Question: Do I need to get genetic testing before trying and MR antagonist (spironolactone, eplerenone or finereone)
Answer: No, you don’t absolutely NEED genetic testing. The gene rs5522 variant drives the symptoms of many chronic diseases. If you suffer from fatigue, pain, allergies or treatment resistant obesity, you could work with your clinician to trial an MR antagonist. These medicines have a long safety profile and are often prescribed for conditions like acne. Nearly 90% of people have this variant, depending on ancestry, making it more likely that your symptoms are driven by rs5522, than not.
Question: Aren't these just regular water pills or diuretics?
Answer: No. Calling these medicines water pills is completely wrong. Standard water pills just force your kidneys to dump water out of your blood. These are a special class of medicine called MR antagonists.
To understand how they work, think of the receptors on your cells like locks, and your body's hormones like keys. With this genetic condition, your locks are "greedy.” They pull keys in too fast and refuse to let them go, keeping the switch permanently jammed in the "on" position. This constant overactivity (stuck in “on”) is what causes your chronic disease symptoms.
This medicine does not stop your body from making keys. In fact, doctors often call these medicines "aldosterone blockers," but that is a complete misnomer because it is actually blocking the MR receptor. The partial blockade stops the receptor from vacuuming up too much cortisol and lets it be used by the glucocorticoid receptors GR. Instead of changing your hormone production, the medicine acts like a dummy key that is specifically shaped to slide into that greedy lock first. It plugs the hole and stays there. Because the greedy lock is blocked, the overactive switch finally calms down and your body gets relief without ever changing your actual hormone levels.
Question: What if I starting Spironolactone made me feel tired or weak?
Answer: Doses should be low. Doses that are too high can impact electrolytes.
Additionally, if a low dose of spironolactone (25mg) (or an alternative MR antagonist) made you more tired it might mean you need a baseline, external physiological dose of cortisol to keep your system from collapsing. In a body managing a continuous genetic capillary leak (rs5522), your adrenal glands are forced to run on high alert, producing constant cortisol to squeeze leaky blood vessels shut and keep your baseline blood pressure from crashing. Work with your clinician to trial a standard physiological replacement dose of cortisol. This is typically 20 to 25 mg of hydrocortisone, split into divided daily doses, to stabilize your system.
Question: What is my doctor won’t prescribe an MR antagonist?
Answer: If your doctor isn't open to considering a safe medication that has been around for decades, it might be worth looking for another doctor.
If your condition is not listed below, you may still benefit from an MR antagonist like Spironolactone, Elperenone or Finereone. Your clinical should prescribe a low dose to reset the cortisol imbalance between your receptors. Routine monitoring of potassium is recommended.