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Compendium September 2005 (Vol 27, No 9)

Feline Hypoadrenocorticism

by Bronya Redden, DVM

    Abstract

    Feline hypoadrenocorticism is a rare disease but should be considered in patients with vague clinical signs and electrolyte imbalances. This article reviews the cause, clinical signs, typical blood work abnormalities, diagnosis, and treatment of feline hypoadrenocorticism. A case report of a 2-½-year-old castrated domestic shorthaired cat diagnosed with hypo­adrenocorticism is also presented. The initial hypoadrenal crisis was managed in the ­hospital with intravenous fluids, dexamethasone, and repository intramuscular des­oxy­cor­ticosterone pivalate. Chronic management consisted of mineralocorticoid support with repository intramuscular desoxycorticosterone pivalate every 25 to 30 days and periodic glucocorticoid support with oral prednisolone. Serum electrolytes were monitored periodically. Three years after diagnosis, the cat continues to be well managed and has an excellent long-term prognosis with continued treatment.

    Relatively few cases of feline hypoadrenocorticism have been reported in the literature.1-7 Since the first case was reported in 1983, only 22 have been published.4,8 Currently, the pathogenesis of feline primary hypoadrenocorticism remains unknown.1,6,8 Primary hypoadrenocorticism results from destruction of the adrenal cortex and consequent inadequate production of glucocorticoids and mineralocorticoids.1,3,8 Secondary hypoadrenocorticism is a result of inadequate production of adrenocorticotropic hormone (ACTH) by the pituitary and has not been reported in cats.3,4 However, suppression of ACTH production can be caused by glucocorticoid and progestogen administration3; high doses of methylprednisolone acetate and recommended doses of megestrol acetate have been shown to suppress the plasma cortisol response to ACTH and cause adrenal cortex atrophy in cats.3

    In dogs, primary hypoadrenocorticism is considered idiopathic but is most likely the result of autoimmune destruction of the adrenal cortex.1,2,9 In one case report, necropsy was performed on a cat diagnosed with hypoadrenocorticism; the results showed lymphocytic infiltration of the adrenal cortex, suggesting immune-mediated destruction of the adrenal cortex.2 Currently, most cases of feline hypoadrenocorticism are thought to be immune mediated in origin.5-7 Infiltration of the adrenal glands by lymphoma has also reportedly caused hypoadrenocorticism in two cats.10

    History, Clinical Signs, and Physical Examination

    Cats of any age, breed, or sex can develop primary hypoadrenocorticism.1,3-8 There is no reported sex predilection, and the median age at time of diagnosis is 4 years (age range: 1.5 to 14 years).1,3,4,6 The typical history of a cat with hypoadrenocorticism includes clinical complaints of lethargy, anorexia, and weight loss.1-4,6-8 The following are less commonly reported: vomiting, a waxing/waning course of illness, polyuria, polydipsia, previous response to therapy, reluctance to jump, and muscle tremors.1,3,4,6 Diarrhea and cardiac abnormalities have not been reported as clinical signs in cats with hypoadrenocorticism.1,3,7 The most common findings during physical examination are nonspecific, including depression, weakness, dehydration, and hypothermia.1,3,4 One case report described a cat with a presenting complaint of dysphagia caused by muscle weakness.6

    Laboratory Abnormalities

    Cats with hypoadrenocorticism usually have significant abnormalities on their biochemistry profile and urinalysis. Most have mild to severe prerenal azotemia, hyper­phosphatemia, hyponatremia, and an abnormal sodium:potassium ratio.1-4 The sodium:potassium ratio is often 20:1 or less (30:1 is a normal sodium:potassium ratio).9 The urine specific gravity is usually not greater than 1.030, despite the presence of dehydration and prere­nal azotemia, because loss of renal medullary solutes, especially sodium, results in impaired renal-concentrating ability.1,3,6 Some cats exhibit hyperkalemia, hypo­chlor­emia, and/or hypercalcemia1; 13% of cats reported with hypoadrenocorticism were hypercalcemic at presentation.5 The pathogenesis of hypercalcemia associated with hypo­adrenocorticism is unknown but suspected to be multifactorial.11 The hypercalcemia could be associated with hyperproteinemia secondary to dehydration and hemoconcentration, increased plasma binding of calcium, increased concentration of calcium citrate complexes, and/or increased renal tubular resorption of calcium.11

    There are no consistent hematologic ab­normalities reported in cats with hypo­adrenocorticism.3,4 Lymphocyte and eosino­phil counts may be normal, increased, or de­creased.3,4 A normal or increased lymphocyte and eosinophil count is significant because the expected response to stress would be lymphopenia and eosinopenia.3,5,9,12 Some cats have had mild normocytic, normochromic, nonregenerative anemia.3,4,8 The box on this page summarizes the most common clinical signs, physical examination findings, and blood work abnormalities reported in cases of feline hypoadrenocorticism.

