Central non-diabetes mellitus (CND) - symptoms and signs, diagnosis, treatment
Central diabetes insipidus
Central diabetes insipidus
(Vasopressin-dependent diabetes insipidus)
Diabetes insipidus (ND) develops against the background of vasopressin deficiency, which is formed due to the pathology of the hypothalamic-pituitary region (central ND; CLP) or resulting from kidney resistance to vasopressin (nephrogenic ND; NDI). Clinically developed polyuria and polydipsia. The diagnosis is based on the results of the sample with refraining from taking a liquid that reflects the insufficient concentration ability of the kidneys. Evaluation of the basal level of vasopressin and renal response to the administration of exogenous vasopressin helps to conduct differential diagnosis of LPC and NND.
Polyuria may indicate the development of central diabetes insipidus - symptoms and signs, diagnosis,treatment, which is a consequence of a deficiency of ADH, the development of NDI or the usual or forced consumption of large amounts of fluid (psychogenic polydipsia). The posterior lobe of the pituitary is the main place where the deposition and realization of ADH in the bloodstream occurs, but the synthesis of ADH is carried out in the hypothalamus. The newly synthesized hormone enters the bloodstream, while the hypothalamic nucleus and part of the neurohypophysial tract remain intact. Enough 10% of neurosecretory neurons to avoid the development of LPC. However, the supraoptic and paraventricular nuclei of the hypothalamus or most of the pituitary foot region are always involved in the development of CNS damage.
The low-pressure cylinder may be complete (no vasopressin) or partial (insufficient amount). There are also primary ZND, in which there is a clear decrease in the hypothalamic nuclei of the neurohypophysis. Genetic abnormalities of the gene for vasopressin localized on the 20th chromosome pair are responsible for autosomal dominant inheritance of the primary LPC, but in many cases the CND can also be secondary (acquired) due to various lesions,including hypophysectomy, cranial injuries (especially at the base of the skull fracture), pituitary tumors of the supersellar and intracellular localization (primary or metastasis), Langerhans cell granulomatosis (histiocytosis - Chythe-Schueller-Chrysler’s disease), granulomatosis of the Langerhans cells (histiocytosis - Chromatic-Chroesel-Chromatic Disease), a heart-time, histoxicosis of the 4-st, and a 4-point-4-d-5-luminee cell granulomatosis (histiocytosis - Chyne-Schueller-Chrysler-Chropsis), a heart-wrap of the Langerhans cell granulomatosis (histiocytosis - Chronicle-Chronicle-Chromalis), a short-term, 3-dimensional vascular anomalies (aneurysm and thrombosis) and infections (encephalitis or meningitis).
Symptoms and signs of central diabetes insipidus
The manifestation may be invisible or suddenly developing, occur at any age. Only polyuria and polydipsia are symptoms of a primary LPC. In secondary LPCs, clinical signs of associated pathology are also present. A huge amount of fluid consumed by the patient is clinically observed, and a large amount (3–30 l / day) of low-concentrated urine is excreted (density is usually <1.005, and osmolarity is <200 mOsm / l). Nocturia is almost always present. In the absence of replacement rehydration therapy, dehydration and hypovolemia can develop rather quickly.
Diagnosis of central diabetes insipidus
The LPC should be distinguished from polyuria of a different etiology, especially due to psychogenic polydipsia and NND. All diagnostic tests for CNP and NDI are based on the fact that an increase in the os-molarity of blood in healthy people leads to a decrease in urine excretion and an increase in its osmolarity.
- Vasopressin-resistant polyuria
- Congenital nephrogenic ND (usually associated with the X chromosome, recessive inheritance).
- Acquired nephrogenic ND Chronic kidney disease. Systemic and metabolic diseases (for example, multiple myeloma, amyloidosis, hypercalcemic and hypocalymic nephropathy, sickle-like anemia).
- Drug-induced conditions (lithium, dimeclocycline).
- Osmotic diuretics Glucose (with diabetes).
