Joseph Bisignano, DVM
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Primary hyperaldosteronism, also referred to as Conn's syndrome or aldosteronism, is an adrenal disorder characterized by excessive and independent secretion of aldosterone. Conn first described primary
hyperaldosteronism in people in 1955 and discussed three hallmarks—hypertension, hypokalemia, and increased serum aldosterone
concentrations.1 Primary hyperaldosteronism was originally thought to be a rare condition, but the prevalence in people was found to be 6%
in all patients with arterial hypertension and about 11% in patients with therapy-resistant hypertension.2,3
The first case of primary hyperaldosteronism in a cat was described in 1983.4 The disease is not often diagnosed in veterinary practice despite the thought that it is likely one of the most common adrenocortical
disorders in cats.5
Many cases of arterial hypertension, hypokalemia, or both are attributable to chronic kidney disease (CKD) as the primary
disorder, but primary hyperaldosteronism itself has been shown to be a mediator and associated with the progression of CKD.6
This article reviews the physiology and actions of aldosterone and the pathophysiology of primary hyperaldosteronism, and
it describes the typical presentation and clinicopathologic abnormalities. Primary hyperaldosteronism should be included as
a differential diagnosis in cats presenting with hypokalemia, hypertension, or both and should no longer be regarded as a
rare condition.
ALDOSTERONE PHYSIOLOGY
David S. Bruyette, DVM, DACVIM
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Aldosterone is a corticosteroid hormone with strong mineralocorticoid activity produced by the cells within the zona glomerulosa
of the adrenal cortex. The production of aldosterone is driven and regulated through two main mechanisms: 1) the renin-angiotensin-aldosterone
system and 2) direct regulation via potassium ions. The renin-angiotensin-aldosterone system becomes activated in response
to a decrease in circulating blood volume and renal blood flow. This leads to a decrease in the delivery of sodium and chloride
to the cells comprising the macula densa of the distal tubules and results in renin secretion. Renin cleaves angiotensinogen
(produced in the liver) into angiotensin I, which in turn is hydrolyzed into angiotensin II in the lungs by angiotensin-converting
enzyme (ACE). Angiotensin II stimulates the secretion of aldosterone from the adrenal gland.
Potassium ions also regulate aldosterone secretion independent of the renin-angiotensin-aldosterone system by directly depolarizing
the membranes of the zona glomerulosa cells in cases of hyperkalemia.7 Adrenocorticotropic hormone (ACTH) also acts as a third stimulant of aldosterone production, and studies have shown significant
differences between plasma aldosterone concentrations before and after synthetic ACTH administration.8,9
Circulating aldosterone targets tissues of the kidney, colon, and salivary gland and passes through the plasma membranes of
these epithelial cells, binding to cytoplasmic mineralocorticoid receptors. In response to circulating aldosterone, the epithelial
cells of the distal convoluted tubules and collecting ducts of the kidney reabsorb sodium, thereby increasing water retention,
and excrete potassium. Plasma and extracellular fluid volume are increased along with total peripheral resistance because
of vasoconstriction from angiotensin II, thus causing an increase in blood pressure. Potassium is excreted into the urine,
decreasing plasma potassium concentrations.
The increase in extracellular fluid volume results in an increased blood flow to the kidney, thereby decreasing renin secretion.5,10 Hyperkalemia resolves through kaliuresis, and repolarization of the zona glomerulosa cells occurs.7
These two mechanisms make up the negative feedback loop for aldosterone secretion.
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