NAVLE Endocrine

Feline Hyperadrenocorticism Study Guide

📅 March 28, 2026 ⏱ 25 min read

Hyperadrenocorticism (HAC), also known as Cushing's syndrome or hypercortisolism, is a rare but clinically significant endocrinopathy in cats caused by chronic excessive cortisol production.

Overview and Clinical Importance

Hyperadrenocorticism (HAC), also known as Cushing's syndrome or hypercortisolism, is a rare but clinically significant endocrinopathy in cats caused by chronic excessive cortisol production. Unlike dogs where HAC is relatively common, feline HAC accounts for fewer than 200 cases reported in veterinary literature, making it an uncommonly tested but high-yield topic on the NAVLE.

The clinical importance of recognizing feline HAC lies in its unique presentation compared to canine HAC, the strong association with concurrent diabetes mellitus (80-90% of cases), and the distinctive clinical sign of extreme skin fragility that occurs in approximately one-third of affected cats. Failure to recognize this condition often leads to poor diabetic regulation and progressive deterioration.

High-YieldWhen you see an older cat with poorly controlled or insulin-resistant diabetes mellitus combined with dermatologic abnormalities (especially skin fragility), always consider hyperadrenocorticism as a differential diagnosis.

Type	Prevalence	Mechanism
Pituitary-Dependent HAC (PDH)	75-85% of cases	Pituitary adenoma (usually benign) secretes excess ACTH causing bilateral adrenal hyperplasia
Adrenal-Dependent HAC (ADH)	15-25% of cases	Functional adrenal tumor (50% adenoma, 50% carcinoma) autonomously secretes cortisol; contralateral gland atrophies
Iatrogenic HAC	Rare in cats	Chronic exogenous glucocorticoid administration; cats are relatively resistant compared to dogs

Etiology and Pathophysiology

Normal HPA Axis Function

The hypothalamic-pituitary-adrenal (HPA) axis regulates cortisol production through a cascade of hormonal signals. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH then acts on the zona fasciculata of the adrenal cortex to produce cortisol. Elevated cortisol levels normally suppress CRH and ACTH through negative feedback.

Classification of Feline HAC

High-YieldCats are relatively resistant to the adverse effects of chronic glucocorticoid therapy compared to dogs, making iatrogenic HAC much less common in feline patients.

Clinical Sign	Frequency	Notes
Concurrent Diabetes Mellitus	80-90%	Often insulin-resistant; may be initial presentation
Polyuria/Polydipsia	Greater than 75%	Usually secondary to DM; urine often still concentrated (greater than 1.020)
Polyphagia	Greater than 75%	Related to diabetes and cortisol effects
Skin Fragility	15-50%	PATHOGNOMONIC when present; thin papery skin tears easily with minimal handling
Abdominal Distension	50-70%	Pot-belly appearance from hepatomegaly, fat deposition, muscle wasting
Alopecia	34-83%	Bilaterally symmetrical; poor hair regrowth after clipping
Muscle Wasting	Common	Net weight loss common despite polyphagia
Curled Ear Tips	Variable	Unique to iatrogenic HAC in cats
Secondary Infections	Common	UTI, pyoderma, respiratory infections due to immunosuppression

Signalment and Clinical Signs

Signalment

Age: Middle-aged to older cats (mean age 10 years; range 4-17 years)
Sex: Female cats are affected more commonly (approximately 75% of cases)
Breed: No breed predisposition; domestic shorthair cats most frequently reported due to population prevalence

Clinical Signs

Clinical signs are typically present for several months before presentation. The presentation in cats differs notably from dogs, with dermatologic abnormalities and unregulated diabetes mellitus being the most common reasons for referral.

NAVLE TipSkin fragility (feline fragile skin syndrome) is pathognomonic for HAC in cats. When you see a cat with extremely thin skin that tears easily from routine handling or grooming, DO NOT scruff the cat and think HAC first. This sign is virtually never seen in canine HAC.

