Skip to Main Content




Mr. D is a 42-year-old man who is brought to the emergency department by the police department. He is disoriented and confused. Initial labs reveal a serum sodium concentration of 118 mEq/L.

image What is the differential diagnosis of hyponatremia? How would you frame the differential?


As noted in Chapter 1, the first task when evaluating patients is to identify their problem(s). Mr. D’s problems clearly include delirium and marked hyponatremia. While other causes of delirium should be considered, (see Chapter 11 Delirium & Dementia) the hyponatremia clearly requires evaluation because it is severe and thus likely to be causing the delirium.

Hyponatremia is defined as serum sodium concentration < 135 mEq/L and is significant when the concentration is < 130 mEq/L. The differential diagnosis for hyponatremia is long but the diagnostic approach can be easily framed in a few simple steps. These pivotal steps include (1) a quick search for rapid diagnostic clues; (2) a clinical assessment of the patients volume status to limit the differential; (3) in clinically euvolemic patients, a review of the patients urine sodium and response to a saline challenge to unmask subtle hypovolemia (4) in euvolemic patient further tests to distinguish the syndrome of inappropriate antidiuretic hormone (SIADH) from other less common causes of euvolemic hyponatremia; and finally (5) an exploration for the risk factors, associated symptoms, and signs for the diagnoses within each subgroup. Each of these steps is discussed below.

The first step recognizes that a few key clinical and laboratory features occasionally point to very specific diagnoses. Examples of these include thiazide use (suggesting diuretic-induced hyponatremia), recent participation in marathon events (suggesting exercise-associated hyponatremia [EAH]), hyperkalemia (suggesting kidney disease or primary adrenal insufficiency), very low urine osmolality (suggesting psychogenic polydipsia, Ecstasy use, or beer potomania) or markedly elevated blood glucose, or a normal serum osmolality (suggesting hyperglycemia-induced hyponatremia and pseudohyponatremia, respectively). Thus, the first pivotal step in approaching hyponatremia systematically reviews these few variables to search for clues (Figure 24-1).

Figure 24-1.

Step 1: Searching for pivotal clues in patients with hyponatremia.

For many patients, the previously mentioned clues are absent and the second pivotal step evaluates the patient’s clinical volume status in order to determine whether they are clinically hypervolemic, clinically euvolemic, or clinically hypovolemic. This allows the differential diagnosis to be narrowed to that appropriate subset of diagnoses (Figure 24-2). Correct classification of the patient’s volume status requires a review of the history, physical exam findings, and laboratory results. The clinical recognition of hypervolemic patients is very accurate because hyponatremia typically develops in patients with advanced heart failure (HF), cirrhosis, nephrotic syndrome, and chronic kidney disease when the disease is easily recognized. Similarly marked ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.