Approach

Hypernatremia is defined as plasma sodium concentration of >145 mEq/L. Symptoms of hypernatremia are fairly nonspecific. Symptoms of concurrent or past illnesses may point to the likely cause.

A thorough physical exam should be completed, including evaluation of volume status, mental status, and neurologic assessment. Signs of hypernatremia usually involve central nervous system (CNS) manifestations and include irritability, restlessness, muscle twitching, spasticity, and hyperreflexia, which are all due to a decreased water content in the brain.[23]

Severe hypernatremia (plasma sodium concentration >158 mEq/L) may present with serious signs and symptoms, such as hyperthermia, delirium, seizures, and coma. Having established the presence of hypernatremia, the underlying etiology should be sought.

History

First, consider the age and mobility of the patient. Lack of access to water is a consideration in infants, disabled people, people with impaired mental status, postoperative patients, and intubated patients. The history should include the following:

  • Inquire about symptoms of hypernatremia: irritability, restlessness, lethargy, muscle twitches, delirium and seizures.

  • Inquire about symptoms of concurrent illness that could lead to water loss. Symptoms of viral gastroenteritis include nausea, vomiting, and abdominal pain, in addition to diarrhea. These patients may also have a history of contact with infected people, food, or fluids. Regardless of the cause, these patients may lose more water than sodium, leading to volume depletion and hypernatremia. Increased body temperature and exposure to the elements should also be considered. Prolonged exposure to heat, fever, excessive sweating, exercise, and severe cutaneous burns result in insensible water loss due to evaporation from the skin and may cause hypernatremia.

  • Take a past medical history to identify comorbidities that could lead to hypernatremia, particularly severe uncontrolled diabetes mellitus (may lead to hyperglycemia resulting in glycosuria, hypernatremia, and hyperosmolar hyperglycemic state), Cushing syndrome, primary aldosteronism, underlying kidney disorder (e.g., sickle cell disease, polycystic disease, and obstructive uropathy), or Crohn disease (may have underlying enteric fistulae). Exclude conditions that can cause carbohydrate malabsorption (tropical sprue, pancreatitis, lactose intolerance and a history of bowel surgery). A history of traumatic brain injury or any other insult to the brain (vascular syndromes, infections, tumors, or aggressive neurosurgery for craniopharyngioma, Rathke cleft cyst, or other hypothalamic tumor) may be suggestive of central diabetes insipidus. On rare occasions, the presence of a brain tumor, or vascular occlusion in the brain, may cause primary hypodipsia that presents with hypernatremic volume depletion.

  • A complete medication history is important. Drugs such as colchicine, gentamicin, lithium, rifampin, and propoxyphene may induce nephrogenic diabetes insipidus. Loop diuretics (e.g., furosemide and torsemide) and intravenous mannitol can cause an osmotic diuresis resulting in hypernatremia.[15] If a history of diarrhea or loose stools is present, the patient should be asked about the use of any laxative or bowel cleansing agent (e.g., lactulose or sorbitol).

  • Iatrogenic causes may be a possibility in those patients currently being treated in the hospital. These include inadvertent administration of hypertonic sodium chloride or sodium bicarbonate, or even the use of isotonic saline in a patient with an osmotic diuresis.

  • Take a dietary history. Inadequate breast-feeding without supplementation may lead to severe and potentially life-threatening hypernatremia in the infant.[16] Replacing sugar with salt in infant formula (accidental or intentional) can also result in hypernatremia.​[17] High-protein diets, including high-protein tube feeds, lead to increased urea production and consequently osmotic diuresis, increasing the risk of hypernatremia. In addition, consider ingestion of a highly concentrated emetic agent or gargle (e.g., Epsom salts).

Physical exam

The etiology is most easily elicited by considering the patient's volume status. However, it is important to note that extracellular volume status is better preserved with hypernatremia, at the expense of greater intracellular water depletion, and physical exam can, therefore, underestimate the total fluid deficit.

Hypovolemic hypernatremia

  • Includes renal and nonrenal losses. In patients with signs of volume depletion (dry mucous membranes, poor skin turgor, sunken eyes, irritability, tachycardia, hypotension or postural hypotension, decreased urine output, and weight loss), severe diarrhea, vomiting, and significant burns should be excluded. Temperature measurement is essential because fever may be the cause. The possibility of an enteric fistula should also be taken into account. Patients with hyperosmolar hyperglycemic state (HHS) typically present with signs of severe volume depletion and may have stupor or coma.[12]​ In many cases, the clinical features of HHS and hypernatremia overlap and are observed simultaneously.​

Hypervolemic hypernatremia

  • These patients may present with signs of volume overload, including weight gain, peripheral edema, hypertension, irritating cough, dyspnea, jugular vein distention, and crepitations on auscultation. Usually due to exogenous sodium ingestion and mineralocorticoid excess.[6] Therefore, signs of Cushing syndrome as well as primary aldosteronism should be sought.

