Frequent potassium monitoring is associated with hyperkalemia that is clinically insignificant in females taking spironolactone for dermatologic conditions

Dear Editor,

Spironolactone is used as an off-label treatment for acne, hair loss, and hirsutism. Hyperkalemia risk by patient demographics and daily dosages requires clarification. We aimed to measure hyperkalemia prevalence and risk factors in women taking spironolactone for dermatologic conditions.

After institutional review board approval, demographics and potassium measurements were collected from female patients taking spironolactone for ≥2 weeks for acne, hair loss, or hirsutism from 2006 to 2021. Hyperkalemia was defined as ≥5.2 mEq/L.¹ R Version 4.2.2 was used, with Fisher’s Exact and Wilcoxon rank sum tests with significance p<0.05.

Overall, 1,489 patients taking at least one course of spironolactone were included [Table 1]; 5.6% (n = 83, 81/83 during the first course) experienced hyperkalemia, with 97.6% mild (≤6.0 mEq/L) and none severe (≥7.0 mEq/L). On average, patients with elevated versus normal potassium measurements had more frequent potassium monitoring (4.38 vs. 2.23, p<0.001, Table 1). Using logistic regression, age, and maximum daily spironolactone dose were statistically significant hyperkalemia predictors. The odds of hyperkalemia increased by 2.36%/year of age and by 0.81%/mg. Race, ethnicity, and spironolactone indication were not hyperkalemia predictors (all p>0.05) [Table 1]. Only nine (10.7%) of hyperkalemic courses caused therapy discontinuation [Table 2].

Older patients and those taking higher spironolactone doses more often developed hyperkalemia, and race, ethnicity, and indication did not increase risk. Hyperkalemia was uncommon and most often mild, consistent with retrospective studies of 974 (Plovanich et al.) and 195 (Plante et al.) women taking spironolactone for dermatologic conditions with hyperkalemia rates of 0.72% and 3.3%, respectively, and all cases mild.^1,2 In our study, >70% of hyperkalemic patients took ≥100 mg/day, consistent with Plante et al.’s study, with all hyperkalemic patients taking 100 mg/day.² Older women in our cohort more often experienced hyperkalemia, similar to a retrospective study of 124 women taking spironolactone for acne (16.7% of those aged 45–65 vs. <1% 18–45 [p = 0.0245]).^3,4

More frequent potassium monitoring was associated with clinically insignificant hyperkalemic since >70% of patients with elevated potassium had no change in treatment or potassium normalisation. Similarly, in a retrospective study of 1,863 acne patients taking isotretinoin, there were rare and clinically insignificant triglycerides (grade 3 <1%), total cholesterol (no grade 3), aminotransferase (grade 3 <0.5%), complete-blood-count (none) abnormalities, infrequently changing management and with normalisation.⁵ Potassium measurements are subject to haemolysis. Increased hyperkalemia prevalence with more frequent monitoring may indicate high false positive rates, given that >20% of our patients with hyperkalemia were normalised. Therefore, minimising potassium monitoring in low-risk groups may reduce costs and time burden associated with false positive hyperkalemia.

Limitations include single-centre, retrospective design, majority whites, incomplete race/ethnicity data, lack of control for diet, medication adherence, other treatments, and lack of information about comorbid endocrine disorders.

In sum, hyperkalemic measurements with spironolactone were associated with more frequent monitoring, which more often occurred in older women and patients taking higher daily dosages. Therefore, potassium monitoring in healthy young women taking spironolactone for dermatologic conditions is unwarranted, given cost, time, and patient discomfort considerations that will unlikely change management. Potassium measurements are recommended in older patients and those taking high daily dosages.