Case Report Download full-text
www.thelancet.com Vol 373 March 28, 2009
An unusual cause of ventricular fi brillation
Karin G F Gerritsen, Jan Meulenbelt, Wilko Spiering, Ido P Kema, Ayse Demir, Vincent J H M van Driel
In January, 2007, a 44-year-old previously healthy woman
was admitted to the emergency department following
resuscitation from ventricular fi brillation. Electrocardio-
gram showed ST depression, but coronary angio graphy
showed no noteworthy stenosis. Transthoracic echo cardio-
graphy showed severe concentric left ventricular hyper-
trophy. Repeat electrocardiogram showed no ST depres sion,
but heart-rate -corrected QT interval was prolonged at
579 ms (normal ≤430 ms). Serum potassium was low at
2·0 mmol/L (3·8–5·0); sodium and magnesium were
nor mal. After 100 mEq of sodium bicarbonate infu sion
during resuscitation, bicarbonate was 22·7 mmol/L
(20–26) and lactate was 11·4 mmol/L (0–2·2), with an
arterial pH of 7·43 (7·37–7·45). Potassium chloride was
given. Within hours she developed metabolic alka losis
(pH 7·46 and bicarbonate 28·1 mmol/L) and hypertension
with blood pressure measurements up to 180/105 mm Hg;
intra venous antihypertensive therapy was given.
The triad of hypertension, hypokalaemia, and metabolic
alkalosis raised the suspicion of mineralocorticoid excess.
On day 2, endocrine work-up showed a mildly increased
plasma renin activity of 900 fmol/L per s (100–650 supine),
low plasma aldosterone concentration of 45 pmol/L
(80–450), and normal serum cortisol. Urinary free-cortisol
excre tion was high at 5·3 μmol/24h (0·09–0·45).
Cortisol meta bolite ratio ([tetra hydrocortisol+ 5α-tetra-
hydro cortisol]/tetrahydrocortisone) was high at 2·8
(0·55–1·3), indicating decreased activity of 11-β-hydro xy-
steroid dehydrogenase type 2 (11β-HSD-2).1 Our patient
then admitted that she had consumed 250–500 g of
liquorice daily for several years. Compatible with this, a
high urinary glycyrrhetinic acid was measured (132 μg/L;
normal <5 ug/L), accounting for the observed 11β-HSD-2
defi ciency. No other factors were identifi ed that could
account for the hypokalaemia or dysrhythmia. Potassium
infusion (decreasing dose) was continued for 7 days.
Antihypertensive medication was gradually reduced over
several weeks. 12 weeks later, stress-rest myocardial
SPECT examination showed no perfusion defects,
electrocardio gram was normal, and echocardiography
showed complete resolution of left ventricular hypertrophy.
Urinary free-cortisol excretion and urinary cortisol
metabolite ratio returned to normal. Hypokalaemia did
not recur and plasma renin activity and aldosterone were
normal. 1 year later blood pressure was 140/90 mm Hg
while on metoprolol 50 mg/day. Secondary hypertension
was excluded. She had stopped eating liquorice.
Our patient experienced severe liquorice-induced hypo-
kalaemia resulting in ventricular fi brillation. Although the
endocrine profi le the day after admission should be
interpreted with some reserve since it was infl uenced by
the acute event, the resolution of most of the symptoms
after liquorice cessation convinced us that liquorice was
the major culprit (fi gure).1 The elevated plasma renin
activity the day after admission probably resulted from
very strong stimulation of renin release by acute reduction
in renal blood fl ow and high sympathetic tone during the
cardiac arrest.2 It is remarkable that our patient did not
experience symptoms earlier, since chronic consumption
of 95 mg glycyrrhetinic acid daily (corresponding to
65–165 g liquorice con fectionery) can cause symptoms.3
Susceptibility to liquorice-induced adverse eff ects is
variable as a result of diff erences in the pharmacokinetics
and pharma codynamics of glycy rrhetinic acid among
individuals.4 Various dysrhythmias associated with
liquorice toxicity have been reported,1,5 although ventricular
fi brillation is a rather unusual presentation.
KG was involved in patient management, analysis of data, and writing the
report. JM, WS, VJHMvD participated in patient management, analysis of
the data and in the writing of the report. IK, AD, participated in analysis
of the patient’s samples and data, and in the writing of the report.
1 Quinkler M, Stewart PM. Hypertension and the cortisol-cortisone
shuttle. J Clin Endocrinol Metab 2003; 88: 2384–92.
2 Rouleau JL, Packer M, Moye L, et al. Prognostic value of
neurohumoral activation in patients with an acute myocardial
infarction: eff ect of captopril. J Am Coll Cardiol 1994; 24: 583–91.
3 Boganen H, Van Hee K, Grundmeijer HG. Hypertension due to
liquorice and liquorice tea consumption. Ned Tijdschr Geneeskd
2007; 151: 2825–28.
4 Ploeger B, Mensinga TT, Sips A, et al. A population physiologically
based pharmacokinetic/pharmacodynamic model for the inhibition
of 11-β-hydroxysteroid dehydrogenase activity by glycyrrhetic acid.
Toxicol Appl Pharmacol 2001; 170: 46–55.
5 Bannister B, Ginsburg R, Shneerson J. Cardiac arrest due to
liquorice-induced hypokalaemia. BMJ 1977; 2: 738–39.
Lancet 2009; 373: 1144
Department of Internal
Medicine (K G F Gerritsen MD),
Department of Intensive Care
(Prof J Meulenbelt MD),
Department of Vascular
Medicine (W Spiering MD),
Department of Cardiology
(V J H M van Driel MD),
University Medical Center of
Utrecht, University of Utrecht,
The Netherlands; Department
of Laboratory Medicine
(Prof I P Kema PhD), University
Medical Center of Groningen,
University of Groningen,
Groningen, The Netherlands;
and Department of Clinical
Chemistry, Meander Medisch
Centrum, Amersfoort, The
Netherlands (A Demir MD)
Dr Karin G F Gerritsen,
Department of Internal
Medicine, University Medical
Center Utrecht, University of
Utrecht, PO Box 85500,
3508 GA, Utrecht,
THF + 5α-THF
Figure: Consequences of liquorice ingestion
Liquorice contains glycyrrhizic acid (GD) which is metabolised to glycyrrhetinic acid (GA) by enzymatic hydrolysis
in the intestine. GA is a potent competitive inhibitor of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), an
enzyme highly expressed in mineralocorticoid target tissues such as renal cortex which rapidly converts cortisol (C)
to inactive cortisone (I). The mineralocorticoid receptor (MR) binds C and aldosterone (A) with equal affi nity.
Inhibition of 11β-HSD-2 by GA allows C to bind to the MR, causing manifestations of mineralocorticoid excess.