Efficacy of trilostane for the treatment of equine Cushing's syndrome

REASONS FOR PERFORMING STUDY: Trilostane, a competitive 3-beta hydroxysteroid dehydrogenase inhibitor, has been used successfully to control clinical signs and cortisol excess in canine pituitary dependent hyperadrenocorticism. OBJECTIVES: Trilostane was evaluated for its efficacy in resolving clinical and clinicopathological abnormalities of equine Cushing's syndrome (ECS) and to assess its safety. METHODS: Twenty horses (mean age 21 years) diagnosed with ECS were followed for 1 or 2 years. Affected horses received 0.4-1 mg/kg (mean 0.5 mg/kg) trilostane once daily. RESULTS: Clinical signs assessed over 1 or 2 years, showed a reduction in lethargy in all horses post treatment. Polyuria and/or polydipsia, present in 11 horses, was reduced in all after treatment. Recurrent or chronic laminitis, present in 16 horses, improved in 13/16 (81%) of cases. There were no side effects reported. Combined dexamethasone suppression and thyrotropin releasing hormone (TRH) stimulation tests were significantly different before and 30 days following therapy. There was a significant reduction (P = 0.01) of cortisol following TRH administration before (160 +/- 53.0 nmol/l) and after (130 +/- 46.1 nmol/l) trilostane. CONCLUSIONS: Trilostane caused improvement in clinical signs in horses, without side effects, and a corresponding decrease in cortisol response to TRH administration. POTENTIAL RELEVANCE: Trilostane may be a useful therapy for the treatment of ECS. Further work comparing the effects of trilostane and pergolide is warranted.     

Adrenal necrosis in a dog receiving trilostane for the treatment of hyperadrenocorticism

Clinical and biochemical changes suggestive of hypoadrenocorticism were observed in a 10-year-old male neutered Staffordshire bull terrier shortly after beginning therapy with trilostane for the treatment of hyperadrenocorticism. The dog's condition was stabilised with intravenous fluids, fludrocortisone and prednisolone. An exploratory laparotomy and excisional biopsy of the left adrenal gland were performed. Histopathological analysis showed adrenal cortical necrosis with reactive inflammation and fibrosis. Trilostane is a reversible inhibitor of steroid synthesis and this complication has not been reported previously. Clinicians should be aware that trilostane therapy may result in adrenal necrosis but that prompt treatment might correct a life-threatening situation.     

Treatment of canine Alopecia X with trilostane

Sixteen Pomeranians and eight miniature poodles presenting with clinical signs of alopecia X, elevated blood concentrations of 17-hydroxyprogesterone post stimulation with adrenocorticotropic hormone and increased urinary cortisol/creatinine ratios were treated with trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Trilostane was given once or twice daily at a mean dose of 10.85 mg kg(-1) day(-1). Adrenal function was evaluated with a follow-up of 28 months in the Pomeranians and 33 months in the miniature poodles. Treatment with trilostane led to complete hair re-growth in 85% of the Pomeranians and in all of the miniature poodles within 4 to 8 weeks. No adverse events attributed to treatment with trilostane were recognized. The hair re-growth might have been the result of a down-regulation of adrenal steroids and/or of the noncompetitive inhibition of the oestrogen receptors at the hair follicle level.     

Efficacy of Low‐ and High‐Dose Trilostane Treatment in Dogs (< 5 kg) with Pituitary‐Dependent Hyperadrenocorticism

Background

Trilostane is commonly used to treat pituitary‐dependent hyperadrenocorticism (PDH) in dogs. There are differing opinions regarding the dose and frequency of trilostane administration in dogs with PDH.

Objectives

To compare the efficacy of 2 trilostane protocols in the treatment of dogs with PDH.

Animals

Sixteen client‐owned dogs with PDH and a body weight <5 kg.

Methods

Prospective observational study. Group A (n=9; low‐dose treatment group) received 0.78 ± 0.26 mg of trilostane/kg PO every 12 h and group B (n = 7; high‐dose treatment group) 30 mg of trilostane/dog PO every 24 h. All of the dogs were reassessed at 2, 4, 8, 12, 16, and 24 weeks after the initiation of treatment.

