Primary polydipsia (PP) is a condition where there is excess consumption of fluids leading to polyuria with diluted urine and, ultimately, hyponatremia. Polyuria can be defined as urine production greater than 40-50 ml/kg in a twenty-four-hour period. Primary polydipsia can be categorized into two types. 1) Psychogenic polydipsia and 2) Dipsogenic polydipsia. As the name suggests, psychogenic polydipsia is seen in patients with psychiatric disorders. Dipsogenic polydipsia, also called compulsory water drinking, is seen mostly in people who consciously drink large quantities of water to maintain a healthy lifestyle or in those whose hypothalamus is affected. Compulsory water drinking is perceived to improve, maintain good health, and is on the rise of late given the popularity of lifestyle programs.
This article will discuss the etiology, pathophysiology, diagnosis, and potential treatment options available for psychogenic polydipsia and dipsogenic polydipsia. Another entity to remember is beer potomania, which does not quite fit the definition of polyuria but can present with hyponatremia. This is from acute or chronic alcoholism with excessive beer drinking in patients who are typically malnourished, resulting from low solute intake/high carbohydrate intake. Psychogenic polydipsia is seen in many psychiatric conditions but is more commonly seen in schizophrenic patients. The exact mechanism is unknown, but various hypotheses have been put forward. Hyponatremia is a severe complication of primary polydipsia.
The main differential diagnosis for primary polydipsia is diabetes insipidus (DI). The diagnostic method that has been used for a long time is the indirect water deprivation test (WDT), which is an indirect measurement of the arginine vasopressin (AVP) activity, combined with the administration of desmopressin. This test differentiates primary polydipsia from diabetes insipidus and also helps differentiate central from nephrogenic diabetes insipidus. However, this traditional test is not without flaws. Various new methods have been recently proposed and are being considered as the latest diagnostic standard for the diagnoses mentioned above. These tests include copeptin measurement at baseline and after hypertonic saline infusion, the other method being the measurement of copeptin at baseline and after arginine infusion.
Regarding the treatment of this condition, there is not one particular proven strategy. The recommended treatment is to control the water intake, but this poses a compliance problem, especially in patients with psychogenic polydipsia with compulsive behavior. Changes in medications that have anticholinergic side effects can be tried. Various classes of drugs have been studied, and none is effective. Behavioral treatment trials showed mixed results. Coordination and inter-professional approach can help treat the patients better.
Primary polydipsia is common in patients with developmental disorders like autism and intellectual disability. Polydipsia is seen in patients with psychiatric disorders like schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression. Psychogenic polydipsia was named as such after it was first discovered in schizophrenic patients. Patients, especially the ones with psychotic disorders, have psychotic intermittent hyponatremia-polydipsia syndrome when the psychotic episodes happen.
Other psychiatry patients with nonpsychotic axis-1 psychiatric disorders also have polydipsia, which is more like compulsory water drinking. These people rarely become hyponatremic unless there are other contributing factors like being on thiazide diuretics. Dipsogenic polydipsia can be seen in patients who are affected by inflammation, infiltration, and infection of the hypothalamic region. Habitual polydipsia comes under dipsogenic polydipsia and is seen in individuals who are under the impression that drinking copious amounts of water will maintain good health, which is on the rise in recent years.
Psychogenic polydipsia is seen in patients with several psychiatric conditions like depression, bipolar disorder, and more commonly in schizophrenic patients, with 18% of patients admitted to psychiatric institutions exhibiting polydipsia. Dipsogenic polydipsia prevalence is increasing in the general population with the advent of healthy lifestyle programs. This is more prevalent in women.
The actual incidence of dipsogenic polydipsia is unknown. Dipsogenic form of primary polydipsia also has some overlap with the dipsogenic type of diabetes insipidus. Beer potomania is more common in men. Compulsory water drinking or habitual polydipsia is also seen in physically active and health-conscious people who get into the habit of drinking excessive amounts of water.
