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PubMedDate not supplied

Efficacy of transsphenoidal hypophysectomy in treatment of dogs with pituitary-dependent hyperadrenocorticism.

The long-term survival, disease-free fractions, and the complications of hypophysectomy in 150 dogs with pituitary-dependent hyperadrenocorticism (PDH) were examined in a prospective study. Long-term survival and disease-free fractions in relation to pituitary size were analyzed by the Kaplan-Meijer estimate procedure. The 1-, 2-, 3-, and 4-year estimated survival rates were 84% (95% confidence interval [CI], 76-89%), 76% (67-83%), 72% (62-79%), and 68% (55-77%), respectively. Treatment failures included procedure-related mortalities (12 dogs) and incomplete hypophysectomies (9 dogs). The 1-, 2-, 3-, and 4-year estimated relapse-free fractions were 88% (CI: 80-93%), 75% (64-83%), 66% (54-76%), and 58% (45-70%), respectively. Postoperative reduction of tear production (58 eyes in 47 dogs) was often reversible but remained low until death in 11 eyes of 10 dogs. Central diabetes insipidus (CDI) occurred more frequently (62%) in dogs with enlarged pituitaries than in dogs with nonenlarged pituitaries (44%). Survival and disease-free fractions after hypophysectomy were markedly higher in dogs with nonenlarged pituitaries than in dogs with enlarged pituitaries. Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs. The survival and disease-free fractions after hypophysectomy decrease and the incidence of CDI increases with increasing pituitary size. Therefore, early diagnosis of PDH is important and transsphenoidal hypophysectomy is expected to have the best outcome when used as primary treatment for dogs with nonenlarged or moderately enlarged pituitaries.

Adrenocortical Hyperfunction↗
PubMedDate not supplied

A comparison of the survival times of dogs treated with mitotane or trilostane for pituitary-dependent hyperadrenocorticism.

The survival times of 148 dogs treated for pituitary-dependent hyperadrenocorticism were studied using clinical records from 3 UK veterinary centers between 1998 and 2003. Of these animals, 123 (83.1%) were treated with trilostane, while 25 (16.9%) were treated with mitotane. Treatment groups were compared using t-tests and analysis of variance (or their nonparametric equivalents) and chi-square tests. Survival data were analyzed using Kaplan-Meier survival plots and Cox proportional hazard methods. There was no significant difference between the population attributes from each center or between treatment groups. The median survival time for animals treated with trilostane was 662 days (range 8-1,971) and for mitotane it was 708 days (range 33-1,399). There were no significant differences between the survival times for animals treated with trilostane and those treated with mitotane. In the multivariable model (including drug, center, breed group, weight, diagnostic group, and age at diagnosis), only age at diagnosis and weight were significantly negatively associated with survival. Importantly, there was no significant effect of drug choice on survival.

Adrenocortical Hyperfunction↗
PubMed2005

Hormetic effects of gamma radiation on the stress axis of natural populations of meadow voles (Microtus pennsylvanicus).

We tested the hypothesis that low doses of gamma radiation have beneficial, hormetic effects on the stress axis (the hypothalamic-pituitary-adrenocortical axis) of free-ranging meadow vole populations (Microtus pennsylvanicus). Voles were exposed to chronic gamma radiation from a 137Cs field irradiator. In isolated populations, voles received one of three treatments over a four-year period: Controls (0.19-0.42 microGy/h--levels that were 2-5x above background levels [0.1 microGy/h] and live-trapped in all years--1982--1985), low doses (22.6 microGy/h--50-200x background, live-trapped from November 1982--April 1985), or high doses (3,840 microGy/h--40,000x background, live-trapped from November 1983--April 1985). Voles exposed to a low dose had levels of free and total corticosterone that were significantly higher than those in the control or high-dose groups. Differences in response to radiation between the sexes were apparent for maximum corticosterone-binding capacity, with females exposed to low doses having higher binding capacity than control or high-dose females, whereas males exposed to low doses had lower binding capacity than control or high-dose males. Low-dose voles had higher counts of neutrophils than either the controls or high-dose voles; hematocrit was greater in the controls than in irradiated voles. These results indicate that voles display a hormetic response to radiation, wherein low doses of an otherwise harmful agent produce a beneficial effect. The stimulation of the stress axis resulting in the increased secretion of glucocorticoids, which may protect against the excessive actions of the immune and inflammatory responses, may be a key mechanism producing this effect.