Results

An improvement in both ACTH‐stimulated serum cortisol concentrations and clinical signs occurred more slowly in group A than in group B; however, after 20 weeks of treatment, 2/7 dog in group B had clinical signs and abnormal laboratory findings consistent with hypoadrenocorticism. At 24 weeks, an improvement in the clinical findings of all of the dogs in both groups was detected.

Conclusions and clinical importance

In dogs with PDH, twice‐daily administration of low‐dose trilostane is an effective approach to the management of PDH. In addition, our results suggest fewer potential adverse effects if trilostane is administered twice daily in the lower dose.     

CHANGES IN ULTRASONOGRAPHIC APPEARANCE OF ADRENAL GLANDS IN DOGS WITH PITUITARY-DEPENDENT HYPERADRENOCORTICISM TREATED WITH TRILOSTANE

Trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor, has been used successfully over the last few years for the treatment of canine pituitary-dependent hyperadrenocorticism. In a prospective study of 19 dogs with pituitary-dependent hyperadrenocorticism, the adrenal glands were measured before and at least 6 months after initiation of trilostane therapy. Right adrenal gland length and caudal pole thickness and left adrenal gland caudal pole thickness increased significantly (p < or = 0.05); there was no significant change in left adrenal gland length. Enlargement of adrenal glands during trilostane therapy may occur as a result of suppression of the negative feedback mechanism affecting cortisol production.     

Persistent isolated hypocortisolism following brief treatment with trilostane

A 12‐year‐old male neutered Miniature Poodle with confirmed pituitary‐dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism (‘atypical hypoadrenocorticism’), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life‐threatening situation.     

The use of trilostane for the treatment of alopecia X in Alaskan malamutes

Three Alaskan malamutes with hair loss and slightly elevated blood concentrations of 17-hydroxyprogesterone after stimulation with adrenocorticotropic hormone (ACTH) were treated with trilostane. Trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, was given twice daily at a dose of 3.0 to 3.6 mg/kg per day orally for 4 to 6 months. Routine ACTH stimulation tests were performed over 8 months to evaluate the degree of adrenal function suppression. Treatment with trilostane led to complete hair regrowth in all three dogs within 6 months. No adverse effects associated with trilostane were recognized.     

Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane

Trilostane is thought to be a competitive inhibitor of the 3beta-hydroxysteroid dehydrogenase (3beta-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependant hyperadrenocorticism (PDH). The objective of our study was to investigate the effect of trilostane on precursor concentrations located before (17alpha-OH-pregnenolone, dehydroepiandrostenedione) and after (17alpha-OH-progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol) the proposed enzyme inhibition, on end products of steroid biosynthesis (cortisol and aldosterone) and on endogenous adrenocorticotrophic hormone (ACTH) concentrations in dogs with PDH. Hormones of the steroid biosynthesis pathway were evaluated in 15 dogs before and 1h after injection of synthetic ACTH prior to (t(0)), in weeks 1-2 (t(1)) and in weeks 3-7 (t(2)) of trilostane treatment. Endogenous ACTH concentrations were measured at the same time points before performing the ACTH stimulation test. During trilostane treatment baseline and post-stimulation cortisol concentrations decreased significantly. Baseline serum aldosterone levels showed a significant increase; post-stimulation values decreased. Baseline and post-stimulation 17alpha-OH-pregnenolone and dehydroepiandrostenedione concentrations increased significantly. 17alpha-OH-progesterone and androstenedione levels did not change. Post-stimulation 21-deoxycortisol concentrations decreased significantly, baseline 11-deoxycortisol concentrations increased significantly. Endogenous ACTH levels showed a significant increase. The significant increase in 17alpha-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3beta-HSD. Since 17alpha-OH-progesterone concentrations did not change, but cortisol concentrations markedly decreased, trilostane seems to influence additional enzymes of the hormone cascade, like the 11beta-hydroxylase and possibly the 11beta-hydroxysteroid dehydrogenase.     

