Polyuria

History of present illness should include the amounts of fluid consumed and voided to distinguish between polyuria Polyuria Polyuria is urine output of > 3 L/day; it must be distinguished from urinary frequency, which is the need to urinate many times during the day or night but in normal or less-than-normal volumes... read more and urinary frequency Urinary Frequency Urinary frequency is the need to urinate many times during the day, at night (nocturia), or both but in normal or less-than-normal volumes. Frequency may be accompanied by a sensation of an... read more . If polyuria is present, patients should be asked about the age at onset, rate of onset (eg, abrupt vs gradual), and any recent clinical factors that may cause polyuria (eg, IV fluids, tube feedings, resolution of urinary obstruction, resolving acute kidney injury, stroke, head trauma, surgery). Patients should be asked about their degree of thirst.

Review of systems should seek symptoms suggesting possible causes, including dry eyes and dry mouth (Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more ) and weight loss and night sweats (cancer).

Past medical history should be reviewed for conditions associated with polyuria, including diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , psychiatric disorders, sickle cell disease Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more , amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more , and hyperparathyroidism Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more . A family history of polyuria and excessive water drinking should be noted. Drug history should note use of any drugs associated with nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more (see table Some Causes of Polyuria Some Causes of Polyuria ) and agents that increase urine output (eg, diuretics, alcohol, caffeinated beverages).

The general examination should note signs of obesity (as a risk factor for type 2 diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ) or undernutrition or cachexia that might reflect an underlying cancer or an eating disorder plus surreptitious diuretic use.

The head and neck examination should note dry eyes or dry mouth (Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more ). Skin examination should note the presence of any hyperpigmented or hypopigmented lesions, ulcers, or subcutaneous nodules that may suggest sarcoidosis. Comprehensive neurologic examination should note any focal deficits that suggest an underlying neurologic insult and assess mental status for indications of a thought disorder. Volume status should be assessed. Extremities should be examined for edema.

The following findings are of particular concern:

History can often distinguish polyuria from frequency, but rarely a 24-hour urine collection may be needed.

Clinical evaluation may suggest a cause (see table Some Causes of Polyuria Some Causes of Polyuria ), but testing is usually necessary. Diabetes insipidus ArginineVasopressin Deficiency (Central Diabetes Insipidus) Arginine vasopressin deficiency (central diabetes insipidus) results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder. Polyuria and polydipsia... read more is suggested by a history of cancer or chronic granulomatous disease (due to hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more ), use of certain drugs (lithium, cidofovir, foscarnet, ifosfamide), and less common conditions (eg, sickle cell disease Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more , renal amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more , Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more ) that have manifestations that are often more prominent than and precede the polyuria.

Abrupt onset of polyuria at a precise time suggests central diabetes insipidus, as does preference for extremely cold or iced water. Onset during the first few years of life is typically related to inherited central or nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more or uncontrolled type 1 diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more . Polyuria caused by solute diuresis is suggested by a history of diabetes mellitus. Psychogenic polydipsia is more common in patients with a history of a psychiatric disorder (primarily bipolar disorder Bipolar Disorders Bipolar disorders are characterized by episodes of mania and depression, which may alternate, although many patients have a predominance of one or the other. Exact cause is unknown, but heredity... read more , or schizophrenia Schizophrenia Schizophrenia is characterized by psychosis (loss of contact with reality), hallucinations (false perceptions), delusions (false beliefs), disorganized speech and behavior, flattened affect... read more ) rather than as an initial manifestation.

Once excess urine output has been verified by history or measurements, serum or fingerstick glucose determination should be done to rule out uncontrolled diabetes.

If hyperglycemia is not present, then testing is required:

These tests look for hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more , hypokalemia Hypokalemia Hypokalemia is serum potassium concentration < 3.5 mEq/L (< 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common... read more (due to surreptitious diuretic use), and hypernatremia or hyponatremia:

If the diagnosis remains unclear, then measurement of serum and urine sodium and osmolality in response to a water deprivation test and exogenous ADH administration should be done. Because serious dehydration may result from this testing, the test should be done only while patients are under constant supervision; hospitalization is usually required. Additionally, patients in whom psychogenic polydipsia is suspected must be observed to prevent surreptitious drinking.

Various protocols can be used in water deprivation tests. Each protocol has some limitations. Typically, the test is started in the morning by weighing the patient, obtaining venous blood to determine serum electrolyte concentrations and osmolality, and measuring urine osmolality. Voided urine is collected hourly, and its osmolality is measured. Dehydration is continued until orthostatic hypotension Orthostatic Hypotension Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, > 10 mm Hg... read more and postural tachycardia appear, ≥ 5% of the initial body weight has been lost, or the urinary concentration does not increase > 30 mOsm/kg (30 mmol/kg) in sequentially voided specimens. Serum electrolytes and osmolality are again determined, and 5 units of aqueous vasopressin are injected subcutaneously. Urine for osmolality measurement is collected one final time 60 minutes postinjection, and the test is terminated.

A normal response produces maximum urine osmolality after dehydration (> 700 mOsm/kg [700 mmol/kg]), and osmolality does not increase more than an additional 5% after injection of vasopressin.

In central diabetes insipidus ArginineVasopressin Deficiency (Central Diabetes Insipidus) Arginine vasopressin deficiency (central diabetes insipidus) results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder. Polyuria and polydipsia... read more , patients are typically unable to concentrate urine to greater than the plasma osmolality but are able to increase their urine osmolality after vasopressin administration. The increase in urine osmolality is 50 to 100% in central diabetes insipidus vs 15 to 45% with partial central diabetes insipidus.

In nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more , patients are unable to concentrate urine to greater than the plasma osmolality and show no additional response to vasopressin administration. Occasionally in partial nephrogenic diabetes insipidus, the increase in urine osmolality can be up to 45%, but overall these numbers are much lower than those that occur in partial central diabetes insipidus (usually < 300 mOsm/kg [300 mmol/kg]).

In psychogenic polydipsia, urine osmolality is < 100 mOsm/kg (100 mmol/kg). Decreasing water intake gradually will lead to decreasing urine output, increasing plasma and urine osmolality and serum sodium concentration.

Measurement of circulating ADH is the most direct method of diagnosing central diabetes insipidus. Levels at the end of the water deprivation test (before the vasopressin injection) are low in central diabetes insipidus and appropriately elevated in nephrogenic diabetes insipidus. However, ADH levels are not routinely available. In addition, water deprivation is so accurate that direct measurement of ADH is rarely necessary. If measured, ADH levels should be checked at the beginning of the water deprivation test, when the patient is well-hydrated; ADH levels should increase as intravascular volume decreases.