Hyperadrenocorticism develops most commonly 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.
The most common historical and clinical signs associated with feline hyperadrenocorticism are polyuria, polydipsia, and polyphagia.
These signs likely correspond to the high incidence of concurrent diabetes mellitus (76%) found in cats with hyperadrenocorticism,
and are consistent with the lack of overt signs preceding marked glucose intolerance observed in experimentally-induced disease.
The typical "Cushingoid" pot-bellied appearance with hepatomegaly, weight gain, and generalized muscle wasting is common in
cats as in dogs. Dermatologic abnormalities frequently recognized include an unkempt haircoat with patchy alopecia, and very
thin skin prone to traumatically-induced tears and secondary infections.
Hyperglycemia is the most common laboratory abnormality found on serum biochemistries. Cats appear more sensitive to the
diabetogenic effects of glucocorticoid excess than dogs. Cats with concurrent diabetes mellitus often exhibit cortisol-induced
insulin resistance, requiring high daily doses of insulin to control their hyperglycemia and glucosuria. Hypercholesterolemia
is also common, and may relate to insulin resistance and increased lipolysis. Cats lack the steroid-induced isoenzyme of
alkaline phosphatase found in the canine, and the half-life of the enzyme appears to be significantly shorter in the cat.
Elevation of serum alkaline phosphatase (SAP) is present in only approximately one-third of cats compared to nearly 90% of
dogs with hyperadrenocorticism. Increases in SAP and the hepatocellular enzyme ALT appear to correspond with the regulation
of the diabetic state, rather than representing direct indicators of glucocorticoid excess. These enzymes frequently normalize
with adequate regulation of diabetes, even without therapy directed towards the hyperadrenocorticism. Hematologic findings
associated with hypercortisolemia (lymphopenia, eosinopenia, and neutrophilic leukocytosis) occur inconsistently in feline
hyperadrenocorticism. Despite clinical polyuria and polydipsia, cats appear to maintain urine specific gravities of greater
than 1.020 more frequently than dogs, and only occasionally exhibit dilute urine and decreased blood urea nitrogen concentrations
commonly seen in dogs with hyperadrenocorticism.
Endocrinologic evaluation of cats suspected of hyperadrenocorticism involves screening tests to confirm the diagnosis, and
differentiating tests to distinguish pituitary-dependent disease (PDH) from adrenal tumors (AT). Adrenocorticotropin (ACTH)
stimulation testing in adrenocortical hyperfunction is not as definitive as for hypoadrenocorticism. Fifteen to 30% of cats
with confirmed hyperadrenocorticism have had normal cortisol response to ACTH administration (false negatives). In addition,
stressed cats and those with non-adrenal illnesses may show an exaggerated response to ACTH in the absence of hyperadrenocorticism
(false positives). A normal urine cortisol-to-creatinine ratio (UCCR) can be used to exclude the diagnosis of hyperadrenocorticism
in cats as described in dogs. The UCCR is attractive due to the ease of sampling compared to other endocrine function tests,
but is non-specific and will be elevated in a variety on non-adrenal illnesses. An exaggerated ACTH stimulation test or an
elevated UCCR should be pursued with suppression testing prior to initiating any therapy.
Normal cats are more variable than dogs with respect to the degree and duration of adrenocortical suppression following dexamethasone
administration. Intravenous doses of dexamethasone that have been evaluated in the cat range from 0.005 to 1.0 milligrams
per kilogram. A dosage of 0.01 mg/kg of dexamethasone, commonly used in low-dose dexamethasone suppression testing in dogs,
led to a significant drop in serum cortisol levels in ten normal cats, but 2 of the cats showed a slight escape from suppression
by 8 hours after injection. Intravenous dexamethasone sodium phosphate (DSP), 0.01 and 0.1 mg/kg, produced equivalent reductions
of plasma cortisol levels, but suppression was sustained below baseline longer with the higher dosage. Cats with various
non-adrenal illnesses have also shown inadequate cortisol suppression after a low-dose (0.01 mg/kg) of DSP. The 0.1 mg/kg
dosage of dexamethasone seems to more reliably suppress cortisol levels in normal cats and cats with non-adrenal illnesses.
Elevated cortisol levels eight hours post-dexamethasone injection, using the 0.1 mg/kg dosage, appears to be as sensitive
a diagnostic test for feline hyperadrenocorticism (8/9; 89%) as the low-dose (0.01 mg/kg) screening test in the dog.
The combined dexamethasone suppression/ACTH stimulation test has been used successfully to diagnose hyperadrenocorticism in
the cat. Hyperadrenocorticoid cats displayed inadequate suppression of cortisol 2-4 hours after an injection of 0.1 mg/kg
of dexamethasone, and an exaggerated response 1-2 hours after ACTH stimulation. The ability of the combined test to discriminate
PDH from AT is unclear. Several cats with confirmed pituitary disease failed to suppress 2-4 hours after dexamethasone.