Outcomes of pituitary tumor irradiation in cats

BACKGROUND: Information on tumor control and normal tissue effects of radiotherapy to treat pituitary tumors in cats is limited. HYPOTHESIS: Radiation therapy is effective in controlling the clinical signs associated with pituitary tumors in cats, with a low incidence of adverse effects. ANIMALS: Eight cats were irradiated at Colorado State University between 1991 and 2002 for spontaneous pituitary tumors. METHODS: A retrospective review of records was made to assess tumor control and incidence of radiation-induced adverse effects. RESULTS: Pituitary carcinoma was diagnosed in 2 cats and pituitary adenoma in 6 cats. Total radiation dosage ranged from 4,500 to 5,400 cGy administered Monday through Friday in 270 or 300 cGy fractions. Acute effects were limited to epilation and mild otitis externa. Focal brain necrosis adjacent to regrowth of a pituitary carcinoma and a second tumor in the radiation field were reported as possible late effects. Median survival, regardless of cause of death of the 8 cats, was 17.4 months (range, 8.4 to 63.1 months). Median survival could not be determined if cats were censored for non-tumor-related causes of death. Six cats were alive at 1 year, and 3 cats were alive at 2 years after treatment. Tumor recurrence was seen in 1 cat with a pituitary carcinoma. Neurologic signs improved within 2 months in all 5 cats that presented with abnormal neurologic signs. Clinical signs caused by a concurrent endocrine disorder began to improve within 1-5 months in the 7 cats with hyperadrenocorticism or acromegaly. CONCLUSIONS AND CLINICAL RELEVANCE: Radiation therapy is an effective primary treatment modality for cats presenting with neurologic signs associated with a pituitary mass and can improve clinical signs associated with concurrent hyperadrenocorticism or acromegaly in cats with no neurologic abnormalities.     

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.     

Successful treatment of feline hyperadrenocorticism with pituitary macroadenoma using radiation therapy: a case study

A 10-year-old castrated male cat showing behavioral (irritation, prowling, and tumbling) and cutaneous abnormalities such as dermal fragility was diagnosed as hyperadrenocorticism with pituitary macroadenoma, concurrent with insulin dependent diabetes mellitus. Pituitary enlargement (18.0 mm) was observed during magnetic resonance imaging. High endogenous adrenocorticotropic hormone levels (>2,500 pg/ml) were also observed. Although trilostane treatment (5–10 mg/head, daily) was commenced, the clinical signs did not disappear. Insulin and trilostane treatment were discontinued on day 86 after first day of radiation therapy (4 Gy/12 fractions). After radiation therapy, a decreased pituitary tumor size (10.7 mm) was observed on day 301; neurological and dermatological signs exhibited remission. Radiation therapy is the treatment of choice for feline hyperadrenocorticism with pituitary macroadenoma with neurological signs.     

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.     

The influence of trilostane on steroid hormone metabolism in canine adrenal glands and corpora lutea—an in vitro study

Trilostane is widely used to treat hyperadrenocorticism in dogs. Trilostane competitively inhibits the enzyme 3-beta hydroxysteroid dehydrogenase (3β-HSD), which converts pregnenolone (P5) to progesterone (P4) and dehydroepiandrosterone (DHEA) to androstendione (A4). Although trilostane is frequently used in dogs, the molecular mechanism underlying its effect on canine steroid hormone biosynthesis is still an enigma. Multiple enzymes of 3β–HSD have been found in humans, rats and mice and their presence might explain the contradictory results of studies on the effectiveness of trilostane. We therefore investigated the influence of trilostane on steroid hormone metabolism in dogs by means of an in vitro model. Canine adrenal glands from freshly euthanized dogs and corpora lutea (CL) were incubated with increasing doses of trilostane. Tritiated P5 or DHEA were used as substrates. The resulting radioactive metabolites were extracted, separated by thin layer chromatography and visualized by autoradiography. A wide variety of radioactive metabolites were formed in the adrenal glands and in the CL, indicating high metabolic activity in both tissues. In the adrenal cortex, trilostane influences the P5 metabolism in a dose- and time-dependent manner, while DHEA metabolism and metabolism of both hormones in the CL were unaffected. The results indicate for the first time that there might be more than one enzyme of 3β-HSD present in dogs and that trilostane selectively inhibits P5 conversion to P4 only in the adrenal gland.     

