Incidence and risk factors for hypoadrenocorticism in dogs treated with trilostane.

The aim of this study was to describe the incidence and permanence of hypoadrenocorticism associated with trilostane treatment and to assess potential risk factors for hypoadrenocorticism. A retrospective cohort study was conducted using case records for 156 dogs treated with trilostane after a diagnosis of hyperadrenocorticism. Occurrences of hypoadrenocorticism were categorised as either transient or permanent. After initiation of treatment with trilostane, the estimated cumulative incidence of hypoadrenocorticism was 15% by 2 years and 26% by 4.3 years, respectively. Occurrences of hypoadrenocorticism were transient in 14/19 (74%) affected study dogs. The risk of hypoadrenocorticism was not significantly associated with trilostane dose rate and other potential risk factors assessed were not significantly associated with subhazard of hypoadrenocorticism, but effect estimates for most were imprecise. In conclusion, approximately 15% of dogs being treated with trilostane developed hypoadrenocorticism within the first 2 years of treatment and about one quarter became affected by 4 years. However, first occurrences of hypoadrenocorticism were mostly transient. Over the range of dose rates studied, each 1mg/kg/day increase in trilostane dose rate resulted in, at most, only a small increase in the risk of developing hypoadrenocorticism.

Sudden death in a dog with lymphoplasmacytic hypophysitis.

A 10-year-old dog with a history of progressive anorexia and weight loss died suddenly despite treatment. Histopathological examination revealed severe follicular lymphoplasmacytic adenohypophysitis and atrophy of the zona fasciculata and zona reticularis of the adrenal cortex. It is likely that lack of production of adrenocorticotropic hormone and cortisol was the cause of death of this dog.

Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo).

Endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. Insulinoma is a tumor that produces and releases excessive amounts of insulin. Evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment options for insulinomas. Adrenocortical neoplasia in ferrets usually overproduces one or more sex hormones. Sex hormones which can result in progressive alopecia, vulvar swelling in females, and prostagomegaly in males. Abdominal ultrasonography and sex hormone assays can be used to diagnose adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate, and the hormone melatonin can be used to treat adrenocortical neoplasms in ferrets when surgery is not an option.

Canine hypoadrenocorticism: part II.

Dogs with chronic, vague gastrointestinal signs and those with signs and laboratory abnormalities suggestive of an Addisonian crisis should be tested for hypoadrenocorticism. A previous article (Part I; Can Vet J 2009;50:63-69) discussed the etiology, pathophysiology, clinical signs, and diagnostic abnormalities found in these patients. The present article discusses definitive diagnosis and treatment for both the acute and the chronic Addisonian patient. Expedient treatment remains the cornerstone of management for these patients, particularly those in the former category. The long-term prognosis is excellent for these patients, given well-educated, committed, and vigilant owners.

Assessment of cytologic evaluation of preputial epithelial cells as a diagnostic test for detection of adrenocortical disease in castrated ferrets.

OBJECTIVE: To determine whether results of cytologic evaluation of preputial epithelial cells correspond to results of a serum endocrine hormone assay and clinical signs associated with adrenocortical disease in castrated ferrets. ANIMALS: 13 clinically normal ferrets and 8 ferrets with signs of adrenocortical disease. PROCEDURES: Blood and preputial lavage samples were collected from each ferret. Serum samples were submitted to the University of Tennessee Veterinary Diagnostic Laboratory for performance of an endocrine hormone assay. Differential epithelial cell counts were performed on preputial lavage samples to determine the percentage of cornified cells. Results of cytologic evaluation were compared with results of the endocrine hormone assay and clinical status of ferrets. RESULTS: The percentage of cornified preputial epithelial cells was not significantly correlated with serum 17B-estradiol or androstenedione concentration but was significantly correlated with serum 17-hydroxyprogesterone concentration (r = 0.60). The percentage of cornified preputial epithelial cells was higher in ferrets with clinical signs of adrenocortical disease (mean +/- SD, 71.3 +/- 16.9%) than in clinically normal ferrets (55.5 +/- 19.0%). CONCLUSIONS AND CLINICAL RELEVANCE: Cornification of preputial epithelial cells was correlated with an increase in serum 17-hydroxyprogesterone concentration as well as clinical signs of adrenocortical disease in castrated ferrets. Additional investigation is needed to elucidate the mechanism of preputial epithelial cell cornification in castrated ferrets.