Adrenocortical Hyperfunction↗
PubMedDate not supplied

Value of assessing adrenocorticotropic hormone (ACTH) levels in differential diagnosis of hypercorticism.

Diagnosis and differential diagnosis of Cushing's syndrome remains a challenge in clinical endocrinology. The aim of this study was to establish the value of assessing adrenocorticotropic hormone (ACTH) levels in differential diagnosis of hypercorticism using receiver operating characteristic (ROC) curve. We have evaluated 114 patients with Cushing's syndrome testing the value of pathohistological examination and postoperative testing. The control group consisted of 53 obese healthy persons. ACTH level was determined using a commercial RIA (CIS, France). ACTH secreting pituitary adenoma was found in 56.14% examinees, ectopic secretion in 6.14%, cortisol secreting adrenal adenoma in 37.57%, and adrenal carcinoma in 6.14% of all patients with Cushing's syndrome. Basal ACTH level for pituitary adenoma was 107.29 +/- 75.69 pg/mL; for ectopic secretion 181.63 +/- 149.84 pg/mL; for adrenal adenoma 4.22 +/- 2.32 pg/mL; for adrenal carcinoma 5.50 +/- 7.72 pg/mL; and 34.76 = 10.07 pg/mL in control group. Testing the value of assessing ACTH the area under ROC curve was 0.9965 +/- 0.0071. Test sensitivity was 99.89% and test specificity was 97%. For ACTH cut-off level of 8 pg/mL, test sensitivity was 88.50%, with specificity of 99%. For ACTH cut-off level of 22 pg/mL, test sensitivity was 99.30%, with specificity of 98%. Our intermediate zone from 8 to 22 pg/mL confirms that assessment of ACTH level is a reliable tool in differential diagnosis of Cushing's syndrome.

Adrenocortical Hyperfunction↗
PubMed1991

Opposing actions of dehydroepiandrosterone and testosterone on insulin sensitivity. In vivo and in vitro studies of hyperandrogenic females.

It has been hypothesized that the androgens testosterone and dehydroepiandrosterone (DHEA) may have opposing actions on insulin sensitivity. To test this hypothesis, we selected patients with polycystic ovary syndrome (PCO) and hypertestosteronemia and a group of individuals with adrenal hyperplasia (AH) and elevated DHEA and studied their 1) insulin and glucose responses to a 75-g oral glucose tolerance test, 2) insulin resistance by hypoglycemic responses to a standard dose of intravenous (IV) insulin, and 3) insulin binding and pyruvate dehydrogenase (PDH) responsiveness to insulin in phytohemagglutinin (PHA)-activated T lymphocytes. PCO patients exhibited elevated basal and glucose-challenged insulin levels and had blunted hypoglycemic responses to IV insulin. Conversely, AH patients had hypoglycemic responses to IV insulin significantly greater than and basal and glucose-challenged insulin levels lower than the PCO patients and weight-matched control subjects. In vitro, T-lymphocyte insulin binding of the PCO patients was 40-60% below control values; in AH patients, insulin binding and PDH insulin sensitivity were above those of the control subjects. Testosterone levels in all study subjects were negatively correlated to T-lymphocyte insulin binding and positively correlated to basal insulin, insulin area under the curve (AUC), and insulin-glucose indices. DHEA levels were positively correlated to insulin binding and inversely related to basal insulin, insulin AUC, and insulin-glucose indices. In all instances, the parameters of insulin sensitivity were more strongly correlated to individuals' ratios of DHEA to testosterone than to either of these androgens alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocortical Hyperfunction↗
PubMed2002

Results of clinical examinations, laboratory tests, and ultrasonography in dogs with pituitary-dependent hyperadrenocorticism treated with trilostane.

