Sarcoidosis as a Cause of Diabetes Insipidus
By Norman T. Soskel, MD, FACP, FCCP
Sarcoidosis Center, Memphis, TN

There are a variety of causes of diabetes insipidus, one of the less common is sarcoidosis. And not everyone who has sarcoidosis will also develop DI.

Sarcoidosis is a multi-system disorder characterized in affected organs by a type of inflammation called granulomas (a mass or nodule of chronically inflamed tissue). What causes this inflammation is unknown. Sarcoidosis can occur in any part of the central or peripheral nervous system. When sarcoidosis affects the central nervous system, various cranial nerves can be damaged and may paralyze specific areas of the body. The most common is a facial palsy causing part of the face to droop, which may be temporary or permanent, or it may recur. Sarcoidosis is diagnosed by finding a type of inflammation called non-caseous granulomas on biopsy of various tissues and ruling out tuberculosis and fungal diseases in the biopsy with special stains and cultures.

CDI develops when sarcoidosis involves the posterior part of the pituitary gland. This gland is located just under the brain and just behind the eyes. The back part of the gland is in intimate association with the part of the brain called the hypothalamus. Together they use a hormone called vasopressin, an antidiuretic hormone (ADH) that regulates how the body uses water. When not enough vasopressin is produced, then the body tries to eliminate more water than is normal. Frequency of urination occurs and the urine produced is very dilute. If this is allowed to occur unchecked, very serious dehydration can occur and might even lead to decreased blood pressure and death.

Frequent urination is called polyuria (usually defined as urine output of at least three liters a day). It is important to remember that there are a number of causes of polyuria, diabetes insipidus being just one. Someone experiencing polyuria should get correctly diagnosed so that he or she can receive the appropriate therapy. In patients with sarcoidosis who are exhibiting symptoms of DI, such as polyuria, it is important to know which form of DI is present because, although extremely rare, sarcoidosis can cause both nephrogenic DI and central DI. Of course, diseases other than sarcoidosis can also cause DI, and the habitual drinking of fluids, including just water, can lead to polyuria, without DI really being present. When DI is caused by an abnormality in the central nervous system, such as sarcoidosis granulomas in the pituitary gland or hypothalamus, it is CDI.

There may be other causes of polyuria in sarcoidosis, such as hypercalcemia (increased calcium in the blood) caused by increased calcitrol made by the granulomas, which results in nephrogenic DI (NDI). Hypercalcemia and hypercalciuria (increased calcium in the urine) can occur as a result of the sarcoidosis itself and they also can cause polyuria. This is related to effects on the kidney and can result in NDI.

To diagnose DI and determine whether it is CDI or NDI, a water deprivation test is usually needed. During this test the patient is requested not to take in any water for a prolonged period of time until the urine becomes concentrated to a certain degree. Then a substance like vasopressin is given and the lab tests are repeated. Depending on the changes in lab tests that occur, the distinction can usually be made and the correct diagnosis and therapy initiated. [Editor's note: For more information about the water deprivation test, please refer to DiF's web site at www.diabetesinsipidus.org.]

In a patient with sarcoidosis and polyuria, usually the patient has sarcoidosis documented by biopsy elsewhere and the involvement of the pituitary gland is surmised to be related to the sarcoidosis. If CDI is the only manifestation of the disease, then the diagnosis of sarcoidosis becomes difficult because a biopsy of that gland is not often possible. Frequently in the literature, pituitary involvement is associated with uveoparotid fever (Heerfordt's syndrome) in which a number of craniel nerves may be affected as well as swelling of the parotid gland and ocular disease (such as uveitis) as well.

In the case of sarcoidosis, use of steroids often will be sufficient to treat the condition. Replacing the vasopressin with the synthetic form of that hormone, desmospressin, may also be used or needed.

Dr. Norman T. Soskel founded the Sarcoidosis Center. For more information, go to http://www.sarcoidcenter.com.

References:
1. UpToDate version 10.3 (October 2002) (http://www.uptodate.com)
2. Scadding JG. Sarcoidosis, pp. 161, 307-314, Eyre and Spottiswoode, London, 1967.
3. Sharma OP. Sarcoidosis: Clinical Management, pp. 114-115, 168-169, Butterworths, London, 1990.