Effects of melatonin administration on the clinical course of adrenocortical disease in domestic ferrets.

OBJECTIVE: To evaluate the effect of oral administration of melatonin on clinical signs, tumor size, and serum steroid hormone concentrations in ferrets with adrenocortical disease. DESIGN: Noncontrolled clinical trial. ANIMALS: 10 adult ferrets with clinical signs of adrenocortical disease (confirmed via serum steroid hormone concentration assessments). PROCEDURES: Melatonin (0.5 mg) was administered orally to ferrets once daily for 1 year. At 4-month intervals, a complete physical examination; abdominal ultrasonographic examination (including adrenal gland measurement); CBC; serum biochemical analyses; and assessment of serum estradiol, androstenedione, and 17alpha-hydroxyprogesterone concentrations were performed. Serum prolactin and dehydroepiandrosterone sulfate concentrations were evaluated at the first, second, and last examinations, and serum cortisol concentration was evaluated at the first and last examinations. RESULTS: Daily oral administration of melatonin greatly affected clinical signs of adrenocortical disease in ferrets; changes included hair regrowth, decreased pruritus, increased activity level and appetite, and decreased vulva or prostate size. Mean width of the abnormally large adrenal glands was significantly increased after the 12-month treatment period. Recurrence of clinical signs was detected in 6 ferrets at the 8-month evaluation. Compared with pretreatment values, serum 17alpha-hydroxyprogesterone and prolactin concentrations were significantly increased and decreased after 12 months, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that melatonin is a useful, easily administered, palliative treatment to decrease clinical signs associated with adrenocortical disease in ferrets, and positive effects of daily treatment were evident for at least an 8-month period. Oral administration of melatonin did not decrease adrenal gland tumor growth in treated ferrets.

Clinical and endocrine responses to treatment with deslorelin acetate implants in ferrets with adrenocortical disease.

OBJECTIVE: To evaluate the clinical and endocrine responses of ferrets with adrenocortical disease (ACD) to treatment with a slow-release implant of deslorelin acetate. ANIMALS: 15 ferrets with ACD. PROCEDURE: Ferrets were treated SC with a single slow-release, 3-mg implant of deslorelin acetate. Plasma estradiol, androstenedione, and 17-hydroxyprogesterone concentrations were measured before and after treatment and at relapse of clinical signs; at that time, the adrenal glands were grossly or ultrasonographically measured and affected glands that were surgically removed were examined histologically. RESULTS: Compared with findings before deslorelin treatment, vulvar swelling, pruritus, sexual behaviors, and aggression were significantly decreased or eliminated within 14 days of implantation; hair regrowth was evident 4 to 6 weeks after treatment. Within 1 month of treatment, plasma hormone concentrations significantly decreased and remained decreased until clinical relapse. Mean time to recurrence of clinical signs was 13.7 +/- 3.5 months (range, 8.5 to 20.5 months). In 5 ferrets, large palpable tumors developed within 2 months of clinical relapse; 3 of these ferrets were euthanatized because of adrenal gland tumor metastasis to the liver or tumor necrosis. CONCLUSIONS AND CLINICAL RELEVANCE: In ferrets with ACD, a slow-release deslorelin implant appears promising as a treatment to temporarily eliminate clinical signs and decrease plasma steroid hormone concentrations. Deslorelin may not decrease adrenal tumor growth in some treated ferrets. Deslorelin implants may be useful in the long-term management of hormone-induced sequelae in ferrets with ACD and in treatment of animals that are considered at surgical or anesthetic risk.

Diagnosis of canine hyperadrenocorticism.

Canine hyperadrenocorticism is one of the most common endocrinopathies in dogs. Diagnosis remains difficult in some cases due to factors such as the presence of non-adrenal illness and limitations in the tests. Differentiation between the pituitary and adrenal forms is important for providing accurate prognostic information and delineating treatment options and protocols. This article reviews the tests available for diagnosis (screening) and differentiation and evaluates their advantages and disadvantages. Recommendations for testing are made.

