A 45-year-old woman comes to the physician because of frequent urination for the last six months. She states that she has been waking up several times at night to urinate. These symptoms also disrupt her professional work schedule. She has been taking lithium to treat a mood disorder for the past 5 years. She has tried many other drugs for her mood disorder, but none have been as successful as lithium. She is adherent to her treatment and has her lithium level measured regularly. She had one episode of mild lithium toxicity two years ago.
Her physical examination is unremarkable.
Laboratory results are as follows:

Which of the following would be the best initial treatment for this patient?

Question

A 45-year-old woman comes to the physician because of frequent urination for the last six months.  She states that she has been waking up several times at night to urinate.  These symptoms also disrupt her professional work schedule.  She has been taking lithium to treat a mood disorder for the past 5 years.  She has tried many other drugs for her mood disorder, but none have been as successful as lithium.  She is adherent to her treatment and has her lithium level measured regularly.  She had one episode of mild lithium toxicity two years ago.
Her physical examination is unremarkable.
Laboratory results are as follows:

Which of the following would be the best initial treatment for this patient?

Quizplus · Accepted Answer

This patient's presentation is consistent with lithium-induced nephrogenic diabetes insipidus (DI). Chronic lithium use can cause chronic interstitial nephritis, type I distal renal tubular acidosis, hyperparathyroidism with hypercalcemia, and nephrogenic DI (up to 20-40% of patients). Lithium induces ADH resistance by impairing water channel function and water reabsorption in the collecting duct. Patients typically present with acute onset nocturia and polyuria. However, patients taking lithium may also develop central DI or primary polydipsia due to their underlying psychiatric condition. Thus, the diagnosis must be confirmed with a water deprivation test, since the treatment differs for these conditions. With nephrogenic DI, the change in urine osmolality is minimal after DDAVP administration (central DI has > 50% increase in urine osmolality). water deprivation test Lithium-induced nephrogenic DI may be permanent or partially reversible and discontinuation of lithium is preferred. Patients who cannot stop lithium should be treated with salt restriction and selected diuretics (i.e., amiloride or thiazides). Amiloride blocks sodium channels in the collecting ducts to prevent lithium's cellular entry, while thiazides combined with sodium restriction promote a mild hypovolemia that acts to increase proximal sodium and water reabsorption. However, serum lithium levels increase with both options and require close monitoring. (Choice B) High-dose DDAVP is an alternative therapeutic option in patients who do not respond to diuretics, and it is sometimes effective in partially reversible nephrogenic DI. (Choice C) Fluid restriction will decrease urine volume, but this could lead to significant extracellular fluid volume depletion and worsen this patient's renal function. (Choice D) Urine osmolality is usually fixed in nephrogenic DI; thus, the amount of excreted solute directly affects urine volume. Reducing solute intake can decrease urine volume, but increasing intake will have the opposite effect and worsen this patient's polyuria. (Choice E) NSAIDs decrease glomerular filtration rate, enhance tubular solute reabsorption, and can significantly decrease urine output in some cases of nephrogenic DI. However, this patient has a low GFR (creatinine of 1.6 mg/dL) and NSAIDs could further decrease the GFR. Educational objective: Lithium can be associated with nephrogenic DI in up to 20-40% of patients. Symptomatic patients should discontinue lithium. Patients who cannot stop lithium may be treated with salt restriction and a trial of diuretics (i.e., amiloride or thiazides) with careful monitoring of renal function and serum lithium levels. __________ References: Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. (http://www.ncbi.nlm.nih.gov/pubmed/18596116) alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. (http://www.ncbi.nlm.nih.gov/pubmed/21051735)

A 45-Year-Old Woman Comes to the Physician Because of Frequent