| Abstract |
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INTRODUCTION |
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Potassium is the most abundant cation
in the human body and is important for neuromuscular and cardiovascular
tissue excitability. It is tightly maintained in the narrow range of
3.5 – 5.5 mEq/L. Hypokalemia may manifest with muscle weakness
(as 98% of the intracellular potassium is in the skeletal muscle) or
paralysis including intestinal ileus, cardiac arrhythmias, rhabdomyolysis,
renal dysfunction or hyperglycemia. |
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Hypokalemia may occur due to several
causes including renal and extrarenal losses. |
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We report a case of a young female
with quadriparesis secondary to severe hypokalemia due to acquired Apparent
Mineralocorticoid Excess (AME). |
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CASE REPORT |
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A 31 years female presented to us
with a 15-day history of poor oral intake and occasional vomiting which
occurred after some strenuous exercise. On the day of seeking medical
attention, she had bilateral thigh pain, followed by symmetrical lower
limb weakness and then bilateral upper limb weakness. Features suggestive
of neck and truncal muscle weakness soon followed this. She was treated
at a peripheral center with steroids. |
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She was married since 9 years and
had never conceived. An extensive evaluation for infertility had been
done which did not reveal any signifi cant abnormality. She had been
on alternative medicine for infertility for several months and had discontinued
the same a month prior. |
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On examination she was averagely built,
hemodynamically stable with a blood pressure of 110/70 mm of Hg. General
examination was unremarkable. Central nervous system examination revealed hypotonia and a grade 3/5 power in all the four extremities, proximally and distally. Deep tendon refl exes were absent, abdominal refl ex was absent and plantars were fl exor. |
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Investigations revealed severe hypokalemia
(S. K+ 1.62 mmol/L). Rest of the serum electrolytes and renal functions
were normal (Table 1). Complete hemogram, liver functions, blood sugars,
serum calcium, magnesium and urine analysis were normal. ABG showed
pH 7.407, pCO2 31.9 mmHg, pO2 114.9 mm Hg, HCO3 19.7 mmol/L, tCO2 21.3
mmol/L and saturation 98.5%. Urine spot potassium was 10.86 mmol/L whereas
urinary Na+ and Cl- were 70.7 mmol/L and 82.2 mmol/L respectively. |
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To differentiate between renal and
extrarenal loss a 24 hour urinary Na+ and K+ were estimated. 24-hour
urinary Na+ was 79.9 mmol and K+ was 15.99 mmol. A 24-hour urinary K+
loss more than 20 mmol, in the presence of adequate urinary Na+ excretion
of > 100 mmol/day is indicative of excessive renal K+ loss. Renal
Na+ excretion is measured because distal nephron Na+ delivery is rate
limiting for K+ secretion. If distal nephron Na+ delivery is reduced,
as approximated by the urinary Na+ excretion of <100 mmol/day, renal
K+ excretion may also be limited and thus mask excessive renal K+ losses.
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The transtubular K+ gradient (TTKG)
can provide a semiquantitative urinary index of the activity of the
K+ secretory process in the kidney. This equation describes the ratio
of urinary to venous K+ concentration after adjusting the urine K+ concentration
of medullary water abstraction: Ur K+ / Sr K+ Ur Osmolality/Plasma osmolality |
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The use of TTKG is restricted to situations
in which the urine is not hypotonic and distal nephron sodium delivery
is adequate for normal K+ secretion. In hypokalemic patients with renal
K+ wasting TTKG would be more than 10 and less than 2 in case of extra
renal losses. In our case, we could not estimate TTKG due to non availability
of estimating osmolality. |
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Another way to differentiate between
renal and extra-renal loss of potassium is to estimate fractional excretion
of K+. Patients with hypokalemia resulting from extra- renal K+ losses
would have a mean fractional excretion of 2.8% where as those with renal
loss would have values of more than 15%. Since we did not have a urinary
creatinine value, we could not estimate the fractional excretion of
potassium. |
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She was administered a total of 530
mmol of KCL intravenously over 5 days resulting in Serum K+ correction
to 4.17 mmol/L. Her muscle weakness improved remarkably with correction
of the potassium. She was discharged on day 6 with normal muscle power. |
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On probing, the patient admitted to
consuming some alternative medicine pills for infertility, the contents
of which are noted in Table 2. These capsules contained Glycyrrhiza
glabra, a steroid-like glycoside contained in natural licorice, which
has potent mineralocorticoid properties. |
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DISCUSSION |
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Licorice (Glycyrrhiza glabra) is a
fi avored herb that has been used in food and several medicinal remedies
for thousands of years. It is also known as “sweet root”.