The pathophysiology of psychogenic polydipsia is poorly understood. In patients who drink large amounts of water, the kidneys compensate by excreting water up to a maximum of 12 L/day. There is also a decrease in arginine vasopressin secretion to decrease the retention of water, thereby resulting in hypotonic polyuria. Arginine vasopressin is also called anti-diuretic hormone (ADH). When the intake exceeds the excretory capacity of the kidney or when there is a decrease in the excretory capacity of the kidneys under the influence of external factors, this physiology gets affected. This can result in hyponatremia. Various risk factors can contribute towards hyponatremia: chronicity of primary polydipsia, stimulation of AVP secretion due to psychosis, drugs (antipsychotics, anti-depressants, diuretics), stress, and smoking.
Anticholinergic effects of medications can cause an increased sensation of thirst. In psychogenic polydipsia, improper functioning of the dopaminergic and cholinergic system has been implicated, which results in dysregulation of the thirst center along with the involvement of the hippocampal region, leading to this behavior of constant drinking. Thirst and secretion of arginine vasopressin (AVP) are thought to play an important role in maintaining serum osmolality, and the imbalance has shown to contribute towards psychogenic polydipsia. In schizophrenic patients with psychogenic polydipsia, brain MRI shows a smaller hippocampus when compared to patients with schizophrenia who did not have psychogenic polydipsia.
Many factors can influence the thirst center as well as the secretion of AVP. An increase in serum osmolality stimulates the secretion of AVP. Nausea, vomiting, hypotension, sepsis, exercise, and hypoglycemia can increase AVP secretion as well. The osmoreceptors in the hypothalamic region responsible for the thirst mechanism can be affected by infiltrative, vascular, congenital, neoplastic, and traumatic conditions, which might increase or decrease fluid intake.
Dipsogenic polydipsia can be seen in patients who are affected by these processes of the hypothalamus. Habitual polydipsia or compulsory water drinking is present in people who have a constant motivation to drink excessive amounts of fluids, thereby resulting in a lower thirst threshold over time. On review of the literature, several animal studies demonstrated that dopamine increase in the brain was the cause of polydipsic behavior. In patients with beer potomania and malnourishment, there is decreased excretory capacity of the kidneys down from 12 L/day to 8 L/day or less due to low solute intake. Anti-depressants and antipsychotic medications may add to excessive drinking due to anticholinergic effects.
Patients may have a history of psychiatric illnesses and systemic diseases with brain involvement. People who are health conscious and also have a history of excessive fluid intake may present with symptomatic hyponatremia. Hyponatremia can present as nausea, vomiting, confusion, ataxia, coma, seizures, and even death. History taking should focus on past medical history, surgical/traumatic history to the brain, and inquiry into autoimmune and infectious disease processes. Relevant history should be taken regarding medications as well. Personal history regarding smoking and alcohol use should be inquired as well.
Evaluation should include a good history taking. Lab work should consist of serum electrolytes, serum osmolality, 24-hour urine volume, urine electrolytes, and urine osmolality. Imaging studies to be considered are CT or MRI of the brain if need be, to rule out pathological causes. Inquiry into lifestyle also should be made to elicit a history of alcohol intake and total fluid intake.
Treatment of severe hyponatremia, in clinically unstable patients, includes hypertonic saline (3%) infusion in an ICU setting with frequent monitoring of sodium levels. In hemodynamically stable patients who don't require an ICU level of care, water deprivation is the next step once hypotonic polyuria is established. Care must be taken and one has to be aware of the fact that patients with underlying diabetes insipidus can get dehydrated if they are water restricted. Urine osmolality before and after deprivation is needed for evaluation.