- Solutions of poorly soluble substances (mannitol, sorbitol, urea)
A sample with abstinence from fluid intake is the simplest and most convenient method for diagnosing central diabetes insipidus, conducted only under constant medical supervision. Otherwise, the result may be the development of life-threatening dehydration. In addition, it is necessary to notice the symptoms of psychogenic polydipsia in time in order to prevent patients from consuming large amounts of fluid.The trial begins in the morning with a patient weighing, venous blood sampling for the purpose of determining the concentration of electrolytes and osmolarity of the plasma and measuring the osmolarity of the urine. Excreted urine is collected hourly, is determined by its density or, preferably, osmolarity. The test is interrupted when an orthostatic hypo tension and postural tachycardia appear; or more than 5% of the initial body weight is lost or the density of urine increases by more than 0.001 or osmolarity of more than 30 mOsm / l in each collected portion. The serum electrolytes and its osmolarity are determined immediately and after subcutaneous administration of 5 units of an aqueous solution of vasopressin. The density and osmolarity of all urine collected 60 minutes after the injection of vasopressin is determined, after which the test is stopped.
The normal response to the test is to excrete urine with a maximum osmolarity after dehydration (often> 1.020 or 700 mOsm / l), exceeding the osmolarity of the blood plasma; urine osmolarity does not increase by more than an additional 5% after vasopressin injection. Patients with CND, as a rule, are not able to concentrate urine above the level of osmolarity of blood plasma, but are able to increase the osmolarity of their urine by more than 50% after injection of vasopressin.Patients with partial CND are often able to concentrate urine above the osmolarity of their plasma, but they have an increase in urine osmolarity of more than 9% after stimulation with vasopressin. In patients with NID, an inability to concentrate urine is higher than the level of osmolality of the blood plasma and no additional response to vasopressin stimulation is observed.
Measurement of circulating ADH is a direct method for verifying the diagnosis of central diabetes insipidus; the levels obtained at the end of a sample with a restriction of fluid (prior to injection of vasopressin) are low and, respectively, elevated in the case of NND. However, ADH levels are difficult to measure, and this test is not fully acceptable for clinical practice. In addition, the loss of fluid is so insignificant that a direct measurement of ADH is not necessary. Vasopressin levels are measured both after dehydration and after the infusion of hypertonic solutions.
Psychogenic polydipsia.Psychogenic polydipsia can make certain difficulties in differential diagnosis. Patients can consume and excrete up to 6 liters of fluid per day and often have emotional disorders.In patients, unlike CND and NND, there are differences in the clinical picture: usually there is no nocturia, they also do not wake up at night to quench their thirst. Prolonged use of a large amount of fluid in this situation can lead to a lifetime medication correction hyponatriemii.
Patients with acute psychogenic thirst can normally concentrate their urine during the entire period of refusal from excessive fluid intake. However, chronic consumption of large volumes of water contributes to the death of the medullary layer of the kidneys, therefore, in patients with long-standing chronic polydipsia, the urine concentration is not able to reach the maximum values (peak) during the test with abstinence from fluid intake. A similar response to this provocative test is observed in patients with partial CNS. But in contrast to the CND in patients with psychogenic polydipsia, there is no response to the administration of exogenous vasopressin after dehydration. The presence of such a response is more in favor of NND, except that the level of basal vasopressin is low in comparison with its elevated level, detected in the case of NND.After a long limitation of fluid intake (<2l / day), the ability of the kidneys to concentrate urine normally returns after a few weeks.
Treatment of central diabetes insipidus
Replacement therapy and any other corrective drug therapy can be used in the treatment of CND. In the absence of adequate therapeutic follow-up, patients develop organic kidney damage as a result.
DDAVP - a vasopressin agonist (des-mopressin) is a synthetic analogue of vasopressin with minimally different vasoconstrictor properties and properties, has a prolonged antidiuretic activity that lasts up to 24 hours in most patients, and can be administered intravenously, subcutaneously, intravenously either orally. Desmopressin is the drug of choice in the treatment of patients of all ages, and two forms of the intranasal solution of the drug are convenient in clinical practice. This is a solution in a vial, with a calibrated nasal dispenser, which allows for the dosed introduction of the drug in drops; has the advantage of introducing increasing dosages of the drug from 5 to 20 mg, but inconvenient to use.
