Diabetes Insipidus

How to Cite This Chapter: Rodríguez-Gutiérrez R, Brito JP, Kunert-Radek J, Płaczkiewicz-Jankowska E. Diabetes Insipidus. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.8.1 Accessed September 30, 2020.
Last Updated: June 6, 2019
Last Reviewed: June 6, 2019
Chapter Information

Definition, Etiology, PathogenesisTop

Diabetes insipidus (DI) is a condition characterized by increased water loss (polyuria) and excessive thirst (polydipsia) due to:

1) Central DI (neurohypophyseal): Arginine vasopressin (antidiuretic hormone) (ADH) deficiency. This may result from:

a) Damage to the vasopressin-secreting neurons located in the supraoptic and paraventricular nuclei in the hypothalamus or to the pituitary stalk or posterior pituitary gland (vasopressin transport and storage sites, respectively). The most common cause of central DI is idiopathic (autoimmune process) followed by tumors (germinoma, metastatic lesions, craniopharyngioma), infiltrative diseases (sarcoidosis, Langerhans cell histiocytosis), hypoxic encephalopathy, and head trauma.

b) Genetic defects, such as familial central DI (autosomal dominant gene defect encoding ADH), Wolfram syndrome (DIDMOAD syndrome [diabetes insipidus, diabetes mellitus, optic atrophy, and deafness]), congenital hypopituitarism, and septo-optic dysplasia.

2) Nephrogenic DI: Loss of sensitivity of the renal tubules to ADH (ADH resistance), which may result from a genetic defect of the renal vasopressin receptors (aquaporin-2 water channels). Nephrogenic DI may also occur in hypercalcemia (eg, hyperparathyroidism), hypokalemia (eg, primary hyperaldosteronism), renal diseases (eg, bilaterally urinary tract obstruction, polycystic kidney disease, renal amyloidosis), and drugs (eg, lithium [most common], amphotericin B, cidofovir, and foscarnet).

Clinical FeaturesTop

DI manifests as excessive thirst (polydipsia) and polyuria (>3 L/24 h). Patients characteristically report nocturia (sometimes voiding several times throughout the night) and night thirst. Signs and symptoms due to hypernatremia or an underlying hypothalamic-pituitary tumor may also be present.

Onset of polyuria:

1) Children: Familiar central DI and hereditary nephrogenic DI manifest with severe polyuria in the first week of life.

2) Adults: Central DI manifests in an abrupt manner. Nephrogenic DI has a gradual onset.


Diagnostic Tests

1. Laboratory studies:

1) Urine specific gravity ≤1.005.

2) Plasma sodium concentration: High-normal (≥142 mmol/L).

3) Urine osmolality: Low and characteristically lower than plasma osmolality.

4) Urinary sodium: Usually <20 mmol/L.

5) Water restriction test (combined with the desmopressin stimulation test): In patients with suspected DI before performing this test it is important to confirm hypotonic polyuria (suggested values: Table 5.3-1). The test is performed usually in an inpatient setting only after diabetic polyuria has been excluded. The patient should stop drinking water in the morning before arriving to the clinic (avoid nocturnal water restriction) and have urine volume, urine osmolality, plasma sodium concentration, plasma osmolality, and body weight measured at baseline. Urine specific gravity or osmolality is measured in each consecutive urine sample (with frequency depending on the clinical situation, even hourly if needed) along with plasma osmolality, serum sodium levels, and body weight; serum ADH level may be determined at the end of the test. Terminate the test when: (1) body weight decreases ≥3%; (2) urine osmolality is stable (difference <10%) in 2 or 3 samples despite rising plasma osmolality; (3) serum sodium levels are above the upper limit of normal (≥145 mmol/L) with plasma osmolality >295-300 mOsm/kg (in patients with DI, this usually occurs within a few hours); or (4) urine osmolality reaches a normal value (500-600 mOsm/kg). If the criteria for termination of the test are not met, it should be continued for 18 hours to exclude DI. Interpretation of test results: Table 5.3-1.

6) Desmopressin stimulation test (second phase of the water restriction test) is performed to differentiate central DI from nephrogenic DI. Administer desmopressin 0.2 mg orally, 10 to 20 microg intranasally, or 2 to 4 microg subcutaneously or IV at the end of the fluid deprivation test. Measure the volume, specific gravity, and osmolality every 30 minutes for the next 2 hours. Interpretation of test results: Table 5.3-1.

2. Imaging studies: A confirmed diagnosis of central DI is an absolute indication for magnetic resonance imaging (MRI) of the hypothalamic-pituitary area. The absence of T1 hyperintensity in the posterior pituitary lobe is seen in most patients with central DI.

Diagnostic Criteria and Differential Diagnosis

See Table 5.3-1.


1. Central DI: Replacement therapy with a long-acting ADH analogue desmopressin. Usually desmopressin is administered intranasally 10 to 20 microg once a day or bid, orally 0.05 to 0.2 mg in 1 or 2 doses or, where available, sublingually up to 60 to 120 microg tid. In patients with altered mental status, an IV or subcutaneous injection (2-4 microg daily) may be used. Adjust the dosage individually on the basis of resolution of clinical symptoms and normalization of plasma osmolality and serum sodium levels.

2. Nephrogenic DI: Management depends on the causative factor:

1) Acquired renal injury: Symptomatic treatment involving appropriate fluid replacement and management of the underlying condition.

2) Electrolyte disturbances: Signs and symptoms of DI improve with normalization of electrolyte levels.

3) Genetic defects of ADH receptors: Low-sodium diet plus a thiazide diuretic. Consider high-dose desmopressin in patients with a partial ADH-receptor response.


Prognosis depends on the cause of central DI (tumor, trauma, metastases, inflammation, idiopathic). If the patient maintains appropriate fluid intake, untreated DI is not life-threatening. Special attention (fluid balance!) is warranted in the case of unconscious trauma patients, patients after central nervous system surgery, and patients with an altered sense of thirst due to the damaged hypothalamic thirst center. Advise the patients to carry information about their DI at all times. Patients with DI treated with hormone replacement may lead normal lives. Desmopressin overdose may cause syndrome of inappropriate antidiuretic hormone secretion (SIADH) (water retention and hyponatremia).


Table 5.3-1. Differential diagnosis of psychogenic, central, and nephrogenic DI using water restriction and desmopressin stimulation


Psychogenic polydipsia (psychogenic DI)

Central (neurohypophyseal) DI

Nephrogenic DI

Water restriction test (fluid deprivation test)

Urine specific gravity




Urine osmolality

>500-600 mOsm/kg

<250 mOsm/kg

<250 mOsm/kg

Plasma ADH level

Initially low, then increasing



Desmopressin stimulation test (desmopressin 0.2 mg PO, 10-20 microg intranasally, or 2-4 microg SC or IV)

Urine specific gravity

No indication for the testa

Increased by ≥50%

Low, not increasing

Urine osmolality

No indication for the testa

Increase by 100% in complete central DI and 15% to 50% in partial central DI

No elevation

a As the results of the fluid deprivation test are normal.

ADH, antidiuretic hormone; DI, diabetes insipidus; IV, intravenous; PO, oral; SC, subcutaneous.

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