Edward C. Feldman

Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets.

Long-term euglycemia by intraperitoneal transplantation of microencapsulated islets has not been described in the diabetic large animal model. In this study, we report the successful long-term reversal of diabetes by this method in spontaneous diabetic dogs. We have identified fundamental mechanism (s) associated with alginate-based microcapsule fibrosis, and have devised methods to ameliorate this problem. These include the use of purified alginate of low mannuronic acid content and cytokine suppression. Ten insulin-dependent, spontaneous diabetic dogs (insulin requirement 1–4 units/kg/day; absence of circulating C-peptide and diabetic K-values of 0.6±0.4) were entered into the study. Islets from mongrel donor pancreata were isolated and transplanted intraperitoneally either as free islet controls (n=3) or as microencapsulated islet allografts (n=7). In all seven encapsulated islet recipients, euglycemia was achieved within 24 hr (serum glucose falling from 304±117 to 116±72 mg/dl). IVGTT performed 14 days after islet transplant demonstrated normalization of K-values changing from a pretransplant level of 0.6±0.4 to 2.6±0.6. All animals receiving encapsulated islets remained euglycemic, free of the need for exogenous insulin, for a period of 63–172 days, with a median insulin-independence for 105 days. In contrast, recipients receiving free islets rejected their graft within seven days of implantation. In conclusion, this is the first report of long-term successful reversal of spontaneous diabetes in the large animal model by an intraperitoneal injection of encapsulated islets. The potential exists for this form of therapy to be explored in the treatment of type I diabetes in man.

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN Prospective study. ANIMALS 28 dogs with NOH. PROCEDURES 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.

Predictive Factors and the Effect of Phenoxybenzamine on Outcome in Dogs Undergoing Adrenalectomy for Pheochromocytoma

BACKGROUND Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. HYPOTHESIS Dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs. ANIMALS Forty-eight dogs that underwent adrenalectomy for pheochromocytoma. METHODS A retrospective medical record review for dogs that underwent adrenalectomy for pheochromocytoma at a veterinary medical teaching hospital over the period from January 1986 through December 2005. RESULTS Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly (P = .014) decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age (P = .028), lack of intraoperative arrhythmias (P = .0075), and decreased surgical time (P = .0089). CONCLUSIONS AND CLINICAL IMPORTANCE Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.

Evaluation of six portable blood glucose meters for measuring blood glucose concentration in dogs

OBJECTIVE To evaluate accuracy of 6 portable blood glucose meters (PBGMs) by comparing results of these meters with results obtained with a reference chemistry analyzer. DESIGN Evaluation study. ANIMALS 49 dogs (158 blood samples). Procedures-Venous blood samples were tested with the 6 PBGMs, and results were compared with results of a commercially available analyzer that used a reference method based on the hexokinase reaction. RESULTS Plasma glucose concentrations obtained with the reference analyzer ranged from 41 to 639 mg/dL. There were significant correlations between blood glucose concentrations obtained with the 6 PBGMs and plasma glucose concentrations obtained with the reference analyzer (r > or = 0.96). However, for all 6 PBGMs, results differed from results for the reference analyzer, with the difference increasing as plasma glucose concentration increased. Significant differences in bias were found among meters. For 142 samples classified as hypoglycemic, euglycemic, or hyperglycemic on the basis of results of the reference analyzer, the percentage of samples that were misclassified on the basis of results of the PBGMs ranged from 2.1% to 38.7%. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study suggested that there were substantial differences in the accuracy of currently available PBGMs when used to determine blood glucose concentration in dogs.

Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly

BACKGROUND Serum insulin-like growth factor-I (IGF-I) has been used in place of serum growth hormone quantification for identifying acromegaly in diabetic cats. The utility of IGF-I as a screening test for acromegaly has not been critically evaluated. This retrospective study was performed to evaluate the usefulness of serum IGF-I concentration for identifying acromegaly. HYPOTHESIS Serum IGF-I is a useful screening test for acromegaly in diabetic cats. ANIMALS A review was made of the medical records of 74 diabetic cats that had serum IGF-I quantified. The diabetes was classified as well controlled (15 cats), poorly controlled because of problems with the insulin treatment regimen, concurrent disease, or both (40), or poorly controlled with clinical findings consistent with acromegaly (19). METHODS A review of medical records was made. RESULTS Serum IGF-I concentration was significantly (P < .0001) increased in acromegalic diabetic cats, compared with well-controlled and poorly controlled diabetic cats. Sensitivity and specificity for serum IGF-I concentration were 84% (95%/ confidence interval [CI] = 60.4-96.6%) and 92% (95% CI = 81.3-97.2%), respectively. There was no significant correlation between serum IGF-I concentration and duration of insulin treatment (r = 0.23, P = .089), insulin dosage (r = 0.14, P = .30), age (r = 0.16, P = .12), and pituitary volume (r = 0.40, P = .11), but a modest correlation was found between serum IGF-I concentration and body weight (r = 0.48, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE Results support the use of serum IGF-I concentration as a screening test for acromegaly in diabetic cats that have clinical findings supportive of the disease.

Retrospective Evaluation of Three Treatment Methods for Primary Hyperparathyroidism in Dogs

The medical records of 110 dogs treated for primary hyperparathyroidism were reviewed. Dogs were treated via parathyroidectomy (n=47), percutaneous ultrasound-guided ethanol ablation (n=15), or percutaneous ultrasound-guided heat ablation (n=48). Forty-five of 48 (94%) parathyroidectomies resulted in control of hypercalcemia for a median of 561 days. Thirteen of 18 (72%) ethanol ablation procedures resulted in control of hypercalcemia for a median of 540 days. Forty-four of 49 (90%) heat-ablation treatments resulted in control of hypercalcemia for a median of 581 days.

Survival, Neurologic Response, and Prognostic Factors in Dogs with Pituitary Masses Treated with Radiation Therapy and Untreated Dogs

BACKGROUND Pituitary masses in dogs are not uncommon tumors that can cause endocrine and neurologic signs and, if left untreated, can decrease life expectancy. HYPOTHESIS Dogs with pituitary masses that received radiation therapy (RT) have more favorable neurologic outcomes and longer survival times compared with untreated dogs. ANIMALS Nineteen dogs with a pituitary mass identified on CT or MR imaging were irradiated with 48 Gy given in 3 Gy daily-dose fractions. Twenty-seven untreated control dogs had pituitary masses. METHODS Medical records of dogs with pituitary masses were retrospectively reviewed for clinical signs, mass size, and outcome. RESULTS Median survival time was not reached in the treated group. Mean survival time in the treated group was 1,405 days (95% confidence interval [CI], 1,053-1,757 days) with 1-, 2-, and 3-year estimated survival of 93, 87, and 55%, respectively. Median survival in the nonirradiated group was 359 days (95% CI, 48-916 days), with a mean of 551 days (95% CI, 271-829 days). The 1-, 2-, and 3-year estimated survival was 45, 32, and 25%, respectively. Dogs that received RT for their pituitary tumors had significantly longer survival times than untreated dogs (P = .0039). Treated dogs with smaller tumors (based on maximal pituitary-to-brain height ratio or area of tumor to area of brain) lived longer than those with larger tumors (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE When compared with untreated dogs, RT increased survival and controlled neurologic signs in dogs with pituitary masses.

Acromegaly and hyperadrenocorticism in cats: A clinical perspective

The two most common endocrine disorders in cats are diabetes mellitus and hyperthyroidism. Each of these conditions has been described as the most common endocrine disorder in geriatric cats of North America and each, separately, has been described as one of the most common conditions in geriatric cats of North America. It would seem that all other endocrine disorders of cats are uncommonto-rare. Acromegaly, in cats, is a relatively uncommon endocrine disorder and hyperadrenocorticism is even less common. However, there is interest in their clinical signs, diagnosis and treatment.

