Hyperaldosteronism is defined by an elevated plasma aldosterone concentration, exceeding the upper limit of the reference range, or in the case of primary hyperaldosteronism an increased ratio of plasma aldosterone to plasma renin activity.
Aldosterone is normally secreted by the zona glomerulosa of the adrenal gland in response to stimulation of the renin-angiotensin-aldosterone system.
Aldosterone has effects on mineralocorticoid receptors in the distal renal tubules, colon and salivary glands to stimulate sodium re-absorption, and potassium and hydrogen excretion.
Hyperaldosteronism can be primary or secondary.
Primary hyperaldosteronism is characterized by elevated plasma aldosterone in the face of suppressed plasma renin activity, and occurs as the result of an aldosterone secreting adrenal tumor or adrenal hyperplasia.
Secondary hyperaldosteronism describes an increase in aldosterone production, occurring as a normal response to activation of the renin-angiotensio-aldosterone system, such as occurs with congestive heart failure , severe hepatic dysfunction and renal failure .
In primary hyperaldosteronism there is dissociation of the renin-angiotensin-aldosterone system. Increased aldosterone secretion occurs autonomous of the renin-angiotension-aldosterone system, with loss of negative feedback.
Increased aldosterone causes retention of sodium, and excretion of potassium.
Retention of sodium results in expansion of extracellular fluid volume, leading to hypertension.
Excretion of potassium results in hypokalemic polymyopathy.
Ocular signs: hyphema, blindness resulting from hypertension.
Client history
Presenting problems may be severe and acute in onset or mild and intermittent.
Clinical signs
Muscle weakness.
Hypertension.
Blindness.
Hyphema.
Diagnostic investigation
Blood pressure measurement - may be hypertensive with systolic blood pressure >180 mmHg.
Ocular examination - may be hyphema, retinal/subretinal hemorrhage , hypertensive retinopathy, retinal detachment .
Serum biochemistry - expect hypokalemia and elevated creatine kinase if presenting signs include muscle weakness. Less commonly hypernatremia may be present but usually mild. May be elevated BUN /creatinine particularly in cases of bilateral adrenal hyperplasia.
Measurement of plasma aldosterone concentration - usually severely elevated, can be within normal range in early stages of bilateral adrenal hyperplasia.
Measurement of plasma renin activity (if available) - expected to be low or normal in primary hyperaldosteronism, high in secondary hyperaldosteronism. Determination of ratio of plasma aldosterone to plasma renin activity may be useful - expected to be elevated in cases of primary hyperaldosteronism.
Abdominal ultrasound - may demonstrate unilateral adrenal mass. May be normal in cases of bilateral adrenal hyperplasia.
Exclude causes of secondary hyperaldosteronism - thoracic radiographs, determination of serum liver enzymes and dynamic bile acids, serum BUN/creatinine and urine specific gravity.
Definitive Diagnostic features
Elevated plasma aldosterone concentration in combination with low plasma renin activity.
Elevated ratio of plasma aldosterone to plasma renin activity.
+/- identification of an adrenal mass in combination with either of the above.
The above features are the gold standard for a definitive diagnosis, however a feline validated assay for plasma renin activity is not currently commercially available in the UK. Acceptable for a definitive diagnosis of primary hyperaldosteronism as a result of an adrenal tumor is demonstration of elevated plasma aldosterone concentration in combination with presence of an adrenal mass, and exclusion of causes of secondary hyperaldosteronism (see Introduction and Diagnostic investigation). Note the triad of hypertension, hypokalemia and an adrenal mass in conjunction with elevated aldosterone levels.
Gross autopsy findings
Presence of an adrenal mass.
Less commonly: may be metastases in the case of adrenal carcinoma.
In the case of bilateral adrenal hyperplasia, no gross abnormalities may be evident.
Histopathology findings
Adrenal adenoma, carcinoma or bilateral hyperplasia.
