What is diabetes insipidus - causes and treatment. Diabetes insipidus Diabetes insipidus relative density

The date: 29.06.2020

Publication date October 11, 2019Updated October 11, 2019

Definition of illness. Causes of the disease

diabetes insipidus is a disease in which the kidneys stop concentrating fluid (absorbing it and returning it back to the bloodstream). The disease is accompanied by the release of a large volume of unconcentrated urine, as well as a strong feeling of thirst.

This type of diabetes is associated with the hormone vasopressin (antidiuretic hormone), which regulates the ability of the kidneys to concentrate urine. It is synthesized by the nerve cells of the anterior hypothalamus and released into the blood by the neurohypophysis - the posterior pituitary gland, one of the main endocrine glands.

Reduced production of vasopressin (with central diabetes insipidus) or insensitivity of the kidney receptors to it (with nephrogenic diabetes insipidus) underlie the disease.

Central diabetes insipidus occurs with an average frequency of 1:25,000. The disease can be detected at any age, but more often develops in the range from 20 to 40 years old, affects men and women equally often.

The cause of the disease is not always possible to find out exactly. hereditary forms Central diabetes insipidus occurs in no more than 30% of cases. The remaining cases are acquired diabetes insipidus. The following possible causes are identified acquired central diabetes insipidus:

Causes nephrogenic diabetes insipidus:

hereditary (genetic), more common in men;
kidney failure.

If the cause of diabetes insipidus cannot be determined, they speak of idiopathic diabetes insipidus.

Diabetes insipidus develops rapidly, the first time it manifests itself spontaneously against the background of relative or complete health. There are no early symptoms that herald the imminent onset of the disease.

Congenital forms of diabetes insipidus are rare. In children under 1 year of age, diagnosis is difficult, since early age is generally characterized by immaturity of the kidneys.

If you experience similar symptoms, consult your doctor. Do not self-medicate - it is dangerous for your health!

Symptoms of diabetes insipidus

This disease is based on polydipsia syndrome(unnatural, unquenchable thirst) and polyuria(formation of urine in large quantities). It manifests itself with the following symptoms:

thirst, forcing a person to drink a huge amount of liquid, up to 18 liters per day. Patients prefer simple cold (ice) water. The patient does not drink 1-2 glasses of water at a time;
urine output more than 3 liters per day;
frequent urination with large portions of urine (up to 2.5 liters) 10-15 times a day;
dry skin and mucous membranes;
low blood pressure;
heart palpitations;
general weakness;
stool retention, disruption of the gastrointestinal tract (associated with distension of the stomach with large volumes of water).

Normally, the secretion of vasopressin increases sharply at night, due to which the concentrating function of the kidneys also increases, urination decreases, and the person does not get up at night to urinate. But the symptoms of diabetes insipidus do not depend on the time of day: thirst and frequent urination are as pronounced as in the daytime.

Due to constant thirst and frequent urination, sleep, the usual way of life are disturbed, its quality worsens. At moderate and severe A person with diabetes insipidus cannot be away from home for a long time, cannot sleep, he is worried about constant fatigue. At mild forms the patient gets used to drinking and urinating frequently, so he does not complain.

In diabetes insipidus that occurs after neurosurgical interventions or head trauma, may join symptoms of deficiency of other pituitary hormones:

thyroid-stimulating hormone (clinic: dry skin, severe weakness, swelling, drowsiness, lethargy);
adrenocorticotropic hormone (manifestations of adrenal insufficiency);
gonadotropins (disorders of reproductive function).

There is an extremely rare genetic disease - wolfram syndrome(DIDMOAD - diabetes insipidus, diabetes mellitus, optic atrophy, deafness), transmitted autosomal recessively. It is a combination of type 1 diabetes mellitus, central diabetes insipidus, deafness (not in all patients), and optic nerve atrophy. Accordingly, the symptoms of this condition will include symptoms of diabetes and diabetes insipidus, deafness and blindness. Often such patients suffer from mental disorders.

The pathogenesis of diabetes insipidus

Secretion of vasopressin directly depends on the osmolarity of all dissolved plasma particles (total concentration of sodium, glucose, potassium, urea), circulating blood volume and blood pressure. Fluctuations in the osmolar composition of the blood by more than 1% of the initial one are clearly captured by osmoreceptors located in the hypothalamus. Normally, an increase in blood osmolarity (an increase in sodium levels) stimulates the release of vasopressin into the bloodstream to retain fluid in the body. The decrease in plasma osmolarity caused by excessive fluid intake inhibits the secretion of vasopressin.

Under physiological conditions, plasma osmolarity is in the range of 282–295 mosm/L. The main physiological effect of vasopressin is to stimulate the reabsorption of water in the collecting ducts of the kidneys. In tubular cells, vasopressin acts through the so-called V2 receptors: these receptors normally respond to the effects of vasopressin by incorporating water channels (aquaporins) into the membrane of tubular cells, due to which water flows back (reabsorption) through these channels back into the bloodstream. As a result, urine is concentrated.

The absence or decrease in the effect of vasopressin on the V2 receptors of the kidneys is the basis for the pathogenesis of diabetes insipidus: water reabsorption does not occur, the body loses too much water through very diluted urine, the blood concentrates, the level of sodium in the blood rises, a feeling of thirst appears through the effect on osmoreceptors, causing a person to drink more water.

Classification and stages of development of diabetes insipidus

There are three main types of diabetes insipidus:

Functional diabetes insipidus occurs in children under one year old, due to the immaturity of the concentration mechanism of the kidneys.

