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Basics ⬇

Basics

Overview

Feline Cushing's (hyperadrenocorticism or HAC) syndrome is a disorder of excessive cortisol secretion by the adrenal glands.

Pathophysiology

  • Spontaneous FCS-caused by overproduction of cortisol by the adrenal glands.
  • Approximately 85% of cats with FCS have bilateral adrenocortical hyperplasia resulting from pituitary hyperplasia or tumor. The remaining 15% have an adrenal tumor, half of which are benign and half malignant. Regardless of the cause, FCS is usually (80%) accompanied by diabetes mellitus.

Signalment

  • Cat
  • No known breed or sex predisposition
  • Middle-aged to older cats

Signs

  • Polyuria, polydipsia, polyphagia, fragile (bruising, tearing, thin) skin, weight loss, and muscle weakness are most common.
  • Obesity, hepatomegaly, alopecia, diarrhea, vomiting, abdominal enlargement, curled ear tips, and unkempt appearance are also seen.
  • Lethargy (dullness) has been reported due to muscle weakness or the effects of a pituitary mass.
  • Excess sex hormones can cause signs such as penile barbs and behavioral changes (sexual behavior).

Causes & Risk Factors

  • Pituitary adenoma with subsequent corticotrophic hyperplasia and excess adrenocortical cortisol secretion.
  • Autonomously functioning benign adenoma (50%) or malignant adenocarcinoma (50%).
  • Iatrogenic due to glucocorticoid administration is rare.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Diabetes mellitus
  • Insulin resistance
  • Acromegaly
  • Hepatopathy
  • Renal disease
  • Sex hormone–secreting adrenal tumors
  • Hypothyroidism

CBC/Biochemistry/Urinalysis

  • Stress leukogram.
  • Hyperglycemia, hypercholesterolemia, mild increased ALT due to poorly regulated concomitant diabetes mellitus.
  • High serum alkaline phosphatase not common because cats do not have corticoid-induced isoenzyme.
  • Elevated urine cortisol:creatinine ratio (UC:Cr) is common.
  • Less common-azotemia, proteinuria, and hyperglobulinemia.

Other Laboratory Tests

Screening Tests

  • UC:Cr-sensitive (useful for its negative predictive value, i.e., if a normal UC:Cr is obtained, FCS is unlikely), inexpensive, and easy to perform and interpret. Home collection (non-stressed) of urine is preferred.
  • Low-dose dexamethasone-suppression test (LDDST)-extremely sensitive. Requires ten times the dose used in dogs: 0.1 mg/kg IV. Plasma obtained for cortisol before and 4 and 8 hours after dexamethasone administration. Failure to suppress is consistent with FCS.
  • ACTH stimulation test, mainly a test of adrenal reserve-requires little time, is easy to interpret, is relatively inexpensive, and is specific for FCS when results are abnormal.

Differentiating Tests

  • High-dose dexamethasone-suppression test (HDDST)-1 mg/kg dexamethasone, protocol as with LDDST. An at-home version using multiple UC:Crs and oral dexamethasone is easier to perform and interpret than the in-hospital protocol.
  • Plasma endogenous ACTH measurement is high normal or greater with PDH compared to low plasma ACTH levels with AT (<10 pg/mL). The normal range for cats is 0–60 pg/mL. Blood is collected in EDTA, spun immediately, and the plasma transferred to plastic and frozen.
  • “At home” dexamethasone-suppression protocol-have owners collect morning urine samples on days 1, 2, and 3. Give oral doses of dexamethasone (LDDST [0.1 mg/kg] or HDDST [1 mg/kg]) at 6-h intervals for 2 days. Submit all three urine samples for UC:Cr ratio. days 1 and 2 are basal values. Day 3 suppression less than 50% is not seen in cats with AT but may be seen with PDH.

Imaging

  • Abdominal ultrasound preferred to visualize adrenal glands. Although subjective, ultrasonography can be an excellent tool to discern PDH from AT. Symmetric adrenal glands of normal or enlarged size are suggestive of PDH, whereas unilateral enlargement supports AT.
  • CT and MRI allow visualization of pituitary macroadenomas.

Diagnostic Procedures

Sex hormone panels or insulin-like growth factor-1 (IGF-1) obtained to rule-out differentials.

Treatment ⬆ ⬇

Treatment

Medications ⬆ ⬇

Medications

Drug(s)

  • Mitotane (Lysodren; o,p';-DDD) causes selective destruction of cortisol-secreting adrenocortical cells. Doses of 50 mg/kg/day divided have been used, but even when doubled sometimes failed to demonstrate improvement.
  • Trilostane reversibly inhibits 3--17-hydroxysteroid dehydrogenase, which blocks steroid synthesis. In a majority of cases of FCS with PDH, trilostane reduced clinical signs and improved endocrine test results. Doses up to 60 mg/cat PO q12h have been used.
  • Other medications have been used with some limited success (ketoconazole, metyrapone, and aminoglutethimide).

Follow-Up ⬆ ⬇

Follow-Up

Miscellaneous ⬆

Miscellaneous

Abbreviations

  • ACTH = adrenocorticotropic hormone
  • AT = adrenal tumor
  • CT = computed tomography
  • FCS = feline Cushing's syndrome
  • HAC = hyperadrenocorticism
  • HDDST = high-dose dexamethasone-suppression test
  • LDDST = low-dose dexamethasone-suppression test
  • MRI = magnetic resonance imaging
  • PDH = pituitary-dependent hyperadrenocorticism
  • UC:Cr = urine cortisol:creatinine ratio

Author Deirdre Chiaramonte

Consulting Editor Deborah S. Greco

Suggested Reading

Feldman EC, Nelson RW. Hyperadrenocorticism in cats (Cushing's syndrome). In: Canine and Feline Endocrinology and Reproduction, 3rd ed. Philadelphia: Saunders, 2004, pp. 358–393.

Mellet , K, Bruyette , D, Stanley , S. Trilostane therapy for treatment of spontaneous hyperadrenocorticism in cats: 15 cases (2004-2012). J Vet Intern Med 2013, 27:1471–1477.