Diabetes insipidus in tables. Maybe it's not diabetes: differential diagnosis

Not diabetes , otherwise referred to as diabetes, is a pathological process characterized by impaired reabsorption of fluid in the kidneys, as a result of which urine is not sufficiently concentrated, therefore, it is excreted in very large quantities in diluted form. Against this background, patients develop a constant feeling of thirst, indicating a significant loss of fluid by the body. If the loss of fluid by the body is not compensated sufficiently from the outside, then dehydration develops.

Diabetes insipidus develops as a result of a defect in the production of vasopressin, an antidiuretic hormone produced by the hypothalamus, or a decrease in the sensitivity of the kidney tissue to its effects. Diabetes insipidus belongs to a group of rare endocrine pathologies, which in 20% of cases develops as a complication after brain surgery. According to medical statistics, the development of the disease is not related to the sex and age of patients, but is more often recorded in people 20-40 years old.

Classification of diabetes insipidus

Depending on the level at which violations occur, there are two types of diabetes insipidus:

1. Central or hypothalamic diabetes insipidus- occurs as a result of a violation of the formation or release of antidiuretic hormone. It is further subdivided into idiopathic diabetes insipidus, which is based on hereditary pathology characterized by low production of antidiuretic hormone, and symptomatic diabetes insipidus, which can occur against the background of other diseases, for example, with injuries and tumor processes of the brain, infectious inflammation of the meninges, etc.

2. Nephrogenic or renal diabetes insipidus- occurs due to a violation of the sensitivity of the renal tissues to the effects of vasopressin. This type of diabetes insipidus is much less common. In this case, either the inferiority of the structure of the nephrons, or the vasopressin resistance of the receptors of the renal tissue is noted. This type of diabetes insipidus can be congenital, or it can occur with drug-induced damage to kidney cells.

Some authors also point out gestagenic diabetes insipidus of pregnancy, the development of which is associated with increased activity of a special placental enzyme that destroys vasopressin. In children early age may develop functional diabetes insipidus associated with the immaturity of the mechanism of urine concentration in the kidneys. In addition, against the background of the use of drugs from the group of diuretics, the development of iatrogenic diabetes insipidus.

Endocrinologists also distinguish primary polydipsia as one of the forms of diabetes insipidus, which manifests itself in the form of a pathological feeling of thirst (with damage or tumor processes in the thirst center in the hypothalamus) or a compulsive desire to drink (with neurosis, psychosis and schizophrenia). At the same time, due to an increase in fluid intake, the physiological production of vasopressin is suppressed and the clinical picture of diabetes insipidus develops.

Based clinical picture, diabetes insipidus is also classified according to severity without correction by drugs:

- mild degree the disease is characterized by daily urine output in the range of 6-8 liters;

At medium degree pathology, the amount of urine excreted per day is 8-14 liters;

For severe the daily volume of excreted urine is more than 14 liters.

During the period when the disease is corrected by drugs, three stages are distinguished in its course:

1. compensation stage, which is characterized by the absence of symptoms of thirst and an increase in the volume of urine excreted;

2. subcompensatory stage- with the periodic occurrence of a feeling of thirst and the presence of polyuria.

3. stage of decompensation, which is characterized constant feeling thirst and polyuria even during treatment.

Diabetes insipidus - causes and mechanism of development

Central diabetes insipidus can develop as a result of congenital genetic defects and pathologies of the brain. Acquired diabetes insipidus of the central type develops with tumor processes in the brain, as well as metastases resulting from tumor lesions of other organs, after trauma and infectious diseases affecting the brain. In addition, the disease can develop with ischemia and hypoxia of brain tissues as a result of vascular disorders. Idiopathic diabetes insipidus occurs with the spontaneous appearance of antibodies to cells that produce antidiuretic hormone, while organic lesion the hypothalamus is not found.

Nephrogenic diabetes insipidus can also be congenital and acquired. Congenital forms of this type of diabetes insipidus develop with Wolfram syndrome and genetic defects in receptors that respond to vasopressin. Acquired forms of diabetes insipidus of the renal type can develop with chronic renal failure, amyloidosis of the kidneys, disorders of the metabolic processes of calcium and potassium in the body, and poisoning with drugs containing lithium.

Symptoms of diabetes insipidus

The two most telling symptoms of diabetes insipidus are polyuria(urination exceeding the daily norm) and polydipsia(drinking plenty of fluids). The volume of urine excreted per day in patients with diabetes insipidus can vary in the range of 4-30 liters, depending on the severity of the disease. At the same time, urine is practically colorless, has a low density and practically does not contain salt and other components. Because of the irresistible feeling of thirst, patients with diabetes insipidus consume a lot of fluids. The amount of fluid consumed by patients can range from 3 to 18 liters per day. Both one and the second signs entail sleep disturbance, neurosis, increased fatigue, and emotional imbalance.

Diabetes insipidus in children It is manifested most often by nighttime urinary incontinence, which is subsequently joined by growth retardation and puberty. Over time, there are structural changes in the organs of the urinary system, manifested in the form of expansion of the renal pelvis, ureters and bladder. Due to the consumption of significant volumes of fluid, the stomach also suffers, as its walls, as well as the surrounding tissues, are overstretched, which leads to prolapse of the stomach, dysfunction of the biliary tract and chronic irritable bowel syndrome.

When examining patients with diabetes insipidus, excessive dryness is detected skin and mucous membranes. Patients complain of poor appetite, sudden weight loss, headaches, vomiting, and hypotension. One of the symptoms of diabetes insipidus in women is irregular menstruation. Diabetes insipidus in men is characterized by a decrease in sexual function.

The danger of diabetes insipidus lies in the possibility of developing dehydration, as a result of which persistent neurological disorders can develop. A similar complication occurs if the liquid. lost in the urine is not properly replenished from the outside.

What criteria are used to diagnose diabetes insipidus?

Diagnosis in the typical course of diabetes insipidus is quite simple. It relies on unquenchable thirst and an increased volume of daily urine, exceeding 3 liters per day in history. In a laboratory study, plasma hyperosmolarity and an increased level of sodium and calcium with a reduced level of potassium are important criteria. When examining urine, its hyperosmolarity and low density are also revealed.

The first stage of diagnosing diabetes insipidus is aimed at confirming the very fact of the presence of polyuria (increased amount of urine) with its low density. Usually, in diabetes insipidus, urine output exceeds 40 ml per kilogram of body weight with a relative density of urine less than 1005 g / l. If such urination is established, the second stage of diagnosis is carried out, which consists in performing a test with a dry diet. The test with dry food in the classic version according to Robertson involves the refusal of fluid intake (complete) and (preferably) the refusal of food in the first 8 hours of the test. Before the start of fluid and food restriction, the patient is determined by the osmolality of blood and urine, the level of sodium in the blood, the volume of urine excreted, body weight and blood pressure. After stopping the supply of food and water to the patient, this set of studies should be repeated every 1-2 hours, depending on how the patient feels. The test is terminated if during its course the patient has lost more than 3-5% of his weight, the patient's condition worsens, the sodium level and blood osmolality increase, and also when urine with an osmolality of more than 300 mOsm/l is obtained. In stable patients, such a test can be performed on an outpatient basis, while the patient should not drink for as long as he can stand according to his state of health. If a urine sample with an osmolality of 650 mOsm/L is obtained during fluid restriction, the diagnosis of diabetes insipidus may be ruled out.

Carrying out a test with a dry diet in patients suffering from diabetes insipidus does not lead to a significant increase in the osmolality of urine and the concentration of substances in it. During the test, in patients with diabetes insipidus, due to dehydration developing due to fluid loss, nausea and vomiting, convulsions, agitation, and headache appear. The temperature may rise.

When confirming the diagnosis of diabetes insipidus, a desmopressin test is performed - the administration of despopressin in patients with central diabetes insipidus causes a decrease in the amount of urine, and in patients with renal diabetes insipidus, the volume of urine does not decrease.

