Several aspects need to be considered in the assessment:
Identifying the patient with excess water consumption.
Ruling out other causes of polydipsia, polyuria, or hyponatraemia. The diagnosis of psychogenic polydipsia (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 work-up requires a thorough history, physical examination, 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]Dundas B, Harris M, Narasimhan M. Psychogenic polydipsia review: etiology, differential, and treatment. Curr Psychiatry Rep. 2007 Jun;9(3):236-41.
http://www.ncbi.nlm.nih.gov/pubmed/17521521?tool=bestpractice.com
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]Verghese C, De Leon J, Josiassen RC. Problems and progress in the diagnosis and treatment of polydipsia and hyponatremia. Schizophr Bull. 1996;22(3):455-64.
http://schizophreniabulletin.oxfordjournals.org/cgi/reprint/22/3/455
http://www.ncbi.nlm.nih.gov/pubmed/8873296?tool=bestpractice.com
[31]de Leon J. Polydipsia: a study in a long-term psychiatric unit. Eur Arch Psychiatry Clin Neurosci. 2003 Feb;253(1):37-9.
http://www.ncbi.nlm.nih.gov/pubmed/12664312?tool=bestpractice.com
[32]Illowsky BP, Kirch DG. Polydipsia and hyponatremia in psychiatric patients. Am J Psychiatry. 1988 Jun;145(6):675-83.
http://www.ncbi.nlm.nih.gov/pubmed/3285701?tool=bestpractice.com
[4]Jose CJ, Perez-Cruet J. Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatry. 1979 Feb;136(2):221-2.
http://www.ncbi.nlm.nih.gov/pubmed/760555?tool=bestpractice.com
[33]Blum A, Tempey FW, Lynch WJ. Somatic findings in patients with psychogenic polydipsia. J Clin Psychiatry. 1983 Feb;44(2):55-6.
http://www.ncbi.nlm.nih.gov/pubmed/6826531?tool=bestpractice.com
[6]Meulendijks D, Mannesse CK, Jansen PA, et al. Antipsychotic-induced hyponatraemia: a systematic review of the published evidence. Drug Saf. 2010 Feb 1;33(2):101-14.
http://www.ncbi.nlm.nih.gov/pubmed/20082537?tool=bestpractice.com
[34]Mannesse CK, van Puijenbroek EP, Jansen PA, et al. Hyponatraemia as an adverse drug reaction of antipsychotic drugs: a case-control study in VigiBase. Drug Saf. 2010 Jul 1;33(7):569-78.
http://rd.springer.com/article/10.2165/11532560-000000000-00000/fulltext.html
http://www.ncbi.nlm.nih.gov/pubmed/20553058?tool=bestpractice.com
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.[35]Bremner AJ, Regan A. Intoxicated by water: polydipsia and water intoxication in a mental handicap hospital. Br J Psychiatry. 1991 Feb;158:244-50.
http://www.ncbi.nlm.nih.gov/pubmed/2012917?tool=bestpractice.com
[36]Deb S, Bramble D, Drybala G, et al. Polydipsia amongst adults with a learning disability in an institution. J Intellect Disabil Res. 1994 Aug;38 ( Pt 4):359-67.
http://www.ncbi.nlm.nih.gov/pubmed/7949788?tool=bestpractice.com
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%).[37]Vieweg WV, Godleski LS, Graham P, et al. Abnormal diurnal weight gain among long-term patients with schizophrenic disorders. Schizophr Res. 1988 Jan-Feb;1(1):67-71.
http://www.ncbi.nlm.nih.gov/pubmed/3154509?tool=bestpractice.com
Clinical presentation
Patients present in the following ways.
