Differential Diagnosis for Hypernatremia in a Patient with Normal Pressure Hydrocephalus

The patient presents with severe hypernatremia, as indicated by a sodium level of 163 mmol/L, and an elevated serum osmolality of 355 mOsm/kg. The chloride level is also elevated at 124 mmol/L, suggesting a hyperchloremic metabolic acidosis. Given the patient's history of normal pressure hydrocephalus and the lack of response to D5W, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis
  • Central Diabetes Insipidus (CDI): The patient's severe hypernatremia, elevated serum osmolality, and lack of response to free water (D5W) suggest a deficiency in antidiuretic hormone (ADH), which is consistent with CDI. The patient's history of encephalopathy and normal pressure hydrocephalus may be related to the underlying cause of CDI.
• Other Likely Diagnoses
  • Nephrogenic Diabetes Insipidus: Although less likely than CDI, nephrogenic diabetes insipidus could also present with hypernatremia and elevated serum osmolality. However, the urine osmolality is not particularly low, which might argue against this diagnosis.
  • Hyperglycemia-induced Osmotic Diuresis: The patient's elevated glucose level could contribute to osmotic diuresis, leading to hypernatremia. However, the primary issue appears to be a lack of ADH effect rather than solely a consequence of hyperglycemia.
• Do Not Miss Diagnoses
  • Pituitary Apoplexy: Given the patient's severe hypernatremia and history of encephalopathy, pituitary apoplexy is a critical diagnosis not to miss. It could lead to acute deficiency of ADH, among other hormones, and requires urgent attention.
  • Adrenal Insufficiency: Although the patient's potassium level is not particularly low, adrenal insufficiency could contribute to hypernatremia and should be considered, especially if there are signs of hypotension or other electrolyte imbalances.
• Rare Diagnoses
  • Reset Osmostat: A rare condition where the osmostat is reset, leading to hypernatremia. This diagnosis would be considered if other more common causes are ruled out.
  • Gain-of-Function Mutation in the Vasopressin Receptor: An extremely rare condition that could lead to an inappropriate response to ADH, resulting in hypernatremia.

Workup and Treatment

• Immediate Treatment: Continue to address the hypernatremia with free water replacement, considering the use of desmopressin if central diabetes insipidus is confirmed.
• Diagnostic Workup:
  • Water Deprivation Test: To differentiate between central and nephrogenic diabetes insipidus.
  • ADH Level: To confirm the diagnosis of central diabetes insipidus.
  • Pituitary Function Tests: To evaluate for pituitary apoplexy or other pituitary hormone deficiencies.
  • Imaging: Consider repeating the MRI of the brain to evaluate for any changes or to assess the pituitary gland if pituitary apoplexy is suspected.
• Monitoring: Close monitoring of sodium levels, urine output, and osmolality to adjust treatment as necessary.