For differential diagnosis with diabetes, the level of glucose in blood taken on an empty stomach is determined. To clarify the cause of the development of diabetes insipidus, an x-ray is performed, an examination by an ophthalmologist and a psychoneurologist. If there is a suspicion of volumetric formations of the brain, magnetic resonance imaging is performed. The renal form of diabetes insipidus is diagnosed by ultrasound and computed tomography of the kidneys. If in doubt, a nephrologist is consulted and a kidney biopsy is performed.

How to treat diabetes insipidus?

After the diagnosis is made and the form of diabetes insipidus is established, treatment begins with the elimination of the cause that caused it, i.e. they remove tumors, eliminate the consequences of craniocerebral injuries, treat major diseases, etc.

For replacement of antidiuretic hormone in all forms of diabetes insipidus prescribe its synthetic analogue - desmopressin, which is applied orally by instillation into the nose. Central diabetes insipidus involves the use of chlorpropamide, carbamazepine and other drugs that stimulate the production of vasopressin.

An integral part of therapy are activities that normalize the water-salt balance, which include the infusion of large volumes of saline solutions. To reduce the excretion of urine, hypothiazide is prescribed.

Diet for diabetes insipidus involves reducing the load on the kidneys, therefore, includes products containing a minimum of protein and a sufficient amount of fats and carbohydrates. Patients with diabetes insipidus are advised to fractional nutrition, which includes a lot of vegetables and fruits. To quench your thirst, instead of water, it is preferable to use juices, compotes, fruit drinks.

Idiopathic form of diabetes insipidus does not pose a threat to life, but cases of complete recovery are extremely rare. Gestational and iatrogenic diabetes insipidus are more transient in nature, and most often end in a complete cure. Proper use of substitution therapy allows patients to maintain their ability to work. One of the most unfavorable prognostic forms of diabetes insipidus is renal diabetes insipidus in children.

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Most of us are familiar with the main symptoms of diabetes - usually thirst and copious urination. Less well-known are weight gain, fatigue, dry skin and frequent pustular skin rashes. Often these signs are an indication for a laboratory examination.

But is the diagnosis of diabetes mellitus always so obvious: differential diagnosis disease is of great interest to the scientific world.

It should be noted that in medicine there are two forms of "sugar" pathology: CD-1 (type 1, insulin-dependent) and CD-2 (type 2, insulin-independent).

• It is characterized by the almost complete absence of insulin in the body due to a violation of its synthesis in the beta cells of the pancreas that have undergone autoimmune destruction.
• the problem lies in the violation of the sensitivity of cell receptors: there is a hormone, but the body perceives it incorrectly.

How to distinguish types of pathology? The differential diagnosis of type 1 and type 2 diabetes is shown in the table below.

Table 1: Diagnosis of differential diabetes mellitus:

Important! All basic symptoms of the disease (polyuria, polydipsia, pruritus) are similar for IDDM and NIDDM.

Syndromes and diseases

Differential diagnosis of type 2 diabetes mellitus, like IDDM, is carried out according to the main syndromes.

In addition to diabetes, polyuria and polydipsia may be characteristic of:

• chronic kidney disease and chronic renal failure;
• primary hyperaldosteronism;
• hyperparathyroidism;
• neurogenic polydepsia.

According to the syndrome of hyperglycemia, differential diagnosis of type 1 and type 2 diabetes mellitus is carried out with:

• Itsenko-Cushing's disease/syndrome;
• steroid diabetes;
• acromegaly;
• hemochromatosis;
• pheochromocytoma;
• some diseases of the liver and pancreas;
• alimentary hyperglycemia.

With the development of glucosuria syndrome differential diagnosis type 2 diabetes mellitus and IDDM is carried out with the following diseases:

• alimentary glucosuria;
• glucosuria in pregnancy;
• toxic lesions;
• kidney diabetes.

It is interesting. False-positive results in the study of urine for glucose can be observed when taking large doses of vitamin C, acetylsalicylic acid, cephalosporins.

Differential Diagnosis

diabetes insipidus

Differential diagnosis of diabetes and diabetes insipidus is of great interest to endocrinologists. Despite the fact that the symptoms of these pathologies are similar, their mechanism of development and pathogenesis are strikingly different.

Diabetes insipidus is associated with an acute shortage of the hypothalamic hormone vasopressin, which is responsible for maintaining normal water balance.

Secreted in the hypothalamus, vasopressin is transported to the pituitary gland, and then distributed with the bloodstream throughout the body, including the kidneys. At this level, it promotes the reabsorption of fluid in the nephron and its retention in the body.

Depending on the cause, diabetes insipidus can be central or nephrogenic (renal). The first often develops against the background of traumatic brain injuries, neoplasms of the hypothalamus or pituitary gland. The second is the result of various tubulopathies and impaired sensitivity to the hormone of the renal tissues.

Are both DM and the pathology under consideration clinically manifested by thirst and profuse urination? But what are the differences between them?

Table 2: Diabetes insipidus and diabetes mellitus - differential diagnosis:

Chronic kidney disease

In chronic renal failure at the stage of polyuria, patients often complain of frequent profuse urination, which may indicate the development of hyperglycemia. However, in this case, a differential diagnosis will help: type 2 diabetes mellitus and IDDM are also characterized increased level blood sugar and glucosuria, and with chronic renal failure, signs of fluid retention in the body (edema), a decrease in rel. urine density.

Adrenal disorders and other endocrine disorders

Primary hyperaldosteronism (Conn's syndrome) - clinical syndrome characterized by excessive production of the hormone aldosterone by the adrenal glands.

Its symptoms are quite typical and are manifested by three syndromes:

• defeat of the CCC;
• neuromuscular disorders;
• kidney dysfunction.

The defeat of the CCC is primarily represented by arterial hypertension. Neuromuscular syndrome is associated with hypokalemia and is manifested by bouts of muscle weakness, convulsions and short-term paralysis.

Nephrogenic syndrome is represented by:

• decrease in the contraceptive abilities of the kidneys;
• nocturia
• polyuria.

Unlike both forms of DM, the disease is not accompanied by disturbances in carbohydrate metabolism.

Itsenko-Cushing's disease/syndrome is another neuroendocrine disease with damage to the adrenal glands, which is involved in the differential diagnosis. It is accompanied by excessive secretion of glucocorticosteroids.

Clinically manifested by the following symptoms:

• obesity of a special type (excess weight is deposited mainly in the upper half of the body, the face becomes moon-shaped, and the cheeks are covered with a bright red blush);
• the appearance of pink or purple striae;
• excessive hair growth on the face and body (including in women);
• muscle hypotension;
• arterial hypertension;
• impaired insulin sensitivity, hyperglycemia;
• weakening of the immune system.

Gradually developing insulin resistance and signs of hyperglycemia may prompt the doctor to diagnose type 2 diabetes mellitus: the differential diagnosis in this case is carried out with an assessment of the additional symptoms described above.

In addition, the appearance of signs of hyperglycemia is possible with some other endocrine diseases (primary hyperthyroidism, pheochromocytoma), etc. Diff. Diagnosis of these diseases is based on advanced laboratory tests.

Pancreatitis and other gastrointestinal diseases

Chronic inflammatory damage to pancreatic tissues causes gradual death of functionally active cells with their sclerosis. Sooner or later, this leads to organ failure and the development of hyperglycemia.

It is possible to suspect the secondary nature of the syndrome on the basis of patient complaints (girdle pain in the epigastrium, radiating to the back, nausea, vomiting after eating fatty fried foods, various stool disorders), as well as laboratory and instrumental tests (increased levels of the alpha-amylase enzyme in the blood, ECHO signs of inflammation on ultrasound, etc.).

Note! Separately, it is necessary to highlight such a condition as alimentary hyperglycemia and glycosuria. They develop in response to the intake of excess carbohydrates in the body and, as a rule, persist for a short time.

Thus, the differential diagnosis of the main syndromes of DM is carried out with many diseases. A diagnosis based only on clinical data can be considered only preliminary: it must necessarily be based on data from a complete laboratory and instrumental examination.

