Quiz Page June 2010:
A Case of Severe Hypokalemic Paralysis and Hypertension
Article Outline
Clinical Presentation
A 65-year-old man presented to the emergency department with 4 days of progressive muscular weakness. Weakness developed first in his legs and hands, progressed to his arms and thighs, and finally involved his torso. He denied nausea, vomiting, diarrhea, tingling or numbness in his legs and arms, recent strenuous exertion, and alcohol use. His medical history included diabetes mellitus type 2, hypertension, and hyperlipidemia. He had bilateral leg swelling for 6-8 months, for which he was treated with furosemide. He denied chest pain, shortness of breath, orthopnea, or decrease in urinary output.
Physical examination was significant for increased blood pressure of 182/92 mm Hg, symmetrical flaccid paralysis with areflexia in all extremities, and bilateral pedal edema. Laboratory investigations showed the following values: sodium, 140 mEq/L (140 mmol/L); potassium, 1.8 mEq/L (1.8 mmol/L); chloride, 92 mEq/L (92 mmol/L); bicarbonate, 35 mEq/L (35 mmol/L); serum urea nitrogen, 25 mg/dL (8.92 mmol/L); serum creatinine, 1.7 mg/dL (150.28 μmol/L); estimated glomerular filtration rate, 43.2 mL/min/1.73 m2 (0.72 mL/s/1.73 m2) calculated using the 6-variable Modification of Diet in Renal Disease (MDRD) Study equation; albumin, 2.8 g/dL (28 g/L); calcium, 7.8 mg/dL (1.94 mmol/L); and creatine kinase, 2,980 U/L. Urine electrolyte values were as follows: potassium, 51.9 mEq/L (51.9 mmol/L), and osmolality, 500 mOsm/kg (500 mmol/kg). Serum osmolality was 298 mOsm/kg (298 mmol/kg). Calculated transtubular potassium gradient was 17.2. Further testing showed plasma renin activity (PRA) of 0.31 ng/mL/h (0.08 ng/L/s; reference range for nonhypertensive upright adults, 0.65-5.0 ng/mL/h [0.18-1.39 ng/L/s]); serum aldosterone (upright, 8:00 am), 3 ng/dL (0.08 nmol/L; reference ranges, ≤28 ng/dL [0.78 nmol/L; upright, 8:00-10:00 am]; ≤21 ng/dL [0.58 nmol/L; upright, 4:00-6:00 pm]; and 3-16 ng/dL [0.08-0.44 nmol/L; supine, 8:00-10:00 am]), thyroid-stimulating hormone, 0.70 mIU/mL (reference range, 0.34-4.82 mIU/mL); and cortisol, 12.61 μg/dL (347.9 nmol/L; reference range, 3.09-16.60 μg/dL [85.25-457.99 nmol/L]).
■ What is the differential diagnosis of hypokalemia in this patient?
■ What laboratory investigations are useful in evaluating this condition?
■ What is the treatment for this condition?
Discussion
What is the differential diagnosis of hypokalemia in this patient?
This patient had hypertension, hypokalemia, and bilateral symmetrical muscle weakness associated with low aldosterone and renin levels. Decreased potassium intake is rarely the sole cause of hypokalemia because urinary excretion of potassium can be decreased efficiently to <15 mEq/d.1 Hypokalemia caused by transcellular shift is transient, as seen with thyrotoxic periodic paralysis or hypokalemic periodic paralysis. Hypokalemia more commonly is caused by either increased gastrointestinal loss or urinary loss. In our patient, gastrointestinal loss could be excluded because the patient denied diarrhea. To explore the cause of hypokalemia from urinary losses associated with hypertension, PRA will narrow the differential diagnosis: (1) increased PRA: secondary hyperaldosteronism (renovascular hypertension, diuretics, renin-secreting tumor, malignant hypertension, and coarctation of the aorta); and (2) low PRA: primary hyperaldosteronism, Cushing syndrome, exogenous mineralocorticoids, Liddle syndrome, and licorice and carbenoxolone ingestion.
What laboratory investigations are useful in evaluating this condition?
Plasma aldosterone levels and PRA are the most helpful laboratory tests to make the diagnosis (Fig 1). Both plasma aldosterone concentration and PRA were less than the reference range, which excluded the possibility of primary and secondary hyperaldosteronism. Serum cortisol level was normal; however, the increased transtubular potassium gradient suggested urinary loss of potassium. Careful history taking showed that the patient was ingesting bags of licorice imported from The Netherlands, which led to this mineralocorticoid excess state. Licorice is made from the root of Glycyrrhiza glabra. Metabolized to glycyrrhetic acid, it inhibits the enzyme 11-β hydroxysteroid dehydrogenase 2 (encoded by the HSD11B2 gene), which converts active cortisol to locally inactive cortisone at the renal tubule.2 The accumulated cortisol has mineralocorticoid-like activity that acts on the receptor in the distal convoluted tubules, causing sodium retention and potassium wasting, and leads to a state of hypertension and hypokalemia.3
Figure 1.
An approach to hypokalemia with hypertension. Abbreviations: CAH, congenital adrenal hyperplasia; MC, mineralocorticoid activity; PAC, plasma aldosterone concentration; PRA, plasma renin activity.
What is the treatment for this condition?
Licorice-induced mineralocorticoid effect usually is reversible upon cessation of licorice ingestion. It also responds to spironolactone therapy.3 Dexamethasone may be considered because it suppresses endogenous cortisol production and thus decreases cortisol-mediated mineralocorticoid activity.3 The time required for correction of the potassium deficit after stopping licorice ingestion varies from days to weeks because of the large volume of distribution and long biological half-life of glycyrrhetic acid.3 This patient was admitted to the intensive care unit, and after 3 days of continuous supplements, serum potassium level (Fig 2) normalized and clinical symptoms improved. He was discharged on oral potassium supplement therapy and advised not to eat licorice. At 2 weeks' follow-up, blood pressure was 140/60 mm Hg and chemistry test results included the following values: potassium, 4.5 mEq/L (4.5 mmol/L); serum creatinine, 1.0 mg/dL (88.4 μmol/L); and estimated glomerular filtration rate, 79.7 mL/min/1.73 m2 (1.3 mL/s/1.73 m2) off potassium supplements.
Figure 2.
Serum potassium levels during hospitalization. No units conversion necessary for serum potassium in mEq/L and mmol/L.
Final Diagnosis
Licorice-induced hypokalemic paralysis.
References
- . Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice. Intern Med. 2007;46(9):575–578
- . History of the endocrine effects of licorice. Exp Clin Endocrinol Diabetes. 2002;110(6):257–261
- . Severe hypokalaemic paralysis and rhabdomyolysis due to ingestion of liquorice. Neth J Med. 2005;63(4):146–148
Support: None.
Financial Disclosure: The authors declare that they have no relevant financial interests.
PII: S0272-6386(10)00123-X
doi:10.1053/j.ajkd.2010.02.003
© 2010 National Kidney Foundation, Inc. All rights reserved.
