Managing the Highs & Lows of Adrenal Disease

Sponsored by Dechra

The adrenal gland is an endocrine organ that plays multiple roles in normal body function, including secretion of mineralocorticoids, glucocorticoids, and sex hormones.¹ In dogs, diseases of the adrenal gland primarily include Cushing’s syndrome, which results from an overproduction of cortisol, and Addison’s disease, which results from decreased production of adrenal hormones.¹ Understanding the pathophysiology, diagnosis, treatment, and monitoring of these diseases can help practitioners be prepared to manage adrenal disease in dogs.

Adrenal Highs: Cushing’s Syndrome

Cushing’s syndrome (ie, hyperadrenocorticism) is caused by an overproduction of cortisol by the adrenal glands. This can occur naturally or be iatrogenic due to excess steroid administration.² In cases of naturally occurring Cushing’s syndrome, 80% to 85% of cases are considered pituitary-dependent (PDH).² Excess secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland leads to hyperplasia of the adrenal glands and excessive cortisol production. Less commonly (15%-20% of cases), a primary adrenal tumor causes adrenal-dependent hyperadrenocorticism (ADH).²

Diagnosis

Testing for Cushing’s syndrome should only be pursued in the presence of compatible clinical signs.^2-4 The most common clinical signs include polyuria and polydipsia (PU/PD), polyphagia, panting, pot-bellied appearance, endocrine alopecia, hepatomegaly, muscle weakness, and systemic hypertension.^2,4 The more clinical signs that are present, the stronger the indication to pursue testing.⁴

A low-dose dexamethasone suppression (LDDS) test is the test of choice in the absence of concurrent disease.^2,4 The sensitivity of the LDDS test for naturally occurring Cushing’s syndrome is between 85% and 100%, which is superior to the ACTH stimulation test, which has a sensitivity between 57% and 95%.⁴ Ideally, testing should be postponed until concurrent disease such as pancreatitis has resolved.

Distinguishing PDH from ADH is important for accurate prognostication and treatment selection; differentiation tests include LDDS and high-dose dexamethasone suppression testing, endogenous ACTH determination, ultrasonography, and advanced imaging.²

Treatment

The goal of treatment is control of clinical signs, which can greatly impact quality of life for both the pet and owner.^2,4 Vetoryl® Capsules are the only FDA-approved treatment for both PDH and ADH.² The active ingredient, trilostane, is a reversible inhibitor of 3β-hydroxysteroid dehydrogenase, an enzyme involved in steroid synthesis.² Although Vetoryl is generally given once daily, some patients (25%) may require twice-daily dosing.²

Monitoring

Pet owners are an essential part of monitoring during treatment, both to evaluate for adverse effects and monitor clinical signs. Dechra provides a client form that can be used for patient monitoring at each follow-up visit.⁵ Blood work should also be performed to monitor cortisol levels, electrolytes, and organ function. The manufacturer recommends ACTH stimulation tests be performed 4 to 6 hours after pill administration and used for monitoring.^2,3

If the patient is doing clinically well, the first recheck should be performed 10 to 14 days after starting medication and after any dosage adjustment.^2,3 Additional rechecks should be performed at 30- and 90-days and continue every 3 months for the remainder of the patient’s life.

Adrenal Lows: Addison’s Disease

Primary hypoadrenocorticism occurs most commonly due to immune-mediated destruction of all layers of the adrenal cortex, resulting in mineralocorticoid and glucocorticoid deficiencies.^1,6 The lack of these hormones results in an inability to regulate electrolytes and respond appropriately to stress and maintain homeostasis.^1,6,7

Approximately 10% of Addisonian patients will be presented with glucocorticoid deficiency only.^1,7 This is called atypical hypoadrenocorticism and usually progresses to classic primary hypoadrenocorticism with time.^1,7

Clinical Signs & Diagnosis

The clinical presentation of Addison’s disease varies, with some patients presenting with waxing and waning signs that may include inappetence, lethargy, vomiting, diarrhea, and weight loss.^1,6 Addison’s can become life-threatening, and some Addisonian patients may be presented emergently in hypovolemic shock.¹

Ninety-five percent of traditional Addisonian patients will have hallmark electrolyte abnormalities at the time of diagnosis: hyponatremia and hyperkalemia with a Na:K ratio <27.¹ These electrolyte changes are not seen initially in patients presented with atypical Addison’s, as their mineralocorticoid levels are normal.¹ Checking a resting cortisol level can be an effective screening tool for Addison’s,⁶ with a resting cortisol of ≥2 µg/dL making hypoadrenocorticism unlikely. The ACTH stimulation test is the gold standard for diagnosis.^6,7 The adrenal gland is unable to respond to ACTH stimulation, meaning cortisol levels will be low before and after administration of cosyntropin, a synthetic ACTH.⁷

Treatment

Long-term therapy requires replacement of both mineralocorticoids and glucocorticoids. Ideally, different medications should be used to provide hormone replacements, as this allows more precise dosing for each.⁶

Glucocorticoids are replaced with physiologic dosages of oral prednisone (0.2-0.4 mg/kg/day).⁶ Dosages should be increased in times of stress, with the standard recommendation being to double the dose.^6,8 For patients presented with atypical Addison’s, only glucocorticoid replacement therapy is needed initially.

Desoxycorticosterone pivalate (DOCP) is used for replacement of mineralocorticoids.^6,7 DOCP mimics the actions of aldosterone, the body’s most common natural mineralocorticoid, in the kidney. It restores electrolyte and fluid balances in the body.^6,7 Zycortal® Suspension (DOCP) is FDA-approved for subcutaneous injection at a starting dose of 2.2 mg/kg.⁶

Monitoring

The dose and frequency of Zycortal injections are titrated based on clinical signs and electrolyte monitoring.^6,7 A recheck should be performed 10 days after injection and include an electrolyte check. If clinical signs are not improved at that time, the prednisone dose should be increased and/or other causes of the clinical signs investigated. At day 25 postinjection, a second recheck, including physical examination and electrolyte evaluation, should be performed and the next dose of Zycortal® administered.⁶ If the patient is clinically normal at this recheck, the Na:K ratio from day 10 should be used to determine if the Zycortal dose needs to be increased (a Na:K ratio <27 at day 10) or decreased (a Na:K ratio >32 at day 10) in 0.1-0.2 mg/kg increments.⁶ For some patients, the interval between doses can be extended instead of decreasing the total dose.⁶ All adjustments should be based on monitoring of patient clinical signs and electrolyte values.