Diabetes insipidus must be distinguished from primary polydipsia - pathological thirst or compulsive desire to drink (psychogenic polydipsia), which suppress the physiological secretion of vasopressin, resulting in symptoms of diabetes insipidus. With artificial dehydration of the body, the production of vasopressin is restored.

According to the severity of the flow, several forms are distinguished:

mild (allocation of up to 6-8 liters of urine per day);
medium (allocation of 8-14 liters of urine per day);
severe (excretion of more than 14 liters of urine per day).

Central (pituitary) diabetes insipidus due to acute infection or injury usually appears immediately after exposure to the causative factor or after 2 to 4 weeks. Chronic infectious diseases cause diabetes insipidus, usually after 1–2 years.

Complications of diabetes insipidus

A number of patients with diabetes insipidus and a violation of the feeling of thirst, in the absence of timely fluid intake, may develop dehydration. Considering that the brain is almost 80% water, this condition leads to a decrease in its volume in the skull, which causes bleeding in the tissue and membranes of the brain. All this has a very negative effect on the function of the central nervous system, stupor, convulsions and coma can develop.

Fortunately, in patients with preserved thirst perception mechanisms, these life-threatening manifestations of hypernatremia (increased blood sodium levels) usually do not occur, and the absence of vasopressin itself is not dangerous if thirst is quenched in time. Cases are considered dangerous when, due to age-related changes or impaired consciousness, the patient cannot respond to thirst in time.

With this pathology, complications associated with excessive fluid intake do not develop, since due to the peculiarities of the pathogenesis of the disease, water practically does not linger in the body.

Diagnosis of diabetes insipidus

Diagnosis of diabetes insipidus is carried out in several stages:

I stage. The doctor collects complaints and anamnesis. If they correspond to the clinic of diabetes insipidus, a minimal examination is prescribed, including: calculation of the excreted fluid per day, determination of the specific gravity of all portions of urine per day (Zimnitsky test), determination of urine osmolarity. The reason for suspecting the presence of diabetes insipidus is confirmation of hypotonic polyuria:

constant urine output of more than 3 liters per day (or more than 40 ml per 1 kg of body weight);
low specific gravity of urine according to Zimnitsky.

II stage. After confirmation of hypotonic polyuria, exceptionits other reasons:

elevated sugar level ();
elevated calcium levels (hyperparathyroidism);
kidney failure.

III stage. After excluding the above conditions, the osmolarity of blood and urine is determined: blood hyperosmolarity over 300 mOsm/kg in combination with low osmolarity urine less than 300 mOsm/kg corresponds to the diagnosis of diabetes insipidus.

IV stage. Necessary in doubtful cases requiring a differential diagnosis: performed dry eating test- study of changes in the osmolarity of the patient's plasma and urine against the background of his restriction in the liquid (it is allowed to eat solid food). It is carried out in stationary conditions to exclude primary polydipsia (not associated with diabetes insipidus). With diabetes insipidus, dehydration quickly sets in, confirmed by a sharp increase in blood osmolarity. Then carried out desmopressin test(a synthetic analogue of vasopressin): when the drug is introduced into the body, after 2-4 hours, a sharp improvement in well-being and an increase in urine concentration occurs.

In addition to laboratory diagnostics, contrast enhancement is required to exclude volumetric formations of the hypothalamic-pituitary region, Ultrasound of the kidneys to exclude structural pathology of the kidneys, which can lead to nephrogenic diabetes insipidus. In some cases, a psychiatrist's consultation is needed to exclude primary polydipsia - compulsive (obsessive) drinking of large amounts of water associated with mental disorders.

Treatment of diabetes insipidus

Treatment for diabetes insipidus will depend on the underlying cause of the disease.

Treatment central diabetes insipidus carried out by a synthetic analogue of vasopressin - desmopressin. Desmopressin has a more pronounced antidiuretic (antidiuretic) effect and a longer duration of action than natural vasopressin. The main goal of treatment with desmopressin is to select the minimum effective dose of the drug to eliminate excessive thirst and polyuria. Dose selection is carried out individually, taking into account clinical manifestations - a decrease in episodes of thirst and polyuria. There are the following forms of drugs for the treatment of patients with diabetes insipidus: nasal spray, nasal drops, oral forms (for oral or resorption).

If there is a concomitant formation of the pituitary or hypothalamus (for example, a tumor) that caused central diabetes insipidus, this pathology is treated.

To prevent stretching and further dysfunction of the bladder, all patients with severe polyuria are recommended to frequent "double" urination - after urination, you must wait a few minutes, and then try again to empty the bladder completely.

At nephrogenic diabetes insipidus the intake of salt and protein foods is limited, sufficient water intake is recommended to prevent dehydration. May apply thiazide diuretics or non-steroidal anti-inflammatory drugs. Treatment of nephrogenic diabetes insipidus also involves treating the endocrine or kidney disease that causes this type of diabetes. A low-sodium diet combined with thiazide diuretics paradoxically leads to a reduction in polyuria. With free access to water, serious complications in a patient with this type of disease rarely develop.

During treatment primary polydipsia Fluid restriction is preferred, but in the case of psychogenic polydipsia, it may be difficult to follow this recommendation. Psychiatric disorders that may underlie the condition require appropriate therapy. In the case of psychogenic polydipsia, desmopressin preparations should not be used, this can lead to water intoxication. Patients with inadequate perception of the feeling of thirst (dipsogenic polydipsia) may be recommended to replace excessive fluid intake with sour candies and ice chips (exposure to sour or cold tongue receptors reduces the feeling of thirst).

