Cushing's syndrome

From Felipedia

Cushing's syndrome in a cat, where fragile skin is easily torn during grooming

Dermal atrophy in a cat with iatrogenic Cushing's syndrome

Cushing's syndrome (Hyperadrenocorticism) is a rare disease of the adrenal gland of cats. In the feline patient, it is frequently misdiagnosed as diabetes mellitus (DM)^[1] and is often only recognised after a primary diagnosis of DM has been made. Diabetes mellitus has been documented in approximately 80% of feline hyperadrenocorticism cases. Cats are especially sensitive to the diabetogenic effects of steroids, and insulin resistance is therefore commonly encountered in hyperadrenocorticism^[2].

In addition, adrenal tumours may secrete excess amounts of not only cortisol but also sex hormones such as progesterone. Similar to canine patients, roughly 85% of feline cases of hyperadrenocorticism are classified as pituitary-dependent hyperadrenocorticism (PDH), and approximately 15% of cases are classified as functional adrenocortical tumours.

Clinical signs

Most feline Cushing's syndrome cases develop in middle-aged to older cats (mean age = 10.4 years; range 6–15 years). Of the 26 reported cases of feline Cushing's syndrome and one previously unreported case, 21 (78%) have been females. This female sex predilection resembles the human syndrome and contrasts with canine hyperadrenocorticism, where no sex predilection occurs. It can affect the ability to control the blood sugar level in cats with diabetes mellitus concurrently. Hyperadrenocorticism may be caused by pituitary tumours (90% are adenomas), pituitary hyperplasia, adrenal tumours, adrenal hyperplasia, by non-endocrine tumours (usually lung) or may be iatrogenic (external corticosteroid use)^[3].

Cats do not show as much drinking and urinating (polydipsia and polyuria) as dogs do, unless they have diabetes mellitus concurrently^[4]. Most cats are presented in a more advanced state of Cushing's disease because the early symptom of drinking and urinating are not observed. They might also have hepatomegaly, weight gain, pot-bellied appearance, and muscle wasting^[5].

Diagnosis

Cats do not routinely show any specific changes on a regular blood panel or urinalysis, although it is common to see hypercholesterolemia, hyperglycaemia, mild leukocytosis and erythroid regeneration (nucleated RBCs). The most consistent finding on a blood panel is hyperglycaemia. Abnormalities on serum biochemistry included persistent mild azotaemia, hypochloridaemia, hypokalaemia, metabolic alkalosis and elevated creatine kinase.

The urine cortisol: creatine ratio test is helpful in cats, especially since it is a relatively stress free test compared to blood sampling. If the test is normal then there is much less of a chance that Cushing's is present. It the test is elevated it might be Cushing's, but there are also other situations that cause this elevation^[6].

• ACTH stimulation test
• Dexamethasone suppression test

In general, results of these tests can be variable, and must be interpreted in conjunction with the history and clinical findings. In light of the fact that Cushing's is uncommon in cats, these tests need careful interpretation.

If the above tests suggest Cushing's then radiology can be helpful since up to 30% of feline adrenal tumours are mineralised. Other radiographic findings include hepatomegaly and obesity. Ultrasonic evidence of an enlarged adrenal gland (especially if unilateral) or changes in internal adrenal architecture is strong evidence of an adrenal tumour (AT).

Adrenal tumours occur in about 20% of feline Cushing's. They can be malignant or benign^[7]. In these more rare cases, a progesterone-secreting adrenal tumour exists, rather than a cortisol secreting tumour, and in such cases results of functional adrenal tests may appear more like hypoadrenocorticism. Where clinical signs are suspicious but routine diagnostic tests do not support the diagnosis, assay of serum progesterone levels, or better still ‘an adrenal profile’ should be considered. Trilostane therapy may also be worth trying in these cases.

Serum cortisol levels high and low dexamethasone suppression tests. In a healthy individual, the administration of a low dose of oral dexamethasone (0.5mg 6-hourly) will lead to suppression of cortisol levels below 50 nmol/L. No fall occurs in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome, even with high doses of dexamethasone. This contrasts with the responses seen in patients with pituitary-dependent disease in whom inadequate suppression after low-dose administration of dexamethasone, and at least 50% suppression after administration of a high dose of dexamethasone (2mg 6-hourly) are characteristic.

Treatment

Medical therapy is generally unrewarding. Ketoconazole can be used, but the effects are variable, and side effects can occur. Mitotane might help, along with metyrapone. Metyrapone may be more helpful as a pre-surgical stabilization prior to surgery. Anipryl has not been used in cats.

• Trilostane is an inhibitor of the 3-β hydroxysteroid dehydrogenase enzyme and reduces synthesis of cortisol, aldosterone and adrenal androgens. It is now commonly used to treat HAC in dogs and reports have emerged of its use in cats^[8]. From what has been published, although relatively limited numbers of cats have been involved, this appears to be a safe and effective treatment in cats, and would currently be regarded as the treatment of choice. A starting dose of 30 mg/cat is appropriate, but this can be administered twice daily (and at higher doses if necessary) if initial response is inadequate. Successful therapy will result in improved clinical condition, improved routine blood tests and normalisation of the ACTH response test. Repeat evaluations at

2-4 week intervals would be appropriate, with dose-adjustment as necessary until satisfactory control has been achieved.

• Irradiation of pituitary masses has been used but its limited availability severely restricts this treatment modality. It may be most appropriate for management of pituitary macroadenomas.
• Transsphenoidal hypophysectomy offers a good response to primary pituitary tumours
• Surgery is needed to remove one of the adrenal glands if the gland has a tumour, and both glands if the problem is PD. If both glands are removed the cat has to be on supplemental cortisone and mineralocorticoids for the rest of its life. Some cats with concurrent diabetes mellitus will no longer have the disease when their adrenal tumour is removed.

Unfortunately, cats with Cushing's can be poor aesthetic risks due to diabetes mellitus and fragile skin. When this occurs we sometimes will use medical therapy to help control the problem and make our patient a better anaesthetic risk.

References

1. ↑ Norsworthy, GD (2006) The feline patient. Blackwell Publishing, Iowa, USA
2. ↑ Quante S, Sieber-Ruckstuhl N, Wilhelm S, Favrot C, Dennler M, Reusch C. (2009) Hyperprogesteronism due to bilateral adrenal carcinomas in a cat with diabetes mellitus Schweiz Arch Tierheilkd. 151(9):437-42
3. ↑ August, JR (2006) Consultations in feline internal medicine, Vol 5. Elsevier Saunders, USA
4. ↑ Fracassi F, Mandrioli L, Diana A, Hilbe M, Grinwis G, Gandini G. (2007) Pituitary macroadenoma in a cat with diabetes mellitus, hypercortisolism and neurological signs. J Vet Med A Physiol Pathol Clin Med 54(7):359-63
5. ↑ Briscoe K, Barrs VR, Foster DF, Beatty JA. (2009) Hyperaldosteronism and hyperprogesteronism in a cat. J Feline Med Surg. 11(9):758-62
6. ↑ Herrtage, ME (2005) Hypoadrenocorticism. In:Ettinger, SJ Feldman, EC, eds. Textbooks of verterinary internal medicine. 6th edn. St Louis: Elsevier Saunders. pp:1612-1622
7. ↑ Millard RP, Pickens EH, Wells KL. (2009) Excessive production of sex hormones in a cat with an adrenocortical tumor. J Am Vet Med Assoc. 234(4):505-8
8. ↑ Sparkes, A (2009) Hyperadrenocorticism in cats – a brief overview. CVE, Control & Therapy 225:29-30