Introduction

The mineralocorticoid aldosterone is synthesized exclusively in the outer zone, the zona glomerulosa, of the adrenal cortex and has two important activities: 1) It is a major regulator of sodium homeostasis and hence extracellular fluid volume, and 2) it is a major regulator of potassium homeostasis. In response to (a tendency to) hypovolemia, renin is released from the juxtaglomerular cells in the kidney. In the bloodstream renin acts upon its only known substrate, angiotensinogen, to form angiotensin I. This angiotensin I, which is physiologically inactive, is converted to angiotensin II by the action of a converting enzyme (ACE). One of the biological actions of angiotensin II is synthesis and release of aldosterone. In addition to angiotensin II, potassium and the pituitary hormone ACTH are involved in aldosterone secretion.

Primary Hyperaldosteronism (PHA) is a disorder of the adrenal cortex and can be divided in two main subtypes: an unilateral aldosterone-producing adenoma or adenocarcinoma (APA) and bilateral adrenal hyperplasia or idiopathic hyperaldosteronism (IHA) (Wheeler and Harris, 2003). Both subtypes result in elevated circulating aldosterone levels. The increased aldosterone secretion gives rise to increased potassium excretion in the urine and thus lowers the total body potassium concentration. In addition, it increases sodium absorption, which ultimately results in a higher circulating volume. Consequently, the main clinical symptoms of PHA are muscle weakness due to hypokalemia and arterial hypertension. Hypokalemia is, however, not always present in patients with PHA. Eventually the hypertension can cause failure of target organs like the heart, eyes and kidneys.

Systemic arterial hypertension is a relatively common clinical entity in especially middle-aged to older cats. Arterial hypertension may lead to blinding ocular complications, resulting from hypertensive retinopathy, hypertensive choroidopathy and hypertensive optic neuropathy. In fact, ocular signs such as (recurrent) intraocular haemorrhage or acute blindness resulting from retinal detachment are often the reason for first presentation of these hypertensive patients to a veterinarian, and for the diagnosis to be frequently made by a veterinary ophthalmologist. If untreated, the hypertension-induced posterior segment lesions quickly result in irreversible damage to the retina and optic nerve and, thus, in permanent blindness. It is therefore of paramount importance that the diagnosis is instantly made and an appropriate therapy is initiated at once.

The etiology of feline systemic arterial hypertension may be quite diverse, and classically includes chronic renal disease, hyperthyroidism and hyperadrenocorticism. Only recently, primary hyperaldosteronism has been identified as an important cause of feline systemic arterial hypertension (Flood et al., 1999; Javadi et al., 2005).

Feline primary hyperaldosteronism has long been considered a rare entity. Its incidence, however, may be underestimated (Ash et al., 2005; Javadi et al., 2005). Since feline primary hyperaldosteronism has been identified as a cause of progressive renal disease (Javadi et al., 2005), quite a number of hyperaldosteronism cases may in the past have been falsely attributed to progressive renal failure.

The occurrence of primary hyperaldosteronism may be suspected based upon a low plasma potassium concentration, high arterial blood pressure and/or indications for target organ failure. A specific diagnosis can be made by measuring plasma renin activity (PRA) and plasma aldosterone concentration (PAC) and determining the ratio between these two, i.e., the aldosterone/renin ratio (ARR). Recently, in cats the reference values of the aldosterone concentration (PAC) and renin activity in plasma (PRA) have been determined and published (Javadi et al. 2004). In case of primary hyperaldosteronism, diagnostic imaging of the adrenals is required to differentiate between a unilateral aldosterone producing adenoma or adenocarcinoma (APA) and bilateral adrenal hyperplasia or idiopathic hyperaldosteronism (IHA) (Rijnberk et al. 2001; Ash et al., 2005; Javadi et al., 2005.

Therapy

Depending on the underlying pathology of the primary hyperaldosteronism, a number of interventions are available. For cats with unilateral adrenal neoplasia without demonstrable metastases, unilateral adrenalectomy is the treatment of choice. Cats with adrenocortical hyperplasia as well as cats with bilateral or metastasised adrenal neoplasia may benefit from administration of aldosterone antagonists, such as spironolactone (Aldactone®). However, in addition to spironolactone drugs which lower the arterial blood pressure (e.g., calcium blocking agents such as amlodipine) and potassium supplementation are often required to completely normalize blood pressure and the plasma potassium concentration.

References

1.  Ash RA, Harvey AM, Tasker S. Primary hyperaldosteronism in the cat: a series of 13 cases. Journal of feline medicine and surgery 2005; 7: 173-82.

2.  Flood SM, Randolph JF, Gelzer ARM, Refsal K. Primary hyperaldosteronism in two cats. Journal of the American Animal Hospital Association 1999; 35: 411-6.

3.  Javadi S, Slingerland LI, van de Beek MG, Boer P, Boer WH, Mol JA, Rijnberk A, Kooistra HS. Plasma renin activity and plasma concentrations of aldosterone, cortisol, adrenocorticotropic hormone, and alpha-melanocyte-stimulating hormone in healthy cats. Journal of veterinary internal medicine 2004; 18: 625-31.

4.  Javadi S, Djajadiningrat-Laanen SC, Kooistra HS, van Dongen AM, Voorhout G, van Sluijs FJ, van den Ingh TSGAM, Boer WH, Rijnberk A. Primary hyperaldosteronism, a mediator of progressive renal disease in cats. Domestic Animal Endocrinology 2005; 28: 85-104.

5.  Rijnberk A, Voorhout G, Kooistra HS, van der Waarden RJ, van Sluijs FJ, IJzer J, Boer P, Boer WH. Hyperaldosteronism in a cat with metastasised adrenocortical tumour. Veterinary Quarterly 2001; 23: 38-43.

6.  Wheeler MH, Harris DA. Diagnosis and Management of Primary Aldosteronism. World J. Surg. 2003; 27: 627-631.