PA is an Endocrine Disease
Primary Aldosteronism is a Common Cause of Hypertension
The terms Primary Aldosteronism, Hyperaldosteronism, and Primary Hyperaldosteronism are used to designate a group of disorders that all share a common characteristic: an inappropriately high production of aldosterone that is independent from the renin-angiotensin system, and cannot be suppressed by sodium loading. Also known as Conn’s Syndrome, primary aldosteronism was discovered in 1955 by Dr Jerome W Conn. The severity of the disease ranges from mild to severe. It is a common cause of hypertension (i.e., what is traditionally called “essential hypertension”), and the most common cause of secondary hypertension (i.e., blood pressure caused by a medical condition).
Primary Aldosteronism is a Disease of the Adrenal Glands
Hormones are chemical messengers that regulate key bodily functions such as metabolism, growth, blood pressure, electrolytes balance, reproduction, sleep, and even mood. Every cell in the body has receptors for specific hormones that, when activated, cause the cell to take certain actions.
Hormones are also used to coordinate action between glands through complex feedback loops to keep the body’s system in balance or to respond to changes in the environment.
Primary aldosteronism is an endocrine disease that can affect one or both adrenal glands, and is most often caused by a benign tumor or by excess growth of aldosterone-producing cell clusters in both adrenal glands, termed bilateral hyperplasia.
An essential part of the endocrine system, the adrenal glands are very small triangular-shaped organs which sit atop of the kidneys. The adult adrenal glands weigh some 4 to 5 grams each (less than 1/5th of an ounce). Aldosterone is produced by the outer most layer (glomerulosa) of the cortex of the adrenal glands. Besides aldosterone, adrenal glands also produce and excrete cortisol, adrenaline, epinephrine, and sex hormones into the blood stream.
Renin and the RAAS Feedback Loop
The production of aldosterone is normally regulated by a feedback loop in the Renin-Angiotensin-Aldosterone System (RAAS). Renin, a hormone produced in the kidneys, plays a key role in the regulation of blood pressure by controlling extracellular fluid and the constriction of arterial blood vessels. It also works indirectly through the activation of the RAAS to stimulate the production of aldosterone.
While aldosterone and renin levels vary during the day, the levels move in concert with each other, going up and down at the same time. This is why, in a healthy person, the ratio between aldosterone and renin is small. In primary aldosteronism, aldosterone production is partially or completely unregulated by the RAAS feedback system. One or both adrenal glands produce too much aldosterone compared to the body’s needs and renin levels will drop very low (i.e., become suppressed) in an unsuccessful effort to reduce blood pressure. This is why the ratio between aldosterone and renin levels is higher in people with PA. In fact, the aldosterone-to-renin ratio (ARR) is the initial test to detect whether a patient has primary aldosteronism.
Too Much Aldosterone Sends Electrolytes out of Balance
Aldosterone is classified as a mineralocorticoid hormone because its primary role is to regulate the balance of sodium (i.e., salt) and potassium in the body. These minerals are critical electrolytes which must be maintained in a fairly narrow range for the body to function.
Through mineralocorticoid receptors (MR), aldosterone acts on cells throughout the body. Its main action is to cause the tubules in the kidney to reabsorb sodium and excrete potassium. While pushing out potassium, it also stimulates sodium reabsorption in the gut, sweat, and salivary glands.
When a healthy person reaches sufficient salt intake, his/her aldosterone levels decline. When someone has PA, aldosterone remains high. This drives the kidneys into reabsorbing more sodium and excreting more potassium in exchange. The resulting high level of sodium causes the body to retain water and increase blood volume. This, in turn, leads to severe hypertension. Hypokalemia occurs when potassium falls below normal values. Since it causes cardiac, muscle and nerve dysfunction, severe hypokalemia must be promptly addressed. All patients with PA lose potassium, but not all patients with PA experience hypokalemia. Most people with PA find they must keep their potassium levels above the middle of the range to prevent irregular heartbeat and muscle cramps.
Primary Aldosteronism is Much More than Just Hypertension
While hypertension may be the most evident sign of PA, the disease also affects many other systems and organs in the body — even if blood pressure is controlled. Primary aldosteronism is associated with atrial fibrillation, myocardial infarction, heart failure, stroke, and kidney failure. Other less recognized deleterious effects of excess aldosterone include insulin resistance and diabetes mellitus, liver fibrosis, osteoporosis, hyperparathyroidism, disturbances of calcium and collagen metabolism, and depression and anxiety. All people with PA have a substantially reduced quality of life.
Because most of these conditions are not specific to primary aldosteronism, they are often treated separately, and PA is seldom considered as the underlying cause. As a result, patients with PA are often left undiagnosed and untreated, and experience a significantly higher rate of mortality than people with essential hypertension.
References
- Funder, J. W., Carey, R. M., Mantero, F., Murad, M. H., Reincke, M., Shibata, H., Stowasser, M., & Young Jr, W. F. (2016). The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline, The Journal of Clinical Endocrinology & Metabolism, 101(5), 1889-1916.
- Young Jr, W. F. (2019). Diagnosis and treatment of primary aldosteronism: practical clinical perspectives, The Journal of Internal Medicine, 285(2), 126-148.
- Rossi, G. P., & Seccia, T. M. (2019). Primary aldosteronism: a glimpse into the most common endocrine cause of arterial hypertension. In Aldosterone-mineralocorticoid receptor – cell biology to translational medicine. IntechOpen.
- Vaidya, A., Mulatero, P., Baudrand, R., & Adler, G. K. (2018). The expanding spectrum of primary aldosteronism: implications for diagnosis, pathogenesis, and treatment, Endocrine Reviews, 39(6), 1057-1088.