May be renal histopatholgical abnormalities, particularly in association with bilateral adrenal hyperplasia. Renal abnormalities may include hyaline arteriolar sclerosis, glomerular sclerosis, tubular atrophy and interstitial fibrosis.
Differential diagnosis
Hypertension:
Renal disease.
Hyperthyroidism .
Idiopathic.
Less likely: phaeochromocytoma , obesity, hyperadrenocorticism , diabetes mellitus .
Oral potassium gluconate 2-6 mmol 2-3 times daily depending on severity of hypokalemia and response to treatment.
Intravenous potassium chloride can be used initially if severe hypokalemic polymyopathy, 20-60 mmol/l added to intravenous fluids, dependant on severity of hypokalemia (do not exceed a rate of 0.5 mmol/kg/hr). Most of cases will require much higher rates of K supplementation to correct the hypokalemia and reverse clinical signs. Potassium supplementation should be based on serial K determinations in order to avoid persistent hypokalemia. Hyperkalemia is extremely rare as long as renal function is adequate.
Amlodopine besylate if hypertensive: 0.625-1.25 mg per cat, orally, once to twice daily.
Standard treatment
Potassium supplementation - as above.
Amlodopine - as above.
Spironolactone (an aldosterone antagonist): 2.5 mg/kg orally once daily.
Monitoring
Blood pressure measurement and serum potassium concentration.
Clinical signs of weakness, and ocular signs of hypertension.
Subsequent management
Treatment
Medical management - as above.
Surgical management - unilateral adrenalectomy for unilateral adrenal adenoma or carcinoma.
Long-term monitoring: as above, monitor for recurrence in surgically managed cases.
Monitoring
Medically managed - continued monitoring as for initial monitoring, also monitor BUN/creatinine.
Surgically managed - post-operative monitoring for signs of intra-abdominal hemorrhage, post-operative measurement of plasma aldosterone concentration.
Overall fair to good, but unpredictable due to surgical complications.
Carcinomas do not appear to be associated with a worse prognosis than adenomas.
Expected response to treatment
Good initial response to medical management expected.
Excellent long term response to surgical management expected if survive the intra- and peri-operative period, however a high risk of severe and often fatal hemorrhage is associated with surgery due to close proximity of adrenal glands to major vasculature.
Reasons for treatment failure
Hypertension and hypokalemia may become refractory to medical treatment as the disease progresses.
May get progression of renal disease, particularly in association with bilateral adrenal hyperplasia.
Adrenal tumors often in close association with caudal vena cava resulting in a high risk of severe and often fatal hemorrhage during or following surgical resection.
Less commonly: adrenal tumor may be unresectable, metastasis may have occurred.
Rose S A, Kyles A E, Labelle P, Pyepndop B H, Mattu J S, Foreman O, Rodriguez C O Jr & Nelson R W (2007) Adrenalectomy and caval thrombectomy in a cat with primary hyperaldosteronism. JAAHA43 (4), 209-14 PubMed.
Ash R A, Harvey A M, Tasker S (2005) Primary hyperaldosteronism in the cat: a series of 13 cases. J Feline Med and Surg 7 (3), 173-182 PubMed.
Javadi S, Djajadiningrat-Laanen SC, Kooistra HS, Van Dongen AM, Voorhout G, van Sluijs FJ, van den Ingh T S G A M, Boer W H, Rijnberk A (2005) Primary hyperaldosteronism, a mediator of progressive renal disease in cats. Domest Anim Endocrinol 28(1), 85-104 PubMed.
Vetstream contributor(s)
Dr David Bruyette DVM DipACVIM, VCA West Los Angeles, 1818 South Sepulveda Boulevard, Los Angeles, CA 90025, USA.
Andrea M Harvey BVSc DSAM(Feline) DipECVIM-CA MRCVS, University of Bristol Veterinary School, Langford House, Langford, Bristol, BS40 5DU, UK.
autonomous of the renin-angiotension-aldosterone system, with loss of negative feedback.
Note the triad of hypertension, hypokalemia and an adrenal mass in conjunction with elevated aldosterone levels.
