Introduction

Feline primary hyperaldosteronism was first reported in 1983, and has been diagnosed with increasing frequency since. The condition may be the result of either adrenocortical neoplasia or bilateral adrenocortical hyperplasia.^1-6

The excessive secretion of aldosterone causes increased renal reabsorption of sodium and water and increased renal excretion of potassium. These aldosterone-induced changes may result in systemic arterial hypertension and potassium depletion. Signs may comprise hypokalemic paroxysmal flaccid paresis, acute blindness due to retinal detachment and/or intraocular hemorrhage, and other changes attributable to hypertensive damage in target organs such as the kidney, heart or brain.

Diagnosis

In primary mineralocorticoid excess, the plasma concentration of aldosterone is characteristically high and plasma renin activity (PRA) is immeasurably low. In hyperaldosteronism due to adrenocortical tumor plasma aldosterone concentration (PAC) is usually highly elevated. In idiopathic hyperaldosteronism PAC is usually only slightly elevated or within the upper limit of the reference range. As hypokalemia is a predominant factor in lowering PAC, in the presence of hypokalemia moderately elevated aldosterone values can be regarded as inappropriately high. The PRA must also be taken into account. The combination of a high-normal or elevated PAC and low PRA indicates persistent aldosterone synthesis in the presence of little or no stimulation by the renin-angiotensin system. In humans the PAC:PRA ratio (ARR) is considered to be a very useful aid in diagnosing primary hyperaldosteronism. This also seems to be true for cats with idiopathic hyperaldosteronism.⁶

The ARR is elevated in 10-20% of human patients with arterial hypertension and most of these have excess aldosterone production from both adrenal cortices. The diagnostic value of the ARR is principally determined by the sensitivity of the renin assay and interpretation should rest upon comparison with an appropriate control population. The ARR is currently regarded as the most reliable means of detecting primary hyperaldosteronism, but the measurements should be repeated if the initial result is inconclusive or difficult to interpret because of suboptimal sampling conditions.

An alternative diagnostic approach may be measurement of the urinary aldosterone: creatinine ratio (UACR). Cats excrete smaller quantities of aldosterone and its 18-glucuronidated metabolite in urine than do humans or dogs, but nevertheless the UACR can be determined.⁷ This would allow the development of a dynamic test, such as employing a suppressive agent that would reduce the UACR in healthy individuals but have little or no effect in those with primary hyperaldosteronism. In 42 healthy cats the upper limit for the UACR was 46.5 x 10^-9. The administration of sodium chloride did not significantly lower the UACR but administration of fludrocortisone (0.05 mg/kg body weight) reduced it by 44-97% (median 78%). In a cat with an aldosterone-producing adrenocortical carcinoma the UACR was within the reference range and was not lowered by fludrocortisone administration.⁸ This test may prove to be a practical noninvasive diagnostic tool, but further evaluation is required, particularly with regard to its discriminatory power in diagnosing idiopathic hyperaldosteronism.

Subtype classification--differentiating between tumorous and nontumorous mineralocorticoid excess--requires diagnostic imaging. Ultrasonography and computed tomography have been used in cats to identify and characterize adrenal tumors.⁹ As in humans the findings are not always immediately conclusive. The visualization of a small aldosteronoma may pose problems while nodular hyperplasia might be interpreted as microadenoma.

Treatment

Unilateral adrenalectomy is the treatment of choice for confirmed unilateral primary hyperaldosteronism. Preoperatively and perioperatively hypokalemia should be controlled as well as possible, by oral and intravenous supplementation. Analogous to the postoperative management of hypercortisolemia due to adrenocortical tumor, temporary fludrocortisone therapy could be considered. However, in the reported cases such postsurgical measures have not been necessary and their omission does not seem to have had deleterious effects.

If surgery is not possible or if the adrenocortical disease is bilateral, medical treatment is possible with the mineralocorticoid-receptor antagonist spironolactone and oral supplementation with potassium gluconate. The initial doses are 2 mg spironolactone/kg and 0.5 mmol potassium gluconate/kg, twice daily. Persistent arterial hypertension can be treated with the calcium blocker amlodipine (1-2 mg/kg). In cases of adrenocortical tumor medical treatment may lead to resolution of symptoms and signs such as the myopathy in cats, but complete normalization may not be achieved. Particularly plasma potassium tends to remain below the reference range, despite increasing doses of both spironolactone and potassium. Doses of spironolactone >4 mg/kg may cause anorexia, diarrhea, and vomiting. These side effects may be due to interference by spironolactone with aldosterone action on transepithelial electrolyte transport in the distal colon.

Experience is very limited, but medical treatment appears to be preferable in cats with hyperaldosteronism due to bilateral adrenocortical hyperplasia. The hyperaldosteronism is usually somewhat milder than in cases due to tumor and normokalemia may be maintained for a long period with spironolactone alone or together with low doses of potassium.

Prognosis

After complete removal of a unilateral nonmetastasized mineralocorticoid-producing tumor, the prognosis can be excellent, without any medication. In both forms the disease may be associated with renal insufficiency. Successful removal of the tumor will probably prevent further progression of aldosterone-induced arteriolar sclerosis and interstitial fibrosis in the kidneys. The prognosis may not be as favorable in cats with idiopathic hyperaldosteronism treated with spironolactone, for this treatment will not abolish the mineralocorticoid excess as definitely as surgery may do.

References

1.  Eger, et al. JSAP 1983;24:293.

2.  Flood, et al. JAAHA 1999;35:411.

3.  Rijnberk, et al. Vet Q 2001;23:38.

4.  Ash, et al. JFMS 2005;7:173.

5.  DeClue, et al. JVIM 2005;19:355.

6.  Javadi, et al. DAE 2005;28:85.

7.  Syme, et al. JSAP 2007;48:202.

8.  Djajadiningrat-Laanen, et al. JVIM 2008;22:1283.

9.  Moore, et al. JAVMA 2000;217:211.