Hyperaldosteronism

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Introduction0:00–0:13

With hyperaldosteronism, hyper means too much, and aldosteronism refers to the hormone aldosterone. Which is made by the adrenal glands, so hyperaldosteronism is a condition where the adrenal glands produce too much aldosterone.

Adrenal Glands0:13–0:55

Now each of the two adrenal glands sits on top of a kidney and has two main parts. The inner part, the medulla, produces the hormones epinephrine and norepinephrine.
On the flip side, the outer part, the cortex, has 3 layers. The innermost layer, the zona reticularis, produces androgens such as dehydroepiandrosterone, which is a precursor of testosterone.
The middle layer, the zona fascicuata, produces glucocorticoids like cortisol. With glucocorticoids, gluco refers to glucose because they help increase blood glucose levels.
The outermost layer, the zona glomerulosa, produces mineralo corticoids such as aldosterone. With mineralo corticoids, minerallo refers to minerals because these hormones help regulate sodium and potassium levels.

Aldosterone0:55–2:08

On the other hand, the zona glomerulosa is controlled by the renin angiotensin aldosterone system. When BP or sodium levels drop.
The juxagglomerular cells in the kidneys release renin into the bloodstream. In the bloodstream, renin cleaves angiotensinogen into angiotensin 1, which is later converted by angiotensin converting enzyme or ACE.
Into angiotensin too. Angiotensin 2 raises BP through two mechanisms.
First, it triggers vasoconstriction of small arterioles, subsequently increasing peripheral vascular resistance. Also, angiotensin 2 stimulates the zona glomerulosa to release aldosterone.
Once in the bloodstream, aldosterone travels to the kidneys, more specifically to the distal tubules and collecting ducts of the nephron.
Here aldosterone squeezes into principal cells and stimulates mineralocorticoid receptors. When aldosterone activates mineralocorticoid receptors, the sodium potassium pumps kick into high gear.

Primary Causes2:08–3:03

They begin to pump more sodium ions from the cell into the bloodstream. This intracellular drop in sodium pulls more sodium from the tubule into the cell, following its concentration gradient.
As sodium moves, water follows, so more water leaves the tubule and enters the blood vessels, eventually increasing blood volume and raising BP.
At the same time, pumps pull potassium from the blood into the cells. From here, potassium flows down its concentration gradient into the tubule to get excreted in the urine.
That's why another key trigger for the zona glomerulosa to release aldosterone is a high potassium level in the blood. Aldosterone helps the body remove extra potassium while holding on to sodium and water.

Secondary Causes3:03–3:26

Now, based on the underlying pathology, hyperaldosteronism can be further subdivided into primary and secondary types. Primary hyperaldosteronism means that the adrenal glands are responsible for the excess production of aldosterone.
The most common cause of primary hyperaldosteronism is bilateral idiopathic hyperaldosteronism. Bilateral means it affects both adrenal glands, and idiopathic means we're not sure what's causing it.

Symptoms3:26–4:11

But if we slice through the adrenal glands, we can recognize this condition by focal or widespread hyperplasia of cells that resemble those in the zona glomerulosa, which produce aldosterone.
Next, there are adrenocortical neoplasms. These can be adrenocortical carcinomas, which are a rare cause of hyperaldosteronism, or aldosterone producing adenomas.
Aldosterone producing adenomas, also known as Khn syndrome, are a much more common cause of hyperaldosteronism and typically affect biologically female individuals.
In these cases, there's almost always a well-defined tumor less than 2 centimeters in size. When you cut it open, it looks bright yellow and is made up of lipid-laden cortical cells.

Diagnosis4:11–4:59

Interestingly, these cells are similar to the ones found in the zona fasciculata, which produce cortisol, rather than the ones found in the zona glomerulosa, which produce aldosterone.
Additionally, in patients taking the BP medication spironolactone, adenoma cells might contain spironolactone bodies, which are eosinophilic laminated cytoplasmic inclusions.
A third cause is familial hyperaldosteronism, which is a genetic condition that runs in families. In this condition, the zono glomerulosa inappropriately makes too much aldosterone.
It does this not only in response to the usual trigger, renin, but also to adrenocorticotropic hormone. Normally, the pituitary gland releases this hormone to stimulate the zona fasciculata to release cortisol, but in these individuals, adrenocorticotropic hormone also triggers the release of aldosterone.

Treatment4:59–5:29

On the flip side, in secondary hyperaldosteronism, the renin angiotensin aldosterone system goes into overdrive, causing adrenal glands to produce excessive aldosterone.
One common trigger is decreased renal perfusion. For example, in renal artery stenosis and arteriolar nephrosclerosis, juxaglomerular cells think there is a drop in renal perfusion, which triggers them to release renin.

Review5:29–9:06

Next, a real systemic drop in BP, which can occur due to congestive heart failure and cirrhosis, lowers kidney profusion and triggers renin release.
Finally, during pregnancy, estrogen tells the liver to make more angiotensinogen. And when there's more angiotensinogen in the blood, renin has more to work with, causing the body to produce more angiotensin 1 and 2, and in turn more aldosterone.
Regardless of the cause, high aldosterone levels make the kidneys reabsorb more sodium, leading to high sodium levels in the blood or hypernatremia.
As sodium shifts back into the blood, water follows, which increases blood volume and raises BP. Over time, this can put extra strain on the heart, causing the left ventricle to thicken, which is also known as left ventricular hypertrophy.
Over time, this can lead to heart failure and in more severe cases, a heart attack or stroke. At the same time, aldosterone tells the kidneys to get rid of potassium, which lowers potassium levels in the blood, a condition called hypokalemia.
This ongoing potassium loss in the urine is known as renal potassium wasting. When potassium drops too low, it can lead to symptoms like muscle weakness, tingling, or numbness called paresthesia, and cardiac arrhythmias.
In serious cases, it can even cause muscle cramps or tetany. The diagnosis of hyperaldosteronism primarily relies on renin and aldosterone levels.
In primary hyperaldosteronism, the main problem is that the zona glomerulosa secretes too much aldosterone, and since aldosterone normally lowers renin through negative feedback, renin production drops.
So in this case, aldosterone is high and renin is low. On the flip side, in secondary hyperaldosteronism, the issue is that the juxagglomerular cells release too much renin.
Which leads to excessive aldosterone production. Even though aldosterone tries to reduce renin release through negative feedback, the kidneys continue to produce renin because they mistakenly think the body needs more.
As a result, both renin and aldosterone levels are high. Treatment of hyperaldosteronism is usually with an aldosterone antagonist, also known as potassium sparing diuretics, especially spironolactone.
Spironolactone competitively binds to mineralocorticoid receptors in the kidneys and blocks its effects. Additionally, if a tumor is the cause, surgical removal can reduce aldosterone production.
All right, as a quick recap, hyperaldosteronism is a condition where the adrenal glands produce too much aldosterone. In primary hyperaldosteronism, the adrenal glands make too much aldosterone on their own, usually because of bilateral idiopathic hyperplasia or an aldosterone producing adenoma.
It can also occur due to a genetic condition called familial hyperaldosteronism, where both renin and adrenocorticotropic hormone trigger aldosterone release.
On the flip side, in secondary hyperaldosteronism, the problem starts with too much renin, which leads to high aldosterone levels.
This type often occurs when kidney blood flow is reduced, like in heart failure or renal artery stenosis.