Primary hyperaldosteronism in cats results from excessive, autonomous secretion of aldosterone, usually from an adrenocortical tumor. Common clinical signs are hypokalemia and systemic hypertension. Diagnosis is based on documentation of inappropriately high aldosterone concentrations and (when possible) low plasma renin activity with an adrenal tumor. Treatment includes surgical removal of the affected adrenal gland, medical management to correct hypertension and hypokalemia, and aldosterone antagonists.
Primary hyperaldosteronism is a disorder that results from the autonomous hypersecretion of aldosterone, independent of control by the renin-angiotensin-aldosterone system (RAAS). Typical signalment is middle-aged to older cats without reported breed or sex predilection.
Most recognized cases of primary hyperaldosteronism in cats are due to an adrenocortical tumor that secretes aldosterone (as well as other mineralocorticoids). These tumors can be benign or malignant. Some cases of feline primary hyperaldosteronism are not associated with adrenal tumors; however, histological assessment of the adrenal glands shows bilateral hyperplasia of the zona glomerulosa.
Clinical Findings of Feline Primary Hyperaldosteronism
Excessive concentrations of aldosterone result in loss of potassium and the development of hypokalemia. The retention of sodium and water leads to systemic hypertension that can be accompanied by hypernatremia.
Weakness and lethargy are the most common clinical signs reported in cats with primary hyperaldosteronism. Complications of severe hypokalemia include cervical ventroflexion or a plantigrade stance. Polyuria/polydipsia is also reported and can occur secondary to hypokalemia or concurrent chronic kidney disease (CKD). Cats with primary hyperaldosteronism can also have a history of GI signs.
Severe systemic hypertension can result in ocular changes such as retinal detachment or hemorrhage. Hypertension can be an incidental finding during a geriatric wellness examination; if an obvious cause is not apparent, primary hyperaldosteronism should be considered, even if serum potassium concentrations are within the reference range.
On routine laboratory evaluation, hypokalemia is the most common abnormality reported in cases of feline primary hyperaldosteronism. Because renal sodium retention is accompanied by water retention, laboratory sodium concentrations often remain within the reference interval. Because aldosterone promotes renal excretion of hydrogen ions, metabolic alkalosis can also be present. Increased creatine kinase activity is common and thought to occur because of hypokalemic myopathy.
Hyperaldosteronism is damaging to the kidneys, and affected cats can have concurrent CKD. Because CKD can also lead to systemic hypertension and hypokalemia, clinicians may fail to consider primary hyperaldosteronism as a differential diagnosis.
Some cats with primary hyperaldosteronism have tumors that secrete other corticosteroids. In such cases, other abnormalities, such as diabetes mellitus, may be present.
Diagnosis of Feline Primary Hyperaldosteronism
Diagnostic imaging
Aldosterone concentration, plasma renin activity, and aldosterone:renin ratio
Urine aldosterone:creatinine ratio
Imaging
Abdominal imaging (ultrasonography or CT) should be performed in any cat in which primary hyperaldosteronism is suspected. The disorder is most commonly associated with a unilateral adrenal mass; however, a small number of cats with bilateral tumors have been reported.
These adrenal tumors can have associated vascular invasion. Bilateral hyperplasia has been reported in some cats, which may not be easily detected on imaging.
Simply finding an adrenal mass is not sufficient to establish a diagnosis of primary hyperaldosteronism, because the lesion can be nonfunctional or secreting catecholamines, cortisol, or sex hormones.
Thoracic radiography should also be considered. This imaging technique can identify metastatic lesions or evidence of cardiomegaly.
Aldosterone Concentrations
High plasma aldosterone concentrations, particularly in combination with associated clinical signs, clinicopathological abnormalities, and an adrenal tumor, suggest primary hyperaldosteronism. However, documentation of a high plasma aldosterone concentration alone does not enable differentiation of primary hyperaldosteronism from secondary causes of hyperaldosteronism.
Aldosterone concentrations should be interpreted in light of concurrent potassium status because hypokalemia should suppress aldosterone release by the zona glomerulosa. In the face of hypokalemia, aldosterone concentrations within or above the reference range are homeostatically inappropriate and suggestive of primary hyperaldosteronism.
Plasma Renin Activity and Aldosterone:Renin Ratio
Documenting suppressed plasma renin activity along with high aldosterone concentrations (or a high aldosterone:renin ratio) confirms the autonomous secretion of aldosterone independent of renin activity, consistent with primary hyperaldosteronism. However, this assay is not consistently available for cats.
The aldosterone:renin ratio is usually very high in cats that have an adrenocortical tumor because renin release is totally inhibited. The ratio can be less dramatic in cats with nodular hyperplasia, in which some renin activity can be present.
If available, this test is widely regarded as the gold standard for establishing a diagnosis of primary hyperaldosteronism.
Urine Aldosterone:Creatinine Ratio
Measurement of the urine aldosterone:creatinine ratio has been proposed as a suitable screening test for primary hyperaldosteronism in cats. It is superior to simply measuring the aldosterone concentration in serum or plasma, because it reflects events over several hours and not at just one time point. However, the reference range is quite wide, and the test can lack sensitivity when used alone.
Suppression tests can be used to support the presence of autonomous aldosterone secretion. Administration of the mineralocorticoid fludrocortisone or the angiotensin receptor blocker telmisartan decreases aldosterone concentrations in healthy cats. Protocols for a fludrocortisone suppression test have been described that enable confirmation of primary hyperaldosteronism in some cases. A telmisartan suppression test has yet to be described that effectively identifies cats with primary hyperaldosteronism.
Treatment of Feline Primary Hyperaldosteronism
Adrenalectomy
Aldosterone antagonists
Supportive care and medical management to correct systemic hypertension and hypokalemia
In cases of primary hyperaldosteronism resulting from a unilateral adrenal tumor, surgical removal of the affected adrenal gland is the treatment of choice. Although this is an advanced procedure with considerable risk, cats without metastasis that survive to discharge have long survival times and typically die of comorbidities.
When surgery is not an option, medical management can be implemented with the aldosterone receptor blocker spironolactone (2 mg/kg, PO, every 12 hours, longterm).
In both circumstances, sequelae of hypokalemia and systemic hypertension must be treated medically. Severely hypokalemic cats need to be stabilized on an inpatient basis with potassium-supplemented IV fluids and subsequently transitioned to oral potassium. The treatment of choice for hypertension is amlodipine (0.625–1.25 mg/cat, PO, every 12–24 hours, longterm).
Most cats treated surgically for primary hyperaldosteronism require no medication over the long term. Cats treated medically with spironolactone can require concurrent treatment with oral potassium or amlodipine to maintain normokalemia and normotension, respectively.
Key Points
Primary hyperaldosteronism is likely underdiagnosed, especially in senior cats with azotemia.
Although hypertension and hypokalemia are the most common abnormalities, the absence of one of these abnormalities does not rule out the diagnosis.
Early diagnosis and intervention to lower or block the effects of aldosterone can result in decreased rates of morbidity and mortality from cardiovascular and renal disease.
For More Information
Laanen S, Galac S, Kooistra H. Primary hyperaldosteronism: expanding the diagnostic net. J Feline Med Surg. 2011;13(9):641-650. doi:10.1016/j.jfms.2011.07.017
Schulman RL. Feline primary hyperaldosteronism. Vet Clin North Am Small Anim Pract. 2010;40(2):353-359. doi:10.1016/j.cvsm.2009.10.006
