Transcript Seminars in nephrology 2006 : 26(6) 434-440

Hypokalemia and Mineralocorticoid hypertention
Nephrology
R3 이 홍 주
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Hypokalemia
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Mineralocorticoid hypertension
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Licorice & hypokalemia
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defined as a plasma K+ concentration <3.5 mmol/L
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decreased net intake
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shift into cells
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increased net loss.
Harrison
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Triad
hypertension
metabolic alkalosis
Hypokalemia
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Caused by
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increased retention of sodium by the nephron
expansion of the extracellular fluid compartment
suppression of plasma renin
Diagnosis based on responsible mineralocorticoid…
Aldosterone
adrenal adenoma
bilateral adrenal hyperplasia
adrenal carcinoma
GRA(glucocorticoid-remediable hyperaldosteronism)
Cortisol via 11 β-hydroxysteroid dehydrogenase deficiency/inhibition
AME(apparent mineralocorticoid excess)
Licorice and carbenoxolone ingestion
Ectopic ACTH syndrome
?? Essential hypertension variant
?? Pre-eclampsia
Deoxycorticosterone
Congenital adrenal hyperplasia
Glucocorticoid receptor mutations
Metyrapone, mifrestone ingestion
Seminars in nephrology 2006 : 26(6) 434-440
Figure 2 Relation of the Plasma
Aldosterone Concentration to
the Ratio of Plasma
Aldosterone to Plasma Renin
Activity in Various Conditions
of Mineralocorticoid
Deficiency or Excess.
N Engl J Med 1994; 331:250-258
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root of the Glycyrrhiza glabra
used throughout the millennia for its taste and for medical purposes
name "liquorice" or "licorice" is derived from the old French licoresse and
the ancient Greek work glukurrhiza, meaning "sweet root.“
Glycyrrhizin (GL), a component of licorice roots
 Metabolized to glycyrrhetinic acid (GA)
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In the Middle Ages) used for treatment of hypotension.
In 1946) good results in the treatment of stomach ulcers
… developed hypokalaemia and an increase in blood pressure.
Ned Tijdschr Geneeskd. 1946;90:135-137 F.E. Revers
aldosterone secretion was suppressed in liquorice-induced hypertension :
‘pseudohyperaldosteronism’
Conn
reported use
Adrenal insufficiency (Davis, 1991)
Aphthous ulcers/cancer sores (Worner, 1974)
Atopic dermatitis (Saeedi, 2003)
Body fat mass reduction (Armanini, 2003)
Crohn's disease (pharmacologic activity)
Expectorant and antitussive (Bradley, 1992)
Gastrointestinal ulceration (Dehpour, 1994)
Herpes simplex (Sekizawa, 2001)
Hyperkalemia (Murakami, 1993)(Nicola, 2008)
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J Clin Hypertens 2008;10:153–157
glycyrrhetinic acid
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Fatigue and muscle cramping
Dark urine (myoglobinuria)
Weakness (hypokalemia, myopathies)
Polyuria/nocturia (increased extracellular volume)
Edema (increased extracellular volume)
Dyspnea (pulmonary edema)
Headache (hypertension)
Paresthesias/dysesthesias
Impotence and diminished libido
Amenorrhea
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High blood pressure
Hypertensive encephalopathy with stroke-like effects
Spasms/tetany
Hyporeflexia, muscle wasting, weakness, flaccid paralysis
Myoglobinuria/rhabdomyolysis
Trousseau and Chvostek signs (from hypokalemia with alkalosis)
Cardiac arrest, dysrhythmias (rare) from hypokalemia
Hypokalemia, increased urinary excretion of potassium
Mildly elevated creatine, metabolic alkalosis
Elevated creatine kinase
Decreased plasma renin activity, aldosterone levels
Increased urinary cortisol , decreased cortisone
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Relatively small amounts of licorice, as little as 50 g daily for two weeks,
produce a rise in blood pressure in normal people
Regular daily intake of glycyrrhizic acid 100mg (licorice 2.5g) produces
adverse effects in sensitive individuals
Glycyrrhizic acid 400mg (licorice 10g) produces adverse effects in most
subjects  edema HTN
World Health Organization
Severe hypokalemia & rhabdomyolysis
1개월간 500g 가량의 감초를 복용
7 년간 280 mg/d의 글리시리진을 복용
5 g of licorice per day for the last 7 years
200 g of licorice a day for 4 weeks
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Cessation of licorice ingestion
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The time required for correction : varies from days to weeks
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Large volume of distribution and long biological half-life of glycyrrhetic
acid
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Spironolactone
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KCl supplementation
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Dexamethasone
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causes suppression of endogenous cortisol production
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reduces the cortisol-mediated stimulation of the mineralocortcoid
receptor