E-Poster Presentation ESA-SRB-ANZBMS 2021

A pharmacological Conn artist: The hazards of licorice in complementary medicine (#397)

Justin J Lee 1 , Annabelle M Warren 1 , Jeffrey D Zajac 1
  1. Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia

Background

Glycyrrhizin glabra, licorice root, is an ingredient in traditional herbal remedies and confectionery products. Its main active ingredient, glycyrrhizin, has anti-inflammatory and antioxidant effects,(1) but also has a potentially hazardous association with pseudohyperaldosteronism.(1)

Case

A 17-year-old girl presented to the emergency department with chest pain, nausea and tremors. She had been suffering from intermittent nausea and abdominal pain for two years but had no other medical conditions, no regular prescription medication, and denied any substance abuse. Physical examination was unremarkable except for a tachycardia of 110 beats per minute with a blood pressure of 102/62mmHg. Blood tests revealed hypokalaemia 2.8mmol/L (3.6-5.2mmol/L), elevated lactate 8.7mmol/L (0.5-2.2mmol/L), and leukocytosis 17.9 x 109/L (4.0-12.0 x 109/L). Serum aldosterone and renin were 151pmol/L and 28pmol/L respectively, with an aldosterone-renin ratio of 5.4.

Further history revealed she had taken “GIT Regenex”, a herbal remedy containing Glycyrrhizin glabra, for ten days prior. Dosing instructions for this remedy recommended a daily glycyrrhizin intake of 157.34mg, exceeding the daily maximum of 100mg recommended by the World Health Organisation. She responded well to oral potassium and intravenous magnesium replacement overnight and was discharged home.  A safety report was sent to the Therapeutic Goods Administration for GIT Regenex.

Discussion

Intestinal bacteria convert glycyrrhizin to 3-monoglucoronyl-18-glycyrrhetinic acid and glycyrrhetinic acid (GA).(2) GA inhibits the 11β – hydroxysteroid dehydrogenase 2 enzyme in the distal nephron, decreasing conversion of cortisol to cortisone, and increasing mineralocorticoid receptor activation through cortisol binding.(2) This causes kaliuresis and fluid retention similar to primary aldosteronism, but with normal or low serum aldosterone and renin.(3) At least 16 individual cases and 18 clinical trials have described weakness, hypertension, and even ventricular arrhythmias associated with licorice since 1970.(3-18)

Conclusion

Our case highlights the need to consider licorice-induced pseudohyperaldosteronism caused by complementary therapies in the differential diagnosis of hypokalaemia.

  1. 1. Kwon YJ, Son DH, Chung TH, Lee YJ. A Review of the Pharmacological Efficacy and Safety of Licorice Root from Corroborative Clinical Trial Findings. J Med Food. 2020;23(1):12-20.
  2. 2. Sabbadin C, Bordin L, Donà G, Manso J, Avruscio G, Armanini D. Licorice: From Pseudohyperaldosteronism to Therapeutic Uses. Front Endocrinol (Lausanne). 2019;10:484.
  3. 3. Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Hum Hypertens. 2017;31(11):699-707.
  4. 4. Varma R, Ross CN. Liquorice: a root cause of secondary hypertension. JRSM Open. 2017;8(2):2054270416685208
  5. 5. Flores-Robles BJ, Sandoval AR, Dardon JD, Blas CA. Lethal liquorice lollies (liquorice abuse causing pseudohyperaldosteronism). BMJ Case Rep. 2013;2013.
  6. 6. Kageyama Y. A case of pseudoaldosteronism induced by glycyrrhizin. Nihon Jinzo Gakkai Shi. 1992;34(1):99-102.
  7. 7. Hamidon BB, Jeyabalan V. Exogenously-induced apparent hypermineralocorticoidism associated with ingestion of "asam boi". Singapore Med J. 2006;47(2):156-8.
  8. 8. Holmes AM, Young J, Marrott PK, Prentice E. Pseudohyperaldosteronism induced by habitual ingestion of liquorice. Postgrad Med J. 1970;46(540):625-9.
  9. 9. Hataya Y, Oba A, Yamashita T, Komatsu Y. Hyponatremia in an Elderly Patient due to Isolated Hypoaldosteronism Occurring after Licorice Withdrawal. Intern Med. 2017;56(2):175-9.
  10. 10. Gallacher SD, Tsokolas G, Dimitropoulos I. Liquorice-induced apparent mineralocorticoid excess presenting in the emergency department. Clin Med (Lond). 2017;17(1):43-5.
  11. 11. Foster CA, Church KS, Poddar M, Van Uum SH, Spaic T. Licorice-induced hypertension: a case of pseudohyperaldosteronism due to jelly bean ingestion. Postgrad Med. 2017;129(3):329-31.
  12. 12. Kwon YE, Oh DJ, Choi HM. Severe asymptomatic hypokalemia associated with prolonged licorice ingestion: A case report. Medicine (Baltimore). 2020;99(30):e21094.
  13. 13. Eriksson JW, Carlberg B, Hillörn V. Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia. J Intern Med. 1999;245(3):307-10.
  14. 14. Cumming AM, Boddy K, Brown JJ, Fraser R, Lever AF, Padfield PL, et al. Severe hypokalaemia with paralysis induced by small doses of liquorice. Postgrad Med J. 1980;56(657):526-9.
  15. 15. Crean AM, Abdel-Rahman SE, Greenwood JP. A sweet tooth as the root cause of cardiac arrest. Can J Cardiol. 2009;25(10):e357-8.
  16. 16. Smedegaard SB, Svart MV. Licorice induced pseudohyperaldosteronism, severe hypertension, and long QT. Endocrinol Diabetes Metab Case Rep. 2019;2019.
  17. 17. de Klerk GJ, Nieuwenhuis MG, Beutler JJ. Hypokalaemia and hypertension associated with use of liquorice flavoured chewing gum. BMJ. 1997;314(7082):731-2.
  18. 18. Buhl LF, Pedersen FN, Andersen MS, Glintborg D. Licorice-induced apparent mineralocorticoid excess compounded by excessive use of terbutaline and high water intake. BMJ Case Rep. 2018;2018.