Hyperadrenocorticism, commonly known as Cushing’s disease, is a frequently diagnosed endocrine disorder in dogs, characterized by excessive production or administration of glucocorticoids. As a serious health concern, accurate and timely Canine Hyperadrenocorticism Diagnosis is paramount for effective management and improving the quality of life for affected dogs. This article provides an in-depth look at the diagnosis of this condition, drawing upon expert veterinary knowledge to guide both pet owners and professionals.
Understanding the Etiology of Canine Hyperadrenocorticism
Hyperadrenocorticism in dogs can arise from two primary sources: spontaneous or iatrogenic. Iatrogenic hyperadrenocorticism is caused by the prolonged use of glucocorticoid medications. Spontaneous cases, however, are naturally occurring and further classified into two types based on their origin: pituitary-dependent and adrenal-dependent hyperadrenocorticism.
Pathophysiology: Pituitary vs. Adrenal Dependent Hyperadrenocorticism
Pituitary-Dependent Hyperadrenocorticism (PDH)
PDH accounts for the majority, over 80%, of naturally occurring hyperadrenocorticism cases in dogs. This form is triggered by the excessive secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland. This overproduction of ACTH leads to bilateral adrenocortical hyperplasia, causing the adrenal glands to enlarge and consequently produce excessive cortisol. The normal negative feedback loop of cortisol on ACTH secretion is disrupted, yet the episodic nature of ACTH release results in fluctuating cortisol levels, sometimes falling within the normal range, which can complicate canine hyperadrenocorticism diagnosis.
Pathologically, PDH is often associated with pituitary microadenomas (less than 1 cm in diameter) or macroadenomas (greater than 1 cm). Studies using immunocytochemical staining have identified pituitary adenomas in over 80% of dogs with PDH. Macroadenomas, while less common, can compress the pituitary gland and extend into the hypothalamus, though neurological signs are not always present due to their slow growth. Malignant pituitary tumors are rare.
Adrenal-Dependent Hyperadrenocorticism (ADH)
Adrenal-dependent hyperadrenocorticism represents 15–20% of spontaneous cases. ADH is caused by tumors in one or both adrenal glands. These tumors can be benign (adrenocortical adenomas) or malignant (adrenocortical carcinomas).
Adrenocortical adenomas are typically small, encapsulated, non-metastatic, and non-invasive. Approximately half of these are partially calcified. In contrast, adrenocortical carcinomas are usually larger, locally invasive, hemorrhagic, and necrotic. Calcification is also seen in about 50% of carcinomas. These malignant tumors can invade major blood vessels like the phrenicoabdominal vein and caudal vena cava and metastasize to organs such as the liver, lungs, and kidneys.
In dogs, adrenocortical adenomas and carcinomas occur with roughly equal frequency. The adrenal cortex surrounding the tumor and the contralateral adrenal gland often atrophy due to the functional tumor’s presence. This atrophy is clinically significant, especially if surgical removal of the tumor is considered, as the dog may experience glucocorticoid insufficiency post-operatively.
Recognizing Clinical Signs: Clues for Canine Hyperadrenocorticism Diagnosis
While any breed can develop hyperadrenocorticism, certain breeds such as Poodles, Dachshunds, and small terriers (Yorkshire, Jack Russell, Staffordshire Bull Terriers) show a higher predisposition to PDH. Larger breeds are more prone to adrenocortical tumors. Cats do not exhibit breed predispositions.
PDH typically affects middle-aged to older dogs, with a median age of 7–9 years and an age range of 2–16 years. Dogs with ADH tend to be slightly older, with a median age of 10–11 years and a range of 6–16 years. Sex distribution is generally equal for PDH, but female dogs are significantly more likely to develop adrenal tumors than males.
Hyperadrenocorticism usually develops insidiously, progressing slowly over months or years. Owners often mistake early signs for normal aging. Clinical signs can be intermittent or rapidly progressive.
Common clinical signs that should prompt consideration of canine hyperadrenocorticism diagnosis include:
- Polydipsia and Polyuria (PU/PD): Excessive drinking and urination are seen in almost all cases. Owners often notice increased thirst, nighttime urination (nocturia), and accidents in the house. The increased drinking is secondary to the increased urination.
- Increased Appetite (Polyphagia): A heightened appetite is common and may be perceived as good health by owners initially. However, a voracious appetite, food stealing, or scavenging can become concerning.