Forecast. Prevention

Without treatment, diabetes insipidus does not pose an immediate threat to life if there is enough drinking water, but it can significantly reduce the quality of life, working capacity and adaptation in society.

Replacement therapy with desmopressin preparations can completely normalize the condition of patients with central diabetes insipidus. A cure for central diabetes insipidus is possible (and expected) when the known immediate cause is removed, such as a tumor compressing the pituitary gland or an infection. The doctor decides to stop drug treatment based on the objective condition of the patient, his complaints and laboratory tests.

Central diabetes insipidus is very difficult to prevent, so there is no specific prevention for it. Of particular importance is the recommendation to avoid traumatic brain injury as a possible cause of acquired pituitary diabetes insipidus.

The prognosis for acquired diabetes insipidus is determined by the underlying disease that led to damage to the pituitary or hypothalamus.

Treatment for diabetes insipidus is long-term. In cases of idiopathic, hereditary, or autoimmune diabetes insipidus, lifelong treatment is required.

Diabetes insipidus is a disease resulting from a lack of antidiuretic hormone (vasopressin) or a violation of the sensitivity of the kidney tissue to it. The main symptoms of the disease are excessive urination (which is why the condition is called "diabetes" and the word "sugar insipid" refers to the absence of problems with blood sugar in this disease) and intense thirst. Diabetes insipidus can be congenital or acquired, affecting both men and women. There are many causes for diabetes insipidus. Treatment of the disease consists in replacement therapy with a synthetic analogue of the hormone. In this article, you will learn basic information about diabetes insipidus.

Antidiuretic hormone is produced by cells of the hypothalamus, and then enters the pituitary gland through special fibers and accumulates there. The hypothalamus and pituitary gland are the constituent parts of the brain. From the pituitary gland, the hormone is released into the bloodstream, with the blood flow getting to the kidneys. Normally, antidiuretic hormone ensures the absorption of fluid in the kidneys back into the bloodstream. That is, not everything that has filtered through the renal barrier is excreted and is urine. Most of the fluid is reabsorbed back. In diabetes insipidus, everything that is filtered is excreted from the body. Liters and even tens of liters per day are obtained. Naturally, this process creates a strong thirst. A sick person is forced to drink a lot of liquid in order to somehow make up for its deficiency in the body. Endless urination and a constant need for fluid exhaust a person, so the term “diabetes insipidus” is synonymous with diabetes insipidus.

Diabetes insipidus is a fairly rare disease: its incidence is 2-3 cases per 100,000 population. According to statistics, the disease equally often affects the female and male sex. Diabetes insipidus can occur at any age. You can be born with it, you can get it in old age, but still the peak incidence falls on the second or third decade of life. The disease is multifactorial, that is, it has many causes. Let's dwell on this moment in more detail.

Causes of diabetes insipidus

Doctors divide all cases of diabetes insipidus into central and renal. The basis of such a classification is the causes of occurrence.

Central diabetes insipidus is associated with problems in the hypothalamus and pituitary gland in the brain (that is, as it were, "in the center"), where antidiuretic hormone is formed and accumulates; the renal one is due to the immunity of the excretory organs to the completely normal hormone vasopressin.

Central diabetes insipidus occurs as a result of the formation of an insufficient amount of antidiuretic hormone, a violation of its release, its blockade by antibodies. Such situations may arise when:

genetic disorders (defects in the genes responsible for the synthesis of vasopressin, skull defects in the form, for example, microcephaly, underdevelopment of certain parts of the brain);
neurosurgical operations (intervention can be carried out for any reason: traumatic brain injury, tumors and other reasons). There is anatomical damage to the structures of the hypothalamus or the fibers going from it to the pituitary gland. According to statistics, every 5th case of diabetes insipidus is the result of neurosurgical intervention. However, there are cases of transient (transient) diabetes insipidus after brain surgery, in such cases the disease goes away on its own at the end of the postoperative period;
irradiation of the brain in tumor diseases (the tissue of the hypothalamus and pituitary gland is very sensitive to x-rays);
(destruction of the hypothalamus, pituitary gland, swelling or compression of these areas);
tumors of the hypothalamic-pituitary region and the area of the Turkish saddle;
neuroinfections ( , );
vascular lesions of the hypothalamic-pituitary region (, aneurysm, vascular thrombosis and other conditions);
autoimmune diseases (antibodies are produced that damage those parts of the brain where the hormone is produced and accumulates, or block the hormone itself, rendering it inoperative). This situation is possible with sarcoidosis, tuberculosis, granulomatous lung diseases;
the use of Clonidine (Clonidine);
for no apparent reason. In such situations, one speaks of idiopathic diabetes insipidus. It accounts for about 10% of all cases of central diabetes insipidus and develops in childhood.

Sometimes diabetes insipidus appears during pregnancy, but after pregnancy, the symptoms may go away.

The renal form of the disease is much less common. It is associated with a violation of the integrity of nephrons (kidney cells) or a decrease in sensitivity to vasopressin. This is possible with:

renal failure;
mutations in the gene responsible for vasopressin receptors in the kidneys;
amyloidosis;
an increase in the concentration of calcium in the blood;
the use of drugs containing lithium (and some others that have a toxic effect on the kidney parenchyma).

