Page 51 - Read Online
P. 51

Berardi et al. J Cancer Metastasis Treat 2019;5:79  I  http://dx.doi.org/10.20517/2394-4722.2019.008                       Page 19 of 33

               Table 5. Causes of hypokalemia
               Causes of hypokalemia
                Reduced potassium intake  Malnutrition, anorexia, refeeding syndrome
                                      Gastrointestinal injuries
                                      Vomit (caused by anticancer therapies, intestinal obstruction, etc.)
                                      Diarrhea (caused by anticancer therapies, cancer, surgery)
                Redistribution of the potassium  Drugs (catecholamine, nasal decongestants, insulin, granulocyte growth factors, beta-2 agonists,
                into intracellular compartment   barium intoxication, theophylline, bicarbonate, verapamil)
                                      Alkalosis
                                      Hypothermia
                Increased potassium losses  Non-renal losses:
                                      Losses (diarrhea, vomiting, fistula, laxative abuse, villous adenoma)
                                      Profuse sweating
                                      Extended burns
                                      Toxic epidermal necrolysis
                                      Renal losses:
                                      Metabolic alkalosis
                                      Use of diuretics
                                      Osmotic diuresis
                                      Renal tubular diseases (tubular acidosis, Liddle syndrome)
                                      Endocrine dysfunctions (excess of glucocorticoids or mineralocorticoids, primary hyperaldosteronism
                                      due to adenoma or adrenal carcinoma, renin-secreting neoplasms, ectopic secretion of ACTH)
                                      Concomitant electrolyte disorders (hypercalcemia, hypomagnesemia)
                                      Drugs (amphotericin B, cisplatin, ifosfamide, glucocorticoids, anti-EGFR agents, mTOR inhibitors,
                                      eribulin, abiraterone)

               ACTH: adrenocorticotropic hormone; EGFR: endothelial growth factor receptor

               kallikrein hypersecretion inducing flushing, severe secretory diarrhea with cramps and hypokalemia,
               tachycardia, hypotension until heart failure, and bronchial constriction [122] . Another rare syndrome due
               to tumor hypersecretion of vasoactive intestinal polypeptide induces important watery diarrhea with
               hypokalemia and achlorhydria [123] .


               Renal losses have several potential causes. Endocrine disorders should be considered in cancer patients.
               For example, Cushing syndrome can be due in rare cases to ACTH-producing tumors, especially in
               patients with small-cell lung cancer, medullary thyroid carcinoma, islet cell adenoma or carcinoma,
               pheochromocytoma, and ganglioneuroma, inducing an excessive production of cortisol able to blind
               mineralocorticoid receptors inducing hypokalemia [124] . Another rare cause is primary aldosteronism, due to
               the excessive and autonomous secretion of aldosterone by adrenal adenomas or carcinoma. This syndrome
               is characterized by polydipsia, polyuria, resistant hypertension, and severe hypokalemia [125] .

               Furthermore, a common cause of potassium renal losses in cancer patients is drug-related tubular toxicity.
               Several chemotherapeutic agents, target therapies, and immunotherapeutic drugs [Table 5] might induce
               renal injury associated to hypokalemia. Renal function should be evaluated before drug administration to
               avoid further renal damage [126] . Concomitant therapies such as thiazide diuretics and glucocorticoids can
               favor potassium renal losses.

               Finally, some kinds of tumor induce renal damage. For example, patients with multiple myeloma producing
               Bence-Jones proteins develop a progressive renal injury leading to hypomagnesemia and hypokalemia.
               Acute myeloid leukemia, through secretion of lysozyme, induces renal tubular damage [127] .


               In hematological patients, especially in those with marked leukocytosis (e.g., in acute myeloid leukemia),
               hypokalemia can be confused with pseudo-hypokalemia, due to potassium intake in the stored blood
               sample before the laboratory analysis [128] .


               Management
               Clinical presentation depends on severity of hypokalemia. Patients are often asymptomatic, especially
               those with mild hypokalemia [129] . Symptoms and sign of hypokalemia are non-specific and due to
   46   47   48   49   50   51   52   53   54   55   56