Approach

Several aspects need to be considered in the assessment:

  • Identifying the patient with excess water consumption.

  • Ruling out other causes of polydipsia, polyuria, or hyponatremia. The diagnosis of PPD is one of exclusion.

  • Identifying the presence or absence of concomitant syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and renal hypersensitivity to antidiuretic hormone (ADH).

Comprehensive workup requires a thorough history, physical exam, and routine laboratory tests including plasma and urine osmolality, and plasma and urine sodium. Urinary sodium and osmolality are best measured by 24-hour urine collection. A water restriction test is the gold standard for diagnosis.[29]

History

Many individuals with polydipsia will have a medical history of a psychiatric disorder or neurodevelopmental disorder. PPD occurs in 6% to 20% of psychiatric patients, most commonly in schizophrenia.[30][31][32][33][34][35][36] Affective disorders, anxiety disorders, anorexia nervosa, obsessive-compulsive disorder, and personality disorders have all been associated with PPD. PPD has been noted in people with neurodevelopmental disorders, including autism spectrum disorder and Kleine-Levin syndrome.[37][38]

Physical exam

There are no definitive findings of PPD on physical examination; however, it can be useful to weigh the patient diurnally for up to one week to assess water loading and severity of polydipsia. In a monitored setting (e.g., in a hospital or group home), patients may be weighed up to 4 times a day. In the community, patients should ideally be weighed 3 times a day, although this may not always be feasible. Differences in diurnal weight gain in patients with PPD can be much greater than those in controls (2.2% vs. 0.6%).[39]

Clinical presentation

Patients present in the following ways.

  • Water-seeking and drinking noted by clinical staff or other observers.

  • Those at risk include patients with psychiatric disorders and patients with neurodevelopmental disorders.

  • Patients with psychiatric disorders often drink from nonpotable sources (e.g., toilets), but may also be seen to have a cup or other drinking vessel with them at all times.[10] Unlike other people with polydipsia, they are unlikely to complain of excessive thirst and instead provide other nonsensical explanations for their excessive drinking.[10]

  • Polyuria.[40]

  • Hyponatremia (serum sodium concentration <135 mEq/L).

    • It is important to note that not all individuals with PPD will present with abnormal serum sodium levels. Between 3% and 6% of patients with PPD and schizophrenia have hyponatremia.[10][41] This is likely the result of years of water loading.[42]

    • Hyponatremia is more likely to develop in older people with comorbid medical conditions (cardiac, renal, and hepatic diseases). Hyponatremia is typically mild and asymptomatic in the absence of another contributing comorbidity.[33]

    • Symptomatic hyponatremia is more likely after an acute 3- to 4-liter fluid ingestion, or if patients continue to drink excessively (>10 liters daily) after reaching their limit of urine dilution (100 mOsm/kg H₂O in osmolality) and ADH suppression.[4][22]

    • Acute symptomatic hyponatremia can develop over a period of <48 hours and presents clinically with symptoms related to central nervous system dysfunction as a result of cerebral edema. An acute drop in serum sodium below 125 mEq/L manifests clinically with headache, nausea, cramping, hyporeflexia, dysarthric speech, restlessness, lethargy, confusion, seizures, delirium, and coma.[43][44]

    • Rhabdomyolysis secondary to dilutional hyponatremia has also been reported.[45][46]

Laboratory tests

The diagnosis of PPD is one of exclusion.

Initial tests include plasma and urine osmolality, and plasma and urine sodium.[29] Urinary sodium and osmolality are best measured by 24-hour urine collection. Typically, hyponatremia is hypotonic and euvolemic. Urinary osmolality is <100 mOsm/kg H₂O, and serum osmolality is also low (<280 mOsm/kg H₂O).

Intensity of polydipsia should be measured by the extent of polyuria (complete 24-hour urine collection). In patients with acute hyponatremia, this may be difficult, and estimates of 24-hour urine volumes based on measurement of urinary creatinine excretion may be used.

Other tests that may be of benefit include a complete electrolyte and metabolic panel, urinalysis, and BUN.[29] These tests may be useful to exclude other conditions such as diabetes mellitus (with elevated blood glucose on metabolic panels and glucosuria noted on urinalysis) and osmotic diuresis (high plasma osmolality).

Water restriction test

  • A water restriction test is the definitive test for diagnosis, often coupled with a test of urine-concentrating ability in response to giving ADH exogenously.[29] Urine osmolality is measured before and after the test.

  • In PPD, the urine is very dilute before water is restricted (<100 mOsm/kg H₂O). It achieves an osmolality of >750 mOsm/kg H₂O after restricting water and giving vasopressin, and is diagnostic of PPD.[47] This result rules out diabetes insipidus (DI).

  • DI is also associated with low urine concentration before a water restriction test. ADH concentration depends on whether the defect is central DI (low ADH secretion) or renal DI (low renal response to ADH).[48][49][50] Hence, before a water restriction test, central DI and PPD can seem similar (low ADH and dilute urine). Concomitant PPD and DI have been reported.[51]

  • Some impairment in concentrating ability is known in patients with chronic PPD, due to medullary gradient washout and downregulation of ADH release. These patients may not be able to maximally concentrate urine following the water deprivation test, and achieve urine osmolalities closer to 600 mOsm/kg H₂O than to >750 mOsm/kg H₂O (normal range).[52]

  • Plasma ADH can also be measured before and after water restriction if other results are equivocal; the plasma ADH before water restriction is low in PPD, and rises following the water deprivation test.[53]

  • Patients with PPD and a comorbid central defect of SIADH may have ambiguous results. Failure to maximally suppress ADH secretion is the foundation of SIADH. Plasma ADH is elevated before water restriction, and the urine is not maximally diluted. SIADH is associated with high urine sodium (>20 mEq/L) due to impaired activation of the renin-angiotensin-aldosterone system.[48][54] Such a result is also observed in those with renal hypersensitivity to ADH, who may have low or normal plasma ADH.[48][50] SIADH is associated with euvolemia or hypervolemia.[55]

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