A Case of Pseudohyperaldosteronism Induced by Yokukansan and Shakuyakukanzoto That Resulted in Severe Hypokalemia.

Pseudohyperaldosteronism can be induced by the excessive use of Chinese herbal medicines (Kampo medicines), resulting in serious disorders. We report a case of pseudohyperaldosteronism induced by two Kampo medicines which resulted in severe hypokalemia. A 70-year-old woman was hospitalized for a left calcaneal fracture. She had no subjective symptoms other than trauma. On her admission, blood test results revealed a low serum potassium level of 2.4 mmol/L by chance, as well as low levels of both renin and aldosterone. The patient had been taking 5 g of Yokukansan per day for the past three months. In addition, she was on 5 g Shakuyakukanzoto per day for three months until a month prior to hospitalization. The daily licorice content from the aforementioned herbs was 1.0 g and 4.0 g, respectively. After hospitalization, the administration of the Kampo medicines was discontinued, and 610 mmol of potassium was administered over a period of 13 days, which resulted in the normalization of serum potassium levels. Pre-existing hypertension slowly improved as well. Patients consuming licorice at doses of 2.5 g per day or more, as in our case, are at a high risk of developing pseudohyperaldosteronism. Furthermore, the risk is particularly high with long-term licorice consumption as well as for women and elderly patients. To this end, high-dose potassium supplementation may be necessary for normalizing serum potassium levels. Therefore, awareness regarding the adverse effects of licorice is crucial, even in cases of low dosages of licorice.

Close Call From a Sweet Twist: A Case of Licorice-Induced Torsades De Pointes.

Torsades de pointes (TdP) is a life-threatening cardiac arrhythmia that can result from QT interval prolongation, sometimes secondary to medication adverse effects and electrolyte derangements. We present a 95-year-old Hispanic male with advanced chronic kidney disease (CKD) that was evaluated for dizziness and progressive weakness. The diagnosis of severe symptomatic hypokalemia and QT prolongation was made, and the patient was admitted for telemetry monitoring and aggressive intravenous electrolyte replacements. While under observation, the patient experienced syncope due to ventricular tachycardia (VT) with episodes of torsades de pointes. Due to refractory potassium depletion and hypertension, workup for hyperaldosteronism revealed renal potassium wasting, inappropriately normal plasma renin levels, and almost undetectable aldosterone levels. Careful analysis revealed the excessive chronic daily ingestion of licorice-containing candy twists and tea, which may cause pseudohyperaldosteronism. Licorice is a commonly used natural product that is available in many forms. It is sometimes used as a natural supplement and as a sweetener that can be widely found in many food products. Excessive ingestion can lead to apparent mineralocorticoid excess, reduced plasma potassium, sodium retention, hypertension, and metabolic alkalosis. Hypokalemia can be severe in some patients and lead to fatal cardiac arrhythmias such as ventricular tachycardia and torsades de pointes. Careful analysis is essential in cases of refractive hypokalemia and renal potassium wasting, especially in elderly patients with underlying renovascular disease.

Pseudo Hyperaldosteronism Secondary to Herbal Medicine Use.

Glycyrrhizic acid, better known as licorice, is commonly found in various food and cosmetic products. Excessive consumption is known to cause a syndrome of apparent mineralocorticoid excess or pseudo hyperaldosteronism. Patients typically present with resistant hypertension and hypokalemia mimicking symptoms of primary hyperaldosteronism however laboratory workup will reveal low or normal levels of plasma renin and aldosterone in the serum. While diagnosis of licorice toxicity is relatively straight forward, the challenge lies in determining the culpable agent. We report the case of a Chinese man who initially presented with resistant hypertension and hypokalemia refractory to therapy and was later diagnosed with pseudo hyperaldosteronism secondary to licorice toxicity.

A Case Report of Recurrent Hypokalemia During Pregnancies Associated With Nonaldosterone-Mediated Renal Potassium Loss.

