Poorly Controlled Diabetes in a Cat
A 16-year-old, castrated male domestic shorthair cat initially presented with primary signs of polyuria and polydipsia.
Results of routine blood analysis revealed hyperglycemia and glycosuria. Diabetes mellitus was diagnosed, and treatment with 2 units of recombinant human ultralente insulin given twice a day was begun. A senior maintenance diet was fed. Over the ensuing 3 months, glycemic control remained poor despite increasing the dose of ultralente insulin and changing to recombinant human lente insulin given at increasing doses (Figure 1). The cat had been losing weight despite a good appetite and had recently developed a nontraumatic skin laceration of unknown cause, despite being an indoor cat and the only household cat.
Physical examination. The following was found: weight, 3.5 kg; body condition score, 3 of 9; dry, unkempt hair coat; thin skin; mild plantigrade stance; hepatomegaly; and small, irregular kidneys bilaterally.
Diagnostics.Results of routine blood and urine tests are given in the Table. Thoracic radiographs were unremarkable. Abnormalities identified on abdominal ultrasonography revealed echogenic renal cortices bilaterally and adrenal glands measuring approximately 0.62 cm in maximum width (Figure 2).
Ask yourself ...• What differential diagnoses could result in the blood glucose curves obtained in this cat?• How do these diagnoses change after evaluating the history, physical examination findings, and results of the diagnostic tests?• What would be your next diagnostic step?
Diagnosis: HyperadrenocorticismTesting for Hyperadrenocorticism in Cats. Approximately 20% of normal cats "escape" the suppressive effects of dexamethasone-in other words, their cortisol concentrations fall outside the normal 8-hour postdexamethasone reference interval. Because of this, when evaluating the pituitary-adrenocortical axis in cats, I typically use only 1 dexamethasone-suppression test protocol (0.1 mg/kg dexamethasone IV; blood obtained before and 4 and 8 hours after dexamethasone administration). An 8-hour postdexamethasone serum cortisol concentration less than 1.0 µg/dl is suggestive of a normal pituitary-adrenocortical axis; values between 1.0 and 1.4 µg/dl are inconclusive; and values greater than 1.4 µg/dl support the diagnosis of hyperadrenocorticism. The higher the 8-hour postdexam-ethasone serum cortisol concentration above 1.4 µg/dl, the more diagnostic the test.
Results of the urine cortisol-creatinine ratio and dexamethasone-suppression test were consistent with the diagnosis of hyperadrenocorticism, and bilateral adrenomegaly confirms the diagnosis of pituitary-dependent hyperadrenocorticism. Of note was the normal ACTH-stimulation test in this cat. This test lacks sensitivity in cats-more than 50% of cats with confirmed hyperadrenocorticism seen at our hospital have normal results on the ACTH-stimulation test. For this reason, I no longer use it to evaluate cats for hyperadrenocorticism.
Hyperadrenocorticism is an elusive diagnosis in cats, in part because the clinical signs are often vague and can easily be attributed to diabetes mellitus until late in the disease and because the diagnostic tests used to establish the diagnosis are unreliable. I prefer the urine cortisol-creatinine ratio and dexamethasone-suppression test for diagnosis. The urine cortisol-creatinine ratio determined on urine collected at home is used as the initial screening test for hyperadrenocorticism. A normal ratio is strong evidence against the diagnosis; an increased ratio does not establish the diagnosis by itself, but supports performing the dexamethasone-suppression test.
Treatment. Treatment of pituitary-dependent hyperadrenocorticism in cats is problematic because the disease is usually advanced by the time of diagnosis. Bilateral adrenalectomy is the most effective treatment, but this cat was ineligible because of its fragile skin. Treatment with an enzyme inhibitor that blocks production of cortisol is indicated for 4 to 6 weeks to reverse the catabolic state of the cat, improve skin fragility and wound healing, and decrease the potential for perioperative complications.