Questions to the doctor

Asymptomatic course of diabetes

Hello! I am 45 years old, a woman, and there were no special complaints. Recently measured sugar - 8.3. I didn't donate blood on an empty stomach, maybe that's the reason.

A little later, I decided to take the test again. On an empty stomach from a vein, the result was also elevated - 7.4 mmol / l. Is it diabetes? But I have absolutely no symptoms.

Hello! Hyperglycemia in laboratory tests most often indicates the development of diabetes mellitus. Be sure to consult with an endocrinologist in person to decide whether to undergo an additional examination (first of all, I would advise you to donate blood for HbAc1, ultrasound of the pancreas).

Self-diagnosis

Good evening! Tell me if there are any reliable signs that will help determine if you have diabetes. I recently noticed that I began to eat a lot of sweets. It cannot be a symptom of a health problem.

Hello! Craving for sweets is not considered as a manifestation of DM. From the point of view of physiology, such a need may indicate a lack of energy, overwork, stress, hypoglycemia.

About SD, in turn, may indicate:

• dry mouth;
• intense thirst;
• frequent and profuse urination;
• weakness, decreased performance;
• sometimes - skin manifestations(severe dryness, pustular diseases).

Signs of diabetes in a child

With adults, everything is more or less clear. How to suspect diabetes in a child? I heard that in babies the disease is very difficult, up to coma and death.

Hello! Indeed, children are a special category of patients requiring close attention from both medical workers as well as from the parents.

The first thing that attracts attention in case of a disease in childhood- thirst: the child begins to drink noticeably more, sometimes he can even wake up at night, asking for water.

The second most common "childish" symptom of diabetes is frequent urination and enuresis. Sticky urine stains can be seen on the potty or near the toilet, if the baby wears a diaper, due to the high sugar content in the urine, it can stick to the skin.

Then weight loss becomes noticeable: the baby quickly loses kilograms even despite a good appetite. In addition, there are signs of asthenia: the baby becomes lethargic, drowsy, rarely participates in games.

All this should alert attentive parents. Such symptoms require immediate examination and medical advice.

Not many people know that in addition to the usual type 1 and type 2 diabetes, there is also diabetes insipidus. This is a disease of the endocrine glands, it is a syndrome of the hypothalamic-pituitary system. Therefore, such a disease really has nothing to do with diabetes, except for the name and constant thirst.

In diabetes insipidus, there is a partial or complete deficiency of the antidiuretic hormone vasopressin. It overcomes osmotic pressure and stores and then distributes fluid throughout the body.

So, the hormone provides the necessary amount of water that allows the kidneys to function normally. Therefore, vasopressin is necessary for natural homeostasis, because it ensures its normal operation even with a lack of moisture in the body.

In critical situations, for example, during dehydration, the brain receives a signal that regulates the functioning of organs. This contributes to the fact that fluid loss is reduced by reducing the flow of saliva and urine.

So, diabetes insipidus differs from diabetes in that during its course, the blood glucose indicator remains normal, but both diseases have a common symptom - polydipsia (strong thirst). Therefore, diabetes insipidus, which is characterized by the reabsorption of fluid from the tubules of the kidneys, received this name.

The course of ND is often acute. It is considered a disease of the young, so the age category of patients is up to 25 years. Moreover, a violation of the endocrine glands can occur in both women and men.

Diabetes insipidus: types

There is central and nephrogenic diabetes insipidus. CND, in turn, is divided into 2 types:

1. functional;
2. organic.

The functional type is categorized as an idiopathic form. The factors influencing the appearance of this species are not fully established, but many doctors believe that heredity plays a significant role in the development of the disease. Also, the reasons lie in a partial violation of the synthesis of the hormone neurophysin or vasopressin.

The organic form of the disease appears after various injuries, surgical intervention and other damage.

Nephrogenic diabetes insipidus develops when the natural functioning of the kidneys is disrupted. In some cases, there is a failure in the osmotic pressure of the renal tubules, in other situations, the susceptibility of the tubules to vasopressin decreases.

There is also such a form as psychogenic polydipsia. It can be caused by abuse medicines or PP is one of the types of manifestation of schizophrenia.

They also distinguish such rare types of ND as the gestagenic type and transient polyuria. In the first case, the placental enzyme is very active, which has a negative effect on the antidiuretic hormone.

Transient form of diabetes develops before the age of 1 year.

This occurs when the kidneys are underdeveloped, when the enzymes involved in metabolic processes begin to behave more actively.

Causes and symptoms of the disease

Sugar level

There are many factors that lead to the development of diabetes insipidus:

• tumor formations;
• chronic and acute infections(postpartum sepsis, influenza, syphilis, typhus, scarlet fever, etc.);
• radiation therapy;
• nephritis;
• damage to blood vessels and parts of the brain;
• brain injury or surgery;
• amyloidosis;
• granulomatosis;
• hemoblastosis.

Autoimmune diseases and psychogenic disorders also contribute to the appearance of ND. And in the idiopathic form of the disease, the cause of the occurrence is the sharp appearance of antibodies against hormone-producing cells.

The clinical picture of diabetes insipidus is varied, ranging from headache to dehydration in the absence of adequate fluid intake. Therefore, in addition to screening, various tests for diabetes insipidus are performed.

The main signs of the disease include:

1. malfunctions in the digestive tract - constipation, gastritis, colitis, poor appetite;
2. strong thirst;
3. sexual dysfunction;
4. mental disorders - bad dream, irritability, headache, fatigue;
5. frequent urination with copious amounts of fluid (6-15 liters);
6. drying of mucous membranes and skin;
7. visual impairment in diabetes;
8. weight loss
9. anorexia;
10. asthenic syndrome.

Often, diabetes insipidus is accompanied by increased internal pressure and decreased sweating. Moreover, if the patient does not drink enough water, then his condition will deteriorate greatly. As a result, the patient may develop such manifestations as blood clotting, vomiting, nausea, tachycardia, fever, and a collapse occurs against the background of dehydration. In women with ND, it goes astray menstrual cycle, and men have a poor potency.

In children, the course of the disease can lead to a slowdown in sexual and physical development.

Diagnostics

To detect the presence of ND, a three-stage diagnostic examination is carried out:

• detection of hypotonic polyuria (urinalysis, Zimnitsky test, biochemical research blood);
• functional tests (desmopressin test, dry eating);
• detection of the causes that provoked the development of the disease (MRI).

First stage

Initially, if diabetes insipidus is suspected, a study is performed to determine the density of urine. Indeed, with the disease, the functioning of the kidneys worsens, as a result, the urine density is less than 1005 g / l.

To find out the level of density during the day, a study is being carried out according to Zimnitsky. This analysis is done every three hours for 24 hours. During this period, 8 urine samples are taken.

Normally, the results are deciphered in this way: the number daily allowance urine should not exceed 3 liters, its density is 1003-1030, while the ratio of night and day diuresis is 1: 2, and excreted and drunk - 50-80-100%. The osmolarity of urine is 300 mosm/kg.

Also, to diagnose ND, a biochemical blood test is performed. In this case, the osmolarity of the blood is calculated. In the presence of a high concentration of salts in the plasma of more than 292 mosm / l and an excessive sodium content (from 145 nmol / l), diabetes insipidus is diagnosed.

Blood is taken from a vein on an empty stomach. Before the procedure (6-12 hours) you can drink only water. As a rule, the results of the tests need to wait one day.

In addition, at biochemical analysis blood tests such quantities as:

1. glucose;
2. potassium and sodium;
3. total protein, including hemoglobin;
4. ionized calcium;
5. creatinine;
6. parathormone;
7. aldosterone.

The normal blood sugar level is up to 5.5 mmol / l. However, with ND, glucose concentrations often do not rise. But its fluctuations can be noted with a strong emotional or physical activity, diseases of the pancreas, pheochromocytoma and chronic liver and kidney failure. A decrease in sugar concentration occurs with violations in the functioning of the endocrine glands, starvation, tumors, and in case of severe intoxication.

