Diabetes insipidus

Diabetes insipidus (DI) is a disease characterized by pronounced seat and the excretion of large quantities of very dilute urine. This dilution does not decrease when liquid intake is reduced. This denotes the failure kidney to concentrate urine. The DI is caused by a deficiency of antidiuretic hormone (vasopressin) or the insensitivity of the kidneys to this hormone.

The antidiuretic hormone is normally produced in the brain's hypothalamus and released by the neurohypophysis. It controls how the kidneys remove, filter and reabsorb fluid into the bloodstream. When there is a lack of this hormone (or when the kidneys can not respond to the hormone) fluids pass through the kidneys and lost through urination. Thus, a person with diabetes insipidus need to eat large amounts of water in response to extreme thirst to compensate for water loss.

Signs and symptoms

The intense thirst and excessive diuresis are typical of DI. The symptoms of diabetes insipidus are similar to those of diabetes mellitus, with the distinction that there is glycosuria (sweet urine) and no hyperglycemia (elevated blood glucose). Vision problems are rare. The first manifestation of diabetes insipidus usually nocturia by the loss of ability to concentrate urine during the night. The clinical presentation occurs with polyuria increased urinary frequency and volume (urine volume in 24 hours> 3 l [> 40 ml / kg] in adolescents and adults> 2 litres/m2 body surface [> 100 ml / kg] in children ) and consequent increase in water intake (polydipsia), intense thirst, with ingestion of large amounts of liquid. The rate of onset of symptoms is important because, in the majority of patients with hereditary renal diabetes insipidus, the manifestation occurs in the first week of life. In cases of central diabetes insipidus hereditary manifestation can occur in childhood after the first year of life or during adolescence. In adults, the onset of symptoms usually occurs abruptly in cases of central diabetes insipidus and insidiously in cases of renal diabetes insipidus. The increase in urinary volume, which can reach 18 l in 24 hours is compensated with increased water intake. Excessive diuresis continues day and night. These patients have a high susceptibility to dehydration and electrolyte disturbances. In patients without free access to water (eg, sedation), with changes in hypothalamic thirst center (eg, hypothalamic lesions) and those with high urine volume, electrolyte disturbances may be severe. In children, DI can interfere with appetite, weight gain and growth. It can lead to fever, vomiting or diarrhea. Adults with untreated DI remain healthy for decades as long as the water intake is sufficient to compensate for urinary losses. However, there is a continuous risk of dehydration.

Treatment

The Central DI and gestational DI respond to desmopressin. In dipsogenica DI and nephrogenic DI desmopressin no effect.

INCLUSION CRITERIA

Regardless of the presence or absence of the tumor, treatment of central diabetes insipidus indicated. This will include patients who have a diagnosis of central diabetes insipidus based on two criteria below:

• polyuria (in 24 hours urine volume above 3 l [> 40 ml / kg] in adults and adolescents> 2 body surface l/m2 [> 100 ml / kg] in children), and • response to the administration of desmopressin - in the presence of plasma osmolality> 295 mOsm / kg or plasma sodium> 147mEq / l - increase in urinary osmolality> 15% and urine osmolality> 600 mOsm / kg.

EXCLUSION CRITERIA

Be excluded from this treatment protocol patients who experience hypersensitivity or intolerance to desmopressin.

SPECIAL CASES

Patients with gestational diabetes insipidus that meet the inclusion criteria should receive treatment throughout pregnancy until normalization of the frame, as specified in Item Monitoring, and be monitored after delivery to identify the need for maintenance of desmopressin.

TREATMENT

Desmopressin is a synthetic analogue of ADH with longer duration, higher power antidiuretic effect and lower blood pressure when compared to ADH. Treatment of diabetes insipidus with desmopressin has basis in case series. The first reports of its use in the treatment of central diabetes insipidus involved a series of 10 patients with the condition. In this study, we used as controls the historical data of 10 patients in the period in which the ADH used as treatment, desmopressin was safe and advantageous in relation to ADH, especially as the number of applications of the drug (6-10 doses / day with ADH and 1-3 drinks / day desmopressin) and adverse effects (common with ADH and not detected with desmopressin. Through unequivocal demonstration that this is a drug with safety profile and effectiveness favorable desmopressin treatment of central diabetes insipidus was widely adopted, and no randomized trials comparing ADH and desmopressin in the treatment of the condition. Desmopressin, a peptide that is resistant to the action of placental vasopressinases, is also the treatment of choice in gestational diabetes insipidus, with data security favorable for both the pregnant woman and the fetus

DRUG

• Desmopressin: 0.1 mg / ml (100 mg / ml) with nasal application (2.5 ml vial of solution

SCHEMES OF DIRECTORS

There are two presentations of desmopressin nasal application available, with some particulars as to its administration. The nasal solution is applied through tubular plastic which must be filled with the dose to be used by capillarity (abutting one end of the tubule in the solution contained in the vial). After ensuring that the dose is correct, one end of the tubule is placed at a nasal cavity and another in the patient's mouth. By the end placed in the mouth, the medicament is blown into the nasal cavity where it is absorbed. While application nasal spray jet is carried out through nasal fixed dose of 10 mg / jet. The use of the nasal spray is simpler, but does not allow the flexibility that the doses of nasal solution enables. The nasal spray provides multiple fixed doses of 10 mg (for example 10, 20, 30 mg). As for nasal solution enables the use of multiple doses of 5 mg (for example 5, 10, 15, 20 mg), which may be more suitable for some patients, especially for pediatric patients. The initial dose of desmopressin dose is 10 mg in adults and adolescents and 5 mg in children. It is suggested that the initial dose is administered at night and that the gradual increase in the number of applications and the dose is made individually according to the patient's response. There are widely varying degrees of deficiency of ADH, which affects the variability of the maintenance dose of desmopressinna as follows:

• nasal desmopressin solution - from 5 to 20 mg 1 to 3 times a day • desmopressin nasal spray - 10-20 mg 1 to 3 times a day or spray)

TREATMENT TIME

The treatment of central diabetes insipidus must be maintained for life, since the suppression of desmopressin may cause risk to the patient.

EXPECTED BENEFITS

The treatment of central diabetes insipidus with desmopressin causes improvement in symptoms and quality of life and prevent complications of electrolyte disturbances in patients with severe deficiencies ADH9.