Cushing’s Disease in Pets: Understanding Hyperadrenocorticism

Introduction

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Figure 1. The pituitary gland is often called the body's "master gland": beyond ACTH, it releases hormones that regulate growth, the thyroid, reproduction, water balance, and more. Cushing's disease arises when just one of these signals — ACTH, aimed at the adrenal cortex — becomes chronically overactive, while the gland's many other roles continue as normal (Merck Veterinary Manual).

As our cherished pets enter their senior years, it is common to attribute changes such as decreased activity, increased thirst, or alterations in body shape to the natural ageing process. However, these seemingly innocuous signs and subtle changes can sometimes indicate a more serious underlying condition known as hyperadrenocorticism, commonly referred to as Cushing’s disease. This intricate endocrine disorder primarily affects middle-aged and senior dogs, though it can also occur in cats, albeit less frequently (AAHA Selected Endocrinopathies Guidelines, 2023). Recognising the pathophysiology of Cushing’s disease, identifying its symptoms early, and staying updated on contemporary diagnostic protocols can significantly enhance your pet's quality of life. If you have already read our companion article on Addison's disease, this condition will feel like its mirror image. Where Addison's disease (hypoadrenocorticism) is caused by too little cortisol, Cushing's disease is caused by too much—and the two conditions can even trade places in the same patient during treatment, which is one reason your veterinary team monitors so closely once therapy begins. This article walks through the anatomy involved, why the disease develops, how it is recognised and confirmed, and how it is managed long-term. Understanding the underlying mechanics of this condition, recognising its classic clinical symptoms, and staying informed about the latest diagnostic protocol updates can drastically improve a patient's quality of life.

What is Cushing’s Disease?

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Cushing’s disease, or Hyperadrenocorticism, is a common endocrine disorder characterised by the chronic overproduction of cortisol, a crucial steroid hormone responsible for stress management, weight regulation, blood sugar control, and immune function. When the body is flooded with too much cortisol over an extended period, it disrupts multiple metabolic pathways, leading to a range of health issues (García San José et al., 2025). Cushing's disease is one of the most common hormonal disorders diagnosed in older dogs, primarily affects middle-aged and senior dogs, and — although far less frequent — it can also affect cats, often manifesting as insulin-resistant diabetes mellitus.

Pathophysiology

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Naturally occurring Cushing's syndrome is a multi-systemic disease that stems from a chronic disruption of the hypothalamic-pituitary-adrenal axis. According to the American Animal Hospital Association (AAHA) Selected Endocrinopathies Guidelines, Cushing's Syndrome is classified into two primary types:

• Pituitary-Dependent Hyperadrenocorticism (PDH): This form accounts for approximately 80% to 85% of cases and is triggered by a benign tumour on the pituitary gland at the base of the brain. The tumour prompts the gland to release excessive and inappropriate amounts of adrenocorticotropic hormone (ACTH), causing bilateral adrenal hyperplasia and subsequent cortisol overproduction by the adrenal glands.

  
  

• Adrenal-Dependent Hyperadrenocorticism (ADH): This type represents the remaining 15% of cases and arises from a tumour located directly on one or both adrenal glands, located near the kidneys (AAHA Selected Endocrinopathies Guidelines, 2023).

  
  

• A third form, known as iatrogenic Cushing’s disease, may occur as a result of an adverse effect of long-term, high-dose corticosteroid treatment for chronic conditions like severe allergies or autoimmune disorders or diseases.

Clinical Presentation

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The signs of Cushing's disease develop gradually, leading pet owners to misinterpret early symptoms as normal ageing. The most notable clinical features include:

• Polyuria and Polydipsia (Increased Urination and Thirst): Pets will drink excessively (excessive thirst) and require frequent trips outside (frequent urination) or begin having accidents indoors.

• Polyphagia (Ravenous Appetite): Your pet may show a sudden, insatiable hunger, leading to food stealing or begging.

• The "Pot-Bellied" Appearance: A combination of muscle weakness, fat redistribution to the abdomen, and an enlarged liver (hepatomegaly) causes the stomach to take on a distended, sagging shape (distended belly) – the hallmark "pot-belly".

• Dermatological Issues: Hair loss (often symmetrical along the flanks), thinning skin that bruises easily, and recurrent skin infections are highly common.

The physiological impact of chronic hypercortisolism, therefore, translates into progressive clinical signs often referred to as the "five big P's": polyuria (increased urination), polydipsia (increased thirst), polyphagia (increased appetite), panting, and a classic pot-bellied appearance.

In cats, the presentation is often subtler and dominated by concurrent, hard-to-control diabetes mellitus and, in advanced cases, unusually fragile skin that can tear during routine handling (AAHA, 2023a).

The Diagnostic Challenge

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Diagnosing Cushing’s disease is rarely straightforward. It is complex because its symptoms overlap with other conditions like diabetes or standard liver disease. Veterinarians often rely on a battery of blood, urine, and imaging tests.

However, recent studies have highlighted the need for improved diagnostic protocols to avoid errors. A milestone study published in the Journal of Veterinary Internal Medicine by Carvalho et al. (2025) highlighted a critical issue in primary veterinary care. The researchers found that up to 60% of primary care veterinarians surveyed performed screening tests on dogs lacking distinct clinical signs of Cushing's, heavily increasing the risk of false-positive diagnoses. This underscores the veterinary consensus that testing should only occur when clear physical or historical symptoms match the profile of the disease.