Potassium and sodium are chemical elements that endow cell membranes with electrical properties. The normal content of potassium is 3.5 - 5.5 mmol / l. If its value is too high, then this indicates liver and adrenal insufficiency, cell damage and dehydration. Low rate potassium is noted with starvation, kidney problems, an excess of certain hormones, dehydration and cystic fibrosis.

The norm of sodium in the blood stream is from 136 to 145 mmol / l. Hypernatremia occurs with excessive salt intake, malfunctions in the water-salt balance, hyperfunction of the adrenal cortex. And hyponatremia occurs with the use of a large volume of fluid and in the case of pathologies of the kidneys and adrenal glands.

An analysis for total protein allows you to determine the level of albumin and globulins. The normal rate of total protein in the blood for adults is 64-83 g / l.

Of no small importance in the diagnosis of diabetes insipidus is glycosylated hemoglobin. Ac1 shows the average blood glucose over 12 weeks.

Hemoglobin is a substance present in red blood cells that delivers oxygen to all organs and systems. In people who do not suffer from diabetes, glycosylated hemoglobin in the blood does not exceed 4-6%, which is also characteristic of diabetes insipidus. Thus, elevated Ac1 values ​​make it possible to differentiate these diseases.

However, fluctuations in hemoglobin levels can be observed with anemia, the use of food additives, taking vitamins E, C and an excess of cholesterol. Moreover, glycosylated hemoglobin may have different indicators in diseases of the liver and kidneys.

The level of ionized calcium is an indicator responsible for mineral metabolism. Its average values ​​range from 1.05 to 1.37 mmol / l.

Also, tests for diabetes insipidus involve a blood test for aldosterone content. Deficiency of this hormone often indicates the presence of diabetes insipidus.

An increased level of creatinine and parathyroid hormone can also indicate the presence of the disease.

Second phase

At this stage, it is necessary to draw up a protocol for a dry diet test. The dehydration phase includes:

• blood sampling to check osmolality and sodium levels;
• taking urine to determine its quantity and osmolality;
• weighing the patient;
• measurement of pulse and blood pressure.

However, in hypernatremia, such tests are contraindicated.

It is worth noting that during the test you can not eat fast carbohydrate food with. Preference should be given to fish, lean meat, boiled eggs, grain bread.

The dry eating test is stopped if: the osmolality and sodium level exceed the norm, there is unbearable thirst and there is a weight loss of more than 5%.

The desmopressin test is done to distinguish between central and nephrogenic diabetes insipidus. It is based on testing the patient's sensitivity to desmopressin. In other words, the functional activity of V2 receptors is tested. The study is done after a dry diet test with the highest exposure to endogenous AVP.

Before testing, the patient must urinate. Then he is injected with desmopressin, while he can drink and eat, but in moderation. After 2-4 hours, urine is taken to determine its osmolality and volume.

Normally, the test results are 750 mOsm / kg.

With NDI, the values ​​rise to 300 mOsm/kg, and in the case of CND after dehydration, they are 300, and desmopressin - 750 mOsm/kg.

Third stage

An MRI is often done to detect diabetes insipidus. At healthy person in the pituitary, clear differences are seen between the anterior and posterior lobes. Moreover, the latter on the T1 image has a hyperintense signal. This is due to the presence in it of secretory granules containing phospholipids and AVP.

In the presence of CND, the signal emitted by the neurohypophysis is absent. This is due to a failure in the synthesis and transport and storage of neurosecretory granules.

Also, with diabetes insipidus, a neuropsychiatric, ophthalmological and x-ray examination can be performed. And in the renal form of the disease, ultrasound and CT of the kidneys are done.

The leading method of therapy for NND is the use of synthetic analogues of vasopressin (Desmopressin, Chlorpropamide, Adiuretin, Minirin). In the renal form, diuretics and NSAIDs are prescribed.

Any kind implies an infusion treatment based on the introduction saline solution. This is necessary to correct the water-salt metabolism.

Of no small importance is the observance of a certain diet, including limited intake of salt (4-5 g) and proteins (up to 70 g). These requirements correspond to the diet number 15, 10 and 7.

What tests should be taken if diabetes insipidus is suspected is described in the video in this article.

Central diabetes insipidus (ND) (diabetes insipidus) - serious disease characterized by the inability of the kidneys to reabsorb water and concentrate urine, which is based on a defect in the secretion or synthesis of vasopressin and is manifested by severe thirst and excretion a large number diluted urine. The prevalence of ND in the population (0.004-0.01%) is several times lower than that of diabetes mellitus (2-5%), but still the number of patients is quite significant and in Russia is approximately 21.5 thousand people. There is a global trend towards an increase in the prevalence of central ND, which is explained by an increase in the number of operations and brain injuries.

The term "diabetes" (from the Greek. diabaino- to pass through) was introduced by Areteus from Cappadocia in the 1st century. n. e. Areteus became famous for his detailed clinical descriptions of various diseases, comparable only to the descriptions of Hippocrates. He wrote: “Diabetes is a terrible affliction... dissolving flesh and limbs into urine. Patients continually excrete water in a continuous stream, as through open water pipes; ... thirst is insatiable, fluid intake is excessive and not commensurate with the huge amount of urine due to even more diabetes. Nothing can keep them from drinking liquids and passing urine. If they refuse liquid for a short time, their mouth dries up, the skin and mucous membranes become dry. Patients are nauseous, agitated, and die within a short time." Only in 1794, the German physician Johann Frank invented the yeast method for determining glucosuria, on the basis of which he divided diabetes into diabetes and insipidus. His namesake Alfred Frank in 1912 linked ND to neurohypophysis lesion, describing a patient with a gunshot wound who had a bullet lodged in the back of the Turkish saddle on x-ray. The second confirmation of this connection belongs to Maurice Simmonds, who observed a woman with breast cancer and central ND, in whom an autopsy revealed a tumor metastasis in the sella turcica with destruction of the posterior pituitary gland and an intact anterior lobe.

ND is heterogeneous and combines several diseases with different etiologies, which are characterized by hypotonic polyuria.

Diseases of the ND group:

• Central(hypothalamic, pituitary): impaired synthesis, transport or osmoregulated secretion of vasopressin.
• Renal(nephrogenic, vasopressin-resistant): kidney resistance to the action of vasopressin.
• Primary polydipsia:

  Psychogenic - compulsive fluid intake;

  Dipsogenic - lowering the threshold of osmoreceptors for thirst.

• gestagenic: during pregnancy; increased destruction of endogenous vasopressin by the placental enzyme - arginine aminopeptidase.
• Functional: in children under one year old; increased activity of type 5 phosphodiesterase, leading to rapid deactivation of the vasopressin receptor.
• iatrogenic: doctor's advice to drink more fluids, uncontrolled reception diuretics, taking drugs that disrupt the action of vasopressin (demeclocycline, lithium preparations, carbamazepine).

In clinical practice, as a rule, three main types of ND are encountered: central ND, nephrogenic ND, and primary polydipsia.

Vasopressin, or antidiuretic hormone, is the most important regulator of water and electrolyte metabolism in the human body, its function is to maintain osmotic homeostasis and the volume of circulating fluid. Vasopressin is synthesized in the bodies of neurons that form the supraoptic and paraventricular nuclei of the hypothalamus; it binds to the carrier protein neurophysin. The vasopressin-neurophysin complex in the form of granules is transported to the terminal extensions of the axons of the neurohypophysis and the median eminence, where it accumulates. For the manifestation of central ND, a decrease in the secretory capacity of the neurohypophysis by 85% is necessary.

