Case Presentation: LF is a 63 year-old female with a history of schizoaffective disorder, gastroparesis, and stage III chronic kidney disease (CKD) who was initially admitted to the inpatient psychiatric unit for psychosis with suicidal and homicidal ideation in the context of medication nonadherence. Mental status exam was remarkable for persecutory delusions and auditory hallucinations. She expressed severe paranoid delusions regarding oral intake and was concerned that her meals and drinks contained toxins. Labs revealed an initial serum sodium of 144 meq/L and a creatinine of 1.4 mg/dL, consistent with her baseline. The patient was started on risperidone and valproic acid. Her course was complicated by refractory nausea and vomiting, noted to be common for her due to longstanding gastroparesis of unknown etiology. Her serum sodium peaked at 165 meq/L with urine osmolality of 140 mosm/L on hospital day 12, prompting transfer to the medicine service for further management. She had suboptimal response to desmopressin (DDAVP) on fluid restriction, yielding a diagnosis of nephrogenic diabetes insipidus. On further history, the patient stated that her psychiatric symptoms began in the 1970s after an episode of post-partum psychosis. She was eventually started on lithium in the year 2000. This medication was continued for 10 years; however, it was discontinued in 2010 when she developed CKD. During this admission, she was started on hydrochlorothiazide and naproxen with appropriate improvement in serum sodium.

Discussion: Lithium-induced diabetes insipidus occurs in up to one third of patients on long-term lithium therapy and cases of persistent symptoms have been reported even after cessation. Patients typically present with early symptoms of polyuria and polydipsia. These patients are unable to concentrate urine, as lithium damages the principal cells in the collecting duct and reduces expression of aquaporin channels in the apical membrane of these cells. Aquaporin channels, mediated by vasopressin, are responsible for water resorption. A decrease in functional aquaporin channels leads to excretion of excess water yielding elevated serum sodium levels, elevated serum osmolality and low urine osmolality. The consequences of uncontrolled nephrogenic diabetes insipidus can be severe, as it can cause neurologic dysfunction and possibly osmotic demyelination syndrome.Initial treatment includes cessation of lithium and administration of free fluids with a salt and protein-restricted diet. In refractory cases, amiloride, hydrochlorothiazide, and non-steroidal anti-inflammatory drugs have been used. NSAIDs have the ability to benefit patients with diabetes insipidus, as they inhibit synthesis of prostaglandins that are known to have inhibitory effects on vasopressin. In this case, the patient responded appropriately to hydrochlorothiazide and naproxen. She was subsequently transferred back to the psychiatric unit with instructions for close follow-up with nephrology in the outpatient setting.

Conclusions: This case reinforced the diagnosis and management of nephrogenic diabetes insipidus. LF had a prolonged period of decreased PO intake, exacerbating her underlying nephrogenic diabetes insipidus. Her urine osmolality remained low despite fluid restriction and DDAVP challenge. In the setting of chronic lithium use, the diagnosis of lithium-induced diabetes insipidus was confirmed. She responded appropriately to hydrochlorothiazide and naproxen with stabilization of her serum sodium.