1.2.2 Hyponatremia

Suggested citation: The Endocrine Society. Endocrine Facts and Figures: Hypothalamic-Pituitary. First Edition. 2016.

Hyponatremia is an electrolyte disorder. Serum sodium concentrations < 125 mmol/L are considered an indication of severe hyponatremia, and serum levels < 115 mmol/L are associated with substantial morbidity and increased mortality.59,60

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia.61 It’s caused by excess of renal water reabsorption due to inappropriate antidiuretic hormone (vasopressin) secretion.62 Sherlock et al. reported that 62% of cases of hyponatremia resulted from SIADH.63

1.2.2.1 Prevalence and Incidence

Hyponatremia is the most common electrolyte disorder encountered in hospital inpatients and clinical practice.61,64 Data from NHANES 1999-2004 (n=14,697) showed that the prevalence of US adults (age ≥ 18 years) with hyponatremia (serum sodium < 133-145 mmol/L for years 1999-2002, and <136-144 mmol/L for years 2003-2004) was 1.72%.  Table 10 lists the prevalence of hyponatremia by cause.

Table 10. Hyponatremia by cause
POPULATION STUDY DESIGN CAUSE PREVALENCE (%)
Ireland (n=1,698) patients with hyponatremia Retrospective analysis of hospital data Pituitary disorders  6.25
Traumatic brain injury 9.6
Intracranial neoplasm 15.8
Subarachnoid hemorrhage 19.6
Spinal disorders 0.81

Source: Sherlock et al. 200963

1.2.2.2 Demographic Differences

Data from NHANES indicated hyponatremia was more common in females as opposed to males (2.1% vs. 1.3%), and patients with hyponatremia were significantly older (52.8 vs. 45 years). Overall, hyponatremia was more common in subjects with comorbidities than those with none (2.3% vs. 1.04%); specifically, hyponatremia was significantly higher among patients with hypertension, diabetes, coronary artery disease, cancer, stroke, chronic obstructive pulmonary disease, and psychiatric disorders.65

1.2.2.3 Life Expectancy and Mortality

Hyponatremia is associated with greatly increased morbidity and mortality,61 and if not treated appropriately may lead to death.64 Untreated acute hyponatremia can cause substantial morbidity and mortality as a result of osmotically induced cerebral edema, and excessively rapid correction of chronic hyponatremia can cause severe neurologic impairment and death as a result of osmotic demyelination, particularly of the pons.66

Hyponatremia, which can be profoundly symptomatic, has also been linked to longer hospital stays, admission to the ICU, and costly readmissions.63,67-70 A recent analysis of NHANES data reported the overall mortality rate over the period 1999-2006 at 11% for hyponatremic subjects versus 4% for their normal counterparts. In addition, among subjects with hyponatremia, mortality rates were not affected by sex or race/ethnicity.65 Table 11 presents data on factors that have been shown to significantly increase mortality rate among hyponatremic patients.

Table 11. All-cause mortality among hyponatremic patients.
DATA SOURCE POPULATION FACTOR MORTALITY RATE (%)
NHANES 1999-2004 (followed-up 2006) US (n=14,679) Sex Males 13
Females 9.8
Race/ethnicity Non-Hispanic whites 12
Non-Hispanic blacks 8.6
Hispanic 6.7
Other 11
Body mass index * Normal weight 17
Obese 0.2
Poverty income ratio * 0-0.99 19
≥ 5 1.6
Comorbidities * No comorbidities 2.5
Coronary artery disease 30
Congestive heart failure 38
Liver disease 37
Kidney disease 32
Cancer 25
Abbreviations: US, United States.
Note: *, factors showing a statistically significant increase in mortality rate (p<0.001).

Source: Mohan et al. 2013 65

1.2.2.4 Key Trends and Health Outcomes

According to recently published expert panel recommendations on the diagnosis, evaluation, and treatment of hyponatremia, in cases where there is a remote possibility that the primary diagnosis is SIADH and either significant central nervous system symptoms from hyponatremia are present or the starting serum [Na] is 120 mmol/L, hypertonic saline (e.g., 3% NaCl) should be used for the initial diagnostic volume challenge to avoid any risk of lowering the serum [Na] further.71

Initial treatment consists of withholding all diuretics and cautiously repleting the patient with isotonic fluid if central nervous system abnormalities are mild. Clinicians should use hypertonic saline to raise the serum [Na] by 4-8 mmol/L acutely when seizures or a significantly altered level of consciousness are present. However, they should not use furosemide with the hypertonic saline because of the risk of precipitating hypotension, and clinicians should administer a minimum of hypertonic fluid in anticipation of the water diuresis that will ensue.71

The Food and Drug Administration has approved vasopressin receptor antagonists for the management of hyponatremic disorders. However, proper and effective use of these and other therapies requires careful thought and guidance.71

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