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Page 2 of 8 Marquina et al. J Cancer Metastasis Treat 2020;6:6 I http://dx.doi.org/10.20517/2394-4722.2019.39

Table 1. Physical examination approach to classify hyponatremia regarding volume status [18]
Physical examination
Orthostatism Orthostatism can often be found in hypovolemia
Manual ocular pressure Manual ocular pressure can be low in hypovolemia
Internal jugular venous Inspection of internal jugular vein. The maximum height of the pulse of this vein reveals the pressure in the
pressure right cardiac atrium:
A maximum pulse height below the angle of the sternum in a reclining patient indicates hypovolemia;
A height between 1 and 3 cm above the sternal angle indicates euvolemia or hypovolemia with cava vein
thrombosis or severe pulmonary hypertension;
A height over 4 cm indicates elevated right atrial pressure, as is found in congestive heart failure
Edema/increase of Hypervolemic status usually presents with an increased third space such as edema or ascites
liquids in a “third space”

frequency of hyponatremia varies depending on the type of tumor, clinical scenario, and the threshold
[3]
used for definition of hyponatremia. However, up to 47% of patients in the oncology ward have been
found to present hyponatremia. Furthermore, hyponatremia can precede the diagnosis of malignancy, with
[4]
incidences between 1% and 40% .

Historically, hyponatremia has been more frequently associated with small cell lung cancer than with
[5]
other tumors . However, other publications establish that this hydro-electrolytic alteration can be
[3,6]
detected in any cancer patient . Direct cancer-induced hyponatremia could be due to ectopic arginine
vasopressin secretion, inducing the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).
[7]
Furthermore, there is emerging evidence for expression of sodium-transporting proteins in cancer .
Hyponatremia can also be attributed to other etiologies that are not related per se to the cancer. What is
more, hyponatremia can be induced by cancer-related complications, as well as the anti-cancer treatment
[8]
itself or the side effects of cancer therapy. These include diarrhea, nausea, vomiting, pain, nephrotoxicity,
[5]
adrenal insufficiency (due to adrenal metastases), etc. .
Hyponatremia can be a potential negative prognostic factor in patients diagnosed with solid tumors or
[5]
hematological malignancies such as lung cancer, breast cancer, lymphoma, and colorectal cancer . In
cirrhosis, hyponatremia is associated with a higher morbidity and mortality. Decompensated cirrhosis in
[9]
liver cancer patients represents an additional complicating factor .

Hyponatremia detected in in-hospital cancer patients is associated with a longer hospital length of stay and
an increased risk of mortality [4,6,10-13] .

The impact of correction of hyponatremia on patient survival has yet to be ascertained. In some patient
series, the correction of hyponatremia correlates with an improvement in quality of life and an improved
prognosis [4,14] .

THE DIAGNOSTIC APPROACH TO HYPONATREMIA IN CANCER PATIENTS
The diagnostic approach in cancer patients should be the same as for any patient with hyponatremia [2,15] .
The physical examination is fundamental, since it can establish the volume status of the patient
[Table 1]; the clinical history, blood and urine tests are also necessary [Table 2] to determine the etiology
[Table 3] [16,17] .

The initial step in laboratory evaluation of hyponatremia, after detecting a sodium level below 135 mmol/L,
is to assure that hyponatremia is truly present. High glycemic levels, or mannitol infusion can induce
translocational hyponatremia. In fact, total blood or serum sodium levels must always be corrected in
patients with hyperglycemia. In patients receiving mannitol infusion, a normal plasma osmolality will rule