had significantly higher urinary epinephrine, norepinephrine and normetanephrine to creatinine ratios than healthy dogs. Urinary epinephrine, norepinephrine, and metanephrine to creatinine ratios did not differ between dogs with HAC and dogs with PHEO, whereas the urinary normetanephrine to creatinine ratio was significantly higher (P= .011) in dogs with PHEO (414, 157.0-925.0, median, range versus (117.5, 53.0-323.0). Using a cut-off ratio of 4 times the highest normetanephrine to creatinine ratio measured in controls, there was no overlap between dogs with HAC and dogs with PHEO. The variables determined in urine samples collected at home did not differ from those collected in the hospital. CONCLUSION AND CLINICAL IMPORTANCE Dogs with HAC might have increased concentrations of urinary catecholamines and normetanephrine. A high concentration of urinary normetanephrine (4 times normal), is highly suggestive of PHEO.

Thyroid enlargement and its relationship to clinicopathological parameters and T4 status in suspected hyperthyroid cats

To relate thyroid size to routine blood parameters and T4 status the ventral neck of 161 cats with clinical signs consistent with hyperthyroidism was examined by two independent observers using a semi-quantitative palpation system. Thyroid gland size of each side was scored from 0 (non-palpable) to a maximum of 6 (>25 mm). In 127 of the 161 cats, at least one thyroid gland was palpable. The palpation score was significantly correlated with the T4 concentration. The 17 hyperthyroid cats had significantly higher palpation scores than the 110 euthyroid cats. Euthyroid animals with a palpation score ≥3 were significantly older, had higher body weights, lower alkaline phosphatase, alanine aminotransferase, phosphate, and urine specific gravity, but higher lipase and creatinine concentrations than hyperthyroid cats. Our study demonstrates that although no reliable conclusion on the functional status of the thyroid can be drawn based on its size the likelihood of hyperthyroidism increases with increasing size of the gland.

Salivary cortisol concentrations in healthy dogs and dogs with hypercortisolism.

BACKGROUND Measurement of salivary cortisol is a useful diagnostic test for hypercortisolism (HC) in humans. OBJECTIVES To determine whether measurement of salivary cortisol concentration is a practical alternative to plasma cortisol to diagnose HC, to validate the use of salivary cortisol, and to examine the effect of time of day and sampling location on salivary cortisol. ANIMALS Thirty healthy dogs and 6 dogs with HC. METHODS Prospective, observational clinical trial including healthy volunteer dogs and dogs newly diagnosed with HC. Salivary and plasma cortisol concentrations were measured with an immunoassay analyzer. Intra- and interassay variability, linearity, and correlation between salivary and plasma cortisol concentrations were determined. RESULTS The required 300 microL of saliva could not be obtained in 88/326 samples from healthy dogs and in 15/30 samples from dogs with HC. The intra-assay variability for measurement of salivary cortisol was 5-17.7%, the interassay variability 8.5 and 17.3%, and the observed to expected ratio 89-125%. The correlation (r) between salivary and plasma cortisol was 0.98. The time of day and location of collection did not affect salivary cortisol concentrations. Dogs with HC had significantly higher salivary cortisol values than healthy dogs (10.2 +/- 7.3 nmol/L versus 1.54 +/- 0.97 nmol/L; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE The ROCHE Elecsys immunoassay analyzer correctly measured salivary cortisol in dogs. However, a broad clinical application of the method seems limited, because of the large sample volume required.

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.

Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats.

