Rhabdomyolysis Complicating Psychogenic Polydipsia

A 26-year-old man with a history of bipolar I disorder with psychotic features presented to our clinic with altered mental status and seizures, which occurred while he was incarcerated in a correctional facility. On admission, he was minimally responsive. His temperature (39.3°C) and other vital signs were normal. Initial laboratory workup showed that the patient had hyponatremia (blood sodium level, 120 mmol/L). His creatine kinase level was 17,463 U/L. He was emergently intubated. A lumbar puncture was performed, and no abnormalities were found in his CSF. Prophylactic antibiotics were initiated, although blood cultures and urine toxicology results were negative and other laboratory findings, including for thyroid functioning and cortisol, lactic acid, and ammonia levels, were found to be within normal limits. Further workup, including EEG, chest X-ray and MRI, was unremarkable.

A repeat basic metabolic panel demonstrated minimal improvement in the patient's electrolytes. His blood sodium levels remained low (120 mmol/L), and his serum osmolality measured 253 mOsm/kg (normal range, 280–300 mOsm/kg). Urine collected at that time revealed a urine sodium level of 68 mmol/L (normal range, 40–220 mmol/L) and osmolality of 118 mOsm/kg (normal range, 300–900 mOsm/kg). The patient was started on fosphenytoin and levetiracetam due to ongoing epileptiform activity. Intravenous fluids and desmopressin acetate (a synthetic analogue of an antidiuretic hormone) were administered to rapidly correct the underlying hyponatremia.

The patient was clinically stabilized, and psychiatry was consulted for medication management and emerging psychotic symptoms. On examination, the patient displayed inappropriate affect and laughter as well as paranoid behaviors, and he was responding to internal stimuli. Given the cluster of his symptoms, including seizure activity, an elevated creatine kinase level, and hyperthermia as well as his psychiatric medication history (risperidone [1 mg b.i.d.] and bupropion [150 mg/day]), neuroleptic malignant syndrome and serotonin syndrome were considered, and his home psychiatric medications were initially held.

Further data collection revealed that the patient had not been adherent to medications while in the correctional facility, and his psychotic symptoms and paranoia had worsened significantly before presentation to our clinic. For more than 1 week, while in the correctional facility, he refused to eat food served to him, believing that it was "made of human flesh," and instead would only drink water from the toilet.

Although his seizures improved with time, his creatine kinase level reached 36,978 U/L on day 2 of his hospital stay, before decreasing (Figure 1). He was diagnosed with psychogenic polydipsia and transferred to inpatient psychiatry, where his psychosis was stabilized with valproic acid and risperidone.

Polydipsia is defined as fluid intake of more than 3 liters per day, and psychogenic polydipsia is characterized by a volitional intake of excess fluid due to an underlying psychiatric disorder. Psychogenic polydipsia affects 6%–20% of persons with psychiatric disorders (1). The etiology of psychogenic polydipsia is multifactorial, although the unifying concept is hypothalamic thirst dysfunction. In nonaffected persons, thirst cues and antidiuretic hormone activity are closely paired. However in psychogenic polydipsia, this relationship becomes dysregulated (2), which is hypothesized to be the result of elevated dopamine levels (and increased sensitivity of dopamine receptors associated with long-term use of antipsychotic medication) that stimulate thirst in the hypothalamus. Anticholinergic side-effects of antipsychotic medications are also thought to contribute to the condition (3). Hyponatremia is one of the more dangerous consequences of psychogenic polydipsia, because it can lead to lethargy and seizures and, in the most severe cases, coma.

Fluids and electrolytes are maintained by a complex interplay of renal, pituitary, and hypothalamic physiology. Antidiuretic hormone, produced by the hypothalamus and stored in the posterior pituitary gland, is secreted in response to hypertonic states. The function of antidiuretic hormone is to increase the amount of free water that can be reabsorbed from the kidneys into circulation. In psychogenic polydipsia, excessive fluid intake can overwhelm the body's natural protective ability to suppress antidiuretic hormone, and the limit of urine dilution is reached (100 mOsm/kg), resulting in fluid retention and dangerous electrolyte disturbances.

The patient in the above case had a urine osmolality of 118 mOsm/kg, indicating that his antidiuretic hormone was near complete suppression. Our patient also experienced neurological manifestations as a rare complication of hyponatremia. The alterations in sodium levels and other electrolytes in psychogenic polydipsia disrupt neuron excitability and synchronization, leading to abnormal neuronal discharge and epileptiform activity (4).

The above case is a unique presentation of psychogenic polydipsia, because rhabdomyolysis is a rare but significant outcome that can occur. Rhabdomyolysis is a condition characterized by rapid breakdown of skeletal muscle that can lead to kidney failure and dangerous electrolyte imbalances, among other complications. Rhabdomyolysis is a known complication of hyponatremia that occurs as a result of cellular swelling; shifting osmotic loads lead to a disruption in cellular transmembrane potentials and ion exchange pumps, damaging skeletal muscle (5). Rhabdomyolysis is more likely to occur in circumstances of hyponatremia that are attributed to psychogenic polydipsia because of the rapid nature of the fluid and electrolyte shifts (6). Rhabdomyolysis is not only a direct result of hyponatremia, but it can also be caused by rapid correction of hyponatremia, which can lead to cellular breakdown and release of creatine kinase by similar proposed mechanisms (7).

Our patient presented with a creatine kinase level of 17,463 U/L, which increased to a high of 36,978 U/L. His clinical status and hyponatremia improved; however, creatine kinase normalization lagged and levels were even noted to increase as electrolytes normalized. It was hypothesized that it was not the hyponatremia itself that caused the elevation of creatine kinase but the rapid correction of sodium (from 120 to 135 mmol/L over 18 hours) contributed to further elevation in the levels (Figure 1). Sodium levels were rapidly corrected because of concerns regarding neurologic complications that the patient was experiencing as a result of hyponatremia. Rhabdomyolysis was not causative of the epileptiform activity, but it was more likely that the seizure-like activity contributed to the rise in creatine kinase.

Before making a diagnosis of psychogenic polydipsia, a thorough evaluation of hyponatremia should include investigation of other potential causes, such as the syndrome of inappropriate antidiuretic hormone secretion, congestive heart failure, and intrinsic renal disease. Psychiatric medications such as carbamazepine, oxcarbazepine, and fluoxetine, among others, have been associated with inappropriate antidiuretic hormone secretion and increased renal responsiveness to antidiuretic hormone (8). Laboratory investigation should include tests of urinalysis, urine sodium, serum and urine osmolality, comprehensive metabolic panel, morning cortisol level, and thyroid-stimulating hormone, since hypothyroidism may be associated with increased antidiuretic hormone secretion and decrease glomerular filtration rate (9). Cortisol levels should be evaluated to assess for adrenal insufficiency, which can limit the reuptake of sodium through the action of aldosterone. Evaluating for hyperlipidemia, hyperproteinemia, and hyperglycemia is important, since increased osmotic loads could artificially lower sodium levels. Chest X-ray can be considered to rule out tumor-related conditions, and head imaging can assess for structural conditions in the brain that may lead to cerebral salt wasting.

Rhabdomyolysis is a rare but known complication of hyponatremia that can occur more frequently in psychogenic polydipsia as a result of rapid cellular fluid shifts. Because correction of sodium can lead to worsening of rhabdomyolysis, careful clinical consideration of the risks of both untreated symptomatic hyponatremia and worsening rhabdomyolysis must take place. When neurologic symptoms are evident, treatment of hyponatremia should take precedence over any concern of rhabdomyolysis.