In humans, the maintenance of normal water balance is achieved by the relationship of three components: vasopressin, thirst and kidney function. The secretion of vasopressin from the neurohypophysis is under very tight control. Small changes in the concentration of electrolytes in the blood (plasma osmolality) regulate the release of vasopressin. An increase in plasma osmolality usually indicates a loss of extracellular fluid, stimulates the secretion of vasopressin, and vice versa - a decrease in plasma osmolality inhibits its release into the systemic circulation. Further, vasopressin acts on the main target organ - the kidneys. The hormone binds to its V2 receptors located on the basement membrane of the main cells of the collecting ducts and activates the adenylate cyclase system, which ultimately leads to the “embedding” of type 2 “water channel” proteins, aquaporins-2, into the apical cell membrane and the flow of fluid from lumen of the nephron into the cells of the collecting ducts in the direction of the osmotic gradient. From the cells of the collecting tubules, water passes through the basement membrane aquaporins 3 and 4 into the renal interstitium and ultimately into the circulatory bed.

Clinically, ND (except for primary polydipsia) is a state of severe dehydration of the body, which manifests itself in the concentration of blood with an increase in hematocrit and concentration of substances dissolved in plasma, mainly sodium, as well as a decrease in all types of exogenous secretion (perspiration and salivation, gastrointestinal secretion ). Systolic blood pressure (BP) may be normal or slightly low with a characteristic increase in diastolic blood pressure. ND is characterized by a preference for cold/icy drinks that are low in salt and carbohydrates. Often, even during examination, the patient cannot part with a bottle of water.

Differential diagnosis is based on four main stages. The first is confirmation of the presence of hypotonic polyuria. The second is the exclusion of the most common causes of polydipsia-polyuria. At the third stage, a dehydration test and a desmopressin test are performed to separate the three main types of ND, at the fourth stage, an active search for causes is carried out ( ).

Polyuria is defined as urine output greater than 2 L/m 2 /day or approximately 40 ml/kg/day in older children and adults. First of all, it is necessary to confirm the presence of polyuria according to the criteria described above, for example, to appoint a collection of daily urine, a urine test according to Zimnitsky. The amount of fluid drunk / urine output in patients usually ranges from 3 to 20 liters. Consumption of more than 20 liters per day, some authors refer to signs of psychogenic polydipsia, since such a volume of fluid is not justified by the physiological needs of the body to maintain water-salt homeostasis in ND.

Next, you need to exclude osmotic diuresis (diabetes mellitus, taking mannitol), kidney pathology (chronic renal failure, post-obstructive uropathy), uncontrolled intake of diuretics (including as part of teas, medicinal fees), taking drugs that interfere with the action of vasopressin (demeclocycline, lithium preparations, carbamazepine), as well as metabolic disorders such as hypercalcemia and hypokalemia.

ND is characterized by an increase in blood osmolality, hypernatremia, constantly low osmolality (< 300 мОсм/кг) или относительная плотность мочи (< 1005 г/л).

Osmolality and Osmolarity are quantitative measures of osmotically active substances dissolved in liquid. Osmolality is measured with an osmometer as the drop in the freezing point of a liquid in mOsm/kg. Osmolarity is calculated according to the formula in mOsm / l, and for plasma, urea and total protein can be ignored. Normal values osmolality: blood plasma - 280-300 mOsm / kg, urine - 600-1200 mOsm / kg. For osmolarity, the norm is 10-15 mOsm lower.

If this triad of laboratory signs is identified, along with the relevant history data, a dry food test is not required, a test with desmopressin is immediately performed.

GL Robertson Classic Dry Food/Desmopressin Test Protocol

Dehydration phase (to exclude ND):

• Take blood for osmolality and sodium content.
• Collect urine for determination of volume and osmolality.
• Weigh the patient.
• Measure blood pressure and pulse.

In the future, at regular intervals, depending on the condition of the patient, after 1 or 2 hours, repeat the above steps.

During the test: the patient is not allowed to drink, it is also desirable to restrict the diet, at least during the first 8 hours of the test; food should not contain a lot of water and easily digestible carbohydrates (boiled eggs, grain bread, lean varieties meat, fish).

The test is terminated:

• with a loss of more than 3-5% of body weight;
• unbearable thirst;
• objectively serious condition of the patient;
• an increase in sodium levels and blood osmolality above the normal range;
• an increase in urine osmolality of more than 300 mOsm / l.

Desmopressin test(if the presence of a central ND has not yet been ruled out):

• Ask the patient to empty completely bladder.
• Administer 2 µg of desmopressin intravenously, intramuscularly, or subcutaneously, or 5 µg intranasally, or 0.2 mg desmopressin tablets per os.
• The patient is allowed to eat and drink (the amount of liquid drunk should not exceed the amount of urine excreted in the dehydration phase).
• After 2 and 4 hours, collect urine for determination of volume and osmolality.
• The next morning, draw blood to determine the sodium level and osmolality, collect urine to determine the volume and osmolality.

In the majority of patients, the functional state of the thirst center is completely preserved, and therefore the normal sodium level and normal blood osmolality in these patients are maintained by fluid intake adequate to losses. Biochemical changes become apparent only when the patient's access to water is limited and in the pathology of the thirst center. Thus, the purpose of conducting a test with a dry diet or with fluid restriction is to achieve physiological stimulation of vasopressin secretion to increase blood osmolality, i.e., dehydration, and thereby differentiate primary polydipsia and ND. In ND, despite severe dehydration, urine osmolality does not exceed blood osmolality, i.e. 300 mOsm/kg.

When collecting an anamnesis, it is necessary to ask the patient how long he can not drink, whether he must get up at night to drink, whether he can not drink if he is passionate about something (hobby, theater, cinema, walking, meeting friends). This will allow you to approximately determine the duration of the test with a dry diet, as well as to suspect the presence of a psychogenic genesis of polydipsia. The test should be carried out in specialized institutions where it is possible to ensure proper monitoring of the patient and quickly determine the osmolality and sodium content in the blood. In case of suspicion of the presence of primary polydipsia in a stable condition of the patient, it is possible to conduct a test with a dry diet on an outpatient basis. This allows you to limit yourself to only determining the osmolality of urine, to avoid stress for the patient associated with hospitalization, multiple blood sampling, etc.

Carrying out a test with a dry diet on an outpatient basis. The test is carried out only in patients in a stable condition, with suspected polydipsia and urine output up to 6-8 l / day.

The patient should be asked to completely refrain from taking liquids for as long as possible. It is most convenient to stop fluid intake a few hours before bedtime and during a night's sleep. The goal is to obtain the most concentrated (last) portion of urine. The patient himself stops the test, guided by his well-being. Storage of urine before analysis can be carried out in a closed form in the refrigerator.

An indicator exceeding 650 mOsm/kg makes it possible to exclude any genesis of ND.

After the end of the dehydration phase, in case of confirmation of the presence of ND, a desmopressin test is performed to separate the central and nephrogenic types of diseases of the ND group, taking into account the above protocol of the classical test. An increase in urine concentration of more than 50% indicates central ND, and less than 50% indicates nephrogenic ND. With the introduction of desmopressin to a patient with psychogenic polydipsia after the phase of dehydration, the increase in urine osmolality, as a rule, does not exceed 10%, since with chronic consumption of large volumes of fluid, salts are washed out from the renal interstitium, which can manifest itself in a decrease in the concentration ability of the kidneys. In the diagnosis of psychogenic polydipsia, determination of the level of uric acid in the blood can help: with polydipsia, it is usually less than 5 mmol / l, and with ND it is higher, since a violation of the action of vasopressin on the kidneys leads to a violation of the excretion of uric acid. Determination of low blood osmolality and sodium concentration in it after the administration of desmopressin testifies in favor of the diagnosis of psychogenic polydipsia, since the dose of the drug used in the test is physiological and in the central type of the disease it should completely stop thirst and polyuria, and in nephrogenic this dose practically does not change the initial state patient. Criteria for the differential diagnosis of ND are summarized in .

Despite the fact that ND is a consequence of vasopressin deficiency, its level is rarely measured in the diagnosis of this disease due to the complex technical extraction of vasopressin from the blood, the high cost, and the relatively low information content of the method. Its definition is important only for identifying particular forms of the disease (both central and nephrogenic).

