Recently in the clinic we were asked to review a patient with suspected diabetes inspidus. She had been taking lithium for more than 20 years for bipolar disorder that was very well controlled. During a routine medical examination, her blood tests revealed a serum creatinine of 1.4 so she proceeded to have a 24-hour urine collection. The result of this showed that her GFR was moderately reduced at 40mls/min but the striking finding was a 24 hour urine volume of 10 liters. The patient herself had no complaints regarding this as she was accustomed to drinking large volumes. She had been advised many years before to take a high salt diet in order to reduce the potential for nephrotoxicity (this sodium would compete for Li uptake in the DCT). Reducing her salt intake cut her urine volume by half which in itself was a great result.
One thing that did not fit entirely with the story was that her serum Na was never >140mEq/L. The impetus for water intake in DI is a high serum Osm but she was often in the 137-138 range suggesting that she was actually keeping her Osm lower than would be expected. The question arose as to whether or not there was a component of polydipsia here unrelated to the possible DI so we admitted her for a water deprivation test.
As mentioned by Nate before, the protocol for this test involves restricting a patient’s access to water and then measuring the plasma and serum osmolarity every 1-2 hours until:
(a) the urine osmolality reaches a normal value (e.g., above 600 mosm/kg, suggesting that both ADH secretion and response to ADH are intact).
(b) the urine osmolality is stable on two successive measurements despite a rising plasma osmolality, or
(c) the plasma osmolality is greater than 295-300 mosm/kg.
At that point DDAVP is administered.
There is one caveat, in the case of this patient, her initial urine Osm was 104 with a serum Osm of 307. According to the protocol above, this would be the time to give her DDAVP. However, her serum Na was only 141. The additional Osmoles were a result of a slightly elevated fasting blood sugar and a high BUN (because of her CKD). Her calculated Osmolarity was 306. As a result, we postponed giving DDAVP at that stage. Her results during the day were as follows:
Serum Na 141 144 149 153 154
Serum Osm 307 315 319 326 329
Urine Osm 104 126 142 154 153
We administered DDAVP when her serum Na was 149 and allowed her to drink again as soon as the next lab was taken. Her final result was after she had been allowed to start drinking again and she was already preventing her Na from increasing any further. The lack of response to DDAVP indicates a diagnosis of nephrogenic DI, almost certainly due to lithium.
The take home points for me here were that a low serum sodium in the steady state does not necessarily mean that the patient does not have DI – in someone like this who has had this problem for years, she has just become accustomed to staying ahead of her thirst. The second point was that a serum sodium always has to be sent with the serum osmolarity as if there are other osmoles around, they can give you a misleading result.