OBJECTIVE: To determine the efficacy of trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor, in dogs with pituitary-dependent hyperadrenocorticism (PDH). ANIMALS: 11 dogs with PDH. PROCEDURE: The initial dose of trilostane was 30 mg, PO, q 24 h for dogs that weighed < 5 kg and 60 mg, PO, q 24 h for dogs that weighed > or = 5 kg. A CBC count, serum biochemical analyses, urinalysis, ACTH stimulation test, and ultrasonographic evaluation of the adrenal glands were performed in each dog 1, 3 to 4, 6 to 7, 12 to 16, and 24 to 28 weeks after initiation of treatment. RESULTS: All dogs responded well to treatment. All had reductions in polyuria-polydipsia and panting and an increase in activity. Polyphagia decreased in 9 of 10 dogs, and 9 of 11 dogs had improvement of coat quality and skin condition. Concentration of cortisol after ACTH stimulation significantly decreased by 1 week after initiation of treatment. After treatment for 6 months, clinical signs resolved in 9 dogs. In the other 2 dogs, marked clinical improvement was reported for 1 dog, and moderate improvement was reported in the other dog. Ultrasonographically, there was a considerable change in the parenchyma and an increase in size of the adrenal glands. Adverse effects consisted of 1 dog with transient lethargy and 1 dog with anorexia. CONCLUSIONS AND CLINICAL RELEVANCE: Trilostane is an efficacious and safe medication for treatment of dogs with PDH. Additional studies in a larger group of dogs and characterization of progressive changes in adrenal glands are needed.

Adrenocortical Hyperfunction↗
PubMed2004

Effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To evaluate the effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism (PDH), compare the degree of reduction of aldosterone with that of cortisol, and compare aldosterone concentrations of healthy dogs with those of dogs with PDH. ANIMALS: 17 dogs with PDH and 12 healthy dogs. PROCEDURE: For dogs with PDH, the initial dose of trilostane was selected in accordance with body weight. A CBC count, serum biochemical analyses, and ACTH stimulation tests were performed in each dog. Dogs were evaluated 1, 3 to 4, 6 to 8, and 10 to 12 weeks after initiation of treatment. Healthy dogs were evaluated only once. RESULTS: Serum aldosterone concentrations before ACTH stimulation did not change significantly after initiation of treatment with trilostane. At each evaluation after initiation of treatment, serum aldosterone concentrations after ACTH stimulation were significantly lower than corresponding concentrations before initiation of treatment. The overall effect of trilostane on serum aldosterone concentration was less pronounced than the effect on serum cortisol concentration. Median potassium concentrations increased slightly after initiation of treatment with trilostane. Dogs with PDH had significantly higher serum aldo sterone concentrations before and after ACTH stimulation than healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with trilostane resulted in a reduction in serum cortisol and aldosterone concentrations in dogs with PDH, although the decrease for serum aldosterone concentration was smaller than that for serum cortisol concentration. There was no correlation between serum concentrations of aldosterone and potassium during treatment.

Adrenocortical Hyperfunction↗
PubMed2000

Correlation between age at neutering and age at onset of hyperadrenocorticism in ferrets.

OBJECTIVE: To determine prevalence of hyperadrenocorticism in ferrets in The Netherlands and evaluate age, sex, and age at neutering in affected ferrets. DESIGN: Prevalence survey and retrospective study. ANIMALS: 50 ferrets with hyperadrenocorticism and 1,267 ferrets without hyperadrenocorticism. PROCEDURE: A questionnaire was sent to 1,400 members of a ferret-owners organization in The Netherlands; 492 (35%) owners returned the questionnaire, providing usable data on 1,274 ferrets. Seven of these ferrets developed hyperadrenocorticism during the survey period; medical records for these ferrets and 43 ferrets with confirmed hyperadrenocorticism were reviewed. Hyperadrenocorticism was confirmed by histologic examination of an excised adrenal gland (92% of ferrets) or clinical improvement after excision. RESULTS: Prevalence of hyperadrenocorticism in the survey population was 0.55%. Sex was not associated with prevalence of disease. Median time interval between neutering and diagnosis of hyperadrenocorticism was 3.5 years. A significant linear correlation between age at neutering and age at time of diagnosis was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Age at neutering may be associated with age at development of hyperadrenocorticism in ferrets.

Adrenocortical Hyperfunction↗
PubMed2000

Hyperadrenocorticism treated with metyrapone followed by bilateral adrenalectomy in a cat.