Standardized proven treatment for primary polydipsia has not been established. Ideally, water restriction is the treatment, but compliance is of great concern with this strategy, given the compulsive water drinking behavior in psychogenic polydipsia. Better results by educating health-conscious people who have polydipsic behavior can be obtained, by consciously decreasing water intake. There has been a systematic review in 2006 done from the Cochrane database that found two clinical trials worthy of analysis. This review looked at randomized trials that included patients with psychiatric illness and psychogenic polydipsia, evaluated drug treatments, and looked at meaningful outcomes.
One trial used demeclocycline, and the other used naloxone. As per the systematic review, the results were not promising to inculcate into clinical practice. Studies that looked at various drug classes were included. Antidepressants, antipsychotics, beta-blockers, ACE inhibitors, mood stabilizers, angiotensin receptor blockers, tetracyclines, opiate antagonists, alpha-adrenergic receptor blockers and placebo were included. Behavioral treatments showed variable results.
Overall there is no proven pharmacological treatment or a behavioral method for the treatment of primary polydipsia. The evidence in support of either is low. Treatment must be provided on a case by case basis, depending on the patient, at the provider's discretion.
First, conditions that are more common like hyperglycemia and hypercalcemia, which can cause polyuria, have to be ruled out. The differential diagnosis of primary polydipsia (PP) includes mainly diabetes insipidus, either central or nephrogenic. The other condition to differentiate is beer potomania, the differentiating feature being the total amount of urine produced falls below the definition for polyuria. Primary polydipsia is a diagnosis of exclusion. Polydipsic behavior in primary polydipsia is usually not seen at night.
After polyuria (>40-50 ml/kg/24hrs) is confirmed, and urine osmolality is <800 mOsm/kg, serum sodium level has to be checked. If the serum sodium level is <135 meq, it is diagnostic of PP. If the serum sodium levels are >147, it is diagnostic of diabetes insipidus. If the serum sodium is between 135 and 147, the next step would be the water deprivation test. The traditional test that has been utilized by providers for a long time is the indirect water deprivation test that indirectly measures the activity of AVP. This test is started once hypotonic polyuria is confirmed, and serum sodium is between 135 and 147. Polyuria in primary polydipsia decreases with water deprivation (typically >8hrs), and urine osmolality increases (>800 mOsm/kg typically), this is diagnostic of PP. In diabetes insipidus, polyuria does not get better with water deprivation. If the urine osmolality remains <300 mOsm/kg after water deprivation, it is diagnostic of DI.
The administration of desmopressin differentiates between central and nephrogenic insipidus. If, after the administration of desmopressin, there is an increase of >50% in the urine osmolality, it is diagnostic of central DI. If there is an increase of <50% in the urine osmolality, it is diagnostic of nephrogenic DI. If the urine osmolality is between 300 mOsm/kg and 800 mOsm/kg after the water deprivation test, this could either be partial central DI or PP. To differentiate partial central DI from PP, desmopressin is administered. If the urine osmolality increases by > 9%, it is diagnostic of PP. If the Urine osmolality increases by <9%, it is diagnostic of partial central diabetes insipidus.
However, there have been queries regarding the specificity and sensitivity of the water deprivation test. It also takes a prolonged amount of deprivation time to accurately diagnose and differentiate patients with PP and the types of DI, the same reason for diagnosing partial central DI and partial nephrogenic DI. WDT was found to have low diagnostic accuracy of 70% overall for polydipsia (DI and PP). The diagnostic accuracy of the subgroup of people with primary polydipsia was only 41%.
A study done by Penelope et al. to evaluate the diagnostic value of the water deprivation test demonstrated that with the overnight WDT (8hrs), only 20% of the subjects met the diagnostic criteria for DI, and the majority were diagnosed at 16 hrs of deprivation. The same study also found that 25% of the patients with possible partial DI could have been misdiagnosed as PP. This highlights the inaccuracy as well as the cumbersomeness of the WDT.