Comparison of the Polymerase Chain Reaction and Culture for the Detection of Feline Chlamydia psittaci in Untreated and Doxycycline-Treated Experimentally Infected Cats

The diagnostic sensitivity of the polymerase chain reaction (PCR) was compared with that of culture on conjunctival swabs over the course of infection in 4 doxycycline-treated and 4 untreated cats that were experimentally infected with feline Chlamydia psittaci. Treated cats were given 25 mg (5 mg/kg) of doxycycline orally twice daily for 3 weeks from day 6 after challenge. Clinical signs improved within 3 days of institution of treatment. Culture remained positive for 1 day and PCR remained positive for up to 5 days after treatment was commenced. No recurrence of clinical signs occurred and the organism could not be detected by either PCR or culture for 2 weeks after cessation of therapy. In the 4 untreated cats, conjunctival swabs were taken daily to day 14 and every 2nd weekday to day 64 after challenge. PCR was significantly more sensitive than culture in untreated cats overall (PCR 85.7%, culture 72.9%, P approximately 0) and for cats with clinical signs (PCR 89.2%, culture 79.2%, P = .008). PCR and culture had equivalent sensitivity (100%) for cats showing clinical signs in the 1st month of infection, whereas PCR was considerably more sensitive than culture for cats showing clinical signs in the 2nd month (PCR 72.9%, culture 47.9%, P = .028). Organisms were not detected by PCR in blood or any tissue collected from treated or untreated cats at postmortem. Thus, effective treatment of chlamydiosis in cats is possible with much shorter treatment regimens than currently recommended, and PCR is the more sensitive diagnostic method in chronically infected cats.     

Study of the effects of once daily doses of trilostane on cortisol concentrations and responsiveness to adrenocorticotrophic hormone in hyperadrenocorticoid dogs

The effects of trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor on basal cortisol concentrations and the results of ACTH stimulation tests in dogs with pituitary-dependent hyperadrenocorticism were investigated. In eight of nine dogs trilostane suppressed the concentration of cortisol below the lower limit of the reference range (<50 nmol/l) for a mean (sd) of 3.5 (2.3) hours during the day, but for no longer than 13 hours. In another 10 dogs, there was a clear difference between the post ACTH cortisol concentrations observed four and 24 hours after the administration of trilostane. Furthermore, in the six dogs whose clinical signs were poorly controlled the post-ACTH concentrations observed four and 24 hours after the administration of trilostane were always higher than the equivalent cortisol concentrations in the four dogs whose clinical signs were controlled. A short duration of drug action may be responsible for the failure of some dogs to respond adequately to once daily trilostane administration.     

Linear-Accelerator-Based Modified Radiosurgical Treatment of Pituitary Tumors in Cats: 11 Cases (1997–2008)

Objective: Determine the efficacy and safety of a linear-accelerator-based single fraction radiosurgical approach to the treatment of pituitary tumors in cats.
Design: Retrospective study.
Animals: Eleven client-owned cats referred for treatment of pituitary tumors causing neurological signs, or poorly controlled diabetes mellitus (DM) secondary either to acromegaly or pituitary-dependent hyperadrenocortism.
Procedures: Cats underwent magnetic resonance imaging (MRI) of the brain to manually plan radiation therapy. After MRI, modified radiosurgery was performed by delivering a single large dose (15 or 20 Gy) of radiation while arcing a linear-accelerator-generated radiation beam around the cat's head with the pituitary mass at the center of the beam. Eight cats were treated once, 2 cats were treated twice, and 1 cat received 3 treatments. Treated cats were evaluated for improvement in endocrine function or resolution of neurological disease by review of medical records or contact with referring veterinarians and owners.
Results: Improvement in clinical signs occurred in 7/11 (63.6%) of treated cats. Five of 9 cats with poorly regulated DM had improved insulin responses, and 2/2 cats with neurological signs had clinical improvement. There were no confirmed acute or late adverse radiation effects. The overall median survival was 25 months (range, 1–60), and 3 cats were still alive.
Conclusions and Clinical Importance: Single fraction modified radiosurgery is a safe and effective approach to the treatment of pituitary tumors in cats.     

