(Vasopressin-Sensitive Diabetes insipidus)
Diabetes insipidus (DI) is produced either by a vasopressin deficiency (synonym: antidiuretic hormone, ADH) as a result of hypothalamic-pituitary disorder (central DI [CDI]) or by renal vasopressin resistance (renal DI [NDI]). It comes to polyuria and polydipsia. The diagnosis is made by a thirst test that shows an inability to urine concentration; Vasopressin levels and response to vasopressin administration help to distinguish the CDI from NDI. The treatment is carried out by intranasal administration of desmopressin or lypressin. Non-hormonal therapies consist of diuretics (thiazides primarily) and the administration of vasopressin-stimulating drugs such as chlorpropamide.
(Also syndrome of inappropriate antidiuretic hormone secretion and nephrogenic diabetes insipidus.)
Diabetes insipidus (DI) is produced either by a vasopressin deficiency (synonym: antidiuretic hormone, ADH) as a result of hypothalamic-pituitary disorder (central DI [CDI]) or by renal vasopressin resistance (renal DI [NDI]). It comes to polyuria and polydipsia. The diagnosis is made by a thirst test that shows an inability to urine concentration; Vasopressin levels and response to vasopressin administration help to distinguish the CDI from NDI. The treatment is carried out by intranasal administration of desmopressin or lypressin. Non-hormonal therapies consist of diuretics (thiazides primarily) and the administration of vasopressin-stimulating drugs such as chlorpropamide. (Also syndrome of inappropriate ADH secretion and nephrogenic diabetes insipidus.) The pathophysiology posterior pituitary gland is the primary storage and Sekretionsort for vasopressin, while the vasopressin synthesis takes place in the hypothalamus. Newly synthesized hormone can be secreted into the circulation in case of loss of the posterior pituitary continues as long as the hypothalamic nuclei and parts of the neurohypophysealen tract are functional. Only 10% of the neurosecretory neuron must be obtained in order to avoid a CDI. The pathology of a CDI thus always includes the supraoptic and paraventricular nuclei of the hypothalamus or a substantial portion of the pituitary stalk with a. A CDI can be complete (total vasopressin deficiency) or partially (lowered vasopressin). The CDI may be primary, in which a reduction in the hypothalamic nuclei of the neurohypophysealen system is the cause. The primary etiology CDI Genetic abnormalities of the vasopressin gene on chromosome 20 responsible for an autosomal dominant form of a primary CDI, but many cases are idiopathisch.Sekundärer A CDI CDI can also be secondary (acquired) and be by various disorders, including a hypophysectomy, head injuries (especially Schädelbasisbruch), suprasellar and intraselläre tumors (primary or metastatic), Langerhans cell histiocytosis (hand-Schuller-Christian disease), lymphocytic hypophysitis, granulomas (sarcoidosis or tuberculosis), vascular malformations (aneurysms and thrombosis) and infection ( encephalitis, meningitis) Constituted. Symptoms and signs The onset can be insidious or abrupt and occur at any age. The only symptoms of primary CDI are polydipsia and polyuria. In secondary CDI, the symptoms and findings of the associated disease are present. Enormous amounts of fluid are used and large volumes (3-30 l / day) diluted urine (specific gravity usually <1.005 and osmolality <200 mOsm / l) excreted. Nocturia is almost always. Dehydration and hypovolemia developing rapidly if the renal water losses are not continuously replaced. Polyuria can result from diabetes mellitus (most common) CDI (a lack of vasopressin) NDI (renal resistance to vasopressin) Compulsive or habitual drinking of water (psychogenic polydipsia) Diagnostic thirst test Occasionally vasopressin levels CDI must be distinguished from other causes of polyuria, especially psychogenic polydipsia (see table: Common causes of polyuria) and NDI. All studies on CDI (and NDI) are based on the assumption that an increase in plasma osmolality leads in healthy people to decreased urine output with increased urine osmolality. Common causes of polyuria mechanism as vasopressin Sensitive polyuria Decreased vasopressin synthesis Primary diabetes insipidus, congenital (usually autosomal dominant) Primary diabetes insipidus, congenital and associated with diabetes mellitus, atrophy of the optic nerve, neuronal numbness and atony of the bladder and ureters Acquired ( secondary) diabetes insipidus (causes are mentioned in the text) Decreased vasopressin release psychogenic polydipsia (polydipsieverursachter Diab etes insipidus) vasopressin-resistant polyuria Renal resistance to vasopressin Congenital nephrogenic diabetes insipidus (usually X-linked recessive insipidus) Acquired nephrogenic diabetes: chronic Nierenerkrankheit, systemic or metabolic disease (eg. B. myeloma, amyloidosis, hypercalcemic or hypokalemic nephropathy, sickle cell anemia), certain drugs (eg., Lithium, demeclocycline) osmotic diuresis hyperglycemia (diabetes mellitus) heavy absorbable substances (mannitol, sorbitol, urea) The thirst test is the most simple and reliable test for the diagnosis of CDI, should be carried out under continuous monitoring of the patient but as a severe dehydration can occur. If the suspected psychogenic polydipsia is, the patient should also be monitored to prevent secret drinking. The test begins in the morning with the determination of the patient's weight, taking a blood sample to measure the concentrations of electrolytes and osmolality and with the determination of urine osmolality. Spontaneous urine (even better) collected for determination of specific gravity or osmolality hour. The removal of water is continued until orthostatic Hpotonie and postural tachycardia occur ? 