Symptoms

In most cases, diabetes insipidus develops acutely. The main manifestations of the disease are the release of a large amount of urine (more than 3 liters per day) and intense thirst. In this case, excess urine is the primary symptom, and thirst is secondary. Sometimes the amount of urine per day can be 15 liters.

Urine in diabetes insipidus has its own characteristics:

low relative density (specific gravity) - less than 1005 (always, in any portion of urine, regardless of the amount of liquid drunk);
has no color, does not contain enough salts (compared to normal urine);
devoid of pathological impurities (for example, an increased content of leukocytes, the presence of erythrocytes).

A characteristic feature of diabetes insipidus is the excretion of urine during any time of the day, including at night. The constant urge to urinate makes it impossible to fall asleep, exhausting the patient. Sooner or later, this situation leads to nervous exhaustion of the body. Neurosis and depression develop.

Even if a person is not allowed to drink, urine will still form a lot, leading to dehydration. This phenomenon is based on a diagnostic test that confirms the presence of diabetes insipidus in a patient. This is the so-called dry food test. Within 8-12 hours, the patient is not given any liquid (including with food). At the same time, in the case of existing diabetes insipidus, urine continues to be excreted in large quantities, its density does not increase, osmolarity remains low, and weight is lost by more than 5% of the original.

The intake of excess urine leads to the expansion of the renal-pelvic system, ureters and even the bladder. Of course, this does not happen immediately, but with a certain experience of the disease.

Thirst in diabetes insipidus is a consequence of the loss of a huge amount of fluid in the urine. The body is trying to find ways to restore the contents of the bloodstream, and therefore thirst arises. I want to drink almost constantly. A person consumes liters of water. Due to such a water overload of the gastrointestinal tract, the stomach is stretched, the intestines are irritated, there are problems with digestion, constipation. At first, with diabetes insipidus, the fluid that comes with drinking compensates for losses in the urine, and the cardiovascular system does not suffer. However, over time, fluid deficiency still occurs, the blood flow becomes insufficient, the blood thickens. Then there are symptoms of dehydration. There is a pronounced general weakness, dizziness, headache, the heart rate increases, blood pressure drops, and collapse may develop.

Signs of a chronic lack of fluid in the body with long-term diabetes insipidus are dry and flabby skin, almost complete absence of sweat, and a small amount of saliva. Weight is constantly lost. Disturbs the feeling of nausea and occasional vomiting.

In women, the menstrual cycle is disturbed, in men, potency is weakened. Of course, all these changes occur in the absence of adequate treatment for diabetes insipidus.

Treatment

The main principle of the treatment of diabetes insipidus is substitution therapy, that is, replenishing the deficiency of the hormone vasopressin in the body by introducing it from the outside. For this purpose, a synthetic analogue of the antidiuretic hormone Desmopressin (Minirin, Nativa) is used. The drug has been used since 1974 and is effective in the treatment of central diabetes insipidus.

There are forms for subcutaneous, intravenous, intranasal (spray, nose drops) and oral (tablets) administration. The most commonly used spray, nose drops and tablets. Injectable forms are required only in severe cases or, for example, in the treatment of mentally ill people.

The use of a dosage form in the form of a spray or drops in the nose allows you to get by with much lower dosages of the drug. So, for the treatment of adults, 1 drop or 1 injection into the nose (5-10 mcg) is prescribed 1-2 times a day, and when using tablets, the dose is 0.1 mg 30-40 minutes before meals or after 2 hours after meals 2-3 times a day. On average, it is considered that 10 micrograms of the intranasal form is equivalent to 0.2 mg of the tablet form.

Another nuance of using drops or spray in the nose is a faster action. For colds or allergic diseases, when the nasal mucosa swells, and adequate absorption of the drug is impossible, a spray or drops can be applied to the oral mucosa (the dose is increased by 2 times).

The dose of the drug depends on how much antidiuretic hormone is produced in the patient, and how pronounced its deficiency is. If the deficiency of the hormone is, for example, 75% - this is one dose, if 100% (complete absence of the hormone) - another. The choice of therapy is carried out individually.

You can partially increase the synthesis and secretion of your own antidiuretic hormone with the help of Carbamazepine (600 mg per day), Chlorpropamide (250-500 mg per day), Clofibrate (75 mg per day). Daily doses of drugs are divided into several doses. The use of these funds is justified in partial diabetes insipidus.

Adequate replacement therapy of diabetes insipidus with Desmopressin allows a person to lead a normal life with few restrictions (this applies to diet and drink). In this case, full preservation of working capacity is possible.

Renal forms of diabetes insipidus do not have developed and proven treatment regimens. Attempts are being made to use Hypothiazid in high doses, non-steroidal anti-inflammatory drugs, but such treatment does not always give a positive result.

Patients with diabetes insipidus should follow a specific diet. It is necessary to limit the intake of proteins (to reduce the burden on the kidneys), increase the content of foods rich in fats and carbohydrates in the diet. The diet is set fractional: it is better to eat more often and in smaller portions to ensure the absorption of food.

Separately, it should be noted the water load. Without adequate fluid replacement, diabetes insipidus causes complications. But replenishing the loss of fluid with ordinary water is not recommended. For this purpose, it is necessary to use juices, fruit drinks, compotes, that is, drinks rich in minerals and trace elements. If necessary, the water-salt balance is restored with the help of intravenous infusions of saline solutions.