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.     

Bromide-associated lower airway disease: a retrospective study of seven cats

Seven cats were presented for mild-to-moderate cough and/or dyspnoea after starting bromide (Br) therapy for neurological diseases. The thoracic auscultation was abnormal in three cats showing increased respiratory sounds and wheezes. Haematology revealed mild eosinophilia in one cat. The thoracic radiographs showed bronchial patterns with peribronchial cuffing in most of them. Bronchoalveolar lavage performed in two cats revealed neutrophilic and eosinophilic inflammation. Histopathology conducted in one cat showed endogenous lipid pneumonia (EnLP). All cats improved with steroid therapy after Br discontinuation. Five cats were completely weaned off steroids, with no recurrence of clinical signs. In one cat, the treatment was discontinued despite persistent clinical signs. The cat presenting with EnLP developed secondary pneumothorax and did not recover. Br-associated lower airway disease can appear in cats after months of treatment and clinical improvement occurs only after discontinuing Br therapy.     

Treatment of fibroadenomatous hyperplasia in cats with aglépristone

Fibroadenomatous hyperplasia (FAH) is characterized by a rapid proliferation of mammary stroma and duct epithelium of 1 or more glands and predominantly affects younger female cats. Endogenous progesterone and exogenous progestogens play an important role in the genesis of FAH. The presence of progesterone receptors in fibroadenomatous tissue allows for targeted endocrine therapy with progesterone receptor blockers. We report on 22 young cats with FAH, none of which had responded to the withdrawal of progestogens or ovariectomy. The common signs were tachycardia (11 cats); skin ulceration, painful mammary glands, or both (16 cats); lethargy (8 cats); and anorexia (4 cats). The cats were treated with subcutaneous injections of the progesterone receptor blocker aglépristone on 1 (7 cats, 20 mg/kg) or 2 consecutive days (15 cats, 10 mg/kg/d) once weekly. All but 1 cat responded with a complete and lasting remission of signs after 1-4 weeks of treatment. Two cats had a short-term skin irritation at the site of the aglépristone injection. Two pregnant cats with FAH aborted after treatment with aglépristone and subsequently developed endometritis. In conclusion, the results of this study demonstrate that FAH in cats can be treated successfully with the progesterone receptor blocker aglépristone.     

Haptoglobin concentrations in dogs undergoing trilostane treatment for hyperadrenocorticism

BACKGROUND: Increased concentrations of haptoglobin (Hp), a moderate acute phase protein, have been demonstrated in dogs with hyperadrenocorticism (HAC). Monitoring serum concentrations of Hp in hyperadrenocorticoid dogs before and after trilostane administration may provide valuable information on the response to therapy. OBJECTIVE: The aim of this study was to measure Hp concentrations in dogs with spontaneously occurring HAC at the time of diagnosis and after treatment with trilostane. METHODS: Serum Hp concentration was measured using an automatic biochemical assay based on Hp-hemoglobin binding and utilizing SB-7 reagent in 12 dogs with spontaneous HAC before and after treatment with trilostane (30 or 60 mg PO q 12-24 h). Post-treatment Hp concentrations were measured at the time the owner reported an improvement in clinical signs. Pretreatment and post-treatment Hp values were compared with reference values and with values from 4 healthy control dogs. RESULTS: Two dogs with HAC had pretreatment Hp values within the reference interval; 10 dogs had moderate (n = 8) or marked (n = 2) increases in Hp concentration. After treatment with trilostane, Hp concentration remained within the reference interval (n = 2), decreased to within the reference interval (n = 3), or remained moderately increased (n = 7; 3-10 g/L). Overall, a significant decrease was observed in Hp concentration after trilostane treatment compared with pretreatment values (P <.005). Both untreated and treated dogs with HAC had significantly higher Hp concentrations (P <.001) when compared with control dogs. CONCLUSIONS: Clinical control of HAC did not closely relate to serum Hp concentration. Further studies are required to assess whether this is because of inadequate control of disease or because a build-up of cortisol precursors or secondary effects of HAC affect Hp concentration.