Like cortisol, aldosterone is a steroid hormone.
1. Aldosterone formation
Cholesterol becomes aldosterone via pregnenolone and progesterone.
Aldosterone is formed in the outermost layer of the adrenal cortex, the zona glomerulosa.
The half-life of aldosterone is 20 minutes.
Degradation of aldosterone to (mainly) tetrahydro-glucuronide derivatives occurs in the liver, and to a lesser extent to an 18-glucuronide in the liver and kidney. Excretion occurs via the urine.
1.1. Aldosterone agonists
- Renin from the kidney
- Decrease in blood volume and blood pressure
- Hyperaldosteronism (due to angiotensin II at AT1 receptors)
- Angiotensin II is increased by
- Sodium deficiency
- Hypovolemia (blood deficiency)
- Drop in renal blood flow.
- Hyperkalemia (excessive potassium blood level)
- Hyponatremia (low sodium blood level)
1.2. Aldosterone antagonists
- Hypernatremia (high sodium blood level)
2. Effect of aldosterone
- Increased secretion in the event of fluid deficiency
- Conveys feeling of thirst
- Regulation of blood pressure (significant)
- Electrolyte balance
- Aldosterone deficiency triggers salt starvation
- Binding to mineralocorticoid receptor (MR)
- With the same receptor affinity, aldosterone is 1000 times more effective than cortisol.
This is because cortisol is converted to cortisone in aldosterone-sensitive cells by 11β-hydroxysteroid dehydrogenase type 2. Cortisol cannot activate the receptor
3. Aldosterone deficiency
3.1. Effect of aldosterone deficiency
- Hyponatremia (sodium deficiency)
- Hyperkalemia (excess potassium)
- Decrease in plasma volume
- Circulatory insufficiency
3.2. Causes of aldosterone deficiency
The cause may be disorders of aldosterone biosynthesis. These are very rare.
- 21-hydroxylase deficiency
- Extent different
- Partial 21-hydroxylase deficiency (reduction of aldosterone production to 1-2%) can maintain adequate mineralocorticoid function
Other effects to be reviewed
- Aldosterone synthetase deficiency
- 3b-hydroxysteroid dehydrogenase deficiency
- Cholesterol desmolase deficiency
- Primary adrenal insufficiency
- Whereas in central (secondary and tertiary) adrenal insufficiency there is usually “only” a significant glucocorticoid deficiency, in primary adrenal insufficiency there are usually deficiencies of glucocorticoids, mineralocorticoids (aldosterone) and androgens (e.g. dehydroepiandrosterone = DHEA).
In general, aldosterone deficiency is more common in low cortisol stress response and alpha-amylase stress response, which are typical in atopy (inflammatory health problems).
3.3. Treatment of aldosterone deficiency
In primary adrenal insufficiency, aldosterone is usually substituted in addition to cortisol. This is done by means of the mineralocorticoid fludrocortisone.
In cases of cortisol deficiency due to pituitary failure, aldosterone administration is usually not required.
In addition, there is so-called pseudohypoaldosteronism. The body produces sufficient or even too much aldosterone, but this is not recognized as such at the target organs. Pseudohypoaldosteronism thus causes the same complaints as an aldosterone deficiency in the blood.
3.4. Hypothesis: aldosterone deficiency as ADHD-HI co-cause
We hypothesize, purely theoretically, that aldosterone deficiency could be a contributor to ADHD-HI (with hyperactivity/reduced cortisol stress response).
ADHD-HI can be viewed from the perspective that the insufficient cortisol stress response causes a deficient shutdown of the HPA axis, which triggers an endurance run of the HPA axis stress system along with the resulting phenomena of inability to recover, causing a self-reinforcing enduring stress response.
Aldosterone binds to mineralocorticoid receptors (MR). In the case of aldosterone deficiency, the MR are too weakly occupied. Then, in an acute stress situation, before cortisol can occupy the lower affinity glucocorticoid receptors (GR) that cause the HPA axis to shut down again, it must first address the unoccupied MR. Above a certain level of aldosterone deficiency and low cortisol stress response, the system is no longer able to bind enough GR to shut down the HPA axis again after activation by an acute stressor.
Significantly decreased basal aldosterone levels (in addition to decreased corticosterone, which is the predominant glucocorticoid in rats) were found in SHR (spontaneously hypertensive rat) rats, which are model animals for a purely genetic cause model of ADHD-HI (with hyperactivity) and hypertension.
A search for “aldosterone” and “ADHD” at PubMed did not reveal any relevant references. This possible connection seems to have been completely ignored so far.