Canine Hyperadrenocorticism

Canine hyperadrenocorticism is a common endocrine disorder caused by chronic excess cortisol production, most often due to a pituitary adenoma (PDH) or an adrenal tumor (AT). Clinical signs are progressive and include polyuria, polydipsia, polyphagia, abdominal distension, muscle weakness, and dermatologic changes such as alopecia and thin skin. Diagnosis requires integration of clinical findings with screening tests like the low-dose dexamethasone suppression test (LDDS), ACTH stimulation test, and abdominal ultrasound.

Canine hyperadrenocorticism (HAC), commonly known as Cushing's syndrome, is an endocrine disorder characterized by chronic excessive production of cortisol. It is one of the most frequently diagnosed endocrinopathies in middle-aged to older dogs.

Etiology:

HAC can be classified into three primary forms:

Pituitary-Dependent Hyperadrenocorticism (PDH): Accounts for approximately 80-85% of cases. It results from a functional adenoma in the pituitary gland, leading to excessive secretion of adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal glands to overproduce cortisol.
Adrenal-Dependent Hyperadrenocorticism (ADH): Comprises about 15-20% of cases. Caused by a cortisol-secreting adrenal tumor, which can be either benign (adenoma) or malignant (carcinoma).
Iatrogenic Hyperadrenocorticism: Results from prolonged or excessive administration of exogenous glucocorticoids.

Clinical Presentation:

Dogs with HAC often present with a combination of the following clinical signs:

Polydipsia and Polyuria: Increased thirst and urination are among the most common signs.
Polyphagia: Elevated appetite is frequently observed.
Abdominal Enlargement ("Pot-bellied" Appearance): Due to redistribution of fat, hepatomegaly, and weakening of abdominal muscles.
Dermatologic Changes: Symmetrical alopecia, thin skin, hyperpigmentation, comedones, and calcinosis cutis.
Muscle Weakness and Lethargy: Resulting from protein catabolism.
Panting: Often noted due to increased abdominal fat and muscle weakness.

Signalment:

HAC typically affects middle-aged to older dogs, with a higher prevalence in certain breeds such as Poodles, Dachshunds, Boxers, and Terriers. There is no significant sex predilection.

Pathophysiology:

In PDH, a pituitary adenoma secretes excessive ACTH, leading to bilateral adrenal hyperplasia and increased cortisol production. In ADH, an adrenal tumor autonomously secretes cortisol, suppressing ACTH production and causing atrophy of the contralateral adrenal gland. Iatrogenic HAC results from exogenous glucocorticoid administration, leading to suppression of the hypothalamic-pituitary-adrenal axis and adrenal atrophy.

Laboratory Findings:

Complete Blood Count (CBC): May reveal stress leukogram characterized by neutrophilia, lymphopenia, eosinopenia, and monocytosis.
Serum Biochemistry:
- Elevated Alkaline Phosphatase (ALP): Commonly increased due to steroid-induced isoenzyme.
- Hypercholesterolemia: Frequently observed.
- Mild Hyperglycemia: May be present.
Urinalysis:
- Low Urine Specific Gravity: Due to impaired renal concentrating ability.
- Proteinuria: May be detected.

Diagnostic Imaging:

Abdominal Ultrasound: Useful for assessing adrenal gland size and morphology. In PDH, bilateral adrenal enlargement is typical, whereas in ADH, unilateral enlargement with contralateral atrophy is expected.
Thoracic Radiographs: May be indicated to evaluate for metastasis in cases of suspected adrenal carcinoma.

Differential Diagnoses:

Diabetes mellitus
Hypothyroidism
Chronic renal failure
Liver disease
Primary skin disorders

Confirmatory Diagnostic Tests:

Low-Dose Dexamethasone Suppression Test (LDDST): Considered the test of choice for diagnosing HAC. Involves measuring baseline cortisol, followed by administration of dexamethasone, and subsequent cortisol measurements at 4 and 8 hours. Lack of suppression indicates HAC.
ACTH Stimulation Test: Involves measuring baseline cortisol, administering synthetic ACTH, and measuring cortisol levels post-stimulation. Exaggerated response suggests HAC.
Endogenous ACTH Measurement: Helps differentiate between PDH (elevated or normal ACTH) and ADH (low ACTH).

Treatment:

Medical Management:
- Trilostane: A competitive inhibitor of 3β-hydroxysteroid dehydrogenase, reducing cortisol synthesis. Initial dosing typically starts at 2-3 mg/kg orally every 12 to 24 hours, with adjustments based on clinical response and monitoring.
- Mitotane (o,p'-DDD): An adrenocorticolytic agent that selectively destroys cortisol-producing cells. Induction phase involves daily dosing until clinical signs abate, followed by a maintenance dose.
Surgical Management:
- Adrenalectomy: Indicated for unilateral adrenal tumors. Requires careful perioperative management due to potential for adrenal insufficiency postoperatively.

Monitoring and Follow-Up:

Regular monitoring is essential to ensure therapeutic efficacy and to detect potential adverse effects. This includes periodic clinical evaluations, laboratory testing, and imaging as indicated.

Clinical Monitoring: Owners should observe and report any changes in their dog's behavior, appetite, water consumption, and urination patterns. Signs such as lethargy, vomiting, diarrhea, or anorexia may indicate adverse effects or complications.
Laboratory Monitoring: Regular assessment of serum electrolytes, liver enzymes, blood urea nitrogen (BUN), and creatinine is recommended. Monitoring adrenal function through ACTH stimulation tests or measuring pre- and post-pill cortisol levels can guide dose adjustments.

Anesthetic Management:

Dogs with HAC may have increased anesthetic risks due to comorbidities such as hypertension, diabetes mellitus, and poor wound healing. Pre-anesthetic evaluation should include blood pressure measurement, blood glucose assessment, and a thorough cardiovascular examination. Perioperative management may require adjustments in medication, fluid therapy, and vigilant monitoring to mitigate potential complications.

Nutritional Management:

While no specific diet is universally recommended for dogs with HAC, addressing individual nutritional needs is important. Obesity management through caloric restriction and a balanced diet can help mitigate muscle wasting and support overall health. Monitoring and managing comorbid conditions, such as diabetes mellitus, may necessitate specific dietary modifications.

Hospital Management:

In cases requiring hospitalization, such as for surgical intervention or management of complications, maintaining a low-stress environment is beneficial. Strict aseptic techniques are crucial due to the increased susceptibility to infections. Pain management, appropriate wound care, and monitoring for signs of thromboembolism or other complications are essential components of inpatient care.

Prognosis:

The prognosis for dogs with HAC varies depending on the underlying cause and response to treatment.

Pituitary-Dependent HAC: With appropriate medical management, the median survival time is approximately 2 to 2.5 years. Advanced treatments, such as hypophysectomy or radiation therapy, may offer extended survival times of up to 2 to 5 years.
Adrenal-Dependent HAC: Surgical removal of adrenal tumors can result in a median survival time of 1.5 to 4 years, depending on tumor type and presence of metastasis. Medical management alone typically offers a median survival time of around 1 year.

Further Reading:

Feldman, E. C., & Nelson, R. W. (2014). Canine and Feline Endocrinology (4th ed.). Saunders.
Peterson, M. E., & Kintzer, P. P. (1995). Medical treatment of pituitary-dependent hyperadrenocorticism (Cushing's disease) in dogs. Journal of the American Veterinary Medical Association, 206(11), 1700-1706.
Behrend, E. N., Kooistra, H. S., Nelson, R., Reusch, C. E., & Scott-Moncrieff, J. C. (2013). Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal). Journal of Veterinary Internal Medicine, 27(6), 1292-1304.