Case 47 Index
Case Published: July 2020

Diagnosis: Hypernatremia due to Nephrogenic Diabetes Insipidus (DI)

Case Summary: Great work! In this case, we have a patient with a long-standing history of bipolar disorder with lithium use. She also describes polyuria and thirst for which she drinks large amounts of water, with no known prior history of kidney disease. Her serum sodium level on admission is normal at 140 mEq/L.

So, why does this patient become hypernatremic in the hospital?

So we see our patient has many reasons to develop hypernatremia, and it is not uncommon in the hospital setting with impaired thirst, limited access to free water, GI losses, insensible losses, or a combination thereof. Our patient, however, has the additional hit of urinary water losses. How do we know this?

For this we must give some thought to her history of polyuria, which should be differentiated from urgency, frequency, nocturia, or other urinary symptoms. Polyuria in adults is >3L urine output / day, and can be the result of primary polydipsia, solute/osmotic diuresis, or diabetes insipidus (DI). The most common cause of osmotic diuresis is glucosuria, which can be seen in poorly-controlled diabetes mellitus. In the hospital it can be due to high sodium load (IV saline) or hypertonic fluids (mannitol, hypertonic saline).

Check out our infographic on the work-up of polyuria:

Our patient’s urine osmolality is 130 mosm/kg with 4.8 L of urine output in 24 hours. Calculated serum osmolality is 330 mosm/kg. A urine osm < serum osm is consistent with urinary water losses and our water deprivaiton test confirms a diagnosis of  DI. Another way to look for solute diuresis is to assess the patient’s daily osmolar output:

Total Daily Osmolar Output = (Urine osm) x (24-hour urine volume) Total Daily Osmolar Output = 130 mosm/kg x 4.8 L/24 hours = 624 mosm / 24 hours

The average US diet is 600-900 mosm/day. This patient’s daily osmolar output therefore is not suggestive of a solute diuresis, as it does not exceed the expected osmolar output.

We’ve identified diabetes insipidus!

Our patient’s history of chronic lithium use is highly suspicious for nephrogenic DI. Lithium has been shown to cause nephrogenic DI in up to a third of patients with chronic use. Lithium enters principal cells of the collecting tubule via luminal sodium channels. There are several postulated mechanisms, but all involve interference with ADH function and response.

Before we wrap up, here’s a nice infographic from The Curbsiders on correction of hypernatremia

For more on correction of hypernatremia and management of nephrogenic DI, check these out:

1. de Groot T, et al. Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus. J Am Soc Nephrol. 2016;27(7):2082–2091. doi: 10.1681/ASN.2015070796.
2. Topf J, Abrams HR, Brigham SK, Okamoto E, Watto MF. “170 Hypernatremia is Easy with Joel Topf MD”. The Curbsiders Internal Medicine Podcast. https://thecurbsiders.com/episode-list. September 2, 2019.
3. Skeleton Key Case #4 from our colleagues at Renal Fellow Network

Case 47 Index
Case 47 Introduction
Case 47 Physical Exam
Case 47 Diagnostic Testing
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