    • Cushing syndrome: moon face, facial plethora, supraclavicular and/or dorsicocervical fat pads, truncal obesity, purple striae, proximal muscle weakness, hirsutism, growth retardation (children), hypertension.

    • Primary aldosteronism: hypertension, proximal muscle weakness.

Euvolemic hypernatremia

  • Signs of volume depletion and overload absent. Nephrogenic diabetes insipidus or central diabetes insipidus are usually the underlying cause. A patient with central diabetes insipidus may show signs of recent trauma, pituitary surgery, or hypoxic or ischemic encephalopathy.

Signs of hypernatremia include muscle twitches, spasticity, hyperreflexia, hyperthermia, delirium, seizures and coma.

Baseline laboratory investigations

A plasma sodium concentration of >145 mEq/L confirms the presence of hypernatremia.

Urine osmolality may help determine the underlying etiology. Normal kidney response to hypernatremia is to excrete a minimal amount of urine that is maximally concentrated (urine osmolality >800 mOsm/kg). Hypertonic urine is usually observed with extrarenal fluid losses, as is the case with vomiting, diarrhea, burns, and excessive sweating. Isotonic urine can be seen with diuretic use, osmotic diuresis, and salt wasting. Hypotonic urine associated with polyuria is seen with diabetes insipidus (central or nephrogenic).

A metabolic panel, including serum glucose, potassium, chloride, BUN, and creatinine, should also form part of the initial work up to exclude associated electrolyte abnormalities and renal impairment. In addition, a CBC should be considered a baseline investigation in cases of severe burns to exclude sepsis, and an ABG may be necessary in patients with prolonged vomiting or breast-feeding hypernatremia to rule out an associated acid-base disturbance.

Specific laboratory investigations

For patients with severe diarrhea, stool studies (fecal leukocytes, fecal pH, fecal reducing substance/sugar) may be of use in determining whether the etiology is infectious in origin or is a consequence of carbohydrate malabsorption. Stool ion gap helps distinguish between the presence of an osmotic or secretory diarrhea; secretory diarrhea does not typically produce hypernatremia.

Diabetes insipidus can usually be confirmed on the basis of hypernatremia and increased output of hypotonic urine (>3 L/24 hours), with commensurately increased thirst-driven fluid intake. Partial or more subtle cases may need to be confirmed by elective investigation in a specialist unit with a water deprivation test. Plasma arginine vasopressin (AVP) levels may not readily distinguish central from nephrogenic diabetes insipidus; the medical background will typically indicate whether central or nephrogenic diabetes insipidus is most likely, with confirmation arising from the response (or lack of it) to an AVP (desmopressin) stimulation test.

If primary aldosteronism is suggested by history or physical exam findings, an abnormally low plasma renin activity (PRA) level and an abnormally high plasma aldosterone concentration (PAC) level, resulting in high aldosterone-to-renin ratio, supports this diagnosis. Diagnostic specificity can be improved by ensuring that the patient has first been rendered potassium replete and, where possible, by temporarily withdrawing drugs such as diuretics (in particular, loop diuretics), beta blockers, ACE inhibitors, and angiotensin-II receptor antagonists several weeks beforehand. Confirmation of the diagnosis may require an aldosterone suppression test. A 24-hour urinary potassium may be considered if plasma renin activity and plasma aldosterone concentration are normal or if there is a clinical suspicion of surreptitious vomiting or laxative misuse.

Serum osmolality of >320 mOsm/kg together with a plasma glucose of >600 mg/dL in a patient with altered mental status is strongly suggestive of hyperosmolar hyperglycemic state (HHS). A markedly elevated serum osmolality is also seen with primary hypodipsia.

If Cushing syndrome is suspected, diagnosis may be confirmed with a 24-hour urinary free cortisol, low-dose (or overnight) dexamethasone suppression test, and late night salivary cortisol levels.[24][25]

Imaging studies

Head computed tomography (CT) scan or magnetic resonance imaging (MRI) may reveal a central cause for hypernatremia and should be performed in all patients with severe hypernatremia and no occult etiology.[21] If a diagnosis of central diabetes insipidus is made on laboratory testing, a brain MRI needs to be performed to look for structural lesions.[14]​ In addition, brain imaging helps to exclude intracranial hemorrhage caused by traction on the dural bridging veins and sinuses as a result of brain shrinkage. Dural sinus thrombosis may occur from the hemoconcentration of total body water loss and can also be detected with head CT scan or MRI.[26]​ CT scan or MRI of the adrenal glands may reveal an underlying adrenal mass lesion in patients with suspected primary aldosteronism.

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