Management and Treatment of Hyperadrenocorticism in Dogs

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MANAGEMENT AND TREATMENT OF HYPERADRENOCORTICISM IN DOGS

Author : Sue Paterson

Categories : Vets

Date : September 19, 2011

Sue Paterson considers this common endocrine disease and discusses successful approaches to therapy, including overcoming some of its challenges

Hyperadrenocorticism (Hac) is described as a clinical syndrome that results from a chronic excess of glucocorticoids. it is a common endocrine disease in the dog. two forms of the disease are recognised.

The majority of cases are pituitary-based and usually caused by over-production of adrenocorticotrophic hormone (ACTH) from a small benign pituitary microadenoma (pituitary- dependent hyperadrenocorticism [PDH]). Less commonly (about 15 per cent of cases), disease can be caused by an adrenal tumour (adrenal dependent hyperadrenocorticism [ADH]), of which about 50 per cent are malignant.

To formulate a treatment plan it is important to make a confident diagnosis, but also to establish the site of the lesion. A full discussion of the diagnosis of hyperadrenocorticism is beyond this article, but the reader is referred to other excellent texts that describe diagnosis in detail (see further reading list).

Successful management of hyperadrenocorticism depends on factors other than selection of appropriate drug therapy. Owner compliance is crucially important. It is essential before embarking on therapy that an owner is made aware of the chronic nature of the disease; the costs of drugs, which can be considerable; the time commitment for the owner in the form of continued

1 / 4 reassessment of the pet’s progress at the surgery; and the potential side effects that may be encountered with therapy.

As a clinician, one of the biggest problems encountered by the author with the implication of successful therapy is the unmasking of steroid-responsive diseases. Typically, dogs with problems such as atopy or arthritis may show no signs of disease while they have HAC, but diseases may become apparent as glucocorticoid levels drop. Balancing the therapy for two concurrent problems can then become very difficult.

Several drugs have been proposed as being useful in the management of HAC. The ones most commonly described are trilostane, mitotane, ketoconazole and selegiline. Only trilostane is licensed for the treatment of HAC.

Surgical procedures have also been described in the form of trans-sphenoidal hypophysectomy for PDH and adrenalectomy for ADH. These complex operations need a skilled surgeon and the resources of a referral centre for postoperative care. The reader is referred to other texts for detailed descriptions of these.

Trilostane therapy in HAC

Trilostane is licensed for the therapy of HAC in the UK and should, therefore, be the first drug of choice under the veterinary cascade system. It is a synthetic, short-acting steroid analogue that competitively inhibits the synthesis of several steroids, including cortisol and aldosterone. It is best absorbed if given with food. Trilostane is successful in resolving the signs of HAC in about 70 per cent of cases.

Signs of polyuria, polydipsia and polyphagia usually resolve first within four weeks of starting therapy, while cutaneous lesions will often take three to four months to improve. Investigations have shown that trilostane will cause a depression in post-ACTH stimulation cortisol levels within 10 days of starting therapy, which means monitoring should start as early as this.

Trilostane should be started at a dose rate of 3mg/kg to 6mg/kg once daily with food, and animals should be carefully monitored. Monitoring once treatment has been started is important and post- pill ACTH stimulation tests should be performed at 10 days, 28 days and 90 days, and then every three months, depending on the animal’s degree of stability. The ACTH stimulation test should be performed ideally four to six hours after pill administration.

The author has seen several cases where the requirement for trilostane has dropped dramatically after six to 12 months on therapy, resulting in a reduction or withdrawal of treatment. This has been recorded in the literature and it has been suggested it may be due to adrenal necrosis.

However, the author has seen cases where a dog’s requirement for medication has been reduced

2 / 4 to zero before becoming unstable again. This would suggest that adrenal suppression may be marked, but is not irreversible.

The need for ongoing monitoring is therefore paramount. Adjustment of therapeutic levels of trilostane must be undertaken by assessing not only the post-pill ACTH blood results, but the animal’s general health. If the post-ACTH cortisol concentration is more than 200nmol/L the trilostane dosage is increased. If it is less than 50nmol/L it must be stopped for seven days, then reintroduced at a lower dose rate if the animal is clinically healthy and clinical signs of hyperadrenocorticism have recurred. Table 1 gives a rough guide to how cases can best be monitored. Any dose changes should reflect the bodyweight of the animal, the current dose, the capsule sizes available and the final proposed dose in mg/kg.

Side effects of trilostane therapy can occur and are usually associated with over-dosage of the drug or unmasking of concurrent disease. Over-dosage can lead to hypocortisolism, which usually presents with mild inappetence or vomiting, but occasionally more severe signs of haemorrhagic diarrhoea have been reported.

Where subclinical disease is uncovered by therapy of HAC then other drugs may need to be introduced to manage these secondary problems. Where atopy is unmasked a slight reduction in trilostane therapy may allow a small increase in cortisol to control the allergy without producing detrimental effects of less rigorous control of HAC. Alternatively, a second drug regime may be added, using antihistamines or cyclosporines – glucocorticoids should be avoided if at all possible. Where arthritis is unmasked, then analgesics may be needed. Although it is reported that NSAIDs can be used in dogs with HAC the author prefers to use nutraceuticals or opiates to avoid the risk of gastrointestinal problems.

Neurological signs may develop after starting therapy. Facial nerve paralysis has been recorded in some dogs, but it is not clear whether this is a progression of the disease or due to the therapy. In PDH, expansion of a pituitary mass, due to a reduction in cortisol levels or due to the progression of the HAC, can lead to a range of neurological signs, which include loss of appetite, blindness or seizures.

Other drug therapies in HAC

Several other drugs can be used to treat HAC, but they should only be considered under the cascade when animals with a definite diagnosis of HAC have failed to respond to trilostane or have shown unacceptable side effects. Mitotane, ketoconazole and selegiline have been used to treat HAC with varying degrees of success.

The reader should consult more advanced texts for detailed instructions on how to use these drugs; brief points are outlined in Table 2.

3 / 4 Other drugs that have been used in dogs, but have been found to be ineffectual, include cyproheptadine, metapyrone, phosphatidylserine and aminoglutethimide.