Current diagnostic protocols include:

• Low-Dose Dexamethasone Suppression Test (LDDST): Highly sensitive (85–100%) and often preferred by general practitioners to differentiate between PDH and ADH (AAHA, 2023a; Carvalho et al., 2025).

  
  

• ACTH Stimulation Test: Highly specific but less sensitive (57–61%), meaning it may yield negative results in dogs that actually have the disease (AAHA, 2023a)

The LDDST boasts high sensitivity (85% to 100%) and can help differentiate between PDH and ADH, while the ACTH stimulation test provides higher specificity but lower sensitivity (57% to 61%), occasionally yielding false negatives. Consequently, the consensus remains that testing should never be initiated based on isolated laboratory abnormalities alone; clear clinical symptoms must be present.

• Machine Learning Models: Emerging research (2025–2026) has introduced machine learning (ML) models to veterinary endocrinology. Advanced boosted tree algorithms (such as gradient boosting and AdaBoost) have been trained on routinely collected complete blood counts, biochemistry panels, and urinalysis datasets to diagnose Cushing's with up to 88.5% accuracy, offering general practitioners a powerful, non-invasive screening tool to support clinical decision-making (Ramón et al., 2026; see also).

Innovations in Treatment and Survival Outcomes

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While surgery, surgical adrenalectomy, is an option for certain adrenal tumours, the vast majority of pets are managed medically. Medical management remains the most common approach for PDH, and for decades, veterinarians have balanced the use of different pharmaceuticals to suppress cortisol production. Today, trilostane is the only FDA-approved medication for both PDH and ADH in dogs.

• Trilostane (Vetoryl®): The only FDA-approved medical treatment for both PDH and ADH in dogs, working via the competitive inhibition of the 3β-hydroxysteroid dehydrogenase enzyme system. Recent systematic reviews (2025) suggest trilostane offers an 11% higher survival rate at 36 months compared to the older drug mitotane (AAHA, 2023a; Carvalho et al., 2025).

• Dosing Strategies: Many experts now favour twice-daily, low-dose therapy (starting at ~1 mg/kg) to effectively control signs while minimising life-threatening side effects like acute adrenal necrosis (AAHA, 2023a; Carvalho et al., 2025).

• Survival Times: The median survival time for medically managed pets ranges from 22 to 36 months, though those diagnosed younger without comorbidities can live significantly longer (AAHA, 2023a; Carvalho et al., 2025).

Current dosing protocols have shifted away from aggressive regimens toward twice-daily, lower-dose therapies (typically starting around 0.5 to 1 mg/kg). This approach achieves more stable clinical control while minimising the risk of severe side effects, such as acute adrenal necrosis or iatrogenic hypoadrenocorticism.

Furthermore, translational oncology and cross-species comparative analyses continue to look forward, exploring deep molecular similarities between canine and human Cushing’s disease. These evolutionary bridges allow researchers to test novel cellular targets, paving the way for even safer precision therapies in the future (Cushing’s Disease in the Animal Kingdom, 2025).

Partnering With Your Vet

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While a Cushing's diagnosis can feel overwhelming, it is highly manageable. Medical management requires diligent routine blood monitoring to ensure your pet is receiving the correct dosage without accidentally crashing their cortisol levels too low. With early intervention, a tailored treatment plan, and consistent veterinary follow-ups, your companion can comfortably enjoy their golden years with energy and vitality.

References

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AAHA Selected Endocrinopathies Guidelines. (2023). 2023 AAHA selected endocrinopathies of dogs and cats guidelines. American Animal Hospital Association. aaha.org

Carvalho, S., García San José, P., & Martínez, M. (2025). Diagnostic testing patterns for canine hyperadrenocorticism in primary care veterinary practices. Journal of Veterinary Internal Medicine, 39(1), e17166. doi.org

Cushing’s Disease in the Animal Kingdom. (2025). Translational insights for pituitary oncology and central hypothyroidism in comparative models. International Journal of Molecular Sciences, 26(17), 8626. doi.org

García San José, P., Ramón, J., & Overend, F. (2025). Effectiveness of medical treatment on survivability in canine Cushing’s syndrome: A systematic review and meta-analysis. Veterinary Quarterly, 45(1), 2954–2965. doi.org

García San José, P., Overend, F., & Carvalho, S. (2026). Treatment and monitoring of naturally occurring Cushing’s syndrome by primary care veterinarians: A multicenter survey. Docta Complutense Research Repository, Article 3fa7daad. ucm.es

Marçal, R., Silva, T., & Santos, A. (2025). A retrospective cohort study of 122 dogs treated for hypercortisolism: Low-dose dexamethasone suppression test sensitivity and comparative outcomes in response to mitotane or trilostane. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 77(4), 101–112. doi.org

Ramón, J., Martínez, M., & Silva, T. (2026). Machine learning-assisted screening for canine Cushing’s syndrome using routine hematological and biochemical panels. Veterinary Quarterly, 46(1), 2604–2615. doi.org