Adrenal necrosis has been reported as a complication of trilostane application in dogs with hyperadrenocorticism. One suspicion was that necrosis results from the increase of adrenocorticotropic hormone (ACTH) during trilostane therapy. The aim of the current study was to assess the effects of ACTH and trilostane on adrenal glands of rats. For experiment 1, 36 rats were divided into 6 groups. Groups 1.1 to 1.4 received ACTH in different doses (60, 40, 20, and 10 μg/d) infused subcutaneously with osmotic minipumps for 16 wk. Group 1.5 received saline, and group 1.6 received no therapy. For experiment 2, 24 rats were divided into 3 groups. Group 2.1 and 2.2 received 5 and 50 mg/kg trilostane/d orally mixed into chocolate pudding for 16 wk. Eight control rats received pudding alone. At the end of the experiments, adrenal glands were assessed for necrosis by histology and immunohistochemistry; levels of endogenous ACTH and nucleosomes were assessed in the blood. Rats treated with 60 μg ACTH/d showed more hemorrhage and vacuolization and increased numbers of apoptotic cells in the adrenal glands than rats treated with 20 or 10 μg ACTH/d, trilostane, or control rats. Rats treated with 60 μg ACTH/d had a higher amount of nucleosomes in the blood compared with rats treated with 10 μg ACTH/d, trilostane, or saline. We conclude that in healthy rats ACTH, but not trilostane, causes adrenal degeneration in a dose-dependent manner. Results of this study support the hypothesis that adrenal gland lesions seen in trilostane-treated dogs are caused by ACTH and not by trilostane.

Evaluation of Baseline Cortisol, Endogenous ACTH, and Cortisol/ACTH Ratio to Monitor Trilostane Treatment in Dogs with Pituitary-Dependent Hypercortisolism

BACKGROUND The effectiveness of trilostane treatment is currently monitored by regular ACTH stimulation tests, which are time-consuming and expensive. Therefore, a monitoring system without a stimulation protocol and with less client expense would be preferable. HYPOTHESIS/OBJECTIVES The aim of our study was to evaluate if baseline cortisol, endogenous ACTH (ACTH) concentration or the baseline cortisol to ACTH ratio (cortisol/ACTH ratio) could replace the ACTH stimulation test. ANIMALS Forty trilostane-treated dogs with pituitary-dependent hypercortisolism (PDH) were included in this prospective study. METHODS A total of 148 ACTH stimulation tests and 77 ACTH concentrations and cortisol/ACTH ratios were analyzed. Control of cortisol release was classified according to cortisol concentration after ACTH administration as excessive (<1.5 μg/dL; group 1), adequate (1.5-5.4 μg/dL; group 2), or inadequate (>5.4 μg/dL; group 3). RESULTS Baseline cortisol concentrations had considerable overlap between excessively, adequately, and inadequately controlled dogs. Only baseline cortisol >4.4 μg/dL (in 12% of tests) was a reliable diagnosis of inadequate control. Endogenous ACTH concentrations did not differ between groups. The overlap of the cortisol/ACTH ratio between groups was large. Correct classification was only possible if the cortisol/ACTH ratio was >15, which occurred in 4% of tests. CONCLUSIONS AND CLINICAL IMPORTANCE To monitor trilostane treatment the ACTH stimulation test cannot be replaced by baseline cortisol, ACTH concentration, or the cortisol/ACTH ratio.

Comparison of a continuous glucose monitoring system with a portable blood glucose meter to determine insulin dose in cats with diabetes mellitus

BACKGROUND The continuous glucose monitoring system (CGMS) Guardian REAL-Time(®) allows the generation of very detailed glucose profiles in cats. The performance of CGMS to generate short-term glucose profiles to evaluate treatment response has not been yet evaluated in diabetic cats. HYPOTHESIS Analysis of glucose profiles generated using the CGMS produces insulin dose recommendations that differ from those of profiles generated using the portable blood glucose meter (PBGM) in diabetic cats. ANIMALS Thirteen client-owned diabetic cats. METHODS Prospective, observational study. Simultaneous glucose profiles were generated over an 8-10 hour period using the CGMS, blood glucose concentration was measured every 2 hours with the PBGM. Profiles were submitted to three internal medicine specialists who used them to determine the insulin dose. Differences between insulin doses deduced from paired profiles were compared. Percentages of nadirs recorded with the CGMS that were lower, higher, or equal to those derived with the PBGM were calculated. RESULTS Twenty-one paired glucose profiles were obtained. There was no difference of insulin doses based on CGMS and PBGM profiles (median 0 U; range: -1 to +0.5). Treatment decisions did not differ among investigators. Compared with the observed PBGM nadir, the CGMS nadir was lower, higher, or equal in 17, 2, and 2 of 21 cases, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE Adjustments in insulin dose based on glucose profiles generated with the CGMS are similar to those based on the PBGM. The common occurrence of lower nadirs recorded with the CGMS suggests that this device detects hypoglycemic periods that are not identified with the PBGM.