Diabetes Insipidus

Author: Francesca Bardesono
Date: 22/02/2011




A disease that is characterized by frequent urination, excretion of large amounts of dilute urine, and excessive thirst. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or vasopressin) secreted by the neurohypophysis, impaired kidney response to ADH, and impaired hypothalamic regulation of thirst.


Diabetes insipidus is uncommon disease with a prevalence of 1 case per 25.000 population. Incidence is similar in men and women.


The etiopathogenic classification includes several forms of DI:

DIABETES INSIPIDUS NEUROGENIC OR CENTRAL: is due to a lack of ADH production in the brain, that causes increased urine production and dehydration. It is suddivided in two types:

  1. Primary:
    • Idiopathic
    • It is the most common form, in fact in at least 25% of cases of diabetes insipidus neurogenic is idiopathic, meaning that the lack of vasopressin production arose from an unknown cause. Idiopathic DI can be associated with destruction of cells in the hypothalamus, often as part of an autoimmune process. This is characterized by lymphocytic infiltration of the stalk and posterior pituitary. The presence of antibodies directed against vasopressin cells may help to predict the development of central DI.
    • Congenital
    • It is the most rare form of central DI and it can be caused by:
      • An autosomal dominant mutations of the ADH gene. For the moment, only 45 families worldwide were known to possess this genetic trait. The mechanism by which the mutations impair vasopressin release is not understood but may involve the accumulation of the ADH precursor, leading to the death of the ADH-producing cells.
        • Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). The first manifestations are diabetes mellitus and optic atrophy, which compare during the second or third decades. It is caused by an autosomal recessive mutation of wolframin gene located on 14 chromosome. There is no therapy and the prognosis is poor.

2) Acquired
The lack of vasopressin production usually results from some sort of damage to the pituitary gland. The damage to the brain could have been caused by:
• a benign tumor (20 of cases), as craniopharyngioma, metastasis, pituitary adenomas

• trauma (17
of cases);
• neurosurgery (9 % of cases);
• vascular disease like Sheehan syndrome, aneurysm;
• hemochromatosis;
• Inflammatory disease as sarcoidosis, and histiocytosis;
• Gestational: during pregnancy, all women produce vasopressinase in the placenta, which breaks down ADH. Gestational DI is thought to occur with excessive vasopressinase production.

DIABETES INSIPIDUS NEFROGENIC: is a form of diabetes insipidus due primarily to pathology of the kidney, which has an improper response to ADH, leading to a decrease in the ability of the kidney to concentrate the urine by removing free water. It is subdivided in two types:
1) Primary
Genetic: it is a rare form caused by
• An X-linked defect of the AVP receptor 2 gene (AVPR2); it is almost 90% of hereditary cases of nephrogenic DI.
• An autosomal dominant or recessive variant results from the mutation of AQP2, an aquaporin gene which mutation results in the kidney being unable to absorb water.
2) Acquired: it is a more common form and it caused by
• Renal failure as polycystic kidney disease;
• electrolyte imbalance like hypercalcemia (it causes natriuresis, which is increased sodium loss in the urine, and consequently water diuresis), hypokalemia;
• drugs as litio, tetracycline, Amphotericin B, Ifosfomide;
• other rare diseases like amyloidosis, Sjogren syndrome.

POLYDIPSIC (also known as primary polydipsia), where the water diuresis results from the suppression of ADH release by excessive fluid intake.


The main symptoms are polyuria, polydipsia and nocturia. The daily urine volume is highly variable (3-20 L/day), and patient tolerance of dehydration also varies among individuals and it is correlated with the daily water income. Many patients have a predilection for drinking cold liquids, often water. When it has a nontraumatic cause, diabetes insipidus typically has a much more indolent course. In infants, crying, irritability, growth retardation, hyperthermia, and weight loss may be the most apparent signs.