5% of the initial body weight were lost or the urinary concentration is not risen> 0.001 g / l or> 30 mOsm / l in successively removed spot urine samples. The values ??for serum electrolytes and osmolality are again determined. Exogenous vasopressin is then added (5 units s.c. of aqueous vasopressin, desmopressin i.m. 10 mcg [DDAVP] intranasally or 4 mcg or i.v.). 60 min after injection of a final urine sample for the determination of specific gravity or osmolality is removed and the test ended with it. A normal reaction would be a maximum increase in urine osmolality after dehydration (often> 1,020 g / L or> 700 mOsm / l) that exceeds the plasma osmolality. After injection of vasopressin osmolality does not increase by more than an additional 5%. Patients with CDI are not usually able to concentrate the urine on the plasma osmolality out, but can after administration of vasopressin their urine osmolality by> 50% and> 100% increase. Patients with partial CDI are often able to increase their urine on the plasma osmolality out, but show after the administration of vasopressin an increase in urine osmolality of 15 to 50%. Patients with NDI can not concentrate on the plasma osmolality addition, the urine and point to the administration of vasopressin no response See Table: Results of the tests thirst. The determination of circulating vasopressin is the most direct method in the diagnosis of CDI. The ADH-mirror at the end of the thirst experiment (prior to vasopressin injection), in the case of a low CDI and appropriate increases in a NDI. Unfortunately, the vasopressin levels are difficult to measure and the test is not part of routine program. In addition, the thirst attempt to deliver accurate results so that a direct vasopressin provision is unnecessary. Plasma vasopressin levels can be used both by dehydration and after infusion of a hypertonic saline solution for diagnostics. Results of thirst test parameters Normal Complete CDI part NDI CDI Complete Part NDI psychogenic polydipsia UOSM after dehydration (step 1) Very high (> 700 to 800 mOsm / kg) Very low (less than plasma osmolality) Low (? 300 mOsm / kg) Very Low (less than plasma osmolality) Very low (less than plasma osmolality) high (500-600 mosm / kg) UOSM increase after vasopressin (step 2) minimal (<5%) from 50 to> 100% 15-50% <50 mosm / kg Up to 45% No change UOSM = urine osmolality psychogenic polydipsia psychogenic polydipsia provides a differential diagnosis is a major problem. patients can daily accommodate up to 6 liters of liquid and excrete and often have mental disorders on. Unlike patients with CDI and NDI do not normally suffer from nocturia or be awakened by a feeling of thirst at night. Continued uptake of large amounts of water can cause a life-threatening hyponatremia. Patients with acute psychogenic polydipsia are able to concentrate their urine in case of a water shortage. In contrast, patients with chronic polydipsia no longer able to concentrate their urine maximum in case of a water shortage because of the constant water uptake tonicity is lost in the renal medulla. This is quite similar in patients with partial CDI. Unlike patients with CDI, patients suffering from psychogenic polydipsia, no response to exogenous vasopressin after dehydration. This reaction is similar to that at NDI, except that the basal vasopressin levels are low compared to the elevated levels at NDI. After a longer restriction of the liquid supply ? 2 l / day reverses the normal concentration back within several weeks. Hormonal therapy drugs such. B. desmopressin non-hormonal medicines, such. B. diuretics CDI can be treated by hormone replacement and the elimination of treatable causes. Without adequate treatment permanent kidney damage can occur. One limitation of common salt consumption may also reduce the volume of urine, since the amount of dissolved substances is reduced. Hormonal medication desmopressin, a synthetic analogue of vasopressin with minimal vasoconstrictive properties, showing in most patients a long antidiuretic effect (12-24 h) and can intranasally, s.c., i.v. or p.o. are administered. Desmopressin is in both children and adults the drug of choice and available as an intranasal solution in two preparations. A bottle with a dropper and a calibrated nasal catheter has the advantage of being able to deliver ascending doses of 5-20 