    Diagnostic Testing

    In most cats with hypoadrenocorticism, thoracic radio­graphs usually show microcardia and pulmonary hypo­perfusion.1,3,6 Mineralocorticoid deficiency causes sodium loss, resulting in vascular volume contraction and impaired peripheral circulation.3 Glucocorticoid deficiency reduces vascular responsiveness to catecholamines, contributing to vascular collapse and hypoperfusion on radiographs.3

    In cats, electrocardiograms rarely show changes due to hyperkalemia.1,3 Hyperkalemia decreases myocardial contractility and hampers conduction, helping lead to circulatory failure.3 The typical signs of hyperkalemia on canine electrocardiograms, such as peaking of the T wave, decreased R wave amplitude, and reduced or absent P waves, are not typically seen on electrocardiograms of cats with hypoadrenocorticism.3,6 Cats with documented hypoadrenocorticism have had milder hyperkalemia compared with dogs with hypoadrenocorticism, helping account for the lack of electrocardiographic changes.6,7 Some cats with hypoadrenocorticism have had sinus bradycardia or atrial premature contractions on their electrocardiograms, although these signs have not been commonly reported.1

    Ultrasonography cannot be routinely used to identify small adrenal glands in cats because the right adrenal gland is difficult to see in normal animals.5 Some recent ultrasonographic studies of the normal feline adrenal gland suggest that ultrasonography may become useful in diagnosing diseases of the adrenal gland in the future as machines become more sensitive and ultrasonographers gain more experience with imaging of the adrenal glands.13

    Differential Diagnosis

    The differential diagnosis of feline hypoadrenocorticism includes renal disease, gastrointestinal disease, and other cardiovascular, neurologic, muscular, or metabolic diseases that cause weakness.5,8 If hypercalcemia is present, other causes of hypercalcemia, such as neoplasia and primary hyperparathyroidism, must be considered.14

    Diagnosis

    The main tool used to diagnose hypoadrenocorticism in cats is the ACTH stimulation test.1,3 There are two main protocols for the ACTH stimulation test in cats. One protocol is to use ACTH gel: The serum or plasma cortisol level is measured before and 60 and 120 minutes after administering ACTH gel intramuscularly (2.2 U/kg).3,6-8 A second protocol is to inject synthetic ACTH (Cortrosyn, Organon Pharmaceuticals; 125 µg) intravenously or intramuscularly and measure serum or plasma cortisol levels before and 30 and 60 minutes after injection.3-8 The latter protocol is preferred because synthetic ACTH stimulates the adrenal cortex more consistently and to a greater degree than does ACTH gel.12 In normal animals, basal cortisol concentrations are usually 0.5 to 5 µg/dl and post-ACTH cortisol concentrations are 4.5 to 13 µg/dl.7 A low or low-normal baseline serum cortisol level with little or no increase in the serum cortisol level after ACTH administration is diagnostic of hypoadrenocorticism.1,7,8 In cats with hypoadrenocorticism, pre- and post-ACTH cortisol levels were reported to be less than 2 µg/dl.7

    Elevation of endogenous plasma ACTH concentration is also useful in confirming primary hypoadrenocorticism in cats.1,3-5,7 In one study of 10 cats, endogenous plasma ACTH levels were elevated at 500 to 8,000 pg/ml in all cats with hypoadrenocorticism (normal levels: <10 to 125 pg/ml).3 In cats with primary hypoadrenocorticism, ACTH secretion is increased by a normal pituitary1; decreased cortisol production decreases the negative feedback to the pituitary, resulting in increased production of ACTH.1,5 ACTH rapidly disappears from whole blood, and the diagnostic laboratory should be consulted for information on sample collection and submission if the endogenous plasma ACTH concentration needs to be measured.3-6

    Treatment

    Initial

    Treatment of hypoadrenocorticism is usually initiated before a definitive diagnosis is obtained because usually results of the ACTH stimulation test are not readily available. A presumptive diagnosis should be based on the ­history, clinical signs, and sodium:potassium ratio.9 ­Treatment involves restoring the circulating blood volume, correcting serum electrolyte and acid-base imbalances, and providing glucocorticoid and mineralocorti­coid support.3,7 Initial management includes administration of 0.9% saline fluids at a rate of 40 ml/kg/hr IV to correct fluid deficits over the first 2 hours; this is then tapered to a maintenance rate of 60 ml/kg/day.1,3,4,7 Fluid therapy should be discontinued when azotemia and electrolyte abnormalities resolve and the cat is eating and drinking.12 Intravenous dexamethasone at a dose of 0.5 to 1 mg/kg q12-24h corrects glucocorticoid deficits and does not interfere with ACTH stimulation testing.1,3,4,7,8 Mineralocorticoid support is provided by administering intramuscular repository desoxycorticosterone pivalate (DOCP; Percorten-V, Novartis Animal Health; 10 to 12.5 mg/mo) or oral fludrocortisone acetate (Florinef, Bristol-Myers Squibb; 0.10 mg q24h).1,3,4,7 Most often, the hyperkalemia and mild metabolic acidosis that may be present respond to fluid therapy and other treatment is not needed3; fluid therapy increases renal perfusion, which decreases the serum potassium concentration by dilution and renal potassium excretion.5

