|Classification and external resources|
Primary aldosteronism, also known as primary hyperaldosteronism, is characterized by the overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands, when not a result of excessive renin secretion. Aldosterone causes increase in sodium and water retention and potassium excretion in the kidneys, leading to arterial hypertension (high blood pressure). An increase in the production of mineralocorticoid from the adrenal gland is evident. It is amongst the most common causes of secondary hypertension, renal disease being the most common.
Primary hyperaldosteronism has many causes, including adrenal hyperplasia and adrenal carcinoma. When it occurs due to a solitary aldosterone-secreting adrenal adenoma (a type of benign tumor), it is known as Conn's syndrome. In practice, however, the terms are often used interchangeably, regardless of the underlying physiology.
The syndrome is due to:
- Most commonly Adrenal Adenoma (Conn's Syndrome) (66%)
- Bilateral idiopathic adrenal hyperplasia (30%)
- Primary (unilateral) adrenal hyperplasia—2% of cases
- Aldosterone-producing adrenocortical carcinoma—<1% of cases
- Familial Hyperaldosteronism (FH)
- Glucocorticoid-remediable aldosteronism (FH type I)—<1% of cases
- FH type II (APA or IHA)—<2% of cases
- Ectopic aldosterone-producing adenoma or carcinoma—< 0.1% of cases
Recent studies indicate that the prevalence of aldosteronism due to bilateral idiopathic adrenal hyperplasia (IAH) is higher than had previously been believed, for as many as 75% of aldosteronism cases.
40% of patients with an adrenal aldosterone producing adenoma have somatic gain-of-function mutations in a single gene (KCNJ5). This gene is mutated in inherited cases albeit less frequently. These mutations tend to occur in young women with the adenoma in the cortisol secreting zona fasciculata. Adenomas without this mutation tend to occur in older men with resistant hypertension.
Signs, symptoms and findings
Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are on cells of the late distal tubule and medullary collecting duct. In the principal cells aldosterone increases activity of basolateral membrane sodium-potassium ATPase and apical epithelial sodium channels, ENaC, as well as potassium channels, ROMK. These actions increase sodium reabsorption and potassium secretion. Since more sodium is reabsorbed than potassium secreted, it also makes the lumen more electrically negative, causing chloride to follow sodium. Water then follows sodium and chloride by osmosis. In Conn syndrome these actions cause increased extracellular sodium and fluid volume and reduced extracellular potassium. Aldosterone also acts on intercalated cells to stimulate an apical proton ATPase, causing proton secretion that acidifies urine and alkalizes extracellular fluid.
Finer notes on aldosterone include the fact that it stimulates sodium-potassium ATPase in muscle cells, increasing intracellular potassium and also increases sodium reabsoption all along the intestine and nephron, possibly due to widespread stimulation of sodium-potassium ATPase. Finally, epithelial cells of sweat gland ducts and distal colon surface respond exactly the same as the principal cells of the nephron. These responses are important in climate adaptation and as a cause of constipation with elevated aldosterone.
The sodium retention leads to plasma volume expansion and elevated blood pressure. The increased blood pressure will lead to increased glomerular filtration rate and cause a decrease in renin release from the granular cells of the juxtaglomerular apparatus in the kidney. If there is a primary hyperaldosteronism the decreased renin (and subsequent decreased angiotensin II) will not lead to a decrease in aldosterone levels (a very helpful clinical tool in diagnosis of primary hyperaldosteronism).
Aside from high blood pressure manifestations of muscle cramps (due to hyperexcitability of neurons secondary to hypocalcemia), muscle weakness (due to hypoexcitability of skeletal muscles secondary to hypokalemia), and headaches (due to hypokalemia or high blood pressure) may be seen.
Secondary hyperaldosteronism is often related to decreased cardiac output which is associated with elevated renin levels.
Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. Rather, both renin and aldosterone are measured, and a resultant aldosterone-to-renin ratio is used for diagnosis. A high aldosterone-to-renin ratio indicates presence of primary hyperaldosteronism.
If plasma levels of renin and aldosterone suggest hyperaldosteronism, CT scanning can confirm the presence of an adrenal adenoma. If the clinical presentation primarily involves hypertension and elevated levels of catecholamines, CT or MRI scanning can confirm a tumor on the adrenal medulla, typically an aldosteronoma.
Hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizin. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis (an anise-flavored aperitif containing glycyrrhizinic acid).
The treatment for hyperaldosteronism depends on the underlying cause. In patients with a single benign tumor (adenoma), surgical removal (adrenalectomy) may be curative. This is usually performed laparoscopically, through several very small incisions. For patients with hyperplasia of both glands, successful treatment is often achieved with spironolactone or eplerenone, drugs that block the effect of aldosterone. With its antiandrogen effect, spironolactone drug therapy may have a range of effects in males, including sometimes gynecomastia. These symptoms usually do not occur with eplerenone drug therapy.
A 2008 study conducted in Germany and Argentina proves that the endocannabinoid receptors regulate aldosterone at the level of the adrenal. Anandamide inhibited basal release and stimulated release of the adrenocortical steroids corticosterone and aldosterone. Since cannabinoid receptors are affected by the active ingredient in marijuana, THC, the same way as anandamide, this therapy could prove useful to those who cannot tolerate the side effects of spironolactone or eplerenone, and do not respond to surgery.
In the absence of proper treatment, individuals with hyperaldosteronism often suffer from poorly controlled high blood pressure, which may be associated with increased rates of stroke, heart disease, and kidney failure. With appropriate treatment, the prognosis is excellent.
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- United Bristol Healthcare NHS Trust, the major teaching trust in South West England
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- Columbia Adrenal Center, Hyperaldosteronism (Conn's Syndrome)