Cross‐Sectional Imaging Characteristics of Pituitary Adenomas, Invasive Adenomas and Adenocarcinomas in Dogs: 33 Cases (1988–2006)

BACKGROUND Pituitary tumors in dogs can be adenomas, invasive adenomas, or adenocarcinomas. In people, invasive adenomas and pituitary adenocarcinomas carry a worse prognosis than adenomas. HYPOTHESIS/OBJECTIVE To identify differentiating features on cross-sectional imaging in dogs with pituitary adenomas, invasive adenomas, and adenocarcinomas. ANIMALS Thirty-three dogs that had computed tomography (CT) or magnetic resonance imaging (MRI) performed and a necropsy diagnosis of pituitary adenoma (n = 20), invasive adenoma (n = 11), or adenocarcinoma (n = 2). METHODS Medical records were retrospectively reviewed for signalment, history, and diagnosis. CT and MR images were reviewed for characteristics of pituitary tumors. RESULTS Mean (+/- standard deviation) age for dogs with pituitary adenomas (10.6 +/- 2.9 years) was greater than that of those with invasive adenomas (8.3 +/- 2.7 years, P = .04). Eighteen out of 20 (90%) dogs with adenomas had contrast-enhancing masses. Thirteen out of 20 (65%) had homogeneous enhancement. Mean adenoma height was 1.2 +/- 0.7cm. Eight out of 20 (40%) adenomas were round and 8/20 (40%) compressed surrounding brain. Eleven out of 11 dogs (100%) with invasive adenomas had contrast-enhancing masses. Seven out of 11 (64%) masses were homogeneous. Mean invasive adenoma height was 1.8 +/- 0.7 cm, which was significantly greater than adenomas (P = .03). Mass shape varied from round to oval to irregular. Six out of 11 (55%) masses compressed surrounding brain. Clinical and imaging features were variable for 2 dogs with adenocarcinomas. CONCLUSIONS AND CLINICAL RELEVANCE Invasive adenoma should be suspected if a dog with a pituitary tumor is <7.7 years of age and has a mass > 1.9 cm in vertical height. Adenocarcinomas are uncommon and metastatic lesions were not seen with imaging.

Serum Inhibin Concentration in Dogs with Adrenal Gland Disease and in Healthy Dogs

BACKGROUND Studies in humans identified the synthesis and secretion of inhibin from adrenocortical tumors, but not pheochromocytoma (PHEO). Inhibin has not been examined in dogs as a serum biomarker for adrenal gland tumors. OBJECTIVE To determine serum inhibin concentration in dogs with adrenal gland disease and in healthy dogs. ANIMALS Forty-eight neutered dogs with adrenal disease including pituitary-dependent hyperadrenocorticism (PDH, 17), adrenocortical tumor (18), and PHEO (13), and 41 healthy intact or neutered dogs. METHODS Prospective observational study. Dogs were diagnosed with PDH, adrenocortical tumor (hyperadrenocorticism or noncortisol secreting), or PHEO based on clinical signs, endocrine function tests, abdominal ultrasound examination, and histopathology. Inhibin concentration was measured by radioimmunoassay in serum before and after ACTH stimulation, and before and after treatment. RESULTS In neutered dogs, median inhibin concentration was significantly higher in dogs with adrenocortical tumors (0.82 ng/mL) and PDH (0.16 ng/mL) than in dogs with PHEO and healthy dogs (both undetectable). Median inhibin concentration was significantly higher in dogs with adrenocortical tumors than in those with PDH and decreased after adrenalectomy. Median inhibin concentration was significantly higher in intact than in neutered healthy dogs and was similar in pre- and post-ACTH stimulation. Sensitivity, specificity, and accuracy of serum inhibin concentration for identifying an adrenal tumor as a PHEO were 100, 88.9, and 93.6%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE Adrenocortical tumors and PDH but not PHEOs are associated with increased serum inhibin concentration; undetectable inhibin is highly supportive of PHEO in neutered dogs with adrenal tumors.