Introduction
Aldosterone is the most important mineralocorticoid in the human body, although various other hormones, such as cortisol, display mineralocorticoid activity as well, namely they cause hypertension, hypokalemia, and chloride resistant metabolic alkalosis (urine chloride > 20). In addition, mineralocorticoids can also cause hypernatremia and hypervolemia.
The triad of hypertension, and hypokalemia and chloride resistant metabolic alkalosis should make one think of hypermineralocorticoidism, that is excessive mineralocorticoid activity. This is an important diagnosis to make because it might lead one to catch an early tumor or, more commonly, to an easily-treatable form of hypertension.
Low renin, high aldosterone (hyporeninemic hyperaldosteronism)
- This points to primary aldosteronism, or to exogenous aldosterone
- The most common causes of primary aldosteronism are adrenal hyperplasia (most common) or adrenal adenoma (Conn syndrome)
- The next step is to confirm the diagnosis of primary aldosteronism with a salt suppression test (aldosterone will not be suppressed with a large oral salt load) followed by imaging of the adrenal glands with CT or MRI
- Treatment of adrenal hyperplasia is with spironolactone, while treatment of adrenal adenoma is with surgery.
High renin, high aldosterone (hyperreninemic hyperaldosteronism)
This points to secondary aldosteronism, meaning that the aldosterone is elevated because of something else, namely elevated renin levels. Elevated renin levels, or reninism, can itself be of two varieties:
- Primary reninism: from a reninoma (a renin secreting tumor)
- Secondary reninism: renin is elevated because of a secondary cause, namely low renal perfusion. Causes here include atherosclerosis (older males), fibromuscular dysplasia (younger females) and apparent intravascular volume depletion (CHF, cirrhosis, nephrotic syndrome, hypovolemia, diuretic use). Malignant hypertension is also a cause of reninism.
Low renin, and low aldosterone
- This points to non-hyperaldosteronemic hypermineralocorticoidism; it not “aldosteronism” because it is not caused by an increase in aldosterone
- Most common causes of non-hyperaldosteronemic hypermineralocorticoidism are hypercortisolism (Cushing syndrome), Cushing disease (ACTH-hypersecretion), 11β-hydroxylase deficiency
(a subtype of congenital adrenal hyperplasia), licorice ingestion, and Liddle syndrome. - Workup may continue here with dexamethasone suppression test.
Final Note
The physiologic opposite of hypermineralocorticoidism is type IV (distal) renal tubular acidosis. Patients with Type IV renal tubular acidosis may have orthostatic hypotension, hyperkalemia, and non-anion gap metabolic acidosis, which is the opposite of what patients with hypermineralocorticoidism have.
References
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Marc S. Sabatine MD, MPH, Pocket Medicine, 5e (2013)
- Linda S. Costanzo, PhD, BRS Physiology, 6e (2014)
- Kurtz, Ira, MD, Acid-Base Case Studies, 2e (2004, reviewed here)
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