Spontaneous Waterhouse-Friderichsen syndrome in a gang-housed baboon.

Waterhouse-Friderichsen syndrome can cause acute death in the baboon without specific signs. Furthermore, this syndrome could result from stress-related intestinal permeability changes that allow macromolecules and/or microbiological entities to enter the systemic circulation. The resulting sepsis could cause adrenocortical insufficiency, hypotension and shock leading to death.

Leuprolide acetate treatment of adrenocortical disease in ferrets.

OBJECTIVE: To determine the effects of leuprolide acetate, a long-acting gonadotropin-releasing hormone analog, in ferrets with adrenocortical diseases. DESIGN: Case series. ANIMALS: 20 ferrets with adrenocortical disease diagnosed on the basis of clinical signs and plasma sex hormone concentrations. PROCEDURE: Ferrets were treated with leuprolide (100 microg, IM, once), and plasma hormone concentrations were measured before and 3 to 6 weeks after treatment. RESULTS: Leuprolide treatment resulted in significant reductions in plasma estradiol, 17 alpha-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone concentrations and eliminated or reduced clinical signs associated with adrenocortical disease. Decreases in vulvar swelling, pruritus, and undesirable sexual behaviors and aggression were evident 14 days after treatment; hair regrowth was evident by 4 weeks after treatment. The response to treatment was transitory, and clinical signs recurred in all ferrets. Mean +/- SEM time to recurrence was 3.7 +/- 0.4 months (range, 1.5 to 8 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that leuprolide can be safely used to temporarily eliminate clinical signs and reduce sex hormone concentrations in ferrets with adrenocortical diseases. However, the safety of long-term leuprolide use in ferrets has not been investigated, and the long-term effects of leuprolide in ferrets with nodular adrenal gland hyperplasia or adrenal gland tumors are unknown.

Frequency of pulmonary mineralization and hypoxemia in 21 dogs with pituitary-dependent hyperadrenocorticism.

The purpose of this study was to determine the frequency of hypoxemia and pulmonary mineralization using 99mTc-methylene diphosphonate (99mTc-MDP) in dogs with pituitary-dependent hyperadrenocorticism (PDH). Twenty-one dogs with PDH were prospectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using 99mTc-macro-aggregated albumin [99mTc-MAA]). The radiographs and bone and perfusion studies were evaluated subjectively. An averaged quantitative count density ratio was calculated between the thorax and cranial thoraco-lumbar vertebrae from lateral thoracic 99mTc-MDP images. Thoracic:vertebral ratios were calculated using 99mTc-MDP studies from 21 control dogs. The thoracic:vertebral ratios were compared between the 2 groups (PDH and control). The mean age (+/-SD) of the 21 PDH dogs was 10.2 (+/-3) years, whereas the mean age of the control group was 9.8 (+/-3) years. Seven of the 21 dogs with PDH were hypoxemic (defined as an arterial partial pressure of oxygen [PaO2] < 80 mm Hg) with an average PaO2 (+/-SD) of 62 (+/-15) mm Hg. Of the 7 hypoxemic dogs, 2 were found to have pulmonary mineralization based on bone scintigraphic images. Pulmonary perfusion abnormalities were not identified using 99mTc-MAA in any of the 21 PDH dogs. Six PDH dogs had an abnormal interstitial pulmonary pattern and 5 of these dogs were hypoxemic. The average quantitative thoracic:vertebral ratio was not significantly different between the PDH and control dogs (0.5 +/- 0.4 versus 0.4 +/- 0.1, P = .16). Causes of hypoxemia other than pulmonary thromboembolism should be considered in dogs with PDH. Pulmonary mineralization may contribute to hypoxemia in dogs with PDH.

Pharmacokinetics of exogenous corticotropin in normal dogs, hospitalized dogs with non adrenal illness and adrenopathic dogs.

