Differentials
Diabetes insipidus
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
The defect may be central (low antidiuretic hormone [ADH] secretion) or renal (low renal response to ADH).[48][50] Hence, before a water restriction test, central diabetes insipidus (DI) and PPD can seem similar (low ADH and dilute urine). Concomitant PPD and DI have been reported.[51]
Central DI may be congenital or acquired, and may be associated with other pituitary hormone abnormalities.
INVESTIGATIONS
Serum sodium is elevated.
DI is also associated with low urine concentration before a water restriction test, as with PPD. ADH concentration depends on whether the defect is central DI (low ADH secretion) or renal DI (low renal response to ADH).[48][50]
Inability to concentrate urine presents following a water deprivation test in both central and renal DI.
Adequate urine concentration achieved following vasopressin administration in central DI.
Diuretics
SIGNS / SYMPTOMS
Thiazide diuretics are the most common cause of hypovolemic or euvolemic hyponatremia.[57]
Mechanisms include potassium loss, which contributes to a sodium shift to the intracellular compartment, and volume loss, which stimulates antidiuretic hormone secretion, thereby promoting water retention.
Loop diuretics are less likely to cause hyponatremia. A possible reason is that they wash out solute from the renal medulla, which reduces interstitial osmolality and the driving force for water reabsorption from the renal tubules.
INVESTIGATIONS
Clinical diagnosis.
Trial of discontinuing causative medication: hyponatremia resolves.
Cerebral salt wasting
SIGNS / SYMPTOMS
Produced by a range of intracranial pathologies, including head injury, intracranial surgery, subarachnoid hemorrhage, stroke, and brain tumors. The intracranial pathology causes excessive urinary sodium loss, but the mechanism of the effect is unknown.
Physical signs include those associated with severe hyponatremia or intravascular volume depletion.
INVESTIGATIONS
Urine sodium level: >20 mEq/L.
Urine osmolality: low or normal.
Serum osmolality: <280 mOsm/kg H₂O.
Pseudohyponatremia
SIGNS / SYMPTOMS
Pseudohyponatremia (isotonic hyponatremia) is an artifact produced by high serum lipid or protein levels. The most common cause of high protein levels is multiple myeloma; this diagnosis is already known in most patients.
INVESTIGATIONS
Hyponatremia in the presence of a normal serum osmolality.
Syndrome of inappropriate antidiuretic hormone secretion
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
May be caused by some drugs, such as diuretics, carbamazepine, oxcarbazepine, or fluoxetine (and other selective serotonin-reuptake inhibitors [SSRIs]).[58][59][60] Reducing dose or switching to another medication helps correct the deficit.
Central nervous system causes include head injury, intracranial surgery, subarachnoid hemorrhage, meningitis, brain abscess, stroke, antidiuretic hormone (ADH)-secreting tumors (e.g., small cell lung cancer, pulmonary disease); or syndrome of inappropriate secretion of ADH may be idiopathic.
INVESTIGATIONS
Hyponatremia.
Inappropriately elevated urine osmolality (>100 mOsm/kg H₂O).
Excessive urine sodium excretion (>20 mEq/L, but often >40 mEq/L).
Decreased serum osmolality.
High plasma ADH.
Mineralocorticoid deficiency
SIGNS / SYMPTOMS
Due to autoimmune destruction of the adrenal cortex (Addison disease) or 21-hydroxylase deficiency producing a decrease in production of cortisol, aldosterone, and dehydroepiandrosterone.
The decrease in aldosterone production causes increased sodium loss from the kidneys.
Marked by poor skin turgor and dry mucus membranes.
INVESTIGATIONS
Serum potassium: elevated.
Urine sodium level: >20 mEq/L.
Serum osmolality: <280 mOsm/kg H₂O.
Morning serum cortisol: may be decreased.
Chronic alcohol use
SIGNS / SYMPTOMS
History of alcohol ingestion. Other signs of chronic alcohol use include liver disease, pancreatitis, and central nervous system symptoms.