Test	Expected Findings in Feline HAC
CBC	Stress leukogram (only 50% of cases); lymphopenia, eosinopenia; anemia in 48% of cats
Serum Chemistry	Hyperglycemia (most common); ALP usually NORMAL (cats lack steroid-induced isoenzyme); hypercholesterolemia and hypertriglyceridemia possible
Urinalysis	Glucosuria; USG often greater than 1.020 (unlike dogs who typically have dilute urine); bacteriuria in 20% with UTI

Diagnosis

Diagnosis of feline HAC requires a combination of compatible clinical signs, routine laboratory findings, specific endocrine testing, and diagnostic imaging. No single test is definitive, and results must be interpreted in context of the clinical presentation.

Minimum Database Findings

High-YieldUnlike dogs, cats with HAC typically have NORMAL ALP levels because cats lack the steroid-induced isoenzyme of alkaline phosphatase. This is a key species difference for the NAVLE!

Endocrine Testing

Low-Dose Dexamethasone Suppression Test (LDDST) - Test of Choice

The LDDST is the preferred diagnostic test for feline HAC with sensitivity greater than 90%. CRITICAL: The feline pituitary is inherently more resistant to dexamethasone suppression, requiring a 10-fold higher dose (0.1 mg/kg IV) compared to dogs (0.01 mg/kg).

ACTH Stimulation Test - NOT Recommended for Diagnosis

The ACTH stimulation test has poor sensitivity (only 50-60%) for diagnosing HAC in cats and is NOT recommended as a screening test. Up to 60% of cats with HAC will have falsely negative results. However, it remains useful for:

Diagnosing iatrogenic HAC (diminished or absent cortisol response)
Monitoring response to trilostane therapy

Urine Cortisol:Creatinine Ratio (UCCR)

The UCCR is a useful screening test for HAC. Two morning urine samples should be collected at home on consecutive days to minimize stress-related false elevations. A normal UCCR essentially rules out HAC, but an elevated UCCR requires confirmation with LDDST.

NAVLE TipRemember the 10x rule for cats: Feline LDDST requires 0.1 mg/kg dexamethasone (10 times the canine dose). ACTH stimulation test is NOT recommended for diagnosis in cats due to poor sensitivity (only 50-60%).

Differentiation Testing: PDH vs ADH

LDDST Protocol - FELINE	Interpretation
Protocol: 1. Collect baseline serum cortisol 2. Administer 0.1 mg/kg dexamethasone IV 3. Collect serum at 4 and 8 hours post-injection	Normal: Cortisol suppressed to less than 1.4 mcg/dL at 4 and 8 hours HAC: Lack of suppression (cortisol greater than 1.4 mcg/dL) at 8 hours confirms diagnosis PDH pattern: Suppression at 4 hours with escape at 8 hours

Treatment

Treatment of feline HAC is challenging and the response to medical therapy is generally more variable than in dogs. The treatment choice depends on whether the condition is PDH or ADH, the presence of concurrent diseases, and the availability of surgical expertise.

Medical Management

Trilostane (Vetoryl) - First-Line Medical Therapy

Trilostane is a competitive inhibitor of 3-beta-hydroxysteroid dehydrogenase that blocks cortisol synthesis. It is currently the mainstay of medical therapy for feline HAC.

High-YieldClinical improvement (resolution of PU/PD, improved appetite, weight gain, improved skin) is more important than strict cortisol monitoring in cats on trilostane therapy. Diabetic cats may require less insulin - monitor blood glucose closely.

Other Medical Options

Mitotane (Lysodren): Less effective than trilostane; similar toxicity concerns as in dogs; reserved for trilostane failures
Ketoconazole: NOT effective in cats - does not suppress cortisol adequately and may be hepatotoxic at required doses
Metyrapone: Used in a limited number of cases; difficult to source

Surgical Treatment

Adrenalectomy

Unilateral adrenalectomy: Treatment of choice for ADH; potentially curative if complete excision of benign tumor
Bilateral adrenalectomy: Option for PDH; requires lifelong glucocorticoid and mineralocorticoid supplementation
Considerations: High complication rate due to poor wound healing and skin fragility; pre-operative trilostane therapy recommended to improve surgical candidacy

Hypophysectomy

Transsphenoidal hypophysectomy is potentially curative for PDH but is only available at specialized centers with skilled surgeons. Post-operative management includes hormone replacement therapy for multiple pituitary hormones.

