February 5th - MHH - Polyuria and Diabetes Insipidus

Today at Morning Report, Endocrine consults presented a patient in her third trimester with polyuria and polydipsia.  Here is a general approach to a patient with polyuria, and info on DI

In general, polyuria is defined as at least 3L of urine a day. The frequency of urination does not matter as much as the total amount.  Patients with polyuria will commonly also have polydipsia (to compensate, as long as their thirst center is intact) and will have nocturia.





The basic causes to know for rotations and the boards are:
Diabetes Mellitus
Diabetes Insipidus (Central and Nephrogenic)  - and their multiple causes
Primary/Psychogenic Polydipsia
Diuretic Use (esp in those using it for weight loss)
Hypercalcemia
Medications (either directly or by causing a nephrogenic DI)
Post-ATN or Post-Obstrutive Uropathy

Your exam in these patients may show signs of dehydration, although this is not as common when the patient has an intact thirst mechanism. A Good neurologic examination is essential with the variety of causes of central DI.  Further examination is directed mostly to other causes of Central/Nephrogenic DI or primary polydipsia (i.e. skin findings with sarcoid, amyloid infiltration, lymph nodes with systemic lymphoma, etc)

For the boards, a key topic is being able to identify and contrast Central Diabetes Insipidus, Nephrogenic Diabetes Insipidus and Primary Polydipsia

Central Diabetes Insipidus occurs from inadequate secretion of vasopressin. 
Causes: There are familial/inherited forms, but this is not as common as other causes - tumors of the CNS (including lymphoma and mets), trauma, granulomatous disease (TB/Sarcoid), infections (meningitis) and Sheenhan Syndrome. 

Nephrogenic Diabetes Insipidus occurs from renal insensitivity to vasopressin. 
Causes: This is commonly an inherited disorder, but can be secondary to medications (esp Lithium, Ampho B), systemic conditions (amyloid, Sjogrens, sickle cell disease, pregnancy), or electrolytes (HyperCA and HypoK)

Primary Polydipsia is simply increased water intake, usually psychogenic in nature (but can also be seen with lesions that affect the thirst center of the brain - sarcoid is a commonly tested one. 

Labs: Basic workup should include ruling out causes listed above, if not already obvious.  The best test to do initially is a BMP and Urine Osmolarity.  Patients will not be hypernatremic if they have an intact thirst mechanism, so don't rule out any of the above three if the patient has access to water, and takes in an amount to offset their urine output.  Undiagnosed DM and secondary osmotic diuresis can be ruled out with the glucose on the chemistry.  The electrolytes are also very important - both Hypercalcemia and Hypokalemia can not only cause polyuria, but in most cases, will make the symptoms worse as they interfere with the kidneys ability to concentrate urine.  Therefore, check these labs and correct as needed. 

Urine Osmolarity will be low in patients with Both forms of DI - generally <200. This is usually also the case with Primary Polydipsia. This is the general first step, although it makes sense because of very dilute urine. 

The other test that is done is the much heard about water deprivation test.  Patients are to be started on this protoco , and are instructed to not drink for about 2 hours before coming to the clinic or hospital for testing. During the time frame, the patient is not given access to fluids -> dehydration -> maximum stimulus for Vasopressin Secretion. Basic labs are drawn, and both Urine Volume/osm are measured every 2 hours. During this time frame, patients with Primary Polydipsia will be able to concentrate their urine. Therefore, in patients with Primary Polydipsia, the Urine osm will rise during the test.  In patients with both Central and Nephrogenic DI, the urine osm does not change much, yet the serum sodium may increase. 

So, now with no change in urine osm, the patient has either Central or Nephrogenic DI. How to tell apart - the patient is given desmopressin and we see what happens to the Urine Osm. Those patients with Central  DI will have at least a 50% increase in the Urine Osm after this medication, whereas patients with nephrogenic DI will have none or a slight increase (<10%) in their urine Osm. In those with primary polydipsis, the urine osm will increase at least 50% as well. 

Of NOTE:  On Boards, some other lab info/approaches may be given to differentiate the conditions.  With a low urine osm, and without the use of the water deprivation test, desmopression may be administered to see what happens to the urine osm.  If it changes >50%, then it is central DI.  Also, on various board review materials, they mention measuring ADH during the deprivation test. This is usually not done much clinically. You should be aware that with the water deprivation test - a rising plasma osm with no change in ADH is Central, and a rising ADH with no change in urine osm is Nephrogenic.  This makes sense, and may be presented on boards - but is not usually the way to diagnose this clinically. 

Treatment:
Central DI: Usually get intranasal Desmopressin lifelong
Nephrogenic DI:  Treat the underlying disorder/change medications.  Treatment is also thiazide Diuretic +/- K-sparing diuretic (The cause voume contraction sensed by the kidneys, and the resulting autoregulatory decrease in GFR will help decrease Urine Output)

Reference:
Image Courtesy of www.operationalmedicine.org