Discussion:
AKI due to Tenofovir nephrotoxicity was the primary driver of
hypokalemia in our patient evidenced by transtubular potassium gradient
(TTKG) of 9. However with refractoriness to therapy based on the
calculated potassium deficit, non-renal etiology was suspected.
The intracellular compartment holds 98% of total potassium in the human
body and only about 60 mmol of potassium fills the extracellular
potassium pool [3]. The usual daily requirement is approximately 1
mEq per kilogram. Potassium deficit can be calculated by the formula: K
deficit (in mEq) = (Knormal lower limit − Kmeasured) × kg body
weight × 0.4. In our patient, if we consider the lowest potassium of 1.7
mEq/L and weight of 71 kg, potassium replacement dose in the 1st 24-hour
would be 121.4 mEq. Potassium level after 180 mEq of potassium
replacement within 24h in the 2nd hospital was 1.8 (additional 20mEq was
given in 1st hospital making the total to 200mEq; see Table-2). The case
had an absence of reported instigating factors associated with
hypokalemia such as primary hyperaldosteronism, hypomagnesemia,
hyperglycemia, vitamin B12 therapy, insulin therapy, bicarbonate
therapy, β2-adrenergic agonist therapy. Refractory hypokalemia
presenting as muscle weakness would include thyrotoxic periodic
paralysis in the differential diagnosis. The patient’s thyroid hormone
levels were consistent with primary hyperthyroidism as the thyroid
stimulating hormone (TSH) level was below the reference range and free
triiodothyronine (fT3) level elevated. The T3 toxicosis likely led to
thyrotoxic periodic paralysis precipitating recurrent hypokalemia in the
case. Notably patient’s free thyroxine level was not elevated (Table-1).
Muscle weakness in thyrotoxic periodic paralysis is a medical emergency
and acute hypokalemia correlates with the severity of paralysis [4]
Thyroid hormones are known to increase the expression and activity of
Na+/K+-ATPase [3]. It is estimated that if all the Na+/K+-ATPase
pumps in the skeletal muscles are activated to their maximum potential,
then the entire extracellular potassium pool (approximately 60mmol) may
be taken up into the muscle cells within 25 seconds [5]. Exercising
muscles release potassium and cause vasodilation [6]. In thyrotoxic
periodic paralysis, the potassium is redistributed to intracellular
compartment, predisposing to hypokalemia and rhabdomyolysis. In our
patient, the T3 toxicosis lead to hyperactivity of Na+/K+-ATPase pumps
leading to transcellular potassium shift, causing severe, recurrent,
refractory acute hypokalemia. As expected with thyrotoxic periodic
paralysis, the patient did not respond to potassium replacements in
excess of the calculated potassium deficit. Potassium levels eventually
normalized with introduction of methimazole, an agent that inhibits the
enzyme thyroperoxidase which decreases thyroid hormone synthesis
[7].