- Pendulous Abdomen: A pot-bellied appearance is very common, resulting from fat redistribution to the abdomen, liver enlargement (hepatomegaly), and abdominal muscle weakness. The onset is often gradual and may be overlooked.
An example of the characteristic pot-bellied appearance in a canine patient suffering from hyperadrenocorticism, highlighting abdominal distension and muscle weakness.
- Lethargy and Poor Exercise Tolerance: Reduced energy levels and reluctance to exercise are common, often attributed to aging. These signs are likely due to muscle wasting and weakness.
- Myotonia (Rare): Some dogs develop myotonia, characterized by prolonged muscle contractions after stimulation. This can cause a stiff, stilted gait, especially in the hind limbs.
- Skin Changes: The skin, particularly on the ventral abdomen, becomes thin and inelastic, sometimes leading to striae (stretch marks). Abdominal veins become prominent. Excessive scaling and comedones (blackheads) are common, especially around the nipples. Hyperpigmentation is less common in canine Cushing’s.
Visible skin lesions on a dog with Cushing’s disease, demonstrating thinning skin, prominent veins, and hyperpigmentation associated with the condition.
- Easy Bruising and Poor Wound Healing: Protein catabolism can lead to easy bruising and dehiscence (breakdown) of healing wounds, even old scars.
- Calcinosis Cutis: Calcium deposits in the skin are a frequent finding in biopsies, though clinical signs are less common. These appear as firm, white or cream plaques, often on the neck, axilla, ventral abdomen, and inguinal areas.
- Hair Coat Changes: Thinning hair, bilaterally symmetrical alopecia (hair loss), and a dull, dry coat are common. Hair loss typically affects the flanks, ventral abdomen, chest, perineum, and neck, sparing the head, feet, and tail until later stages. Coat color may lighten.
- Reproductive Changes: Intact female dogs may stop cycling (anoestrus). Male dogs may develop soft, flabby testicles.
- Neurological Signs (Less Common, but Serious): Large pituitary tumors can cause dullness, depression, loss of learned behaviors, anorexia, aimless wandering, head pressing, circling, ataxia, blindness, and seizures. Neurological signs can also emerge during initial treatment with trilostane or mitotane due to rapid tumor enlargement after cortisol feedback removal.
- Systemic Hypertension: High blood pressure is present in over 50% of untreated cases.
Laboratory Findings: Supporting Canine Hyperadrenocorticism Diagnosis
Routine laboratory tests can provide valuable supportive evidence for canine hyperadrenocorticism diagnosis.
- Hematology: A stress leukogram is common, characterized by lymphopenia (low lymphocytes), eosinopenia (low eosinophils), and sometimes neutrophilia (high neutrophils). Red blood cell and platelet counts may be elevated due to glucocorticoid effects on bone marrow.
- Serum Biochemistry:
- Elevated Alkaline Phosphatase (ALP): A significant increase in ALP (5–40 times normal) is one of the most reliable indicators, as glucocorticoids induce a specific hepatic isoenzyme of ALP in dogs.
- Elevated Alanine Aminotransferase (ALT): Mildly elevated ALT is common, likely due to liver damage from glycogen storage in swollen hepatocytes.
- Blood Glucose: Blood glucose is usually in the high normal range. About 10% of dogs develop overt diabetes mellitus due to glucocorticoid-induced insulin resistance.
- Blood Urea and Creatinine: Blood urea is often below normal due to increased urinary loss. Serum creatinine tends to be low to normal.
- Cholesterol and Triglycerides: Elevated cholesterol and triglyceride levels are common due to glucocorticoid-stimulated lipolysis. Cholesterol often exceeds 8 mmol/L.
- Urine Specific Gravity: Urine specific gravity is typically low (less than 1.015) and often hyposthenuric (<1.008), reflecting impaired urine concentrating ability.
- Basal Thyroxine: Decreased basal thyroxine levels are seen in about 70% of cases, though TSH stimulation response is usually normal, just at a lower baseline.
Diagnostic Imaging: Visualizing Clues for Canine Hyperadrenocorticism Diagnosis
Radiography and ultrasonography are useful imaging modalities in the diagnostic process.
Radiography
Thoracic and abdominal radiographs are recommended for suspected hyperadrenocorticism. While direct visualization of adrenal enlargement is uncommon, radiographic changes consistent with Cushing’s disease are helpful, and radiographs can reveal concurrent diseases.
- Hepatomegaly: Liver enlargement is the most consistent radiographic finding. Increased intra-abdominal fat enhances radiographic contrast, making abdominal structures easier to see. The pot-bellied appearance is often evident on lateral radiographs.