I consider trilostane the drug of choice for feline hyperadrenocorticism, even though its efficacy remains to be determined (published recommended initial treatment protocol is 30 mg once a day). Unfortunately, trilostane was not an option at the time this cat was managed. Thus, we treated him with aminoglutethimide 30 mg PO Q 12 H, which inhibits conversion of cholesterol to pregnenolone, thereby reducing cortisol hypersecretion. In addition, the diet was gradually changed to one for suspected early renal insufficiency and the insulin dosage was decreased to 2 units of lente insulin Q 12 H (in preparation for improvement in insulin resistance in response to treatment of the hyperadrenocorticism).
Clinical signs and glycemic control initially improved; however, the owners declined adrenalectomy because of the age of the cat and elected to continue medical treatment. The cat's condition gradually deteriorated despite treatment, and he was euthanized 7 months later because of marked lethargy, inappetence, and weight loss. Findings at necropsy included a large pituitary carcinoma, pancreatic islet amyloidosis, and severe chronic interstitial nephritis.
Did You Answer ...
• Poor diabetic control can be categorized into 2 types: problems with the treatment regimen and problems caused by concurrent disease or medications. In diabetic cats, the most common problems with the treatment regimen include once-daily insulin administration, insulin overdosing causing clinical hypoglycemia or the Somogyi response, duration of insulin effect lasting 8 hours or less, and duration of insulin effect lasting 14 hours or longer (Somogyi response when given twice a day). In this cat, poor absorption of ultralente insulin should also be considered; however, the poor control persisted despite switching to lente insulin. Results of the blood glucose curves, by themselves, suggest insulin underdosage, post-Somogyi response, insulin resistance, or stress hyperglycemia. At the time of the evaluation, the cat's lack of glycemic control despite the high dosage of insulin supports insulin resistance or post-Somogyi response.• Additional findings on the physical examination and results of the initial diagnostic tests suggest concurrent disease causing insulin resistance. In diabetic cats, the most likely causes for severe insulin resistance are hyperadrenocorticism, acromegaly, and a progesterone-secreting adrenal tumor. The small size of the cat combined with thinning and spontaneous tearing of the skin and bilateral adrenomegaly are most consistent with hyperadrenocorticism. Although initial weight loss and bilateral adrenomegaly can occur with acromegaly, the small size of the cat and the skin lesions are inconsistent with this diagnosis. Failure to identify an adrenal mass with abdominal ultrasonography rules out a progesterone-secreting adrenal tumor.• A diagnostic evaluation for Cushing's disease is warranted and may include urine collected at home for testing the cortisol-creatinine ratio, ACTH stimulation, and dexamethasone suppression using 0.1 mg of dexamethasone/kg IV (Table).
POORLY CONTROLLED DIABETES IN A CAT • Richard W. Nelson
Suggested ReadingAdrenalectomy for treatment of hyperadrenocorticism in cats: 10 cases (1988-1992). Duesberg CA, Nelson RW, Feldman EC, et al. JAVMA 207:1066-1070, 1995.Hyperadrenocorticism in cats (Cushing's syndrome). Feldman EC, Nelson RW. In Feldman EC, Nelson RW (eds): Canine and Feline Endocrinology and Reproduction, 3rd ed-St. Louis: Elsevier, 2004, pp 358-393.Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats. Smith MC, Feldman EC. Am J Vet Res 48:1719-1724, 1987.Trilostane therapy for treatment of pituitary-dependent hyperadrenocorticism in 5 cats. Neiger R, Witt AL, Noble A, et al. J Vet Intern Med 18:160-164, 2004.Ultrasonographic examination of the adrenal gland and evaluation of the hypophyseal-adrenal axis in 20 cats. Zimmer C, Horauf A, Reusch C. J Small Anim Pract 41:156-160, 2000.Urinary excretion of glucocorticoids in the diagnosis of hyperadrenocorticism in cats. Goossens MMC, Meyer HP, Voorhout G, et al. Domestic Anim Endocrinol 12:355-362, 1995.