Prevalence rates of hyponatremia in inpatients with chronic alcohol use range from 5% to 17%.[61]
INVESTIGATIONS
Clinical diagnosis.
Electrolytes: often abnormal
Ecstasy (methylenedioxymethamphetamine or MDMA)
Beer potomania
SIGNS / SYMPTOMS
A syndrome of hyponatremia in connection with excess beer intake and low daily solute consumption. Seen in patients malnourished due to high carbohydrate/low sodium loads.
INVESTIGATIONS
Clinical diagnosis.
Urine osmolality is about 250 mOsm/kg H₂O.
Total urine output is reduced to 4 L/day.[65]
Excessive solute
SIGNS / SYMPTOMS
In the setting of hypertonic hyponatremia, patients have normal total body sodium and a dilutional drop in the measured serum sodium, due to the presence of osmotically active molecules in the serum causing water shift from the intracellular compartment to the extracellular compartment.
INVESTIGATIONS
High plasma osmolality in the setting of hyponatremia is usually due to excess solute from osmotic agents such as mannitol and glucose.
Serum osmolality >295 mOsm/kg H₂O.
Salt-wasting nephropathy
SIGNS / SYMPTOMS
History of renal disease.
Due to intrinsic renal diseases that produce excessive sodium loss to the point of causing hypotension. Most often seen with tubular and interstitial kidney diseases. Examples include interstitial nephritis, partial urinary tract obstruction, and polycystic kidney disease.
Clinical signs of volume depletion include decreased skin turgor, reduced jugular venous pressure, decreased blood pressure.
INVESTIGATIONS
Urine sodium level: ≤20 mEq/L.
Serum osmolality: <280 mOsm/kg H₂O.
Serum albumin: decreased.
Serum creatinine: normal or elevated.
Nephrotic syndrome
SIGNS / SYMPTOMS
History of longstanding diabetes mellitus, malignancy, systemic lupus erythematosus, HIV infection, multiple myeloma, connective tissue diseases, or amyloidosis; use of known causative medications (pamidronate, lithium, gold, penicillamine, or nonsteroidal anti-inflammatory drugs [NSAIDs], and, very rarely, interferon-alfa, heroin, mercury, or formaldehyde).
Foamy urine, edema of legs or whole body, Muehrcke lines, xanthelasmas.
INVESTIGATIONS
Serum albumin: decreased.
Serum creatinine: normal or elevated.
24-hour urine collection for protein: >3 g/24 hours proteinuria.
Chronic heart failure
SIGNS / SYMPTOMS
Previous myocardial infarction, fatigue, decreased exercise tolerance, dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea.
Edema, displaced cardiac apex, hepatojugular reflux, jugular venous distension, S3 gallop, pulmonary rales; hepatomegaly can also be present.
INVESTIGATIONS
CXR: cardiomegaly, pulmonary edema, pleural effusion.
ECG: anterior Q waves, bundle-branch block, atrial arrhythmias, ventricular arrhythmias, left axis deviation, ventricular hypertrophy.
Echocardiogram: systolic and diastolic dysfunction, valve lesions, signs of pericardial injury or cardiomyopathy.
Cirrhosis
SIGNS / SYMPTOMS
History of alcohol misuse, intravenous drug use, unprotected intercourse, obesity, blood transfusion, known hepatitis infection; fatigue, weakness, weight loss, or pruritus.
Edema, jaundice, ascites, collateral circulation, hepatosplenomegaly, leukonychia, palmar erythema, spider angiomata, telangiectasia, and jaundiced sclera can be present.
INVESTIGATIONS
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST): elevated with ALT to AST ratio ≥1 if hepatocellular damage; normal in cholestasis.
Bilirubin: normal in compensated cirrhosis; elevated in decompensated cirrhosis.
Serum albumin: decreased.
Prothrombin time or INR: increased.
Platelet count: decreased.
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