Corticotropin (ACTH) pharmacokinetics was assessed in 10 normal dogs receiving exogenous ACTH (0.5 U/kg, i.v.). A two-compartment open model was most appropriate for description of exogenous ACTH pharmacokinetics. The apparent distribution and elimination rate constants (alpha and beta) were 7.4 +/- 2.7 x 10(-2) min(-1) and 5.5 +/- 3.8 x 10(-3) min(-1), respectively. Area under the concentration-time curve (AUC) was 2.91 +/- 0.78 x 10(4) pg x min/mL, mean residence time (MRT) was 45.0 +/- 12.2 min, the distribution half-life (t1/2alpha) was 9.4 min (harmonic mean), and the elimination half-life (t1/2beta) was 128 min (harmonic mean). The total body clearance of ACTH (ClB) was 1.83 +/- 0.46 x 10(4) mL x min/kg and volume of distribution (Vd(area)) was 30 +/- 15 L/kg. Corticotropin pharmacokinetics was also assessed in 12 client owned dogs, six dogs with non adrenal illness (NAI) and six dogs with hyperadrenocorticism (HAC), receiving exogenous ACTH (0.5 U/kg, i.v.). For these patients, data was best fitted to a one-compartment open model. In dogs with NAI, the AUC was 6.23 +/- 0.62 x 10(5) pg x min/mL, MRT was 38.7 +/- 12 min, the apparent elimination rate constant (k(el)) was 0.26 +/- 0.0017 min(-1) elimination half-life was 26.7 min, ClB was 0.84 +/- 0.1 x 10(4) mL/min/kg, and Vd(area) was 31.9 +/- 5.7 L/kg. In dogs with HAC, AUC was 4.74 +/- 0.23 x 10(5) pg x min/mL, MRT was 20.4 min, k(el) was 0.034 +/- 0.009 min(-1), half-life was 20.4 min, CIB was 1.06 +/- 6.0 x 10(4) mL/min/kg and Vd(area) was 29.7 +/- 6.7 L/kg. Dogs with pituitary-dependent hyperadrenocorticism showed more rapid elimination and clearance of exogenous corticotropin than dogs with NAI.

Validation of a commercially available enzyme-linked immunosorbent assay (ELISA) for the determination of cortisol in canine plasma samples.

Samples were obtained from clinically normal dogs before and after ACTH stimulation and dexamethasone suppression tests. The test kit Enzymun-Test (Boehringer Mannheim) for determining cortisol concentrations in human plasma was used in connection with the analyser system Enzymun-Test (Boehringer Mannheim) System ES300 following the manufacturer's instructions. The intra-assay and inter-assay coefficients of variation were 1.28% and 5.64%, respectively. The mean recovery when assaying samples with a cortisol content of more than 100 nmol/L was 95.41%, but this percentage decreased in samples with lower cortisol levels. The sensitivity of the assay was 2.76 nmol/L. The results of the ACTH stimulation and dexamethasone suppression tests were similar to those published previously. The ELISA method evaluated allows a precise and sensitive determination of cortisol concentrations in canine plasma samples. The major drawback observed was the loss of accuracy at low cortisol concentrations. Since the assay tends then to report lower cortisol concentrations, the generally accepted concentration of 40 nmol/L may not be suitable as the cutoff value in dexamethasone suppression tests.

Subcapsular cell hyperplasia and mast cell infiltration in the adrenal cortex of mice: comparative study in 7 inbred strains.

Subcapsular cell hyperplasia (SCH) in the adrenal cortex of aged mice (13-15 months old) was frequent in both sexes of BALB/c, C3H/He, DBA/2J and IQI/Jic mice and in the females of A/J and C57BL/6, although the incidence and severity of SCH were considerably different among mouse strains. Mast cells were closely associated with SCH in the A/J, BALB/c, C57BL/6, DBA/2J and IQI/Jic mice, but not in the C3H/He strain. Compared with other strains, IQI/Jic mice had a significantly larger number of mast cells in the adrenal glands. Our findings suggest that mast cells may participate in the development of SCH, and IQI/Jic would be suitable for studying the pathogenesis of SCH and the role of mast cells in this lesion.