    Once treatment has been initiated, clinical signs usually take longer to resolve in cats than in dogs.1,3,4,7 Lethargy, weakness, and anorexia often persist for 3 to 5 days.1,3,4,7 Cats that are diagnosed with hypoadrenocorticism and respond poorly to treatment should be evaluated for lymphoma (via ultrasonography or biopsy) because lymphosarcoma can infiltrate the adrenal glands.7,12

    Maintenance

    Maintenance therapy consists of lifelong mineralocorticoid support with or without glucocorticoid support. Once a cat has been started on intramuscular repository DOCP or oral fludrocortisone acetate, the dose must be adjusted based on evaluations of serum electrolyte concentrations every 1 to 2 weeks until the patient is stable.4 In most cats, oral fludrocortisone acetate should be administered at a dose of 0.1 mg q24h.1,3,4 Most cats require intramuscular DOCP every 25 to 30 days.3,7 Frequent sampling is recommended to determine the time interval for administering DOCP because dogs with hypoadrenocorticism often require DOCP more frequently than every 30 days.3 Glucocorticoid supplementation is recommended but not required in all cases, and prednisolone (0.5 to 2 mg/cat/day PO) or methylprednisolone (10 mg/cat/mo IM) can be used.4,6-8 Alternate-day therapy with prednisolone is not required because there is not an intact hypothalmic-pituitary-adrenal axis.9 The use of monthly intramuscular methylprednisolone may increase the risk of developing diabetes mellitus.4

    The long-term prognosis for a cat with hypoadrenocorticism is good.1,5-8 With correct glucocorticoid and mineralocorticoid support, cats with hypoadrenocorticism can have a normal life expectancy.3 Periodic monitoring of serum electrolytes, blood urea nitrogen, and creatinine is strongly recommended.7

    Conclusion

    Feline hypoadrenocorticism is an uncommon disease but should not be overlooked. Relatively few cases have been reported in the literature. The disease has the ability to mimic other disorders, especially renal disease, and cases of feline hypoadrenocorticism have likely gone undiagnosed. Feline hypoadrenocorticism is easy to test for using the ACTH stimulation test, and treatment is rewarding because most cats have an excellent response.

    Read the following Case Study .

    Downloadable PDF

    *Dr. Redden became an indepen­dent contractor for Novartis Animal Health after writing this article.

    1. Peterson ME, Greco DS, Orth DN: Primary hypoadrenocorticism in ten cats. J Vet Intern Med 3(2):55-58, 1989.

    2. Johnessee JS, Peterson ME, Gilbertson SR: Primary hypoadrenocorticism in a cat. JAVMA 183(8):881-882, 1983.

    3. Myers NC III, Bruyette DS: Feline adrenocortical disease: Part II—Hypo­adrenocorticism. Semin Vet Med Surg Small Anim 9(3):144-147, 1994.

    4. Mooney C: Unusual endocrine disorders in the cat. In Pract 20(7):345-349, 1998.

    5. Greco DS: Hypoadrenocorticism in dogs and cats. Vet Med June:468-476, 2000.

    6. Stonehewer J, Tasker S: Hypoadrenocorticism in a cat. J Small Anim Pract 42(4):186-190, 2001.

    7. Feldman EC, Nelson RW: Hypoadrenocorticism in cats, in Canine and Feline Endocrinology and Reproduction. Philadelphia, WB Saunders, 1996, pp 302-305.

    8. Duesberg C, Peterson ME: Adrenal disorders in cats. Vet Clin North Am Small Anim Pract 27(2):321-347, 1997.

    9. Kaufman J: Diseases of the adrenal cortex of dogs and cats. Mod Vet Pract 65(7):513-516, 1984.

    10. Parnell KK, Powell LL, Hohenhaus AE, et al: Hypoadrenocorticism as the primary manifestation of lymphoma in two cats. JAVMA 214(8):1208-1211, 1999.

    11. Feldman EC, Nelson RW: Hypercalcemia and primary hyperparathyroidism, in Canine and Feline Endocrinology and Reproduction. Philadelphia, WB Saunders, 1996, pp 455-493.

    12. Peterson ME, Randolph JF, Mooney CT: Endocrine diseases, in Sherding RG (ed): The Cat—Diseases and Clinical Management. New York, Churchill Livingstone, 1994, pp 1490-1493.

    13. Zimmer C, Horauf A, Reusch C: Ultrasonographic examination of the adrenal gland and evaluation of the hypophyseal-adrenal axis in 20 cats. J Small Anim Pract 41:156-160, 2000.

    14. Bruyette DS: Feline endocrinology update. Vet Clin North Am Small Anim Pract 31(5):1063-1081, 2001.

    References »

    NEXT: Letters (September 2005)

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