A 6-year-old spayed female cat was evaluated for uncontrolled diabetes mellitus and poor hair coat. Clinicopathologic abnormalities included high serum activity of liver enzymes, hyperglycemia, hypercholesterolemia, glucosuria, and an exaggerated response to ACTH stimulation. Abdominal ultrasonography revealed large adrenal glands. Hyperadrenocorticism was diagnosed. Treatment for a facial abscess was instituted along with administration of metyrapone for hyperadrenocorticism. After stabilization, bilateral adrenalectomy was performed. The cat recovered without complications and has remained clinically normal for 5 months with treatment of desoxycorticosterone pivalate and prednisone. Treatment with metyrapone appeared to stabilize the cat metabolically and clinically prior to surgery.

Adrenalectomy↗
PubMed2001

Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia.

OBJECTIVE: To evaluate adrenal sex hormone concentrations in neutered dogs with hypercortisolemia. DESIGN: Case series. ANIMALS: 11 neutered dogs with hypercortisolemia. PROCEDURE: Serum samples obtained before and 1 hour after administration of ACTH were evaluated for concentrations of cortisol, progesterone, testosterone, dehydroepiandrosterone sulfate or androstenedione or both, and 17-hydroxyprogesterone. RESULTS: For all dogs, concentrations of 1 or more adrenal sex hormones were substantially greater than reference range values before or after administration of ACTH. Testosterone concentration was not greater than reference range values in any of the dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results emphasize the importance of ruling out hypercortisolemia before measuring adrenal sex hormone concentrations as a means of diagnosing adrenal hyperplasia syndrome (alopecia X) in dogs.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs.

An 11-year-old spayed female Labrador Retriever and a 9-year-old castrated male miniature Poodle were evaluated because of clinical signs of hyperadrenocorticism. Cortisol testing did not support a diagnosis of hypercortisolemia in either dog; however, imaging studies revealed unilateral adrenal tumors in both dogs. Serum concentrations of 17-hydroxyprogesterone, progesterone, and estradiol were high in both dogs, and androstenedione concentrations were also high in 1 dog. It is suspected that sex hormone secretion by the adrenal tumors in these dogs resulted in clinical signs of hyperadrenocorticism. Clinical signs and hormonal abnormalities resolved in the male dog after surgical resection of the tumor. There was no improvement in clinical signs after treatment with mitotane in the female dog, which died 2 months after diagnosis. Histologic evaluation confirmed the presence of adrenocortical carcinoma in both dogs.

Adrenal Cortex Neoplasms↗
PubMed2002

Diagnosis of hyperadrenocorticism in dogs: a survey of internists and dermatologists.

OBJECTIVE: To determine testing protocols used by board-certified internists and dermatologists for diagnosis of hyperadrenocorticism (HAC) in dogs. DESIGN: Survey. STUDY POPULATION: Board-certified internists and dermatologists. PROCEDURE: A questionnaire was mailed to 501 specialists to gather information pertaining to diagnosis of HAC. RESULTS: 206 surveys were returned. Only 26% of respondents indicated they would screen a dog for HAC if the dog had only a few laboratory abnormalities consistent with HAC and no clinical signs consistent with the disease; 31% indicated they would not, and 43% indicated they would sometimes. Overall, 55% of respondents indicated they preferred to use the low-dose dexamethasone suppression test for routine screening of dogs suspected to have HAC. However, many respondents indicated they would use a different screening test than usual in particular circumstances. Sixty-eight percent of respondents indicated they would perform a second screening test for confirmation if results of an initial screening test were positive but there were few clinical or laboratory abnormalities consistent with HAC. Most respondents used some sort of test to differentiate pituitary-dependent HAC from HAC secondary to an adrenal tumor (AT), but no 1 test was clearly preferred. Ultrasonography was commonly used, whereas computed tomography and magnetic resonance imaging were not, even if available. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the low-dose dexamethasone suppression test is the test most commonly used to screen dogs for HAC but that other tests may be used in certain circumstances. A variety of tests were used to differentiate pituitary-dependent HAC from HAC secondary to an AT.

Adrenal Cortex Function Tests↗