Patients with psychiatric disorders often drink from non-potable sources (e.g., toilets), but may also be seen to have a cup or other drinking vessel with them at all times.[10]Ahmadi L, Goldman MB. Primary polydipsia: update. Best Pract Res Clin Endocrinol Metab. 2020 Sep;34(5):101469.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683824
http://www.ncbi.nlm.nih.gov/pubmed/33222764?tool=bestpractice.com
Unlike other people with polydipsia, they are unlikely to complain of excessive thirst and instead provide other nonsensical explanations for their excessive drinking.[10]Ahmadi L, Goldman MB. Primary polydipsia: update. Best Pract Res Clin Endocrinol Metab. 2020 Sep;34(5):101469.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683824
http://www.ncbi.nlm.nih.gov/pubmed/33222764?tool=bestpractice.com
Polyuria.[38]Lawson WB, Karson CN, Bigelow LB. Increased urine volume in chronic schizophrenic patients. Psychiatry Res. 1985 Apr;14(4):323-31.
http://www.ncbi.nlm.nih.gov/pubmed/3860885?tool=bestpractice.com
Hyponatraemia (serum sodium concentration <135 mmol/L [<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 hyponatraemia.[10]Ahmadi L, Goldman MB. Primary polydipsia: update. Best Pract Res Clin Endocrinol Metab. 2020 Sep;34(5):101469.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683824
http://www.ncbi.nlm.nih.gov/pubmed/33222764?tool=bestpractice.com
[39]Gleadhill IC, Smith TA, Yium JJ. Hyponatremia in patients with schizophrenia. South Med J. 1982 Apr;75(4):426-8.
http://www.ncbi.nlm.nih.gov/pubmed/6122272?tool=bestpractice.com
This is likely the result of years of water loading.[40]Koczapski AB, Millson RC. Individual differences in serum sodium levels in schizophrenic men with self-induced water intoxication. Am J Psychiatry. 1989 Dec;146(12):1614-5.
http://www.ncbi.nlm.nih.gov/pubmed/2589556?tool=bestpractice.com
Hyponatraemia is more likely to develop in older people with comorbid medical conditions (cardiac, renal, and hepatic diseases). Hyponatraemia is typically mild and asymptomatic in the absence of another contributing comorbidity.[4]Jose CJ, Perez-Cruet J. Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatry. 1979 Feb;136(2):221-2.
http://www.ncbi.nlm.nih.gov/pubmed/760555?tool=bestpractice.com
Symptomatic hyponatraemia is more likely after an acute 3- to 4-litre fluid ingestion or if patients continue to drink excessively (>10 litres daily) after reaching their limit of urine dilution (100 mOsm/kg H₂O in osmolality) and ADH suppression.[4]Jose CJ, Perez-Cruet J. Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatry. 1979 Feb;136(2):221-2.
http://www.ncbi.nlm.nih.gov/pubmed/760555?tool=bestpractice.com
[22]Gillum DM, Linas SL. Water intoxication in a psychotic patient with normal renal water excretion. Am J Med. 1984 Oct;77(4):773-4.
http://www.ncbi.nlm.nih.gov/pubmed/6486156?tool=bestpractice.com
Acute symptomatic hyponatraemia can develop over a period of <48 hours and presents clinically with symptoms related to central nervous system dysfunction as a result of cerebral oedema. 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.[41]Douglas I. Hyponatremia: why it matters, how it presents, how we can manage it. Cleve Clin J Med. 2006 Sep;73 Suppl 3:S4-12.
https://www.ccjm.org/content/ccjom/73/9_suppl_3/S4.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/16970147?tool=bestpractice.com
[42]Sterns RH. Disorders of plasma sodium - causes, consequences, and correction. N Engl J Med. 2015 Jan 1;372(1):55-65.
http://www.ncbi.nlm.nih.gov/pubmed/25551526?tool=bestpractice.com
Rhabdomyolysis secondary to dilutional hyponatraemia has also been reported.[43]Tomiyama J, Kametani H, Kumagai Y, et al. Water intoxication and rhabdomyolysis. Jpn J Med. 1990 Jan-Feb;29(1):52-5.
https://www.jstage.jst.go.jp/article/internalmedicine1962/29/1/29_1_52/_pdf/-char/en
http://www.ncbi.nlm.nih.gov/pubmed/2214346?tool=bestpractice.com
[44]Wicki J, Rutschmann OT, Burri H, et al. Rhabdomyolysis after correction of hyponatremia due to psychogenic polydipsia possibly complicated by clozapine. Ann Pharmacother. 1998 Sep;32(9):892-5.
http://www.ncbi.nlm.nih.gov/pubmed/9762377?tool=bestpractice.com
Laboratory tests
The diagnosis of PPD is one of exclusion.
