Use of trilostane for the treatment of pituitary-dependent hyperadrenocorticism in a cat

Hyperadrenocorticism occurs much less frequently in cats than in dogs and, at present, is more difficult to manage successfully. This report documents the use of the steroid synthesis inhibitor trilostane for the treatment of hyperadrenocorticism in a domestic shorthaired cat with pituitary-dependent disease. Although trilostane was able to alleviate the severity of the clinical signs and was well tolerated, the cat subsequently died of renal failure secondary to a fungal infection of the urinary tract.     

Parapituitary meningioma in a dog with pituitary-dependent hyperadrenocorticism

A dog with constitutional and cutaneous signs of hyperadrenocorticism had central visual impairment caused by an intracranial mass. Irradiation of the presumed pituitary mass did not improve the dog's condition. At necropsy, the intracranial mass was not of pituitary origin, but rather, was a parapituitary meningioma.     

Trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism

OBJECTIVE: To evaluate the efficacy of trilostane in treating dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at University Veterinary Centre, Sydney from September 1999 to July 2001. PROCEDURE: Thirty dogs with pituitary-dependent hyperadrenocorticism treated with trilostane, a competitive inhibitor of 3beta-HSD, were monitored at days 10, 30 and 90 then 3-monthly by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and by client questionnaire. RESULTS: Twenty-nine of 30 dogs were successfully treated with trilostane (median dose 16.7 mg/kg; range 5.3 to 50 mg/kg, administered once daily); one responded favourably but died of unrelated disease before full control was achieved. CONCLUSION: Trilostane administration controlled pituitary-dependent hyperadrenocorticism in these dogs. It was safe, effective and free of side-effects at the doses used. Most dogs were initially quite sensitive to the drug for 10 to 30 days, then required higher doses until a prolonged phase of stable dose requirements occurred. Urinary corticoid:creatinine ratio was useful in assessing duration of drug effect. Some dogs treated for more than 2 years required reduction or temporary cessation of drug because of iatrogenic hypoadrenocorticism.     

Non-dexamethasone-suppressible, pituitary-dependent hyperadrenocorticism in a dog

A 5-year-old female dog with hyperadrenocorticism was determined to have pituitary-dependent hyperadrenocorticism even though plasma cortisol concentrations were not suppressed after high-dosage dexamethasone administration. The diagnosis was based on a supranormal response of plasma cortisol to ACTH administration and a lack of suppression of plasma cortisol concentration after administration of 0.1 mg of dexamethasone/kg. Although a higher dosage of dexamethasone (1 mg/kg) did not cause suppression of plasma cortisol, plasma ACTH concentrations in the dog were increased above those in clinically normal dogs, supporting a diagnosis of pituitary-dependent hyperadrenocorticism. During treatment with mitotane, the dog became unconscious and died. Necropsy revealed a pituitary tumor that had compressed and displaced the hypothalamus. Although high-dosage dexamethasone suppression tests often are useful in the differential diagnosis of hyperadrenocorticism, a lack of suppression of plasma cortisol does not necessarily exclude pituitary-dependent hyperadrenocorticism.     

Investigation of the role of aldosterone in hypertension associated with spontaneous pituitary-dependent hyperadrenocorticism in dogs

The aim of this study was to evaluate the role of aldosterone as an initiating and/or perpetuating factor in hypertension associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Thirteen dogs with PDH and 11 healthy control dogs were used. In all dogs, arterial blood pressure and plasma sodium, potassium, basal aldosterone, post-ACTH aldosterone, basal cortisol and post-ACTH cortisol concentrations were measured. The tests were repeated 10 days and three months after the beginning of o,p'-DDD treatment in PDH dogs. In untreated PDH dogs, plasma aldosterone was significantly decreased, whereas cortisol, sodium and arterial blood pressure were significantly increased compared to healthy dogs. Hypertension remained in most treated PDH dogs despite normalisation of cortisol and persistently low aldosterone levels. These results did not demonstrate that aldosterone is involved in the development and perpetuation of hypertension in PDH. However, glucocorticoids seemed to play a major role as an initiating and perpetuating factor in PDH in dogs.     

Perianal adenomas and hypertestosteronemia in a spayed bitch with pituitary-dependent hyperadrenocorticism

Hypertestosteronemia was diagnosed in a spayed bitch with pituitary-dependent hyperadrenocorticism and perianal adenomas. Serum concentrations of cortisol and testosterone decreased after treatment with mitotane was instituted. Excessive testosterone in this dog was thought to have been produced by the adrenal cortex, possibly in response to excessive ACTH concentrations. Development of androgen- or estrogen-responsive tumors in castrated dogs may be an early indication of adrenocortical hyperfunction.     