Accurate diagnosis of the disease allows not only to direct further diagnostic search in the right direction, to identify serious concomitant diseases in time, to prescribe effective therapy but also to avoid the complications associated with the misuse of desmopressin.

Among instrumental methods research uses X-ray of the skull, CT scan(CT) and magnetic resonance imaging (MRI) of the brain. Moreover, MRI is the most specific of them, since normally the neurohypophysis on T1-weighted images is visualized as a characteristic crescent-shaped bright spot, which is associated with the vasopressin vesicles contained in it (Fig. 2). With ND central genesis the neurohypophysis is not visualized or its glow is dimmer. It should be noted that the absence of luminescence in this area can also be observed in conditions associated with the constant secretion of vasopressin, for example, in decompensated diabetes mellitus. CT or MRI is necessary to exclude organic causes of the disease, which account for approximately 40% of cases of central ND. This circumstance makes it possible to attribute ND to markers of hypothalamic-pituitary diseases. About 5% of cases are familial, and in more than 40% of patients the etiology cannot be identified (idiopathic variant).

It is assumed that the idiopathic variant of ND is associated with the subclinical growth of tumors of the hypothalamic-pituitary region (invisible with modern imaging techniques due to their small size), the subclinical course of infectious processes in the sella turcica with subsequent sclerosis and compression of the pituitary stalk, as well as autoimmune damage to the structures of the pituitary gland. and the hypothalamus involved in the synthesis and secretion of vasopressin. The first circumstance necessitates a more careful approach to the management of such patients in order to detect the tumor as early as possible. early dates. Dynamic MRI of the brain is recommended with increasing intervals between studies, provided that there are no pathological changes. For example, after 6 months, then after 1, 3 and 5 years.

Congenital nephrogenic ND is treated with thiazide diuretics and non-steroidal anti-inflammatory drugs. When acquired, the concomitant disease is also treated.

With psychogenic polydipsia, after explaining to the patient the cause of his illness, in some cases, “recovery” occurs, although in some patients both psychotherapy and the use of psychotropic drugs may be ineffective.

ND in pregnant women is characterized by manifestations of both central and nephrogenic variants of the disease. Its cause is the destruction of endogenous vasopressin by active enzymes of the placenta - vasopressinase. The level of vasopressin in the blood of patients is reduced. Polyuria usually begins in the third trimester, and spontaneously disappears after childbirth. Polyuria does not resolve with exogenous vasopressin but is treatable with desmopressin.

The history of the treatment of central ND dates back to 1912, with the first application of an extract from the posterior pituitary gland. In 1954, Vincent de Vigno described the structure and synthesized vasopressin, for which he was awarded Nobel Prize. Synthetic vasopressin preparations had the same disadvantage as endogenous vasopressin - very low efficacy and duration of action, frequent side effects when administered intranasally. Vasopressin tannate (pitressin), the maximum duration of which was 5-6 days, was considered the most effective of the drugs at that time. The reason for the limitation of its use was the pain of intramuscular injections of the drug, the development of abscesses at the injection site. The turning point was the appearance in 1974 of desmopressin, a synthetic analogue of natural vasopressin, devoid of vasoconstrictive activity and having a more pronounced antidiuretic effect. For more than 30 years, intranasal desmopressin (adiuretin) has been used as a replacement therapy for central ND, the production of which has now been discontinued. Today, the only drug for the treatment of central ND in Russia is the tablet form of desmopressin, the drug minirin.

Desmopressin (minirin) selectively activates only V 2 -receptors of vasopressin, the main cells of the collecting ducts of the kidney. V 1 -mediated action of desmopressin is minimal, which does not lead to an increase in blood pressure, a spasmodic effect on smooth muscle organs, such as the uterus and intestines. These changes in activity are due to disturbances in the structure of the vasopressin molecule - the absence of an amino group in position 1 and the replacement of L- by D-arginine in position 8. Desmopressin is used only for the treatment of central ND and nocturnal enuresis, the pathogenesis of which is a violation of the rhythm of the nocturnal increase in vasopressin secretion, and ineffective in cases of polyuria caused by kidney disease, nephrogenic ND, psychogenic polydipsia.

Despite the fact that the bioavailability of the oral form of desmopressin, compared with intranasal, is low and ranges from 1 to 5%, it is sufficient to cause an antidiuretic effect lasting from 7 to 12 hours. oral form on an empty stomach 30-40 minutes before or 2 hours after a meal. After oral administration, the antidiuretic effect of the drug occurs within 15-30 minutes.

The initial dose for adults and children is 0.1 mg of desmopressin 3 times a day. The dose is then adjusted according to the patient's response. According to the results of clinical experience, the daily dose varies from 0.2 to 1.2 mg of desmopressin. It is noted that the lowest need for the drug - 0.1-0.2 mg / day - is typical for patients with postoperative and traumatic genesis of ND or due to the presence of a volumetric brain lesion, and a higher need - up to 1.2-1.6 mg /day — for patients with idiopathic genesis of the disease. Moreover, the fact that some idiopathic variants of central ND are compensated only when taking relatively high doses of the drug, divided into 5-6 doses per day under the tongue, has not yet been explained.

In severe cases of the disease, for example, in violation of the regulation of thirst, Special attention when taking the drug, you should pay attention to adequate fluid intake in order to prevent water intoxication and hyponatremia. A significant decrease in plasma osmolality can lead to seizures. The risk groups for the development of complications of therapy are young children and elderly patients.

No controlled studies have been conducted on the use of desmopressin in pregnant women. Currently, more than 56 cases of the use of desmopressin in pregnant women are known, without harm to the patient and the fetus. In therapeutic doses, desmopressin does not pass through the placental barrier. Reproductive studies in rats and rabbits showed no changes in fetuses while taking the drug.

In conclusion, we emphasize once again the high importance of determining the osmolality of blood and urine in the differential diagnosis of polyuria-polydipsia syndrome against the background of the use of a complex of diagnostic methods, including dehydration and desmopressin tests, note the advantages of MRI over other methods of neuroimaging, and recall that desmopressin is a highly effective drug for the treatment ND of central origin.

Literature

L. K. Dzeranova, Candidate of Medical Sciences
E. A. Pigarova
ENTS RAMS, Moscow

Diabetes insipidus or diabetes insipidus- a disease in which, due to a lack of vasopressin (antidiuretic hormone), there is a strong thirst, and the kidneys excrete a large amount of low-concentration urine.

This rare disease is equally common in women, men and children. However, young people from 18 to 25 years old are most prone to it.

Anatomy and physiology of the kidneys

The structure of the kidney

In the kidney, the renal tissue and the pelvicalyceal system are conditionally distinguished directly.

kidney tissue responsible for filtering blood to form urine, and pelvicalyceal system- for the accumulation and excretion of the resulting urine.

There are two substances (layers) in the kidney tissue: cortical (located closer to the surface of the kidney) and cerebral (located medially from the cortical). They contain a large number of closely interconnected tiny blood vessels and urinary tubules. These are the structural functional units of the kidney - nephrons(there are about one million of them in each kidney).

Each nephron begins from the renal corpuscle(Malpighi-Shumlyansky), which is a vascular glomerulus (intertwined accumulation of tiny capillaries), surrounded by a spherical hollow structure (Shumlyansky-Bowman's capsule).

The structure of the glomerulus

The vessels of the glomerulus originate from the renal artery. At first, having reached the renal tissue, it decreases in diameter and branches, forming bringing vessel(afferent arteriole). Further, the afferent vessel flows into the capsule and branches in it into the smallest vessels (actually the glomerulus), from which the efferent vessel(efferent arteriole).

It is noteworthy that the walls of the vessels of the glomerulus are semi-permeable (have "windows"). This provides filtration of water and some solutes in the blood (toxins, bilirubin, glucose, and others).

In addition, in the walls of the afferent and efferent vessels there is juxtaglomerular apparatus of the kidney where renin is produced.