Glycosylated hemoglobin concentrations in the blood of healthy dogs and dogs with naturally developing diabetes mellitus, pancreatic beta-cell neoplasia, hyperadrenocorticism, and anemia.

OBJECTIVE: To characterize glycosylated hemoglobin (GHb) concentrations in the blood of dogs with disorders that may affect serum glucose or blood GHb concentrations, and to determine whether changes in GHb concentration correlate with changes in control of diabetes in dogs. DESIGN: Prospective study. ANIMALS: 63 healthy dogs, 9 dogs with anemia, 24 dogs with untreated hyperadrenocorticism, 12 dogs with pancreatic beta-cell neoplasia, 23 dogs with newly diagnosed diabetes mellitus, and 77 diabetic dogs treated with insulin. PROCEDURE: Control of diabetes in dogs treated with insulin was classified as good or poor on the basis of history, physical examination findings, changes in body weight, and measurement of serum glucose concentrations Sequential evaluations of control were performed and GHb concentration in blood was measured, by means of affinity chromatography, for 5 untreated diabetic dogs before and after initiating insulin treatment, for 10 poorly controlled diabetic dogs before and after increasing insulin dosage, and for 5 diabetic dogs before and after pancreatic islet cell transplantation. RESULTS: Mean (+/-SD) GHb concentration was 3.3 +/- 0.8% in the blood of healthy dogs. Compared with results from healthy dogs, mean GHb concentration was significantly lower in the blood of dogs with anemia and pancreatic beta-cell neoplasia and significantly higher in the blood of untreated diabetic dogs. Mean GHb concentration was significantly higher in the blood of 46 poorly controlled diabetic dogs, compared with 31 well-controlled diabetic dogs (7.3 +/- 1.8 vs 5.7 +/- 1.7%, respectively). Mean GHb concentration in blood decreased significantly in 5 untreated diabetic dogs after treatment (8.7 +/- 1.9 vs 5.3 +/- 1.9%). Mean GHb concentration in blood also decreased significantly in 10 poorly controlled diabetic dogs after control was improved and in 5 diabetic dogs after they had received a pancreatic islet cell transplant. CLINICAL IMPLICATIONS: Measurement of GHb concentration in blood may assist in monitoring control of diabetes in dogs.

Diagnosis of canine hyperadrenocorticism.

Diagnosis of canine hyperadrenocorticism can only be made when a suspicion of the disorder persists after completion of a thorough history and physical examination. The first diagnostic testing steps include a complete blood count, serum biochemical tests, and urinalysis with urine culture. Radiography or ultrasonography may also be necessary, depending on physical findings. Screening tests are next applied to support or exclude the clinical diagnosis of hyperadrenocorticism. After the diagnosis has been made, discrimination tests are applied to determine whether the cause is pituitary or adrenal. The limitations of screening tests, particularly in the presence of nonadrenal diseases, cannot be overemphasized. We recommend that neither screening tests nor discrimination tests for hyperadrenocorticism be used in dogs with concurrent nonadrenal disease.

Imaging of adrenal gland disorders.

In recent years, diagnostic imaging has become an important adjunct to conventional endocrine testing in the evaluation of adrenal gland dysfunction. This article discusses the role of imaging in the diagnostic workup of the following adrenal gland disorders: hypercatacholaminism, hyperaldosteronism, hyperadrenocorticism, and hypoadrenocorticism. The strengths and limitations of radiography, ultrasonography, scintigraphy, CT scanning, and MR imaging are addressed.

Medical treatment of pituitary-dependent hyperadrenocorticism. Mitotane.

Mitotane (o,p'-DDD; Lysodren) is the drug most commonly used to treat dogs with pituitary-dependent hyperadrenocorticism. Although variations of the original protocol, suggested more than 20 years ago, have been reported, most clinicians still use an initial loading dose of mitotane followed by a weekly maintenance dose. Although a gratifying response to treatment is seen in most dogs, some dogs are neither easy nor straightforward to treat and present the practitioner with one or more therapeutic challenges, including failure to respond adequately, development of adverse effects, or development of relapse during treatment. Nevertheless, with careful management and follow-up, such problems can be overcome and a successful outcome achieved in most cases.