Extending the duration of post-dexamethasone monitoring, or using higher doses of DSP may improve the ability of the combined
test to distinguish PDH from AT. Currently, the combined test does not appear to offer more clinical utility than either
the ACTH stimulation or dexamethasone suppression test evaluated separately.
An ultra-high dose, 1.0 mg/kg, dexamethasone suppression test has been used to distinguish PDH from AT in the cat. Two cats
with hyperadrenocorticism diagnosed by the combined high dose dexamethasone suppression/ ACTH stimulation test had exaggerated
responses to ACTH with no cortisol suppression 2-4 hours after 0.1 mg/kg DSP. These cats did suppress following the ultra-high
dose of dexamethasone, and were later confirmed to have PDH. Cortisol levels should be monitored at several time points following
dexamethasone administration to determine if any suppression (a 50% or greater reduction in pre-test values) is occurring.
Cats with PDH may show suppression 2, 4, or 6 hours into the test only to escape from the suppressive effects of dexamethasone
by 8 hours. One cat with an adrenal adenoma failed to suppress following dexamethasone doses ranging from 0.1 to 1.0 mg/kg.
As is the case in dogs, suppression following high doses of dexamethasone is diagnostic for PDH, but failure to suppress requires
further testing to distinguish pituitary from adrenal disease.
Determination of plasma ACTH concentrations was performed in 10 cats. All nine cats with PDH exhibited elevations of plasma
ACTH. The normal range of plasma ACTH is lower in cats than in dogs, and many normal cats may have concentrations of ACTH
below the lower limits of the sensitivity of the assay. One cat with an adrenocortical adenoma had undetectable plasma ACTH
levels. Plasma ACTH samples need to be collected and handled carefully. Veterinarians should consult their diagnostic laboratory
for specific instructions prior to performing the test. Incorrect sample handling can falsely lower measured values. Normal
to elevated plasma ACTH levels support a diagnosis of PDH, whereas low concentrations may require additional diagnostic testing.
As in the differentiation of canine hyperadrenocorticism, ACTH levels should only be used to distinguish PDH from AT after
hyperadrenocorticism has been confirmed by other screening diagnostics.
Pituitary-adrenal function tests need to be interpreted in conjunction with historical, clinical, and clinicopathologic findings
before any conclusions can be drawn. No single diagnostic test is infallible. Equivocal results or discordant findings should
be reevaluated. Hyperadrenocorticism is an uncommon disorder in cats. Consequently, false positive test results should be
anticipated. Interpretation of endocrinologic testing should incorporate all available information before any therapeutic
intervention is attempted.
Diagnostic imaging can facilitate differentiation of PDH from AT when screening tests and clinical findings suggest hyperadrenocorticism.
Approximately half of canine adrenal tumors are mineralized and can be recognized radiographically. The frequency of mineralization
in feline adrenocortical tumors is unknown, but up to 30% of normal cats may have calcification of their adrenal glands.
Abdominal radiographic findings in cats with hyperadrenocorticism included hepatomegaly (69%; 11/16) and obesity. None of
the cats had evidence of adrenal calcification. Ultrasonographic evaluation of adrenal size and morphology has been described
for dogs and cats.39 Nonfunctional adrenal tumors can be incidental findings in humans undergoing abdominal imaging. The incidence of "silent"
adrenal masses in the cat is unknown. The presence of unilateral adrenomegaly or distortion of adrenal architecture in a
cat suspected of hyperadrenocorticism is strong evidence of AT. Abdominal computerized tomography (CT) and magnetic resonance
imaging (MRI) are available at several veterinary institutions, and may offer improved resolution for the detection of adrenal
tumors or hyperplasia. CT and MRI detection of pituitary masses is also now feasible for small animal patients.
Adrenal tumors accounted for 22% (6/27) of the reported cases of feline hyperadrenocorticism. Half of the adrenocortical tumors
were found histologically to be adenomas and half carcinomas. The treatment of choice for adrenal tumors is surgical adrenalectomy.
Two cats with adrenocortical adenomas responded well to unilateral adrenalectomy, with clinical signs resolving over 4 to
8 weeks. One cat with an adrenal adenoma removed surgically developed a recurrence of signs 12 months postoperatively. An
adenoma of the contralateral adrenal gland was diagnosed. The cat survived a second adrenalectomy and was disease-free for
over two years following the second procedure. Surgical therapy and longterm follow-up for adrenocortical carcinomas in cats
has not been reported.