RATIONALE: Geller et al reported a rare mutation in the mineralocorticoid receptor (MR) resulting in constitutive MR activity. Progesterone, normally an MR antagonist, acts as a potent agonist with this mutation. Progesterone levels can increase 100-fold during pregnancy and thus lead to increased MR activity in this setting, resulting in hypertension (HTN) and hypokalemia during pregnancy and resolution of hypokalemia after delivery. PRESENTING CONCERNS: Our patient was a 33-year-old African American female with a history of pregnancy-induced HTN associated with hypokalemia during her last pregnancy. She presented with muscle weakness from profound hypokalemia complicated by nephrogenic diabetes insipidus (DI) and rhabdomyolysis. DIAGNOSIS: Her admission potassium was 1.9 mmol/L (3.5-5.1 mmol/L) with a 24-hour urine potassium of 35 mmol per day and an unmeasurable serum aldosterone level. Her potassium normalized 1 day after delivery off potassium supplementation and amiloride, which were last given 1 day prior to her delivery. Recurrent hypokalemia from nonaldosterone-mediated renal potassium wasting during pregnancy (with normal potassium in a nongestational state) is consistent with the cases of gain-of-function mutation in MR that Geller et al report. A definite diagnosis requires genetic analysis. INTERVENTIONS: Her hypokalemia was refractory to potassium replacement but quickly responded to an inhibitor of the epithelial sodium channel (ENaC), amiloride. OUTCOMES: Her potassium normalized on amiloride 10 mg per day and KCL 40 mEq daily during the remainder of her pregnancy, and her nephrogenic DI resolved after this correction of hypokalemia. After her delivery, her potassium remained normal off the potassium supplements and amiloride. NOVEL FINDINGS: Pregnancy-induced hypokalemia from an activating MR mutation has rarely been reported. Pregnancy-induced HTN is often the first differential diagnosis in a patient who develops worsening in her HTN during pregnancy. We should also consider the possibility of a gain-of-function mutation in MR in these patients who also have associated hypokalemia.

JUSTIFICATION: En 2000, Geller et coll. ont rapporté l'existence d'une rare mutation du récepteur des minéralocorticoïdes (RM) entraînant une activité RM constitutive. La progestérone, un antagoniste des RM, agit comme un puissant agoniste sur cette mutation. Pendant la grossesse, les taux de progestérone peuvent être multipliés par 100 et cela entraîne une augmentation de l'activité des RM dans ce contexte, ce qui provoque de l'hypertension (HTN) et de l'hypokaliémie pendant la grossesse, et la résolution de l'hypokaliémie après l'accouchement. PRÉSENTATION DU CAS: Notre patiente était une Afro-Américaine de 33 ans avec des antécédents d'HTN induite par la grossesse et associée à une hypokaliémie au cours de sa précédente grossesse. La patiente présentait une faiblesse musculaire due à une grave hypokaliémie compliquée par un diabète insipide (DI) néphrogénique et une rhabdomyolyse. DIAGNOSTIC: Son taux de potassium à l'admission était de 1,9 mmol/L (3,5-5,1 mmol/L) avec un taux de potassium urinaire sur 24 heures à 35 mmol par jour et un taux d'aldostérone sérique non mesurable. Son taux de potassium s'est normalisé un jour après l'administration d'amiloride et d'un supplément de potassium, lesquels ont été administrés pour la dernière fois un jour avant l'accouchement. L'hypokaliémie récurrente découlant d'une perte rénale de potassium non médiée par l'aldostérone pendant la grossesse (avec taux de potassium normal dans un état non gestationnel) était conforme aux cas de mutation à gain de fonction des RM rapportés par Geller et coll. Un diagnostic précis nécessite une analyze génétique. INTERVENTIONS: L'hypokaliémie était réfractaire au remplacement du potassium, mais a rapidement répondu à l'amiloride, un inhibiteur du canal sodique épithélial (ENaC). RÉSULTATS: Le taux de potassium a été normalisé par l'administration de 10 mg d'amiloride et de 40 mEq de KCL par jour pour le reste de la grossesse. Le DI néphrogénique s'est résolu à la suite de cette correction de l'hypokaliémie. Après l'accouchement, le taux de potassium de la patiente est demeuré normal sans les suppléments de potassium et d'amiloride. PRINCIPALES OBSERVATIONS: L'hypokaliémie induite par la grossesse et découlant d'une mutation des RM activatrice a rarement été rapportée. L'HTN induite par la grossesse est souvent le premier élément de diagnostic différentiel chez une patiente dont l'HTN s'aggrave pendant la grossesse. Il convient aussi d'envisager une possible mutation à gain de fonction des MR chez ces patientes qui présentent également une hypokaliémie associée.