Thus, diabetes insipidus is the result of a deficiency of antidiuretic hormone in the human body for various reasons. However, modern medicine makes it possible to compensate for this deficiency with the help of replacement therapy with a synthetic analogue of the hormone. Competent therapy returns a sick person to the mainstream of a full life. This cannot be called a complete recovery in the literal sense of the word, however, in this case, the state of health is as close to normal as possible. And this is not enough.

Channel One, the program "Health" with Elena Malysheva on the topic "Diabetes insipidus: symptoms, diagnosis, treatment":

diabetes insipidus(diabetes insipidus) is a rare disorder in which the body cannot properly regulate fluids. This can lead to severe dehydration. People with diabetes insipidus tend to be very thirsty and pass much more urine than usual due to hormonal imbalances.

Epidemiology

There is not much data on epidemiology. However, this rare disease occurs in 1 in 3 out of 100,000 people, equally in women and men.

What is the difference between diabetes and diabetes insipidus?

Diabetes insipidus (ND) should not be confused with (DM), which is the result of a deficiency or resistance to diabetes, due to which the body cannot regulate the level of glucose (sugar) in the blood. ND is a completely different type of disease associated with the regulation of fluid in the body.

When the body's fluid regulation system is working properly, the kidneys filter the blood, excrete waste and excess fluids, which then become urine (urine).

Typically, a person produces 800-1500 ml of urine per day.

From the kidneys, urine travels through small tubes called ureters to the bladder, where it is stored until the bladder is full and the urge to urinate arises.

A hormone called vasopressin (or antidiuretic hormone [ADH]) is the key to all of these processes. Antidiuretic hormone is produced by the hypothalamus, a small gland at the base of the brain. It is then stored in the pituitary gland, which is next to the hypothalamus, and released into the bloodstream when fluid levels in the body decrease.

In the bloodstream, antidiuretic hormone signals the kidneys not to absorb all the fluid from the body and excrete it through the urine, lest dehydration occur.

The pituitary gland secretes less vasopressin, or even none at all, when fluid levels in the body are high. At that time the person will produce more urine.

In diabetes insipidus, this system does not work properly.

Classification

The disease is divided into several main types:

central diabetes insipidus - occurs when the production of vasopressin (a hormone that controls water metabolism in the body) in the hypothalamus (hemisphere in the diencephalon, which includes a large number of cell groups that regulate the neuroendocrine activity of the brain) is insufficient;
nephrogenic diabetes insipidus (NNSD) - occurs due to the inability to concentrate urine due to an impaired response of the renal tubules to vasopressin, which leads to the excretion of a significant amount of unconcentrated urine from the body;
incipidary syndrome - characterized by polydipsia (strong thirst), polyuria (an increase in the volume of urine excreted per day);
gestagenic diabetes insipidus - associated with increased activity of the placental enzyme that destroys vasopressin.

The two most common types are central and nephrogenic.

According to the severity of the course, the following forms of diabetes insipidus are distinguished:

mild - excretion of up to 8 liters of urine per day;
medium - allocation of 8-14 liters / day;
severe - excretion of more than 14 liters / day.

The disease is also congenital or acquired forms.

Causes of diabetes insipidus

While all diabetes insipidus is caused by dysregulation of vasopressin (antidiuretic hormone), this dysregulation can be caused by many different factors. The reason for this violation is the definition of each of the four types of disease.

Central diabetes insipidus is a consequence of insufficient production of antidiuretic hormone (ADH) in the hypothalamus or their inability to accumulate in the posterior pituitary gland, from where they are secreted into the blood. Most often this is associated with hypothalamic syndrome or brain lesions, due to:

craniopharyngiomas;
tuberculosis;

Blunt head trauma and surgery can also damage the hypothalamus, as can metastatic pituitary tumors.

Nephrogenic diabetes insipidus occurs due to improper functioning of the renal tubules, they do not process antidiuretic hormone. This is due to kidney damage as a result of genetics, metabolic disorders (such as hypokalemia and hypercalcemia), heavy metal poisoning. Other diseases can also be the cause, such as:

chronic type;
renal;

incipidary syndrome occurs due to a defect in the thirst mechanism, the body signal that controls fluid intake, located in the hypothalamus. This defect causes permanently abnormal thirst.

When someone is excessively thirsty, they drink a lot more than usual. Their high fluid intake causes the body to release less vasopressin, and this causes the kidneys to produce more urine.

As with the central type, the thirst mechanism of the hypothalamus can be damaged:

head injury;
operation;
infection
inflammation;
brain tumors.

People may also suffer from the syndrome as a result of certain medications or mental health issues.

Gestational diabetes insipidus occurs during pregnancy and can be caused by two different factors:

The placenta produces an enzyme that breaks down vasopressin in the mother's body, which leads to excessive urination because the kidneys take too much fluid from the bloodstream.
The mother's body produces large amounts of a chemical called prostaglandin, which makes the kidneys less sensitive to vasopressin, as in the nephrogenic type of disease.

In many cases of gestational diabetes insipidus, symptoms are mild and not very noticeable, especially since pregnancy itself causes many women to urinate frequently. However, dehydration during pregnancy can lead to complications, including:

neural tube defects;
low amniotic fluid;
premature birth.

If you suspect you have a gestational type of illness, be sure to keep yourself hydrated and talk to your doctor right away.

Because it is caused directly by pregnancy-related factors, gestational disease usually disappears after the baby is born, but is likely to return in future pregnancies.

Approximately about 1/3 of cases of diseases have an unexplained origin. Doctors never manage to figure out the causes of the disease in the body of a perfectly healthy person.