It has traditionally been used to prevent and treat a number of ailments
including respiratory ailments, stomach ulcers, chronic hepatitis and
heart disease. It is also supposed to reduce the blood levels of LDL
cholesterol and triglycerides decrease infi ammation and stimulate the
activity of the adrenal glands. |
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The active ingredient of licorice
is glycyrrhizic acid, which is hydrolyzed into glycyrrhetinic acid in
vivo. Glycyrrhizic and glycyrrhetinic acids have a very low affi nity
for the mineralocorticoid receptor (MR) but are very potent competitive
inhibitors of 11- beta hydroxysteroid dehydrogenase2 (11 bHSD2), coexpressed
with MR in the distal nephron. This enzyme is responsible for the conversion
of cortisol to it inactive metabolite cortisone. Defi ciency of this
enzyme results in an increase in plasma cortisol half life, and a decrease
in circulating cortisone values resulting in an acquired and milder
form of apparent mineralocorticoid excess (AME) syndrome, similar to
congenital mutation of the gene for 11 bHSD2.1 With defi ciency of this
enzyme, the excess of cortisol binds to and activates the mineral-corticoid
receptors2 and exerts a mineralcorticoid like activity leading to sodium
retention, kaliuresis, accounting for the hypokalemia, suppression of
plasma renin activity (PRA), hypertension and metabolic alkalosis.3
Licorice, by inhibiting 11 bHSD2, can induce an acquired AME. |
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The case discussed here had only hypokalemia
and no evidence of metabolic alkalosis. Besides she was also normotensive
and urine potassium was low. The most plausible explanation for the
lack of the other features of chronic licorice ingestion is that since
the patient had discontinued these pills a month prior, the other effects
of metabolic alkalosis and hypertension must have dissipated. Her urinary
potassium was low probably because of excessive conservation by the
kidneys as the potassium was not replenished at any time prior to admission.
Epstein et al studied several subjects with chronic licorice ingestion
and found that the renin aldosterone axis was suppressed while the patient
was consuming licorice, but normal renal function resumed within 2 –
4 months after its discontinuation.4 |
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Licorice ingestion presenting solely
with hypokalemia leading to severe fi accid quadriparesis, without any
hypertension, metabolic alkalosis or kaliuresis is a rare fi nding. Observing
the serum potassium is an important aspect in the follow up of this
case. |
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REFERENCES |
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1. Mario Palermo, Marcus Quinkler,
Paul M.Stewart. Apparent Mineralocorticoid Excess Syndrome: An Overview.
Arq Bras Endocrinol Metab 2004;48:687-96. |
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2. Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CHL, Edwards CRW. Mineralocorticoid activity of licorice: 11-beta-hydroxysteroid dehydrogenase activity comes of age. Lancet 1987;2:821-4. 3. Robert V Farese, Edward G Biglieri, Cedric HL Shackleton, Ilan Irony, Rosita Gomez-Fontes. Licorice-Induced Hypermineralocorticoidism. New Engl J Med 1991;325:1223-7. 4. Epstein MT, Espiner EA, Donald RA, Hughes H. liquorice toxicity and the renin-angiotensin-aldosterone axis in man. BMJ 1977;1:209-10. |
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