Radiation Therapy

Radiation therapy may be beneficial for cats with PDH, particularly those with neurologic signs from pituitary macroadenomas. It may improve clinical signs and potentially extend survival, but availability is limited.

Treatment of Iatrogenic HAC

Treatment involves gradual tapering of exogenous glucocorticoids over weeks to months to allow recovery of the suppressed HPA axis. Abrupt discontinuation can result in an Addisonian crisis.

Treatment Summary Table

Test	PDH	ADH
Abdominal Ultrasound	Bilateral adrenomegaly (width greater than 6 mm); both glands enlarged equally	Unilateral adrenal mass or enlargement; contralateral gland small or atrophied
Endogenous ACTH	Normal to elevated	Low to undetectable (suppressed by autonomous cortisol)
HDDST (1.0 mg/kg)	Suppression to less than 50% of baseline (40-50% of PDH cats)	No suppression
CT/MRI of Brain	Pituitary mass visible in approximately 50% (macroadenomas)	Normal pituitary

Prognosis

The prognosis for cats with untreated HAC is poor. Cats typically suffer from progressive weakness, severe infections, uncontrolled diabetes, and complications from skin fragility. With treatment, prognosis is variable but many cats can achieve good quality of life.

Trilostane therapy: Median survival 617 days; improved quality of life in 13/15 cats in one study
Unilateral adrenalectomy for ADH: Best prognosis if complete excision of benign adenoma; clinical signs resolve in 2-4 months
Overall survival: Reported survival times range from less than 2 months to greater than 63 months depending on treatment and disease severity
Diabetes resolution: Approximately 50% of diabetic cats may have improved insulin requirements or remission after successful HAC treatment

High-YieldThe response of feline HAC to medical therapy is generally inferior compared to canine HAC. Adrenalectomy and hypophysectomy are the only potentially curative options, but appropriate patient selection is essential.

Parameter	Details
Starting Dose	1-2 mg/kg PO q12-24h with food (typically given BID-TID); may require doses up to 2-3 mg/kg/day
Initial Monitoring	Recheck 7-14 days after starting; CBC, chemistry, urinalysis; clinical assessment most important
Ongoing Monitoring	Every 3-4 months; ACTH stimulation or UCCR can monitor for hypocortisolism
Treatment Goals	Control of clinical signs (improved weight, decreased PU/PD, improved skin); strict cortisol monitoring may not be critical
Median Survival	617 days (range 80-1,278 days) in one study of 15 cats

Memory Aids

FELINE HAC = "F.R.A.G.I.L.E"

F - Female predisposition (75%)
R - Rare disease (only 180+ cases reported)
A - ALP is NORMAL (no steroid-induced isoenzyme)
G - Glucose elevated (80-90% have concurrent DM)
I - Insulin resistant diabetes
L - LDDST is test of choice (use 10x dose: 0.1 mg/kg)
E - Extreme skin fragility (pathognomonic sign)

10x Rule for Cats

Feline LDDST requires 10 times the canine dose (0.1 mg/kg vs 0.01 mg/kg) because cats are 10x more resistant to dexamethasone suppression.

PDH vs ADH Ultrasound Finding

PDH = "Parallel" - Both adrenals enlarged equally (bilateral)

ADH = "Asymmetric" - One big, one small (tumor suppresses contralateral gland)

Treatment	Indication	Advantages	Disadvantages
Trilostane	PDH or ADH	Non-invasive; reversible; can improve DM control	Lifelong therapy; not curative; variable response
Unilateral Adrenalectomy	ADH	Potentially curative; long survival if benign	Major surgery; high complications; requires specialist
Bilateral Adrenalectomy	PDH	Eliminates cortisol excess	Lifelong hormone replacement; high surgical risk
Hypophysectomy	PDH	Potentially curative	Highly specialized; limited availability; panhypopituitarism
Radiation Therapy	PDH with neurologic signs	Non-invasive; may reduce tumor size	Limited availability; delayed response; not curative

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