Abstract
Euvolemic hyponatremia in the setting of lung cancer is most commonly due to the syndrome of inappropriate anti-diuretic hormone secretion (SIADH). However, some patients with small cell carcinoma and hyponatremia have low levels of ADH but elevated levels of atrial natriuretic peptide (ANP), which is produced by some small cell tumors. We report the case of a 64-year-old man with a limited-stage small cell carcinoma of the lung undergoing chemoradiation therapy, who was admitted to hospital with a pulmonary embolism. Two months earlier, at the time of diagnosis with lung cancer, he had a hypotonic, euvolemic hyponatremia, presumed to be caused by SIADH. At that time, his serum sodium readily normalized with water restriction and ADH-antagonist therapy with demeclocycline. However, during his second admission, his sodium level slowly declined from 138 mmol/L to a nadir of 118 mmol/L, despite early initiation of water restriction and maximal doses of demeclocycline. Laboratory values revealed a very low level of ADH, an inappropriately low level of aldosterone and an elevated ANP suggesting that SIADH could not explain his hyponatremia. While a causal link between ectopic ANP production and hyponatremia has never been established, an inappropriately high level of ANP can directly decrease sodium re-absorption in the proximal convoluted tubule of the kidney and increase glomerular filtration rate (GFR), resulting in greater excretion of sodium and water. In addition, high circulating levels of ANP can inhibit aldosterone secretion, potentially resulting in further sodium wasting. Here, the low levels of ADH, elevated ANP, and inappropriately low aldosterone suggested the possibility of an ANP-mediated hyponatremia through the suppression of aldosterone response.
Highlights
Hyponatremia is commonly found in patients that have been diagnosed with lung cancer – reportedly as high as 15–30% of patients with small cell lung carcinoma (SCLC) present with hyponatremia[1,2]
A work-up revealed a hypotonic, euvolemic hyponatremia (Na+ 116 mmol/L), with elevated urine osmolality (609 mOsm/Kg) and urine sodium (181 meq/L). He was presumptively diagnosed with SIADH syndrome, and was treated with a mild fluid restriction and anti-diuretic hormone (ADH) antagonist therapy (Figure 2A), While SIADH is clearly responsible for the majority of cases of hyponatremia of malignancy, there have been documented cases of SCLC patients with hyponatremia, but with no detectable levels of ADH in their plasma[7,8] or produced by their cancer cells[9,10,11]
In 1957, Schwartz et al presented the first cases of hyponatremia of malignancy from inappropriate anti-diuretic hormone secretion in two patients with lung cancer who developed low serum sodium levels associated with continued urinary sodium losses[15]
Summary
Hyponatremia is commonly found in patients that have been diagnosed with lung cancer – reportedly as high as 15–30% of patients with small cell lung carcinoma (SCLC) present with hyponatremia[1,2]. A work-up revealed a hypotonic, euvolemic hyponatremia (Na+ 116 mmol/L), with elevated urine osmolality (609 mOsm/Kg) and urine sodium (181 meq/L) He was presumptively diagnosed with SIADH syndrome, and was treated with a mild fluid restriction and ADH antagonist (demeclocycline at 300 mg PO BID) therapy (Figure 2A), While SIADH is clearly responsible for the majority of cases of hyponatremia of malignancy, there have been documented cases of SCLC patients with hyponatremia, but with no detectable levels of ADH in their plasma[7,8] or produced by their cancer cells[9,10,11]. 0.27 – 4.20 2.3 – 19.4 resumption of his radiation therapy with effective treatment of his malignancy
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