Investigations
1st investigations to order
plasma osmolality
Test
Initial test when PPD is suspected.
Result
<280 mOsm/kg H₂O
urine osmolality
Test
Best measured following 24-hour urine collection.
Secretion of antidiuretic hormone (ADH) is suppressed at plasma osmolalities <280 mOsm/kg H₂O, leading to a dilute urine.
Patients with PPD and a comorbid central defect of syndrome of inappropriate secretion of ADH, or renal hypersensitivity to ADH, may have urine osmolality >500 mOsm/kg H₂O.
Result
<100 mOsm/kg H₂O
urine sodium
Test
Best measured following 24-hour urine collection.
Low (<280 mOsm/kg H₂O) plasma osmolality activates the renin-angiotensin-aldosterone (RAA) pathway. Aldosterone activation causes renal retention of urinary sodium, leading to urine sodium excretion of <20 mmol/L (<20 mEq/L).
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is associated with high urine sodium (>20mmol/L [>20 mEq/L]), due to impaired activation of the RAA system.[46][52] Patients with renal hypersensitivity to ADH have the same result.
Result
≤20 mmol/L (≤20 mEq/L)
serum sodium
Test
From 10% to 20% of patients with PPD have hyponatraemia.
Result
normal or <135 mmol/L (<135 mEq/L) (hyponatraemia)
24-hour urine volume
Test
Intensity of polydipsia should be measured by extent of polyuria (complete 24-hour urine collection). May be difficult in patients with acute hyponatraemia; estimates of 24-hour urine volumes based on measurement of urinary creatinine excretion may be used.
Result
increased
urinalysis
Test
Rules out a renal or infectious cause.
Result
normal
serum urea
Test
Rules out renal failure.
Result
normal
water restriction test
Test
Urine osmolality is measured before and after water deprivation.
In PPD, urine is very dilute before water restriction (<100 mOsm/kg H₂O).[45] Osmolality rises to >750 mOsm/kg H₂O after water restriction and is diagnostic of PPD. This result rules out central diabetes insipidus (DI). Concomitant PPD and DI have been reported.[49]
Patients with chronic PPD, due to medullary gradient washout and downregulation of antidiuretic hormone (ADH) release, may not be able to maximally concentrate urine, and achieve urine osmolalities closer to 600 mOsm/kg H₂O.[50]
Plasma ADH can also be measured before and after water restriction if other results are equivocal; plasma ADH before water restriction is low in PPD and rises following the water deprivation test.[51]
Result
urine osmolality >750 mOsm/kg H₂O post-test
Investigations to consider
vasopressin test
Test
Vasopressin (exogenous antidiuretic hormone) can be given immediately following a water restriction test if the diagnosis is still unconfirmed.
Urine osmolality is measured before and after the test. In PPD, urine osmolality rises to >750 mOsm/kg H₂O after vasopressin is given and is diagnostic of PPD. This result rules out central diabetes insipidus.
Result
urine osmolality >750 mOsm/kg H₂O post-test
plasma antidiuretic hormone
Test
Secretion of antidiuretic hormone (ADH) is suppressed at plasma osmolalities <280 mOsm/kg H₂O.
Patients with PPD and a comorbid central defect of syndrome of inappropriate secretion of ADH may not maximally suppress ADH secretion, and plasma ADH is elevated. Plasma ADH in patients with renal hypersensitivity to ADH is low or normal.[46][48]
Result
low
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