Risk Factors for Pseudoaldosteronism with Yokukansan Use: Analysis Using the Japanese Adverse Drug Report (JADER) Database.

Yokukansan is a Kampo formula that is commonly used by the elderly because it is expected to improve peripheral symptoms of dementia and delirium. However, side effects from its use are frequently reported in the elderly. In particular, pseudoaldosteronism caused by the licorice contained in yokukansan leads to hypertension, hypokalemia, and muscle weakness, which may result in death. This study aimed to identify the risk factors of pseudoaldosteronism with yokukansan use. Using cases reported in the Japanese Adverse Drug Report (JADER) database, the reporting odds ratio (ROR) was calculated and compared to assess the risk of pseudoaldosteronism for each licorice-containing Kampo formula. We also analyzed the risk factors for pseudoaldosteronism in patients taking yokukansan. Yokukansan (ROR 2.4, 95% confidence interval (CI) 1.9-2.8; p < 0.001) had a higher risk of pseudoaldosteronism than that of other licorice-containing Kampo formulas. Furthermore, the results of a logistic regression analysis in patients taking yokukansan showed that the licorice dose (OR 1.5, 95% CI 1.2-2.0; p < 0.01), older age (<70 years, OR 5.9, 95% CI 1.8-20; p < 0.01), dementia (OR 2.8, 95% CI 1.6-4.9; p < 0.001), low body weight (<50 kg, OR 2.2, 95% CI 1.1-3.5; p = 0.034) were risk factors for pseudoaldosteronism, Although not significant, treatment with loop diuretics (OR 1.8, 95% CI 0.98-3.5; p = 0.059) tended to increase the risk of pseudoaldosteronism. In summary, patients must understand the risk factors when considering taking yokukansan and reduce the licorice dose they consume.

Liddle syndrome: clinical and genetic profiles.

Liddle syndrome is a rare autosomal dominant monogenic form of hypertension. The authors analyzed clinical and genetic features of 12 cases of Liddle syndrome, the largest sample size ever reported. Clinical data were studied retrospectively. The exon 13 of the ß and γ subunits of the epithelial sodium channel were amplified and sequenced in the peripheral blood leukocytes of the patients. The onset age of the 12 patients was 15.5±3.3 years. Their blood pressures were poorly controlled, and serum potassium levels in most patients were <3.0 mmol/L. Upright plasma renin activity and plasma aldosterone concentration were suppressed in all patients. All patients were treated with triamterene, and blood pressures were well controlled and serum potassium levels returned to normal. The serum creatinine level rose to 124 and 161 µmol/L, respectively, in two patients upon triamterene treatment, and returned to normal soon after treatment was discontinued. Eight mutation alleles were identified, and three mutations were newly identified.

Prevalence of Liddle Syndrome Among Young Hypertension Patients of Undetermined Cause in a Chinese Population.

Liddle syndrome, an autosomal dominant form of monogenic hypertension, has been regarded as a rare disorder, which leads to many Liddle syndrome patients being misdiagnosed and experiencing severe complications at an early age. Little is known about the prevalence of Liddle syndrome. In this study, the authors investigated the prevalence of Liddle syndrome confirmed by genetic testing among young hypertension patients of undetermined causes in China. A total of 330 hypertensive patients aged 14 to 40 years after exclusion of common secondary causes of hypertension were enrolled and serum potassium concentrations were measured. Patients with hypokalemia underwent genetic testing of the 13th exon of genes encoding ß and γ subunits of the epithelial sodium channel (ENaC). Diagnosis was established by identification of mutations that destroy the PY motif of ENaC. Five patients were diagnosed with Liddle syndrome (prevalence, 1.52%), as well as 12 of their relatives. These patients with Liddle syndrome presented with an earlier onset of hypertension, a stronger family history of hypertension, and higher blood pressure than those with essential hypertension. All patients had hypokalemia and suppressed plasma renin activity. The results demonstrated that Liddle syndrome is an important etiology of hypertension in this young population. Screening of Liddle syndrome should focus on young hypertension patients, particularly those with early penetrance, hypokalemia, and low renin levels after exclusion of common secondary causes.

Risk factors for pseudoaldosteronism with rhabdomyolysis caused by consumption of drugs containing licorice and differences between incidence of these conditions in Japan and other countries: case report and literature review.

BACKGROUND: The pathogenesis of licorice-induced pseudoaldosteronism is thought to involve the inhibition of 11ß-hydroxysteroid dehydrogenase type 2 by glycyrrhetinic acid. Some risk factors have been reported, but differences between Japan and other countries have not been reported. CASE PRESENTATION: A 79-year-old woman was hospitalized because of pseudoaldosteronism with rhabdomyolysis caused by ingestion of herbal medicines containing licorice. She had been prescribed shakuyakukanzobushito (decocted, 3 g of licorice) and keishikajutsubuto (decocted, 2 g of licorice) for the treatment of lower back pain and had been taking antihypertensive agents for the treatment of essential hypertension. After taking the herbal medicines for 2 weeks, the patient developed weakness of the extremities and pain in both thighs. On admission, she had hypertension, oliguria, an elevated serum creatine kinase level, hypokalemia, alkalemia associated with metabolic alkalosis, low plasma renin activity, and low plasma aldosterone levels. Intravenous and oral potassium supplementation and the administration of spironolactone resulted in the normalization of her condition within approximately 2 weeks. DISCUSSION: An analysis of case reports of pseudoaldosteronism with rhabdomyolysis revealed that in Japan, most cases occurred in elderly women with essential hypertension and were caused by drugs such as herbal medicines. In contrast, in other countries, many cases involved younger men, and the dominant causes were foods containing licorice. The use of herbal medicines is increasing all over the world, and when a patient with risk factors is prescribed an herbal medicine containing licorice, careful follow-up is required.

High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana.

Liddle syndrome (LS) is an autosomal dominant disorder due to a gain-of-function mutation in the epithelial Na(+) channel and is perceived to be a rare condition. A cross-sectional study of 149 hypertensive patients with hypokalemia (<4 mmol/dL) or elevated serum bicarbonate (>25 mmol/dL) was conducted at a Veterans' Administration Medical Center Hypertension Clinic in Shreveport, LA. Data on demographics, blood pressure, and select blood tests were collected and expressed as percentages for categoric variables and as mean ± standard deviation (SD) for continuous variables. Patients were diagnosed with likely LS when the plasma renin activity (PRA) was <0.35 µU/mL/h and the aldosterone was <15 ng/dL and likely primary hyperaldosteronism (PHA) with PRA <0.35 µU/mL/h and aldosterone level >15 ng/dL. The cohort included predominantly elderly (67.1±13.4 years), male (96%), and Caucasian (57%) patients. The average blood pressure was 143.8/79.8 mm Hg±27.11/15.20 with 3.03±1.63 antihypertensive drugs. Based on the above criteria, 9 patients (6%) satisfied the criteria for likely LS and 10 patients (6.7%) were diagnosed with likely PHA. In this hypothesis-generating study, the authors detected an unusually high prevalence of biochemical abnormalities compatible with likely LS syndrome from Northwestern Louisiana, approaching that of likely PHA.