It consists of two sheets (outer and inner). Between them there is a slit-like space (cavity), into which the liquid part of the blood from the glomerulus penetrates along with some substances dissolved in it.

In addition, a system of convoluted tubes originates from the capsule. Initially, the urinary tubules of the nephron are formed from the inner leaf of the capsule, then they flow into the collecting ducts, which are connected to each other and open into the renal calyces.

This is the structure of the nephron, in which urine is formed.

Physiology of the kidney

In addition, the kidney is involved in the exchange of potassium and sodium ions, the synthesis of red blood cells and blood coagulation, the regulation of blood pressure and acid-base balance, metabolism of fats , proteins and carbohydrates .

However, in order to understand how all these processes are carried out, it is necessary to “arm yourself” with some knowledge about the work of the kidney and the formation of urine.

The process of urine formation consists of three stages:

• Glomerular filtration(ultrafiltration) occurs in the glomeruli of the renal corpuscles: through the "windows" in their wall, the liquid part of the blood (plasma) with certain substances dissolved in it is filtered. Then it enters the lumen of the Shumlyansky-Bowman capsule


• Reverse suction(resorption) occurs in the urinary tubules of the nephron. During this process, water is reabsorbed and useful material that should not be excreted from the body. Whereas the substances to be removed, on the contrary, accumulate.


• Secretion. Some substances that are to be excreted from the body enter the urine already in the renal tubules.

How does urination occur?

This process starts with arterial blood enters the vascular glomerulus, in which its current slows down somewhat. This is due to high pressure in the renal artery and an increase in the capacity of the vascular bed, as well as a difference in the diameter of the vessels: the afferent vessel is somewhat wider (by 20-30%) than the efferent one.

Due to this, the liquid part of the blood, together with the substances dissolved in it, begins to exit through the "windows" into the lumen of the capsule. At the same time, the walls of the capillaries of the glomerulus normally retain formed elements and some blood proteins, as well as large molecules, the size of which is more than 65 kDa. However, they let in toxins, glucose, amino acids and some other substances, including useful ones. This is how primary urine is formed.

Further, the primary urine enters the urinary tubules, in which water and useful substances are reabsorbed from it: amino acids, glucose, fats, vitamins, electrolytes, and others. At the same time, substances to be excreted (creatinine, uric acid, medicines, potassium and hydrogen ions), on the contrary, accumulate. Thus, the primary urine turns into secondary urine, which enters the collecting ducts, then into the pyelocaliceal system of the kidney, then into the ureter and bladder.

It is noteworthy that about 150-180 liters of primary urine is formed within 24 hours, while secondary urine is from 0.5 to 2.0 liters.

How is kidney function regulated?

This is a rather complex process in which vasopressin (antidiuretic hormone) and the renin-angiotensin system (RAS) are most actively involved.

Renin-angiotensin system

Main functions

• regulation of vascular tone and blood pressure
• increased sodium reabsorption
• stimulate the production of vasopressin
• increased blood flow to the kidneys

In response to stimulus nervous system, a decrease in the blood supply to the renal tissue or a decrease in the level of sodium in the blood, renin begins to be produced in the juxtaglomerular apparatus of the kidney. In turn, renin promotes the conversion of one of the plasma proteins into angiotensin II. And already, in fact, angiotensin II determines all the functions of the renin-angiotensin system.

Vasopressin

This is a hormone that is synthesized (produced) in the hypothalamus (located in front of the legs of the brain), then enters the pituitary gland (located at the bottom of the Turkish saddle), from where it is released into the blood.

The synthesis of vasopressin is mainly regulated by sodium: with an increase in its concentration in the blood, the production of the hormone increases, and with a decrease, it decreases.

The synthesis of the hormone is also enhanced in stressful situations, a decrease in fluid in the body, or the ingestion of nicotine.

In addition, the production of vasopressin decreases with an increase in blood pressure, inhibition of the renin-angiotensin system, a decrease in body temperature, alcohol intake and certain medications (for example, Clonidine, Haloperidol, glucocorticoids).

How does vasopressin affect kidney function?

The main task of vasopressin- to promote the reabsorption of water (resorption) in the kidneys, reducing the amount of urine formation.

Mechanism of action

With the blood flow, the hormone reaches the renal tubules, where it attaches to special areas (receptors), leading to an increase in their permeability (the appearance of “windows”) for water molecules. Due to this, water is reabsorbed and urine is concentrated.

In addition to urine resorption, vasopressin regulates several other processes in the body.

Functions of vasopressin:

• Promotes capillary contraction circulatory system , including glomerular capillaries.
• Supports blood pressure.
• Influences the secretion of adrenocorticotropic hormone(synthesized in the pituitary gland), which regulates the production of adrenal hormones.
• Enhances the release of thyroid-stimulating hormone(synthesized in the pituitary gland), which stimulates the production of thyroxine thyroid gland.
• Improves blood clotting due to the fact that it causes aggregation (clumping) of platelets and increases the release of certain blood clotting factors.
• Reduces the volume of intracellular and intravascular fluid.
• Regulates the osmolarity of body fluids(total concentration of dissolved particles in 1 liter): blood, urine.
• Stimulates the renin-angiotensin system.

Types of diabetes insipidus

• Central diabetes insipidus. It is formed with insufficient production of vasopressin in the hypothalamus or a violation of its release from the pituitary gland into the blood.


• Renal (nephrogenic) diabetes insipidus. In this form, the level of vasopressin is normal, but the kidney tissue does not respond to it.

In addition, sometimes the so-called psychogenic polydipsia (increased thirst) in response to stress.

Also diabetes insipidus can develop during pregnancy. The reason is the destruction of vasopressin by placental enzymes. As a rule, the symptoms of the disease appear in the third trimester of pregnancy, but after childbirth they disappear on their own.

Causes of diabetes insipidus

Causes of central diabetes insipidus

Brain damage:

• pituitary or hypothalamic tumors
• complications after brain surgery
• sometimes develops after infections: SARS, influenza and others
• encephalitis (inflammation of the brain)
• skull and brain injuries
• impaired blood supply to the hypothalamus or pituitary gland
• metastases malignant neoplasms to the brain, which affect the functioning of the pituitary or hypothalamus
• ailment may be congenital

• disease may be congenital(most common cause)
• ailment is sometimes caused by certain conditions or diseases in which the medulla of the kidney or the urinary tubules of the nephron is damaged.
• anemia of a rare form(sickle cell)
• polycystic(multiple cysts) or amyloidosis (deposition of amyloid in tissue) of the kidneys
• chronic kidney failure
• an increase in potassium or a decrease in calcium in the blood
• taking medications, which act toxically on the kidney tissue (for example, Lithium, Amphotericin B, Demeclocilin)
• sometimes occurs in debilitated patients or in old age

However, in 30% of cases, the cause of diabetes insipidus remains unclear. Since all the studies conducted do not reveal any disease or factor that could lead to the development of this disease.

Symptoms of diabetes insipidus

However, the severity of the manifestations of the disease depends on two points:

• how responsive to vasopressin are nephron tubule receptors
• degree of deficiency of antidiuretic hormone, or its absence

Most first signs of illness- strong painful thirst (polydipsia) and frequent profuse urination (polyuria), which disturb patients even at night.

From 3 to 15 liters of urine can be excreted per day, and sometimes its amount reaches up to 20 liters per day. Therefore, the patient is tormented by intense thirst.

In the future, as the disease progresses, the following symptoms join:

• There are signs of dehydration (lack of water in the body): dry skin and mucous membranes (dry mouth), weight loss.
• Due to the consumption of a large amount of liquid, the stomach is stretched, and sometimes even lowered.
• Due to the lack of water in the body, the production of digestive enzymes in the stomach and intestines is disrupted. Therefore, the patient's appetite decreases, gastritis or colitis develops, and there is a tendency to constipation.
• Due to the release of urine in large volumes, the bladder is stretched.
• Since there is not enough water in the body, sweating decreases.
• Blood pressure often drops and increases heartbeat.
• Sometimes there is unexplained nausea and vomiting.
• The patient gets tired quickly.
• Body temperature may rise.
• Sometimes there is bedwetting (enuresis).

