This article is more than 5 years old. Information may no longer be current.
Hyperkalemia rare in transgender adolescents prescribed spironolactone
Click Here to Manage Email Alerts
An analysis of transgender teens prescribed spironolactone showed that only 2.2% developed hyperkalemia after initiating therapy, with all cases resolving upon repeat measurement irrespective of spironolactone dose, according to findings published in the Journal of the Endocrine Society.
“All cases of hyperkalemia we identified occurred within the first 6 months of starting treatment,” Yee-Ming Chan, MD, PhD, director of the disorders of sexual development program and attending physician in the division of endocrinology at Boston Children’s Hospital, and colleagues wrote. “Despite monitoring for up to 7 years in patients taking spironolactone, we did not identify any additional cases of hyperkalemia. This observation suggests that if there is no evidence of hyperkalemia in the early treatment period, there is no increased risk with duration of spironolactone exposure.”
In a retrospective chart review, Chan and colleagues analyzed data from 85 gender-diverse adolescents seen in the gender management service program at Boston Children’s Hospital from 2007 to 2017 who were prescribed spironolactone. Researchers defined hyperkalemia as a serum potassium concentration of at least 5 mmol/L. Patients underwent 269 potassium measurements, including 80 measurements before the initiation of therapy and 189 measurements performed during spironolactone treatment (mean number of measurements per patient, 3.2). Doses ranged from 25 mg per day to 400 mg per day, with a mean daily dose of 105 mg per day. Most patients (86%) were using spironolactone as an adjunct to estrogen.
Within the cohort, eight potassium measurements in six patients exceeded 5 mmol/L, with two such measurements in the same patients determined to be hemolyzed by the laboratory, for a rate of hyperkalemia of 2.2%. The researchers observed that all cases of hyperkalemia occurred early in the treatment course (less than 6 months after initiating spironolactone). No measurements exceeded 6 mmol/L.
Among patients with hyperkalemia, none had symptoms, according to researchers, and those with elevated potassium levels had normal levels after repeat measurements. The researchers also found that larger doses of spironolactone were not associated with a higher risk for hyperkalemia and observed a trend toward lower serum potassium concentrations with increasing time taking spironolactone.
“Although this association between potassium measurements and treatment duration may have been caused by the resolution of hyperkalemia in affected subjects, it also raises the possibility that there is renal accommodation to mineralocorticoid antagonism that leads to a slightly lower potassium set point and thus a lower risk for hyperkalemia over time,” the researchers wrote. “Renal accommodation may also explain why we did not see an effect of higher spironolactone doses on serum potassium concentrations and why all cases of hyperkalemia were early, transient and self-resolved.”
The researchers noted that close potassium monitoring beyond the first 6 months of spironolactone therapy should be reserved for patients with medical comorbidities or those who are taking medications that may impair renal potassium handling. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
Perspective
Back to Top
Joshua D. Safer, MD
The paper by Millington and colleagues is an important example of the transgender medical research we need. If we’re going to have an evidence-based approach to transgender medical care, then we need to look at actual data to inform our decision making.
My big caution with their paper is that I think they are too swift to draw a reassuring conclusion from a small, biased cohort. The authors correctly state that concerning hyperkalemia is more associated with the patient than with the medication dose. Young healthy individuals would be less likely to have an issue. Still, the authors found two instances of potassium elevation, albeit self-limited. Older patients with more disease that might impact kidney function would have more risk. The authors also note that potassium elevations are seen after starting therapy, which is consistent with Endocrine Society recommendations to check levels with dose changes and then significantly less frequently thereafter.
Potassium monitoring is easy and inexpensive. Hyperkalemia can be catastrophic with fatal arrhythmias possible without warning symptoms. Therefore, there is still value in large numbers of potassium checks to prevent even one negative event. I am not surprised that a healthy, younger population had only trivial hyperkalemia. However, I would not generalize the findings to the general population where the recommendation is for inexpensive monitoring to avoid a rare catastrophe.
Click Here to Manage Email Alerts