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1
Question:

A 43-year-old woman comes to the emergency department due to confusion.  She has also had increased thirst and has needed to "use the bathroom more frequently."  She has not had any fever, chills, headache, chest pain, shortness of breath, or cough.  Her medical history is significant for bipolar disorder that is well-controlled by medication.  She does not use tobacco, alcohol, or illicit drugs.  Her vital signs are stable, and physical examination is unremarkable.  Laboratory results are as follows:

Sodium151 mEq/L
Potassium4.1 mEq/L
Chloride116 mEq/L
Bicarbonate28 mEq/L
Glucose95 mg/dL
Urine osmolality250 mOsm/kg
Serum osmolality326 mOsm/kg

What is the most likely cause of this patient's symptoms and laboratory findings?

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Explanation:

Diabetes insipidus (DI) is a leading cause of euvolemic hypernatremia.  It typically presents with severe polyuria and mild hypernatremia.  It can be divided into 2 types based on etiology or urine osmolality.

Based on etiology, DI may be central or nephrogenic:

  1. Central DI is due to decreased production of antidiuretic hormone (ADH) by the pituitary.  Common causes include trauma, hemorrhage, infection, and tumors.
  2. Nephrogenic DI results from renal ADH resistance.  The sodium level may be in the high-normal range (intact thirst mechanism).  Common causes of nephrogenic DI include hypercalcemia, severe hypokalemia, tubulointerstitial renal disease, and medications.  The most commonly implicated medications are lithium, demeclocycline, foscarnet, cidofovir, and amphotericin.

Based on urine osmolality, DI may be complete (urine osmolality <300 mOsm/kg, often <100 mOsm/kg) or partial (urine osmolality ranges from 300 to 600 mOsm/kg).  The serum osmolality is elevated in both types.

In this vignette, the patient's clinical history (bipolar disorder), presentation (polyuria, polydypsia), and laboratory findings (hypernatremia, increased serum osmolality, urine osmolality <300 mOsm/kg) are suggestive of nephrogenic DI most likely caused by lithium, which is one of the first-line drugs for bipolar disorder.

(Choice A)  Dehydration is the hallmark of hypovolemic hypernatremia.  Furthermore, patients with this condition have increased urine osmolality.

(Choice C)  Divalproic acid is a mood stabilizer that is also used in the treatment of bipolar disorder.  Common side effects include nausea, vomiting, somnolence, and weight gain.  It is not associated with DI.

(Choice D)  Craniopharyngiomas are relatively rare tumors of the sella and suprasellar space.  These may cause central DI.  The typical presentation includes headaches, focal neurologic changes, or visual problems, which this patient does not have.

(Choice E)  Head trauma is another cause of central DI.  This is an unlikely cause of the patient's condition, as there is no mention of any head trauma in the history, nor is there any external evidence of trauma on physical examination.

(Choice F)  Psychogenic polydipsia results from excessive free water intake by patients who usually have an associated psychiatric condition.  Although DI and psychogenic polydipsia both present with euvolemia and polyuria, patients with the former are hypernatremic, whereas those with the latter are hyponatremic.

Educational objective:
Lithium is a common cause of nephrogenic diabetes insipidus (DI).  Lithium-induced nephrogenic DI is treated with salt restriction and discontinuation of lithium.