Spironolactone and Potassium: Who do we need to Monitor?

Spironolactone is a medication that is commonly used to treat female pattern hair loss (also known as androgenetic alopecia). The drug is an aldosterone antagonist and carriers a low risk of causing elevated blood potassium levels (a phenomenon called hyperkalemia).

We have talked about the risk of hyperkalemia in several prior articles. Interested readers may want to review these articles:

Spironolactone for Hair Loss: Should We be Measuring Potassium Levels or Not

Spironolactone for FPHL: Are Routine Potassium Tests Necessary?

The main point of these articles is that the risk of hyperkalemia seems to be very low in healthy women 45 years of age. By healthy, I mean no heart disease, no kidney disease and not on any medications that affect potassium levels (like blood pressure meds). From these studies, I proposed this algorithm a few years back and it’s one that we’ve been using in our clinic ever since:

Plante et al, 2022

A new study by Plante and colleagues returns to the issue of hyperkalemia from spironolactone. The authors set out to evaluate if the risk of hyperkalemia differs in different age groups.

The authors conducted a retrospective chart review of all female patients at their institution who were given oral spironolactone between May 2012 and June 2020. Patients in the study had used spironolactone for a variety of different diagnoses including acne, androgenetic alopecia, hirsutism, or hidradenitis suppurativa. In this study, hyperkalemia was defined by the authors as serum potassium ≥5.1 mEq/L.

195 patients were included in the study and there were 202 courses of treatments. Most patients were white, and 51 patients (25.2%) were older than 45-years at the start of therapy with spironolactone, with 19 patients older than 60 years.

The mean course duration was 27 months. Higher dosages (>100 mg/day) were used in 26 (12.9%) courses. Concurrent angiotensin-converting enzyme inhibitor (ACE-I) 53 or angiotensin receptor blocker (ARB) therapy was used in 19 courses and more frequently in the older 54 age group (p<.001).

Baseline potassium levels were tested in 125 courses of treatment, monitoring labs in 150 courses of treatment, and both in 73 courses. Patients older than 45 were more likely to have undergone routine testing for potassium levels after starting their treatment (p=.023).

The authors showed that 3 patients (1.5 %) had hyperkalemia associated with the use of spironolactone. However, it could only seemed to be definitively related in 1 patient (0.5 %) as the other two did not have hyperkalemia when their blood was drawn again. The resulting hyperkalemia in the 3 patients as mild, and none of the patients experienced adverse effects.

PATIENT 1:

The first patient was an Asian 65-year-old female who was taking the angiotensin receptor blocker losartan. She was using spironolactone at 100 mg per day for androgenetic alopecia. She experienced mild hyperkalemia (5.3 mEq/L) and had her dose reduced to 50 mg/day with continuation of losartan. The dose was increased to 100 mg/day after her potassium normalized 2 months later.

PATIENTS 2 and 3:

The other patients were 16 and 38-years-old. They experienced mild hyperkalemia (5.7 and 5.5, respectively) during treatment for acne vulgaris with 100 mg per day dosing.

Surprisingly, repeat testing 2 days and 3 months later, respectively, revealed they did not have elevated potassium levels. The patients continued their treatments without dose reduction.

Conclusion

This study supports that general notion that elevated potassium levels are not common among healthy spironolactone users but that medications like angiotensin receptors and ACE inhibitors and age can increase the risk of hyperkalemia. They also support the notion that worrisome hyperkalemia is rare in healthy women under age 40-45.

The authors did not mention in their study the likelihood of falsely elevated potassium levels although perhaps it was interferred from the fact that the 16 year old and 38 year old had normal potassium levels when they were tested again. Potassium is the one lab test that is quite variable and at risk for error in collection or interpretation of the lab test. In fact, so called ‘psuedohyperkalemia’ or falsely elevated potassium from lab error is one of the most common lab errors overall! We have to keep in mind the possibility that some of the patients in the study did not truly have hyperkalemia.

The authors also did not take into account that high potassium does not necessarily intake pathological conditions. In one study, 7% of healthy people had a potassium above 5.2 so there is a bell shape to the normal distribution to potassium levels in human beings. The most important things when encountering elevated potassium levels are therefore to repeat the test and assess for worrying clinical signs of hyperkalemia

REFERENCE

Plante et al. The Need for Potassium Monitoring in Women on Spironolactone for Dermatologic ConditionsJ Am Acad Dermatol. 2022 Jan 21;S0190-9622(22)00081-0.