Trilostane treatment of 78 dogs with pituitary-dependent hyperadrenocorticism

The efficacy of trilostane in the treatment of canine pituitary-dependent hyperadrenocorticism (PDH) was evaluated in 78 dogs with the condition which were treated for up to three years. The drug appeared to be well tolerated by almost all the dogs, and only two developed clinical signs and biochemical evidence of hypoadrenocorticism. Polyuria and polydipsia completely resolved in 70 per cent of the dogs that had these problems, and skin changes resolved in 62 per cent of the dogs that had skin abnormalities. There was a significant reduction (P<0.001 in each case) in both the mean basal and post-adrenocorticotrophic hormone (ACTH) cortisol concentrations after a mean of 12.3 days of treatment. The post-ACTH cortisol concentration decreased to less than 250 nmol/litre in 81 per cent of the dogs within one month of the start of treatment and in another 15 per cent at some later time. The median survival time of the 26 dogs which died was 549 days, and 51 of the dogs were alive at the completion of the study. One was lost to follow up after 241 days treatment.     

Retrobulbar thrombus in a cat with systemic hypertension

This report describes a 14-year-old neutered male Norwegian Forest cat that was evaluated for a complaint of inappetence, lethargy, and ocular protrusion with third eyelid prolapse. The systemic blood pressure was elevated at 205/129 mmHg. Fundic examination revealed severe retinal hemorrhage in both eyes. Based on an ultrasound study of the retrobulbar area, a thrombus caudal to the right globe was suspected. Over 18 days, the cat exhibited significant clinical improvement as well as good blood pressure control. To our knowledge this is the first report of a retrobulbar thrombus in a cat with systemic hypertension.     

Familial canine pituitary-dependent hyperadrenocorticism in wirehaired Dachshunds

Canine pituitary hyperadrenocorticism (Cushing's disease) caused by neoplasia of the corticotrope cells is one of the most common endocrine diseases especially in smaller dog breeds. Cushing's disease was diagnosed in eleven wire-haired Dachshunds and for further six wire-haired Dachshunds Cushing's disease was suspected on the basis of clinical signs. A joined pedigree could be ascertained for all these 17 dogs. Eleven of these dogs were so closely related to each other, that they were summarized in four nucleus families. Two fullsiblings were examined by means of clinical, laboratory diagnostic and morphological methods. The main lesions consisted of atrophic dermatosis with alopecia, increase of activity of liver enzymes in plasma and bilateral adrenocortical hyperplasia and therefore corresponded to the typical signs of a secondary hyperadrenocorticism. A rather unusual finding was the pituitary carcinoma in one of these dogs. Similarly to human patients affected by hyperadrenocorticism, real-time PCR analysis showed a 2.9-fold increase of expression of the canine MDR1 gene in the liver of one affected wirehaired Dachshund. This study documents the first familial occurrence of pituitary-dependent hyperadrenocorticism in wirehaired Dachshunds, the overexpression of the MDR1 gene in the dog and the third case of familial hyperadrenocorticism in dogs ever described.     

Pituitary-dependent hyperadrenocorticism in a cat

Pituitary-dependent hyperadrenocorticism was diagnosed in a 9-year-old, male castrated cat that had polyuria, polyphagia, pendulous abdomen, truncal hair loss, congestive heart failure, and insulin-resistant diabetes mellitus. Results of pituitary-adrenal function testing revealed inadequate serum cortisol suppression following dexamethasone administration, exaggerated serum cortisol responses after exogenous ACTH stimulation, and high plasma ACTH concentrations. The pathologic findings of bilateral adrenocortical hyperplasia and a pituitary adenoma that immunostained well for ACTH-related peptides confirmed pituitary-dependent hyperadrenocorticism.     

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.     

Pulsatile secretion pattern of growth hormone in dogs with pituitary-dependent hyperadrenocorticism

The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (+/-S.E.M.) basal GH level in dogs with PDH (0.7+/-0.1 microg/l) and the control dogs (0.6+/-0.1 microg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6+/-0.6 microg/l per 6 h) was significantly lower than that in the control dogs (7.3+/-1.0 microg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6+/-0.1 microg/l per 6 h) was significantly lower than that in the control dogs (3.7+/-1.0 microg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0-7 pulses/6 h) was significantly lower (P = 0.04) than that (5 pulses/6 h, range 3-9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.     

Inefficacy of selegiline in treatment of canine pituitary-dependent hyperadrenocorticism

OBJECTIVE: To evaluate selegiline, a monoamine oxidase-B inhibitor, for treating dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at The University Veterinary Centre, Sydney, from September 1999 to July 2001. PROCEDURE: Eleven dogs with pituitary-dependent hyperadrenocorticism treated with selegiline were monitored at days 10, 30 and 90 by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and client questionnaire. Endogenous adrenocorticotropic hormone measurements were also performed on most dogs on days 0 and 90. No dog treated with selegiline had satisfactory control of disease. CONCLUSION: Selegiline administration was safe and free of side-effects at the doses used, but did not satisfactorily control disease in pituitary-dependent hyperadrenocorticism affected dogs.