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Figure 6. Algorithm of hyperkalemia management [48,149-154] . In the case of hyperkalemia, the treatment is based on the degree and reported
symptoms. When patients are symptomatic for hyperkalemia, insulin, beta-2 agonist, and sodium bicarbonate should be considered. It is
always useful to associate the identification and correction of the underlying cause. For a correct differential diagnosis, it is necessary to
evaluate renal function through blood creatinine level. If elevated, evaluate uricemia, calcemia, and phosphatemia to distinguish between
renal failure and tumor lysis syndrome. TLS: tumor lysis syndrome; TTKG: transtubular potassium gradient

Adrenal insufficiency secondary to metastasis involving both adrenal glands might cause hyperkalemia
in cancer patients, especially with advanced lung and breast cancer or lymphomas. However, despite the
high frequency of adrenal metastasis (40%-60% of patients), adrenal insufficiency is rarely described,
thanks to concomitant administration of corticosteroids [146] . Finally, in the case of elevated leukocytosis or
thrombocytosis, hyperkalemia should be distinguished from pseudo-hyperkalemia, due cellular potassium
escape after the blood sample is taken [147] .

Management
Diagnosis of hyperkalemia occurs with the detection of elevated serum potassium concentration. The
diagnosis is often an incidental laboratory finding, as patients are often asymptomatic, especially in the
case of plasma potassium concentration of < 5.5 mEq/L. When present, symptoms and signs are related
to altered cellular resting membrane potential, causing muscle, neurological and cardiac dysfunctions,
until life-threatening cardiac arrhythmias. Patients might experience, according to hyperkalemia grade,
fatigue and weakness, fasciculation, cramps, and parenthesis, as well as muscular paralysis and palpitations
in serious cases. Sometimes, the only signs of hyperkalemia are electrocardiographic specific alterations
or cardiac arrhythmias such as pointed T-waves, decrease or absence of P waves, prolonged PR interval,
enlarged QRS complex, reduced QT interval, ventricular fibrillation, or asystole [148] .

For a correct differential diagnosis, clinical history evaluating potassium intake and concomitant
medications should be collected [Figure 6]. Furthermore, other laboratory exams should be performed:
complete blood count, urinary potassium, sodium and osmolality, transtubular potassium gradient (TTKG),
renal function, lactate dehydrogenase, and uricemia. Elevated serum creatinine and urea associated with
hyperkalemia are suspicious for renal failure. Hyperkalemia, concomitant to the presence of hyperuricemia,
hyperphosphatemia, and hypocalcemia, might be suggestive of TLS. In the case of TTKG > 10, hyperkalemia
might depend on excessive potassium intake. Instead, a TTKG < 10 is generally due to a mineralocorticoid