Lithium-induced polyuria and diabetes insipidus: Evaluation

For an introduction to the topic of lithium-induced polyuria and diabetes insipidus, please see:

Lithium-induced polyuria and diabetes insipidus

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Urine volume

We should ask all patients on long-term lithium treatment whether they are urinating more than they used to and how often they have to wake up at night to urinate. We should remember that polyuria occurs in 50 to 70% of patients on long-term lithium treatment.

When interviewing the patient about this issue, we should keep in mind that it is the quantity of urine that we are asking about rather than the frequency of urinating.

Waking up at night more than once to urinate may suggest polyuria unless there is another cause like prostate enlargement.

In case of doubt, a 24-hour urine sample can be collected to measure the volume of urine produced over 24 hours (Gitlin, 1999). But how much urine is too much?

Greater than 3 liters in 24 hours is the generally accepted cut off for polyuria (Makaryus and McFarlane, 2006). This is useful to know.

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Fluid intake

We should also ask the patient how much fluid he or she is consuming. In case of doubt, we can have the patient measure the amount of fluid being consumed. Let’s make sure that the polyuria is not simply due to polydipsia.

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Laboratory tests

Urine osmolality and a basic metabolic panel should be ordered to help determine the cause of the polyuria.

1. In polyuria due to diabetes mellitus, the urine osmolality is 300 mOsmol/kg or more and the serum glucose is elevated.

2. But, in polyuria due to diabetes insipidus, the urine osmolality is low, less than 200 mOsmol/kg, even though the person is not drinking excessive amounts of fluid.

Also, in severe cases of diabetes insipidus, the serum sodium may be elevated.

But the diabetes insipidus could be central (due to inadequate production of ADH/vasopressin) or nephrogenic (due to the kidney not responding to the ADH). The only way to differentiate between the two is to refer the patient for a water deprivation/desmopressin test, which we will discuss

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 Water deprivation/ Desmopressin test

It is rare for mental health patients to need this and lithium must be stopped before water deprivation is attempted. However, in case one of our patients needs to be referred for this, we should know that the gold standard test to differentiate nephrogenic diabetes insipidus from psychogenic polydipsia and central diabetes insipidus (due to lack of ADH/vasopressin secretion) is water deprivation followed by injection of desmopressin.

If this test is needed, it should be done, not by us, but only by a physician experienced in doing it.

In nephrogenic diabetes, even after water deprivation, the urine osmolality remains below plasma osmolality (Makaryus and McFarlane, 2006). That is, the kidney is unable to adequately concentrate the urine even when there is a need to conserve water.

Then, desmopressin (a synthetic analog of ADH/vasopressin) is injected, but there is a limited response because in nephrogenic diabetes insipidus, the problem in the kidney rather than a lack of ADH secretion.

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