What are the common causes of hyponatremia in elderly patients?

Causes of Hyponatremia in the Elderly

Medications—particularly diuretics, antidepressants, ACE inhibitors, and ARBs—are the predominant cause of hyponatremia in elderly patients, often acting in combination with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and hypovolemia. 1, 2

Medication-Induced Hyponatremia

The most critical finding is that 96.1% of elderly patients with hyponatremia are taking at least one sodium-lowering medication, with a median of 3 such drugs per patient 1. The risk escalates dramatically with polypharmacy:

• Four medications triple the likelihood of hyponatremia 3
• Six medications increase the risk seven-fold 3
• Women have significantly higher probability of developing hyponatremia compared to men 1

High-Risk Medications

The following drug classes are most strongly associated with hyponatremia in elderly patients:

• Thiazide diuretics (should be avoided in elderly patients with hyponatremia) 1, 2
• Loop diuretics (38% of hyponatremic elderly patients receive diuretics) 1, 3
• ACE inhibitors and ARBs (36.6% of hyponatremic patients) 1, 3
• Antidepressants, particularly SSRIs (9.8% of cases) 1, 3, 2
• Antipsychotics and neuroleptics 1
• NSAIDs 4, 1
• Carbamazepine and oxcarbazepine 1
• Anti-arrhythmics and opioids 3
• Desmopressin (the 2019 AGS Beers Criteria specifically warns about SIADH risk) 4

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIAD)

SIAD is one of the two most important causes of hyponatremia in the elderly, often coexisting with medication effects 1, 2. The European Society of Cardiology reports that:

• Baroreceptor sensitivity decreases with age, leading to impaired volume regulation and potentially inappropriate ADH secretion 5
• Elderly patients have increased ADH response due to age-related physiological changes 5
• Many elderly patients have no definite identifiable cause for persistent vasopressin release despite thorough evaluation 6

A critical diagnostic pitfall: endocrinopathies must be excluded before establishing SIAD diagnosis in elderly patients, as they can mimic SIAD 2

Volume Status-Related Causes

Hypovolemic Hyponatremia

Hypovolemic hyponatremia was the most common volume status in one large study (131 of 308 hyponatremic patients) 1. Contributing factors include:

• Reduced thirst perception (age-related physiological change) 5
• Impaired urine concentration by the kidney 5
• Decreased total body water (making elderly more vulnerable to volume shifts) 5, 7
• Inadequate dietary salt intake ("tea and toast" syndrome) 2

Hypervolemic Hyponatremia

Dyspnea as an indicator of hypervolemia was noted in 71 patients in the same cohort 1. Common underlying conditions include:

• Heart failure 8, 9
• Liver cirrhosis 8
• Renal failure (23.9% of hyponatremic elderly patients) 1, 3

Comorbid Conditions

The following chronic conditions significantly increase hyponatremia risk:

• Hypertension (78.5% of hyponatremic elderly patients) 1
• Diabetes mellitus (31.2% of cases) 1, 3
• Chronic kidney disease (impairs renal gluconeogenesis and sodium regulation) 4, 1, 3
• Malnutrition (associated with refeeding syndrome and electrolyte abnormalities) 5, 9
• Sepsis (predictive marker for hyponatremia) 4
• Low albumin levels (predictive marker) 4

Age-Related Physiological Changes

Several intrinsic aging processes predispose to hyponatremia:

• Decreased left ventricular compliance and glomerular filtration rate alter fluid regulation 5
• Shift toward increased extracellular and decreased intracellular water 5, 7
• Vulnerable water homeostasis creating tendency for both hypo- and hypervolemia 5, 7
• Impaired counterregulatory mechanisms (reduced glucagon and epinephrine release) 4

Environmental and Dietary Factors

• Rising global temperatures have been linked to increased hyponatremia rates 9
• Insufficient dietary salt content is common in elderly populations 1
• Polypharmacy burden (the likelihood increases exponentially with number of medications) 3

Clinical Significance

Hyponatremia in elderly patients is associated with:

• Higher hospitalization rates (13.7% vs 7.7% in non-hyponatremic patients) 3
• Increased mortality (3.9% vs 1.8%) 3
• Falls, osteoporosis, and fractures 9, 6
• Cognitive and muscular impairment 9, 6
• Confusion and delirium (more common during somatic illness) 5

A major clinical gap: less than 20% of hyponatremic patients have sodium levels rechecked after 1 month, indicating significant underdiagnosis and undertreatment 3

Multifactorial Nature

Hyponatremia in elderly patients is multifactorial in a significant proportion of cases 2. The typical elderly patient with hyponatremia has:

• Multiple chronic conditions (hypertension, diabetes, renal failure) 1, 3
• Polypharmacy with 3+ sodium-lowering medications 1
• Age-related physiological vulnerabilities 5
• Possible underlying SIAD (often without identifiable cause) 6, 2
• Inadequate dietary sodium intake 1