• Signs
 Polydipsia;
 Polyuria: 3-15 l/day with a low urinary osmolality (< 300 mOsm/kg H20) and a specific gravity < 1.010;
 Increase of Plasma osmolality;
 Increase in a plasma sodium level greater than 140-150 mEq/l, that indicates dehydration. If it gets no higher than 155 mEq/1, the dehydration is relatively mild and is unlikely to cause a severe problem but it could and probably would produce slight brain damage that could gradually increase over long periods of time. Therefore, an effort should be made to keep the sodium below 150 mEq/1.
 Increase of hematocrit.

• Diagnostic Test
Water deprivation test: it is used to distinguish among the major forms of Diabetes Insipidus.
It lasts 4-18 hours, with hourly measurements of body weight, urine and plasma osmolality, sodium concentration, until 2-3 consecutive samples vary by <30 mOsm/kg or until the patient loses 5% of body weight.
1) Plasma osmo <300 & urine osmo 300-750 Consider primary polydipsia 2) Plasma osmo <300 & urine osmo >600 Normal response. Stop test. 3) Plasma osmo >300 & urine osmo <600 Indicates diabetes insipidus; stop test & give dDAVP

1) The chronic primary polydipsia can dissipate the renal medullary osmotic gradient, thereby reducing the renal response to endogenous and exogenous AVP.
2) In healthy individuals, water deprivation increases plasma osmolality, which stimulates secretion of vasopressin by the posterior pituitary. This then acts on the kidney to increase urine osmolality to 1000 to 1200 mmol/kg and to restore plasma osmolality to normal levels. Administration of exogenous vasopressin does not increase urine osmolality further because it is already maximal in response to the individual's endogenous release of vasopressin.
3) At this point, the serum ADH level is measured, and then 5 units of ADH or 1 µg of desmopressin is injected (dDAVP). Urine osmolality is then measured 30-60 minutes later. It can differentiate between diabetes insipidus nefrogenic end neurogenic.
• Neurogenic: after ADH injection, urine osmolality increases by >50%.
• Nefrogenic: after ADH injection, urine osmolality not increases or increases <9%.

An MRI of the brain can be made to diagnose a pituitary adenoma, craniopharyngioma or other brain tumor.

The treatment depends on the cause of diabetes insipidus.

• Diabetes insipidus neurogenic
The most important drug is Desmopressin. In the acute situation, like after a trauma or neurosurgery, desmopressin is intravenous administer (1-2 µg every 8-12 hours) plus liquid infusion. In chronic treatment desmopressin is given through an intranasal spray (5-100µ/day), oral (100-1000 µg/day), intramuscular or subcutaneous (1-3 µg/die). The most important complication of desmopressin’s treatment is hyponatremia and hemodilution, which can force to suspend temporarily the drug assumption. A second choice drug is thiazide diuretics.

• Diabetes insipidus nefrogenic.
In the acquired forms it is necessary to remove the cause of pathology. Moreover it is indicated a poor sodium diet and hydration of the patient.
Drug therapy is whit thiazide diuretics, especially with hydrochlorothiazide (50-100 mg/day). This drug is utilized because it has antidiuretic effect due to the hinibition of reabsorption of sodium in the distal tubule of the nephrons and consequent hyponatremia. But hydrochlorothiazide is contraindicated in case of diabetes insipidus caused by litium, because it increases the side effects. In this case it is useful to administrate amiloride (5-20 mg/day).

• Polydipsia.
It is important treating the psychiatric pathology that causes the diabetes insipidus. In this case using desmopressin is not only useless but also injurious because it causes hyponatremia.


Diabetes insipidus can determinate a too little retention of water to function properly, and consequently dehydration, which can cause dry mouth, muscle weakness, hypotension, hypernatremia, sunken appearance to your eyes, fever, headache, rapid heart rate, weight loss
Diabetes insipidus can also cause an electrolyte imbalance, that can cause symptoms, such as: headache, fatigue, irritability, muscle pains.
Excessive fluid intake in dipsogenic diabetes insipidus can lead to water intoxication, a condition that lowers sodium concentration in blood, which can damage brain.

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