• insomnia and headaches
• emotional lability (sometimes even psychoses develop) and irritability
• decrease in mental activity

Symptoms of diabetes insipidus in men

Symptoms of diabetes insipidus in women

Diabetes insipidus in children

However, sometimes the signs of the disease are not pronounced: the child does not eat well and gains weight, suffers from frequent vomiting when eating, he has constipation and bedwetting, complains of pain in the joints. In this case, the diagnosis is made late, when the child is already lagging behind in physical and mental development.

Whereas in newborns and infants (especially with the renal type), the manifestations of the disease are bright and differ from those in adults.

Symptoms of diabetes insipidus in children under one year old:

• the baby prefers water to mother's milk, but sometimes there is no thirst
• baby urinate frequently and in large amounts
• there is anxiety
• body weight is quickly lost (the child literally loses weight “before our eyes”)
• tissue turgor decreases (if the skin is folded and released, it slowly returns to its normal position)
• no or few tears
• frequent vomiting occurs
• heart rate rises
• body temperature can either rise or fall quickly

Diagnosis of diabetes insipidus

• What is the amount of fluid drunk and urine excreted by the patient. If its volume is more than 3 liters, this indicates in favor of diabetes insipidus.

• Whether there is bedwetting and frequent copious urination at night (nocturia), and whether the patient drinks water at night. If yes, then the volume of fluids drunk and urine excreted must be specified.

• Whether the raised or increased thirst and with the psychological reason is connected. If it is absent when the patient is doing what he loves, walking or visiting, then most likely he has psychogenic polydipsia.

• Are there any diseases(tumors, endocrine disorders, and others), which can give impetus to the development of diabetes insipidus.

• the osmolarity and relative density of urine is determined (characterizes the filtering function of the kidneys), as well as the osmolarity of blood serum
• computed tomography or magnetic nuclear resonance of the brain
• X-ray of the Turkish saddle and skull
• echoencephalography
• excretory urography
• Ultrasound of the kidneys
• the level of sodium, calcium, potassium, nitrogen, urea, glucose (sugar) is determined in the blood serum
• Zimnitsky test

Based on laboratory data diagnostic criteria diabetes insipidus are the following indicators:

• increase in blood sodium (more than 155 meq / l)
• increased osmolarity of blood plasma (more than 290 mosm/kg)
• decrease in urine osmolarity (less than 100-200 mosm / kg)
• low relative density of urine (less than 1010)

It is noteworthy that this test allows not only to make a diagnosis, but also to determine the type of diabetes insipidus.

Fluid Restriction Test Procedure

The patient then stops taking liquids (water, juices, tea) for as long as possible.

The test is terminated if the patient:

• weight loss is 3-5%
• an unbearable thirst
• the general condition worsens sharply (nausea, vomiting, headache appear, heart contractions become more frequent)
• sodium and blood osmolarity levels are higher than normal

An increase in blood osmolarity and sodium in the blood, as well as a decrease in body weight by 3-5%, testifies in favor of central diabetes insipidus.

Whereas a decrease in the amount of urine excreted and the absence of weight loss, as well as normal performance serum sodium speak of renal diabetes insipidus.

If diabetes insipidus is confirmed as a result of this test, a minirin test is performed for further diagnosis.

The methodology for conducting the minirin test

What do the test results say?

With central diabetes insipidus, the amount of urine excreted decreases, and its relative density increases. Whereas in renal diabetes insipidus, these indicators practically do not change.

It is noteworthy that for the diagnosis of the disease, the level of vasopressin in the blood is not determined, since the technique is too expensive and difficult to perform.

Diabetes insipidus: differential diagnosis

Treatment of diabetes insipidus

Treatment of central diabetes insipidus

• If the volume of urine is less than four liters per day, drugs are not prescribed. It is only recommended to replenish the lost fluid and follow a diet.


• When the amount of urine is more than four liters per day, substances are prescribed that act like vasopressin (replacement therapy) or stimulate its production (if the synthesis of the hormone is partially preserved).

For more than 30 years, Desmopressin (Adiuretin) intranasally (administration of the drug into the nasal passages) has been used as a replacement therapy. However, it has now been discontinued.

Therefore, at present, the only drug that is prescribed as a replacement for vasopressin - Minirin(tablet form of Desmopressin).

The dose of Minirin, which suppresses the symptoms of the disease, is not affected by the age or weight of the patient. Since everything depends on the degree of deficiency of the antidiuretic hormone or its total absence. Therefore, the dosage of Minirin is always selected individually during the first three to four days of its administration. Treatment begins with minimal doses, which are increased if necessary. The drug is taken three times a day.

For drugs that stimulate the production of vasopressin treat Chlorpropamide (particularly effective in combination of diabetes and diabetes insipidus), Carbamazepine and Miskleron.

Treatment of renal diabetes insipidus.

Medication treatment

The appointment of medicinal substances is practiced, which, paradoxically, reduce the amount of urine - thiazide diuretics (diuretics): Hydrochlorothiazide, Indapamide, Triampur. Their use is based on the fact that they prevent the reabsorption of chlorine in the urinary tubules of the nephron. As a result, the sodium content in the blood decreases somewhat, and the reverse absorption of water increases.

Anti-inflammatory drugs (ibuprofen, indomethacin, and aspirin) are sometimes prescribed as an adjunct to treatment. Their use is based on the fact that they reduce the flow of certain substances into the urinary tubules of the nephron, thereby reducing the volume of urine and increasing its osmolality.

However, successful treatment of diabetes insipidus is impossible without following certain nutritional rules.

diabetes insipidus: diet

Therefore, first of all limited salt intake(no more than 5-6 grams per day), and it is handed out, and food is prepared without adding it.

Useful dried fruits because they contain potassium, which enhances the production of endogenous (internal) vasopressin.

Besides, must give up sweets so as not to increase thirst. It is also recommended to refrain from drinking alcohol.

The diet includes a sufficient amount of fresh vegetables, berries and fruits, milk and lactic acid products. In addition, juices, compotes, fruit drinks are useful.

It is very important that phosphorus enters the body(it is necessary for the normal functioning of the brain), so it is recommended to consume low-fat varieties of fish, seafood and fish oil.

Besides, healthy lean meats and eggs(yolk). However, it must be remembered that in diabetes insipidus, one should still restrict proteins, so as not to increase the burden on the kidneys. Whereas fats (for example, butter and vegetable oil), as well as carbohydrates (potatoes, pasta and others) must present in the diet in sufficient quantities.

It is advisable to eat fractionally: 5-6 times a day.

Diabetes insipidus: treatment with folk remedies

To reduce thirst:

• Take 60 grams of chopped burdock root, place in a thermos and pour one liter of boiling water. Leave overnight and express in the morning. Take two-thirds of a glass three times a day.


• Take 20 grams of elderberry flowers, pour a glass of boiling water and leave for an hour. Then strain and add honey to taste. Take one glass three times a day.


• Take 5 grams (one teaspoon) of crushed young walnut leaves and pour a glass of boiling water over it. Let it brew and take it like tea.

Consume one teaspoon of pea flour per day, which is rich in glutamic acid.

To improve sleep and reduce irritability sedation fees apply:

• Take in equal parts crushed valerian roots, hop cones, motherwort herbs, rose hips, mint leaves and mix everything thoroughly. From the resulting mixture, take one tablespoon of raw materials and pour a glass of boiling water. Let it brew for an hour and then strain. Take 1/3 cup at night for insomnia or increased nervous excitement.


• Take in equal parts crushed valerian roots, fennel and cumin fruits, motherwort herbs and mix everything thoroughly. Then, from the resulting mixture, take two tablespoons of raw materials and pour 400 ml of boiling water, let it brew until cool and strain. Take half a glass for irritability or nervous excitement.