Transient Central Diabetes Insipidus in the Setting of Underlying Chronic Nephrogenic Diabetes Insipidus Associated with Lithium Use
| Title: | Transient Central Diabetes Insipidus in the Setting of Underlying Chronic Nephrogenic Diabetes Insipidus Associated with Lithium Use |
|---|---|
| Authors: | Posner, Laurie; Mokrzycki, MD, Michele H. |
| Publisher: | American Journal of Nephrology |
| Date Published: | January 01, 1996 |
| Reference Number: | 42 |
Nephrogenic diabetes insipidus (NDI) is a well-documented complication of lithium use. The association of central diabetes insipidus (CDI) with lithium use is rare. We report a patient receiving chronic lithium therapy who presented with a transient CDI occurring in the setting of underlying chronic NDI. To the best of our knowledge, this is the first case of lithium-associated CDI and NDI presenting concurrently. Potential mechanisms regarding the pathophysiology of lithium-associated CDI are discussed. This case emphasizes the importance of the evaluation of lithium-associated polyuria with a direct measurement of plasma vasopressin, interpreted with simultaneous plasma and urine osmolality to secure the correct diagnosis and ensure appropriate therapeutic management.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The patient had a history of diabetes mellitus, chronic obstructive pulmonary disease, and psychological instability. In the hospital she experienced excessive urination, a high concentration of sodium in the blood, and a low urine osmolality (i.e., a low concentration of osmotically active particles in her urine).
Normally, the interaction between the antidiuretic hormone (ADH) and the distal nephrons (microscopic kidney units consisting of filtering funnels and tubules) permits the proper concentration of elements in the plasma despite large fluctuations in daily water intake. In the majority of cases of lithium-related excessive urination there is a resistance to ADH in the tubule section of the nephron. This prevents the generation of cAMP, an important metabolic regulator, and decreases the osmotic stimulus for water reabsorption. The kidneys, then, fail to keep the water the body needs and instead funnels it out the body, resulting in excessive urination.
Other research has indicated that the urine osmolality of CDI patients can increase after they are given synthetic ADH. In the case of the 70-year-old woman, her first water deprivation test revealed an inappropriately low ADH level in relation to her plasma hypertonicity. This is consistent with CDI. Over the next several weeks two more water deprivation tests showed the woman's ADH level had risen to the level where it was no longer deficient. But she still experienced excessive urination and low urine osmolality, which suggested the ADH message was not being received by the kidneys, a characteristic of NDI.
ADH is synthesized in and secreted from that part of the brain called the hypothalamus. Though the mechanics by which lithium may impair ADH production or release is unknown, it is known that lithium, when administered over a period of time, accumulates in the brain. (In rats given experimental dosages of lithium, the highest accumulations were found in the thalamus and hypothalamus.) Lithium is known to alter the generation of second messengers in G protein-regulated systems. The G protein is an important sequence in generating an important metabolic regulator called cAMP, which is important to normal kidney function. And this entire sequence depends on the kidney receiving ADH's hormonal message. How lithium impairs the synthesis and/or release of ADH, which results in CDI, is yet to be discovered.