The second form - a spray can containing 10 µg of the drug in 0.1 ml of solution - is easy to use, but allows you to enter only a fixed number of doses of the drug. The duration of the dose received by the patient desmopressin is evaluated individually in each case, since there is a large individual variation in the metabolism of the drug in the patient's body. The duration of the action of desmopressin can be estimated by measuring the amount of urine released per unit of time and its osmolarity. The nightly dose required for the therapeutic effect and the prevention of nocturia is the lowest. Morning and evening doses of the drug should be selected separately. The usual dose of the drug in adults varies in the range of 10-40 µg, most adult patients require 10 µg 2 times a day. Children between the ages of 3 months and years need 2.5 to 10 mcg 2 times a day.
An overdose can lead to fluid retention and a decrease in the osmolarity of the blood plasma, which can cause seizures in young children; in this case, to stimulate diuresis, furo-seven is prescribed. In some cases, side effects in the form of headaches can be fixed, but they usually disappear if the dosage of the drug is reduced.Rarely desmopressin can cause a slight rise in blood pressure. Absorption from the mucosal layer in the nasal cavity can be unstable, especially when there are SARS or allergic rhinitis. In these cases, when the intra-nasal administration of desmopressin does not lead to the expected therapeutic result, the drug may be administered subcutaneously, but in a different dose.
Desmopressin can also be administered intravenously if it is necessary to quickly achieve a therapeutic effect (for example, in case of hypovolemia). The prescription of desmopressin orally, at a dose equivalent to the intranasal form of the drug, is unpredictable from a clinical point of view, therefore, in this case, an individual selection of the dose is necessary. The initial dose of 0.1 mg orally 3 times / day, and the maintenance dose is usually 0.1 to 0.2 mg orally 3 times / day.
Lipressin (lysine-8-vasopressin) is a synthetic agent, administered in the form of an intranasal spray in a dose of 2 to 4 units (7.5–15 mcg) after 3–8 hours, but due to the short period of action of this form of the drug in clinical In practice, treatment is complemented by desmopressin replacement therapy.
An aqueous solution of vasopressin 5-10 units subcutaneously or intramuscularly can be assigned to ensure the antidiuretic effect, which usually lasts for 6 hours. Thus, this drug is little used for prolonged therapy, but can be prescribed as initiating therapy in patients who are unconscious and in those patients with central diabetes insipidus who are undergoing surgical treatment. Synthetic vasopressin in the form of an intranasal spray can be administered with a frequency of 2 to 4 times a day, while the dosage and intervals of the drug are discussed individually with each patient. Vasopressin in the form of an oil solution of 0.3-1 ml (1.5-5 units) is injected intramuscularly and can have a therapeutic effect for up to 96 hours.
To date, in clinical practice, at least 3 groups of non-hormonal drugs are successfully used to relieve polyuria: various diuretics, primarily of the thiazide series; releasing factor-ADH drugs such as chlorpropamide, carbamazepine and clobibrate; inhibitors of prostaglandin.All these medications are not very effective. However, some representatives of these groups are particularly successful in clinical use in partial CNDs and do not have such pronounced side effects as drugs of exogenous ADH.
Thiazides paradoxically reduce the amount of urine excreted in partial and complete LPC (and in the case of NDI too), primarily due to a decrease in glomerular filtration and an increase in the reabsorption of sodium and water in the proximal renal tubules. The volume of urine output can be reduced by almost 25-50% at a dose of chlorothiazide 15-25 mg / kg body weight. Limiting the intake of salt can also increase the therapeutic effect, as a result of decreased production of urine due to a decrease in the intake of sodium salts.
Chlorpropamide, carbamazepine and clobibrate may reduce or eliminate the need for vasopressin in some patients with partial CND. However, with NPD this is ineffective. Chlorpropamide (at a dose of 3-5 mg / kg orally 1 or 2 times / day) causes the release of a certain amount of ADH and also potentiates the effect of ADH on the kidneys. Clo-fibrate (in a dose of 500-1000 mg orally 2 times / day) or carbamazepine (in a dose of 100-400 mg orally 2 times / day) is recommended only for adult patients.These drugs can be used in conjunction with diuretics, however, chlorpropamide can cause severe hypoglycemia.
Prostaglandin inhibitors (usually indomethacin 0.5-1.0 mg / kg orally 3 times / day, although most NSAIDs are effective) can reduce the amount of urine given in general by no more than 10-25%, possibly by reducing the renal blood flow and glomerular filtration rate. Limiting the intake of salt and taking thiazide diuretics together with taking indomethacin provide a further steady decrease in the amount of urine in NND.
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