Signs and symptoms of diabetes insipidus

The disease leads to frequent thirst and urination, these are the most common and obvious symptoms.

In extreme cases, urination can exceed 20 liters per day. Urine has no color, salt precipitation is observed in volume in a small amount.

Also, with diabetes insipidus, the patient may experience the following chain of symptoms:

headache;
sleep is disturbed, insomnia appears;
weight is lost (very often with diabetes insipidus, the patient rapidly loses weight);
libido decreases, the cycle of menstruation in women is disturbed.

If you have found several of these signs and symptoms in your body, an urgent appeal to an endocrinologist is required. .

Children's symptoms of the disease are almost the same as adults. Symptoms of the disease in newborns:

vomit;
the child is very and noticeably losing weight;
abnormally low or very high body temperature;
the baby urinates repeatedly and profusely.

Only in newborn children, the disease can be expressed clearly and have all the ensuing consequences.

Complications

The disease is dangerous by the development of dehydration of the body, in cases where the loss of fluid in the urine is not replenished.

With the disease, the activity of the cardiovascular system is also disrupted, mental disorders occur, as well as neurosis. In women, it may be disturbed.

The female body suffers especially, complications from the ureters and bladder, which manifest themselves at night, are likely. In rare cases, the disease can lead to visual impairment up to blindness.

Complications in diabetes insipidus occur only when the patient does not pay attention to the symptoms that disturb him.

Important! With diabetes insipidus, one should not stop drinking, however, one should not drink too much, this will only aggravate the patient's situation. You need to determine for yourself the golden mean of daily fluid intake. It is advisable to give preference only to clean water, drink moderately, in small sips.

Diagnostics

At the first visit, an endocrinologist / nephrologist will conduct an examination. The examination will help to find out the amount of water that a person drinks per day, whether there are problems with urination and with the menstrual cycle.

Based on the information received, the specialist will either prescribe treatment or send the patient for laboratory diagnostics in order to once again verify the correctness of the diagnosis.

Diagnostics includes:

ultrasound examination of the kidneys;
detailed biochemical blood test;
x-ray examination of the skull;
computed tomography of the brain;
a Zimnitsky test is prescribed (accurate calculation of the daily fluid drunk and excreted).

The diagnosis of diabetes insipidus is made on the basis of the following obtained laboratory data:

high sodium content in the blood;
low relativity of urine density;
high level of osmolarity of blood plasma;
low urine osmolarity.

Doctors may also ask for a blood test for C-peptide to rule out diabetes.

Additionally, the patient can be examined by a neuropathologist and a neurosurgeon.

Treatment of diabetes insipidus

Treatment is often handled by nephrologists, who are doctors who specialize in diseases of the kidneys, or endocrinologists, who specialize in conditions related to the hormone-producing glands (including the hypothalamus and pituitary gland).

The main remedy is to drink enough fluids to prevent dehydration. However, beyond that, treatment is tailored to the specific type of disease.

Treatment of central diabetes insipidus.

Drugs needed to treat the central type of the disease:

Miscleron, Carbamazepine, Chlorpropamide(drugs are used to stimulate the production of the hormone vasopressin);
Minirin(desmopressin). A drug with a vasoconstrictor effect. The composition contains the substance desmopressin, which is similar in structure to the hormone vasopressin. During a meal, Minimirin should be taken orally, an hour before taking the medicine, it is necessary to halve the amount of fluid taken.

Treatment of nephrogenic diabetes insipidus.

Treatment of HNSDM is aimed at addressing the underlying cause of the disorder whenever possible. This may mean clearing a urinary blockage, stopping medication, or normalizing calcium or potassium levels in the blood.

In the treatment of the nephrogenic type of the disease, it will also be important to ensure the flow of fluid directly to the organs and tissues. The following drugs are recommended for treatment:

Indapamide. This medicine will provide a reduced production of urine, which will contribute to the replenishment of fluid in the body;
Triampur. The drug also reduces the production of urine and promotes water replenishment in the body.

These medicinal substances are used to stop the reverse process of chlorine absorption in the kidney channels. When taking these medications, the amount of sodium in the blood is significantly reduced and an enhanced process occurs in which water is reabsorbed into organs and tissues.

Treatment of incipient syndrome.

Incipid syndrome does not yet have effective treatments, so symptom management is the mainstay of therapy. Doctors recommend sucking on hard candies or sour candies to keep the mouth full of saliva, which can help reduce thirst. Small doses of desmopressin at bedtime can help reduce the number of times people have to get up to go to the bathroom.

Treatment of gestagenic diabetes insipidus.

With this type of disease, Desmopressin is also prescribed. The drug can help even in cases where the placental enzyme breaks down vasopressin, because the enzyme does not have the same effect on the synthetic hormone.

Important! Do not take medicines as a therapy for a disease on your own, be sure to consult a specialist before use.

Diet and Nutrition

The main task of therapeutic nutrition in diabetes insipidus is the gradual reduction of excreted urine per day and the fight against strong thirst.

It is necessary to refrain from eating foods that include protein, and introduce a sufficient amount of fats and carbohydrates into the diet. Food is cooked without adding salt.

Foods to include in your diet:

lean meat (such as chicken, red or white);
nuts;
various cereals. It is recommended to give preference to buckwheat, oat and rice;
vegetables and fruits;
berries;
milk;
rosehip decoction;
seafood;
green tea;
water with lemon.

black and red pepper;
mustard;
vinegar;
smoked dishes;
pickles and marinades;
crackers, chips and fast food.