micrograms, but is difficult to handle. A spray bottle with which you can apply 10 micrograms desmopressin in 0.1 ml of liquid, easier to use, but gives only a fixed dose from. For each patient, the duration of action of a particular dose must be determined because the individual duration of action can be very different. The duration of action can be determined by measuring the urine volume and osmolality within a certain time. The nightly dose is the smallest dose that prevents nocturia. The morning and evening dose should be determined individually. Normally, adults need a dose between 10 and 40 micrograms. Most adults get 10 micrograms two times daily. For children aged 3 months to 12 years, the usual dose is 2.5 to 10 micrograms two times daily. An overdose can lead to water retention and decreased plasma osmolality with the risk of seizures in young children. In such cases, furosemide can be given to induce diuresis. Headaches are a bothersome side effect, but disappear when the dose is reduced. Very rarely causes desmopressin a slight increase in blood pressure. The absorption of the nasal mucosa can be unpredictable, especially in the case of infections of the upper respiratory tract or allergic rhinitis. If the nasal application is not reliable, desmopressin can s.c. are given. For this purpose, a tenth of the intranasal dose ranges. If a rapid effect is desired (eg. As in hypovolemia), desmopressin can also i.v. be used. In oral Desmopressingabe it is difficult to derive an equivalent dose to dose nasal administration, so here again individual dose titration is necessary. The initial dose is 0.1 mg p.o. 3 times a day, and the maintenance dose is normally 0.1 to 0.2 mg 3 times daily. Tips and risks The duration of action of a given dose of desmopressin is very individual and must for each patient are determined. Lypressin (Lysine-8- vasopressin), a synthetic drug is, nasally using a spray at a dose of 2-4 units (7.5-15 ug) was administered every 3-8 h. Because of its short duration of action but it has been largely replaced by desmopressin. Vasopressin dissolved in water in a dose of 5-10 units s.c. or i.m. deployed for 6 h ? a antidiuretic effect. Although this drug is used rarely in the long-term treatment, it has its use in the initial treatment unconscious patients and in the treatment of patients with CDI, which have to undergo a surgical procedure. Synthetic vasopressin may be administered 2 to 4 times daily as a nasal spray. The dose and dosing interval must be determined individually for each patient. Vasopressin in oily solution and a dose of 0.3-1 ml (1.5-5 units) i.m. may have a duration of up to 96 h entfalten.Nichthormonelle drugs at least three groups of non-hormonal Arzneimittenl are useful in reducing polyuria: diuretics, especially thiazides vasopressin-releasing drugs (such as chlorpropamide, carbamazepine, clofibrate) prostaglandin inhibitors These drugs are extremely effective in the treatment of partial CDI and do not show the side effects of exogenous vasopressin. Thiazide diuretics, paradoxically, reduce the volume of urine in partial and complete CDI (and NDI), primarily as a result of a reduced extracellular volume and an increase in the absorption at the proximal tubule. With a Chlorothiaziddosis of 15-25 mg / kg the urine volume can be reduced by 25-50%. Chlorpropamide, carbamazepine, and clofibrate can with partial CDI reduce the need for vasopressin and vasopressin have a gift be unnecessary in some patients. With NDI, these substances have no effect. Chlorpropamide (3-5 mg / kg p.o. 1- or 2 times per day) leads to a certain vasopressin release and potentiate the action of vasopressin on the kidney. Clofibrate (500-1000 mg po 2 times a day) or carbamazepine (100-400 mg po 2 times a day) is recommended only for adults. These drugs can be used synergistically with a diuretic. By chlorpropamide significant hypoglycemia may be caused. Prostaglandin inhibitors (eg. B. indomethacin 0.5-1.0 mg / kg p.o. 2 times a day, with most NSAIDs have an activity) are moderately effective. You can reduce the volume of urine, but generally not more than 10 to 25%, possibly due to a reduction in renal blood flow and GFR. Together with indomethacin can be further reduced urine volume in NDI with a sodium restriction and a diuretic. Important points The central diabetes insipidus (CDI) is caused by a lack of vasopressin, which reduces the ability of the kidneys to absorb water, resulting in a massive polyuria (3 to 30 l / day). The cause may be a primary genetic disorder or various tumors, infiltrative lesions, injuries or infections that affect the hypothalamic-pituitary system. The diagnosis is made by means of a dehydration tests; patients can not concentrate urine after dehydration maximum, but can concentrate urine after receiving exogenous vasopressin. The vasopressin levels are diagnostic, but the vasopressin levels are difficult to measure and the test is not part of routine program. All treatable causes are treated and desmopressin, a synthetic analogue of vasopressin is administered.