Feline Primary Hyperaldosteronism

Chapter 54

Feline Primary Hyperaldosteronism

The term primary hyperaldosteronism (PHA) refers to the clinical consequences of mineralocorticoid excess arising from autonomous hyperfunction of the zona glomerulosa of the adrenal cortex. The first case of feline PHA related to an adrenocortical carcinoma was reported in 1983 (Eger, Robinson, and Huxtable, 1983). Since 1999, at least 40 additional affected cats have been described in individual case reports, case series, or book chapters. To date, the best-defined occurrences of PHA in cats are related to unilateral adrenocortical carcinoma or adenoma. Evidence for PHA related to idiopathic nodular hyperplasia of the zona glomerulosa was presented in a series of 11 cats with concomitant renal disease (Javadi et al, 2005). Increased awareness of the clinical manifestations has led to speculation that PHA may be the most common adrenocortical disorder in cats. This chapter summarizes the clinical features, diagnosis, and treatment of PHA in cats.

The Renin-Angiotensin-Aldosterone System: Regulation and Actions

The renin-angiotensin-aldosterone system (RAAS) acts to maintain extracellular fluid volume, circulatory pressure, and electrolyte homeostasis through integrated effects primarily on the vasculature and kidneys. Juxtaglomerular cells incorporated in afferent arterioles of renal glomeruli synthesize prorenin, of which some is converted to active renin and stored in secretory granules. Release of active renin from juxtaglomerular cells can be induced by different mechanisms. The predominant control of renin release is mediated through baroreceptors in the afferent arteriole, where a decrease in perfusion pressure stimulates renin release. In addition, cells of the macula densa in the distal convoluted tubule, in communication with juxtaglomerular cells, monitor sodium content in the glomerular filtrate. A decrease in sodium content stimulates renin secretion. Lastly, activity of sympathetic neurons communicating with cardiac baroreceptors stimulates renin release. In the circulation, renin cleaves angiotensinogen, a protein produced by the liver, into angiotensin I, which is in turn converted to angiotensin II by angiotensin-converting enzymes. Angiotensin II exerts potent biologic effects to mediate vasoconstriction, promote renal tubule reabsorption of sodium, and stimulate release of aldosterone from the zona glomerulosa of the adrenal cortex.

Aldosterone is synthesized from cholesterol through a series of steroid intermediates including progesterone, 11-deoxycorticosterone, and corticosterone in zona glomerulosa cells, mainly via stimulation by angiotensin II. Aldosterone secretion is also stimulated by a direct effect of hyperkalemia and, to a lesser extent, by adrenocorticotropic hormone (ACTH). Epithelial cells of renal tubules, salivary glands, and the colon are the classic mineralocorticoid-responsive tissues, where the effect of aldosterone is to promote reabsorption of sodium in exchange for loss of potassium and hydrogen ions.

In instances of reduced arterial blood volume, the RAAS can respond with sustained release of renin and aldosterone. Renin-stimulated aldosterone hypersecretion is referred to as secondary hyperaldosteronism, which usually occurs as a compensatory response to heart failure, gastrointestinal disease, water deprivation, or other causes of hypovolemia. Persistence of secondary hyperaldosteronism in an attempt to restore or maintain glomerular perfusion may contribute to the onset of hypokalemia or hypernatremia. In an experimental rat model, iatrogenic aldosterone excess promoted increased urinary loss of calcium and magnesium, with subsequent development of secondary hyperparathyroidism and reduced bone mineral content (Chhokar et al, 2005). Interestingly, cats with PHA and concomitant azotemia usually do not have hyperphosphatemia. It is possible that cats with PHA also have elevated parathyroid hormone levels, which would promote urinary excretion of phosphorus and allow serum phosphorus levels to remain normal (Graves, 2011).

Clinical Signs and Physical Examination Findings

Feline PHA is a disease of middle-aged to older cats. The reported age of onset ranges from 5 to 20 years, with a median age of 13 years for cats with adrenal neoplasia. The age for cases of adrenal hyperplasia appears similar, with reported ages ranging from 11 to 18 years. There appears to be no breed or sex predispositions. In 25 cats with PHA related to adrenal neoplasia, unilateral tumors were identified in 14 right and 9 left adrenal glands, with bilateral adrenal adenomas identified at postmortem examination in two cats.

The major clinical signs most commonly relate directly to increased aldosterone concentrations, which result in hypokalemia and arterial hypertension. PHA should be considered as a possible diagnosis in any cat presenting with arterial hypertension and/or hypokalemia, particularly if either appears to be refractory to treatment. The resulting presenting signs fall largely into two main groups:

• Hypokalemic polymyopathy. This is the most common reported presentation for cats with adrenal neoplasia. Cervical ventroflexion is the most frequently encountered sign of muscle weakness, but hind limb weakness and ataxia or, less commonly, limb stiffness, dysphagia, respiratory failure, and collapse may also occur. Signs of muscular weakness may be mild and episodic or insidious in onset, whereas in other cats these signs can be severe and acute in onset. Hypokalemic polymyopathy is reported to be a much less common presenting sign in cases of adrenal hyperplasia

• Ocular signs of arterial hypertension. These are a less common primary presentation in cats with adrenal neoplasia, but appear to be more common major presenting signs in cats with bilateral adrenal hyperplasia that tend to have more severe hypertension. Clinical signs may include intraocular hemorrhage or acute-onset blindness resulting from retinal detachment. This presentation is more likely in cats with systolic blood pressures above 200 mm Hg and can be the sole presenting sign. Subtle signs of hypertensive retinopathy evident on fundic examination (e.g., subretinal, intraretinal, and intravitreal hemorrhages, retinal edema) are more commonly observed.

Less common clinical findings in adrenal neoplasia cases include polyuria and polydipsia, polyphagia, and a systolic heart murmur. An adrenal mass may also be detected as an incidental finding on abdominal ultrasound examination or palpation in a normokalemic cat that may develop additional signs of hyperaldosteronism some time later (Renschler and Dean, 2009).

A different clinical presentation occurs less commonly in cats with excesses of other corticosteroids as well as aldosterone. There are published reports of cats with aldosterone-secreting adrenal tumors that have had concurrent hyperprogesteronism and the authors have also encountered similar cats (Brisco et al, 2009). In these cases signs of hyperprogesteronism/hyperadrenocorticism predominate, namely diabetes mellitus, polyuria, polydipsia, polyphagia, poor coat condition, seborrhea, thin fragile skin, and a potbellied appearance. Hypertension and persistent hypokalemia may be initially overlooked.

Because PHA affects older cats, concomitant nonadrenal illness may divert the clinician’s attention from the possibility of hyperaldosteronism. For example, chronic kidney disease or hyperthyroidism may be assumed wrongly to be the cause of hypokalemia and/or hypertension. Left ventricular hypertrophy may also be present, resulting in typical clinical findings of cardiomyopathy such as a systolic heart murmur, tachycardia, gallop rhythm, or dysrhythmias. The changes could be believed to be secondary to hypertension and/or concurrent disease such as hyperthyroidism. However, the cardiac effects of elevated aldosterone are well recognized in humans, and it is therefore possible that cardiac disease could arise as a consequence of PHA. Consequently, the presence of left ventricular hypertrophy and the associated clinical findings should also prompt consideration of the presence of PHA. Congestive heart failure has been reported in one cat with concurrent PHA and hyperprogesteronism.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Feline Primary Hyperaldosteronism
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