The direct measurement of AVP was studied as well in the past. It was found that upon osmotic stimulation, it provided great accuracy in differentiating primary polydipsia from diabetes insipidus, when compared to the water deprivation test, but did not gain a reputation in clinical practice. This is due to the limitations of the AVP measurement since it is not a stable peptide ex vivo. The vasopressin precursor peptide has a stable c-terminal segment called copeptin, which can be used as a surrogate marker for vasopressin. A copeptin value of >21.4 pmol/l at baseline establishes the diagnosis of nephrogenic DI. If the value is less than 21.4 pmol/l, then osmotic stimulation to bring the serum sodium level to greater than 150 mmol/l is the next step. This can be achieved by water deprivation or hypertonic saline infusion in a hospital setting with frequent monitoring of serum sodium levels. If the level of copeptin is 4.9 pmol/l or greater after stimulation, it is a diagnostic of primary polydipsia.
If the level is less than 4.9 pmol/l, it is diagnostic of central DI. 96% of the patients with polyuria were accurately diagnosed with their respective diagnoses by measuring copeptin along with water deprivation/hypertonic saline infusion test. Given the cumbersomeness of the water deprivation test and the long duration involved with it, hypertonic saline infusion gained a reputation. Stimulation with hypertonic saline also requires frequent sodium checks and close monitoring. Keeping this in mind, a study was done with arginine infusion to measure the stimulated levels of copeptin instead of with hypertonic saline, which was promising. More evidence is needed to substantiate this finding, though.
Another condition that psychiatric patients can present with hyponatremia is pregnancy, where there is no polyuria or polydipsia, but one has to be aware of the fact that this is a physiologic change. Serum sodium levels can be lower, up to 3-6 mmol/l in pregnants, and is normal. This is due to a physiologic lower osmotic threshold for the thirst center and increased vasopressin secretion.
Prognosis depends on the intervention and also the underlying psychiatric disorder. The most effective strategy is preventing water intoxication by limiting water intake. Compliance may be an issue.
Complications from primary polydipsia result from hyponatremia. Symptoms or presentations include nausea, vomiting, blurred vision, tremors, dizziness, ataxia, confusion, lethargy, and, most commonly, seizures. Care should be taken to prevent the rapid correction of sodium level in a patient with hyponatremia to avoid central pontine myelinolysis. Sodium should not be corrected more than 8-10 mmol/l in 24 hours. Water, along with dextrose, can be infused if there is an overcorrection. Central pontine myelinolysis can result in permanent severe neurological damage. Hyponatremia can result in death as well.
Consultants who could be involved in the care of patients with primary polydipsia are as follows:
Patients should be counseled on the effects of hyponatremia and the severe consequences of it. Advice regarding keeping a log on the amount of water ingested will help. Feedback regarding medications being taken for psychiatric conditions to the providers should be encouraged. This will help in changing or adjusting the medicines based on how the patients were doing. Patients can be encouraged to restrict water intake by rewarding them. The family of a patient plays an important role.
Primary polydipsia can present with various nonspecific symptoms. It is a diagnosis of exclusion. More common causes like diabetes, hypothyroidism, adrenal insufficiency have to be considered in the differentials. Once polydipsia is suspected, a careful history should be taken from the patient or family depending on the situation. The patient needs to be monitored in an inpatient setting to quantify the polyuria.
Necessary laboratory tests should be ordered to help in the diagnosis. Care must be taken such that the deprivation test does not dehydrate the patient. Also, serial sodium monitoring is required to prevent rapid correction to avoid central pontine myelinolysis. To identify and treat primary polydipsia requires a multidisciplinary approach. Nurses play an essential role in keeping an account of the intake and output of these patients.
Care can be coordinated by psychiatrists, internists, endocrinologists, emergency providers, and neurologists, given the different settings these patients can be seen. Behavioral therapists also can contribute, but this might become a compliance issue in the long term for the patient. There were few randomized trials done studying the pharmacological treatments for primary polydipsia. Many studies were case reports or small case series and case-control studies. In conclusion, the evidence in support of any pharmacological or behavioral treatment option is low.
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