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CLINICAL PROFILE OF PATIENTS WITH SYMPTOMATIC GLYCYRRHIZIN‐INDUCED HYPOKALEMIA

2008; Wiley; Volume: 56; Issue: 8 Linguagem: Inglês

10.1111/j.1532-5415.2008.01781.x

1532-5415

Satoshi Kurisu, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Yasuharu Nakama, Tatsuya Maruhashi, Eisuke Kagawa, Kazuoki Dai, Toshiyuki Aokage, Junichi Matsushita, Hiroki Ikenaga,

Electrolyte and hormonal disorders

To the Editor: Conn et al. were the first to report licorice-induced hypokalemia in 1968.1 This disorder is also called pseudoaldosteronism2 and is sometimes found in Japan because of the widespread use of glycyrrhizin-containing medications.3,4 We evaluated the clinical profiles of patients with symptomatic glycyrrhizin-induced hypokalemia. The study included 14 patients with symptomatic hypokalemia who had been treated with medications containing glycyrrhizin. Laboratory investigations were performed routinely on admission; hypokalemia was defined as serum potassium levels less than 3.5 mmol/L. Electrocardiograms (ECGs) were routinely obtained; ST-segment depression was defined as greater than 0.5 mm in limb leads and greater than 1.0 mm in precordial leads. Distinct U waves were defined as greater than 0.2 mV. Data were expressed as means±standard deviations. Statistical analysis was performed using paired and unpaired Student t-tests for continuous variables. Differences were considered significant if P<.05. Patient characteristics were listed in the order of potassium concentration (Table 1). There were two men and 12 women, with a mean age of 74±10. Various primary complaints including syncope, paralysis, and hypertension were noted.4–6 All patients had a history of hypertension, and four patients had a history of diabetes mellitus. Laboratory resultes showed serum creatinine, 0.7±0.3 mg/dL; sodium, 137.9±8.1 mmol/L; potassium, 2.3±0.5 mmol/L; creatine kinase, 453±638 IU/L; and pH, 7.55±0.06. Serum creatine kinase was elevated more than 200 IU/L in seven patients (50%). Plasma renin activity and aldosterone concentration measured in 11 patients were suppressed. There was no evidence of adrenal gland masses on computed tomography and ultrasonography of the abdomen. Ten patients (71%) had been taking herbal medicines containing glycyrrhizin, and four (29%) had been taking a glycyrrhizin-containing preparation for chronic hepatitis. Seven patients (50%) had been taking diuretics for hypertension or edema. ST-segment depression was found in seven patients (50%). It was found more frequently in leads V4–6. There was no significant difference in serum potassium levels between patients with ST-segment depression and those without (2.2±0.5 vs 2.2±0.5 mmol/L, P=.76). QT interval was measurable in 11 patients and was 588±76 ms; it could not be measured in the remaining three patients because of an overlap between the end of the T wave and QRS in the next beat. Distinct U waves were found in six patients (43%). These were also found frequently in leads V3–4. There was no significant difference in serum potassium levels between patients with and without apparent U waves (2.3±0.5 vs 2.2±0.5 mmol/L, P=.67). Torsades de pointes (TdP) occurred in four patients (29%) within 24 hours after admission.7,8 There was no significant difference in age, sex, serum creatinine, sodium, or potassium levels (2.4±0.6 vs 2.1±0.4 mmol/L, P=.42) between patients with TdP and those without TdP. All four patients with TdP had a QT interval greater than 600 ms. Medications associated with hypokalemia were discontinued transiently or permanently. All patients were treated with potassium (intravenously or orally), spironolactone, or both. Serum potassium increased to 3.6±0.7 mmol/L after discharge (P<.001). Symptoms improved, and ECG changes resolved gradually during hospitalization. Intravenous magnesium sulfate and temporary overdrive ventricular pacing were required in two patients with TdP. In Japan, glycyrrhizin-containing medications (e.g., herbal medicines) are widely used and are often prescribed by clinicians.3,4 It is not well recognized that these medications may cause severe hypokalemia and various symptoms. Most patients in this study were elderly women. Thirty-seven cases of glycyrrhizin-induced pseudoaldosteronism in the literature were recently reviewed, and it was found that age 60 and older may be a risk factor for developing pseudoaldosteronism.3 The results of the current study were consistent with those of that report. In this study, there were various primary complaints, and syncope was found in three patients. Of these, two patients had TdP within 24 hours after hospital admission and were temporarily unconscious probably because of TdP. TdP is a life-threatening arrhythmia and requires proper treatment. Diuretics are often prescribed for hypertension or edema in patients with pseudoaldosteronism, as shown in this study. Diuretics accelerate hypokalemia, which may further worsen the symptoms. Therefore, a precise diagnosis should be obtained through meticulous history taking and regular follow-ups with patients. In conclusion, clinicians and individuals should be aware that glycyrrhizin-containing medications might cause various complications, including hypokalemia, particularly in elderly women. As a result, clinicians should closely monitor serum potassium levels and ECG when prescribing such medications. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: Study concept: Satoshi Kurisu, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara. Interpretation of data: Yuji Shimatani, Yasuharu Nakama, Tatsuya Maruhashi, Eisuke Kagawa, Kazuoki Dai, Toshiyuki Aokage, Junichi Matsushita, Hiroki Ikenaga. Preparation of letter: Satoshi Kurisu. Sponsor's Role: None.