Diet for the day

With this disease, it is necessary to follow a certain diet. Sample daily meals:

first breakfast - omelette (steamed) from two eggs, vinaigrette (with vegetable oil), tea with lemon;
second breakfast - oatmeal, three bars of dark chocolate, jelly;
lunch - vegetable soup, boiled white meat, stewed carrots, milk;
afternoon snack - cucumber and tomato salad in vegetable oil, one boiled egg;
dinner - boiled fish, boiled potatoes, sour cream, tea with lemon.

Throughout the day, special attention should be paid to drinking plenty of water. In diabetes insipidus, more than ever, the body needs water to compensate for fluid loss due to dehydration.

Food should be taken fractionally: 4-5 times a day.

Important! The patient should follow the use, firstly, white bread, secondly, butter, and finally, thirdly, a particularly harmful product at the moment - sugar.

Compliance with the diet will help the patient speed up the recovery process and return to a full life sooner.

Prevention

For people with a predisposition to the occurrence of pathology, it will not be superfluous sometimes, at least at least 2 times a year, to do an x-ray of the kidneys.

If you have present or persistent thirst, you should immediately consult a doctor to avoid possible consequences.

Forecast

With proper treatment, the prognosis for people suffering from diabetes insipidus is good. Central diabetes insipidus responds to treatment much more easily than nephrogenic.

Although patients with diabetes insipidus rapidly dehydrate, mortality from this is rare in previously healthy adults. But children and the elderly are at a higher risk of dying from severe dehydration.

Interesting

diabetes insipidus - a disease caused by an absolute or relative deficiency of the hypothalamic hormone vasopressin (ADH-antidiuretic hormone).

The frequency of the disease is not known, it occurs in 0.5-0.7% of endocrine patients.

Regulation of vasopressin release and its effects

Vasopressin and oxytocin are synthesized in the supraoptic and paraventricular nuclei of the hypothalamus, packaged in granules with the corresponding neurophysins and transported along the axons to the posterior pituitary gland (neurohypophysis), where they are stored until they are released. The reserves of vasopressin in the neurohypophysis are sharply reduced during chronic stimulation of its secretion, for example, with prolonged abstinence from drinking.

The secretion of vasopressin is caused by many factors. The most important of these is osmotic pressure of the blood, i.e. osmolality (or otherwise osmolarity) of plasma. In the anterior hypothalamus, near but separate from the supraoptic and paraventricular nuclei, is located osmoreceptor . When plasma osmolality is at a certain normal minimum, or threshold value, the concentration of vasopressin in it is very low. If the plasma osmolality exceeds this setpoint, the osmocenter senses this and the vasopressin concentration rises steeply. The osmoregulation system reacts very sensitively and very accurately. Some increase osmoreceptor sensitivity is associated with age.

The osmoreceptor is not equally sensitive to various plasma substances. Sodium(Na +) and its anions are the most powerful osmoreceptor and vasopressin secretion stimulants. Na and its anions normally determine 95% of plasma osmolality.

Very effectively stimulate the secretion of vasopressin through the osmoreceptor sucrose and mannitol. Glucose practically does not stimulate the osmoreceptor, as well as urea.

The most reliable evaluative factor in stimulating vasopressin secretion is the determinationNa + and plasma osmolality.

The secretion of vasopressin is influenced by blood volume and blood pressure. These influences are carried out through baroreceptors located in the atria and the aortic arch. Stimuli from the baroreceptor travel along afferent fibers to the brainstem as part of the vagus and glossopharyngeal nerves. From the brain stem, signals are transmitted to the neurohypophysis. A decrease in blood pressure, or a decrease in blood volume (for example, blood loss) significantly stimulates the secretion of vasopressin. But this system is much less sensitive than osmotic stimuli to the osmoreceptor.

One of the effective factors stimulating the release of vasopressin is nausea, spontaneous, or caused by procedures (vomiting, alcohol, nicotine, apomorphine). Even with incoming nausea, without vomiting, the level of vasopressin in plasma rises 100-1000 times!

Less effective than nausea, but an equally constant stimulus for vasopressin secretion is hypoglycemia, especially sharp. A decrease in the level of glucose by 50% of the initial level in the blood increases the content of vasopressin by 2-4 times in humans, and in rats by 10 times!

Increases the secretion of vasopressin renin-angiotensin system. The level of renin and/or angiotensin required to stimulate vasopressin is not yet known.

It is also believed that nonspecific stress caused by factors such as pain, emotions, physical activity, increases the secretion of vasopressin. However, it remains unknown how stress stimulates the secretion of vasopressin - in some special way, or through a decrease in blood pressure and nausea.

Inhibit secretion of vasopressin vasoactive substances such as norepinephrine, haloperidol, glucocorticoids, opiates, morphine. But it is not yet clear whether all these substances act centrally, or by increasing blood pressure and volume.

Once in the systemic circulation, vasopressin is rapidly distributed throughout the extracellular fluid. Equilibrium between the intra- and extravascular space is achieved within 10-15 minutes. Inactivation of vasopressin occurs mainly in the liver and kidneys. A small part is not destroyed and is excreted in the urine intact.

Effects. The most important biological effect of vasopressin is water retention in the body by reducing urine output. The point of application of its action is the epithelium of the distal and/or collecting ducts of the kidneys. In the absence of vasopressin, the cell membranes lining this part of the nephron form an insurmountable barrier to the diffusion of water and solutes. Under such conditions, the hypotonic filtrate formed in the more proximal parts of the nephron passes unchanged through the distal tubule and collecting ducts. The specific gravity (relative density) of such urine is low.