Licorice: From Pseudohyperaldosteronism to Therapeutic Uses.

Licorice has been used as a medicinal plant from 2.500 years. It shows a wide range of biological and pharmacological activities, including anti-inflammatory and immune regulatory actions. One of its most known effects is the induction of hypertension, and it can induce what appears to be pseudohyperaldosteronism, due to glycyrrhetinic acid, the main active component of the root. Glycyrrhetinic acid and metabolites block the 11 beta-hydroxysteroid dehydrogenase type 2 and also bind mineralocorticoid receptors directly, acting as agonists. However, other interesting therapeutic uses of licorice are linked to its anti-androgen and estrogen-like activity, especially in the treatment of polycystic ovary syndrome (PCOS) in conjunction with spironolactone therapy. In this brief review, we report the main features and possible therapeutic uses of this ancient plant.

Pseudohyperaldosteronism due to mumijo consumption during pregnancy: a licorice-like syndrome.

Herbal supplements are widely used during pregnancy, although there are insufficient data regarding their efficacy and safety. Some of them have been associated with hypertension, including licorice, which induces the so called mineralocorticoid-excess syndrome, a clinical picture resembling to pseudohyperaldosteronism. This action is mediated via inhibition of 11-hydroxysteroid dehydrogenase type 2 (11-HSD2), leading to impaired inactivation of cortisol to cortisone, accumulation of cortisol, and finally to excessive mineralocorticoid activity, especially in the distal and cumulative tubule of kidneys. This syndrome is characterized by hypertension and hypokalemia. Herein, we report a case of a 37-year-old pregnant woman, who was referred from obstetrics department to our department due to persistent hypertension and hypokalemia. She consumed a herbal supplement called "mumijo" during the last 6 months. After a thorough diagnostic work-up, the diagnosis of a "licorice-like syndrome" due to mumijo consumption was made. Potassium supplementation at the acute phase and discontinuation of mumijo were the treatment of choice. This is the first report of pseudohyperaldosteronism due to mumijo consumption in literature. Clinicians should be aware of this side effect and this agent should be included in those causing pseudohyperaldosteronism. Besides all, our case highlights the undeniable value of a detailed medical history.

Licorice abuse: time to send a warning message.

Licorice extract has always been recognized as a sweetener and a thirst quencher. Its nutritive value is overrated by many who consume significant amounts and are prone to complications. Glycyrrhetic acid, the active metabolite in licorice, inhibits the enzyme 11-ß-hydroxysteroid dehydrogenase enzyme type 2 with a resultant cortisol-induced mineralocorticoid effect and the tendency towards the elevation of sodium and reduction of potassium levels. This aldosterone-like action is the fundamental basis for understanding its health benefits and the wide spectrum of adverse effects. Herein, we present a comprehensive review of licorice along with the reported complications related to excess intake. Despite its apparent use in a few clinical scenarios, the daily consumption of licorice is never justified because its benefits are minor compared to the adverse outcomes of chronic consumption. The review highlights the importance of investigating the dietary habits and herbal remedies which are being used worldwide on cultural and habitual bases rather than reliable scientific evidence. Licorice is a US Food and Drug Administration (FDA) approved food supplement used in many products without precise regulations to prevent toxicity. Increased awareness among the public is required through TV commercials, newspapers, internet sites, magazines and product labels regarding the upper limit of ingestion and health hazards associated with excess intake. We hope that this review will serve as a warning message that should be transmitted from physicians to patients to avoid excessive licorice intake as well as a message to the FDA to start regulating the use of this substance.