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].