A canine radiograph displaying hepatomegaly, a common finding in dogs with hyperadrenocorticism, indicated by the enlarged liver shadow.
- Adrenal Enlargement: Less commonly seen, but gross enlargement suggests adrenocortical carcinoma. Unilateral adrenal mineralization also points towards an adrenal tumor.
- Calcinosis Cutis: Nodular mineralization pattern in the skin. Linear mineralization may be seen in fascial planes, like dorsal to the thoracolumbar spine. Mineralization can also occur in the renal pelvis, liver, gastric mucosa, and abdominal aorta.
- Distended Urinary Bladder: May be seen even after urination, consistent with PU/PD. Cystic calculi (bladder stones) may also be present, often with urinary tract infections.
- Osteopenia: Reduced radiographic density of lumbar vertebrae may be observed in some cases.
Ultrasonography
Abdominal ultrasonography is valuable for adrenal gland evaluation. Measuring adrenal gland thickness (ventrodorsal dimension) is more sensitive than length or width. A left adrenal gland thickness greater than 7.5 mm suggests adrenal hyperplasia. Symmetrical enlargement of both adrenal glands in a dog with hyperadrenocorticism suggests PDH.
Ultrasonography can also detect adrenal tumors. Masses are identified by location and clinical signs. Tumor invasion into adjacent vessels and tissues should be assessed. Mineralization in adrenal tumors can create acoustic shadowing, aiding localization.
CT and MR Imaging
Computed tomography (CT) and magnetic resonance (MR) imaging are more advanced and expensive techniques helpful for diagnosing adrenal tumors, adrenal hyperplasia, and large pituitary tumors, offering detailed visualization.
Endocrine Screening Tests: Confirming Canine Hyperadrenocorticism Diagnosis
Clinical signs, physical examination, routine lab tests, and imaging can suggest hyperadrenocorticism, but endocrine screening tests are essential for definitive canine hyperadrenocorticism diagnosis. The primary tests are the ACTH stimulation test and the low-dose dexamethasone suppression test (LDDST).
ACTH Stimulation Test
The ACTH stimulation test is a good screening test for differentiating spontaneous from iatrogenic hyperadrenocorticism and detects over 50% of ADH and about 85% of PDH cases. It directly assesses adrenal gland cortisol production. It’s also useful for monitoring trilostane and mitotane treatment.
However, it’s less reliable in differentiating PDH from ADH and is less sensitive but more specific than the LDDST. A normal ACTH response does not rule out hyperadrenocorticism if clinical signs are suggestive. Stress from other systemic diseases can also cause adrenal hyperplasia and abnormal ACTH responses.
Low-Dose Dexamethasone Suppression Test (LDDST)
The LDDST is more sensitive than the ACTH stimulation test for confirming hyperadrenocorticism, diagnosing nearly all ADH and 90–95% of PDH cases. However, it’s less useful for iatrogenic hyperadrenocorticism detection. It’s also influenced by more variables, takes 8 hours, and doesn’t provide pretreatment monitoring baselines like the ACTH test. Like the ACTH test, it’s not reliable for differentiating PDH from ADH.
Interpretation depends on the laboratory’s cortisol normal range for the dexamethasone used. Failure to suppress cortisol confirms hyperadrenocorticism. Intermediate samples (2–6 hours post-dexamethasone) can be helpful. Suppression below 40 mmol/L at 2–6 hours, followed by escape at 8 hours, suggests PDH. While some PDH cases won’t suppress at any point, any suppression during the 8-hour period largely rules out ADH.
Urine Cortisol:Creatinine Ratio
Evaluating the urine cortisol:creatinine ratio is a simple screening test, but it lacks specificity. Elevated ratios can indicate hyperadrenocorticism but can also be influenced by stress and other factors, making it less reliable for definitive canine hyperadrenocorticism diagnosis compared to ACTH stimulation or LDDST.
Conclusion: Achieving Accurate Canine Hyperadrenocorticism Diagnosis
Accurate canine hyperadrenocorticism diagnosis relies on a combination of recognizing clinical signs, interpreting laboratory findings, utilizing diagnostic imaging, and performing endocrine screening tests like the ACTH stimulation and low-dose dexamethasone suppression tests. While no single test is perfect, a comprehensive approach maximizes diagnostic accuracy, allowing for appropriate treatment strategies to be implemented. Early and precise diagnosis is crucial for managing Cushing’s disease effectively, improving the well-being and longevity of affected canine companions.