Initial tests include plasma and urine osmolality, and plasma and urine sodium.[29]Dundas B, Harris M, Narasimhan M. Psychogenic polydipsia review: etiology, differential, and treatment. Curr Psychiatry Rep. 2007 Jun;9(3):236-41.
http://www.ncbi.nlm.nih.gov/pubmed/17521521?tool=bestpractice.com
Urinary sodium and osmolality are best measured by 24-hour urine collection. Typically, hyponatraemia is hypotonic and euvolaemic. 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 hyponatraemia, 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 urea.[29]Dundas B, Harris M, Narasimhan M. Psychogenic polydipsia review: etiology, differential, and treatment. Curr Psychiatry Rep. 2007 Jun;9(3):236-41.
http://www.ncbi.nlm.nih.gov/pubmed/17521521?tool=bestpractice.com
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]Dundas B, Harris M, Narasimhan M. Psychogenic polydipsia review: etiology, differential, and treatment. Curr Psychiatry Rep. 2007 Jun;9(3):236-41.
http://www.ncbi.nlm.nih.gov/pubmed/17521521?tool=bestpractice.com
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 over 750 mOsm/kg H₂O after restricting water and giving vasopressin and is diagnostic of PPD.[45]Goldman MB, Robertson GL, Luchins DJ, et al. The influence of polydipsia on water excretion in hyponatremic, polydipsic, schizophrenic patients. J Clin Endocrinol Metab. 1996 Apr;81(4):1465-70.
http://www.ncbi.nlm.nih.gov/pubmed/8636352?tool=bestpractice.com
This result rules out 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).[46]Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. 5th ed. New York, NY: McGraw-Hill; 2001:748-57,767-72.[47]Baylis PH, Cheetham T. Diabetes insipidus. Arch Dis Child. 1998 Jul;79(1):84-9.
https://adc.bmj.com/content/79/1/84
http://www.ncbi.nlm.nih.gov/pubmed/9771260?tool=bestpractice.com
[48]Zerbe RL, Robertson GL. A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med. 1981 Dec 24;305(26):1539-46.
http://www.ncbi.nlm.nih.gov/pubmed/7311993?tool=bestpractice.com
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.[49]Costanzo ES, Antes LM, Christensen AJ. Behavioral and medical treatment of chronic polydipsia in a patient with schizophrenia and diabetes insipidus. Psychosom Med. 2004 Mar-Apr;66(2):283-6.
http://www.ncbi.nlm.nih.gov/pubmed/15039516?tool=bestpractice.com
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 over 750 mOsm/kg H₂O (normal range).[50]Moses AM, Clayton B. Impairment of osmotically stimulated AVP release in patients with primary polydipsia. Am J Physiol. 1993 Dec;265(6 Pt 2):R1247-52.
http://www.ncbi.nlm.nih.gov/pubmed/8285264?tool=bestpractice.com
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.[51]Dashe AM, Cramm RE, Crist CA, et al. A water deprivation test for the differential diagnosis of polyuria. JAMA. 1963 Aug 31;185:699-703.
http://www.ncbi.nlm.nih.gov/pubmed/14025190?tool=bestpractice.com
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 mmol/L [>20 mEq/L]) due to impaired activation of the renin-angiotensin-aldosterone system.[46]Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. 5th ed. New York, NY: McGraw-Hill; 2001:748-57,767-72.[52]Tierney LM Jr, McPhee ST, Papadakis MA. Current medical diagnosis & treatment. 42nd ed. New York, NY: McGraw-Hill; 2002:840-5,1076-7. Such a result is also observed in those with renal hypersensitivity to ADH, who may have low or normal plasma ADH.[46]Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. 5th ed. New York, NY: McGraw-Hill; 2001:748-57,767-72.[48]Zerbe RL, Robertson GL. A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med. 1981 Dec 24;305(26):1539-46.
http://www.ncbi.nlm.nih.gov/pubmed/7311993?tool=bestpractice.com
SIADH is associated with euvolaemia or hypervolaemia.[53]Harrigan MR. Cerebral salt wasting syndrome: a review. Neurosurgery. 1996 Jan;38(1):152-60.
http://www.ncbi.nlm.nih.gov/pubmed/8747964?tool=bestpractice.com