Vasopressin increases the permeability of the distal and collecting ducts to water. Since water is reabsorbed without osmotic substances, the concentration of osmotic substances in it increases, and its volume, i.e. quantity decreases.

There is evidence that the local tissue hormone, prostaglandin E, inhibits the action of vasopressin in the kidneys. In turn, non-steroidal anti-inflammatory drugs (for example, indomethacin), which inhibit the synthesis of prostaglandins in the kidneys, increase the action of vasopressin.

Vasopressin also acts on various extrarenal systems, such as blood vessels, the gastrointestinal tract, and the central nervous system.

Thirst serves as an indispensable complement to the antidiuretic activity of vasopressin . Thirst is the conscious feeling of needing water. Thirst is stimulated by many factors that cause the secretion of vasopressin. The most efficient of these is hypertensive environment. The absolute level of plasma osmolality at which thirst appears is 295 mosmol/kg. With this osmolality of the blood, urine is normally excreted with a maximum concentration. Thirst is a kind of brake, the main function of which is to prevent the degree of dehydration, which exceeds the compensatory capabilities of the antidiuretic system.

The feeling of thirst increases rapidly in direct proportion to plasma osmolality and becomes unbearable when the osmolality is only 10-15 mosmol/kg above the threshold level. Water consumption is proportional to the feeling of thirst. A decrease in blood volume or blood pressure also causes thirst.

Etiology

The development of central forms of diabetes insipidus is based on the defeat of various parts of the hypothalamus or the posterior lobe of the pituitary gland, i.e. neurohypophysis. The reasons may be the following factors:

infections acute or chronic: influenza, meningoencephalitis, scarlet fever, whooping cough, typhoid fever, sepsis, tonsillitis, tuberculosis, syphilis, rheumatism, brucellosis, malaria;

traumatic brain injury : accidental or surgical; electric shock; birth trauma in childbirth;

mental trauma ;

pregnancy;

hypothermia ;

tumor of the hypothalamus or pituitary gland : metastatic, or primary. Metastasizes to the pituitary gland more often than cancer of the mammary and thyroid glands, bronchi. Infiltration with tumor elements in lymphogranulomatosis, lymphosarcoma, leukemia, generalized xanthomatosis (Hand-Schuller-Chrispen disease). Primary tumors: adenoma, glioma, teratoma, craniopharyngioma (especially common), sarcoidosis;

endocrine diseases : syndromes of Simmonds, Shien, Lawrence-Moon-Biedl, pituitary dwarfism, acromegaly, gigantism, adinosogenital dystrophy;

idiopathic: in 60-70% of patients, the cause of the disease remains unclear. Among the idiopathic forms, hereditary diabetes mellitus, followed in several generations, has a noticeable representation. The type of inheritance is autosomal dominant and recessive;

autoimmune : destruction of the nuclei of the hypothalamus as a result of an autoimmune process. This form is thought to occur among idiopathic diabetes insipidus, in which autoantibodies to vasopressin-secreting cells appear.

With peripheral In diabetes insipidus, vasopressin production is preserved, but the sensitivity of renal tubular receptors to the hormone is reduced or absent, or the hormone is extensively destroyed in the liver, kidneys, and placenta.

Nephrogenic diabetes insipidus more often observed in children, and is due to anatomical inferiority of the renal tubules (congenital malformations, cystic degenerative processes), or damage to the nephron (amyloidosis, sarcoidosis, lithium poisoning, methoxyfluramine). or decreased sensitivity of renal tubular epithelial receptors to vasopressin.

Diabetes Insipidus Clinic

Complaints

for thirst from moderately severe to painful, not letting go of patients day or night. Sometimes patients drink 20-40 liters of water per day. At the same time, there is a desire to take ice water;

polyuria and frequent urination. Urine is light, without urochromes;

physical and mentalweakness;

decreased appetite,weight loss; possible development obesity if diabetes insipidus develops as one of the symptoms of primary hypothalamic disorders.

dyspeptic disorders from the side of the stomach - a feeling of fullness, belching, pain in the epigastrium; intestines - constipation; gallbladder - heaviness, pain in the right hypochondrium;

mental and emotional disorders: headaches, emotional imbalance, insomnia, decreased mental activity, irritability, tearfulness; psychoses sometimes develop.

violation of menstruation, in men - potency.

Anamnesis

The onset of the disease can be acute, sudden; less often - gradual, and the symptoms increase as the disease worsens. The cause may be traumatic brain or mental injuries, infections, surgical interventions on the brain. Most often, the cause cannot be identified. Sometimes a burdened heredity for diabetes insipidus is established.

Flow chronic diseases.

Inspection

emotional lability;

the skin is dry, salivation and sweating are reduced;

body weight can be reduced, normal or increased;

the tongue is often dry due to thirst, the borders of the stomach are lowered due to constant fluid overload. With the development of gastritis or biliary dyskinesia, increased sensitivity and pain on palpation of the epigastrium and right hypochondrium are possible;

cardiovascular and respiratory systems, the liver usually does not suffer;

urination system: there is frequent urination, polyuria, nocturia;

signsdehydration body, if the fluid lost in the urine is not replenished for some reason - lack of water, a test with a “dry diet”, or the sensitivity of the “thirst” center decreases:

severe general weakness, headaches, nausea, repeated vomiting, aggravating dehydration;

hyperthermia, convulsions, psychomotor agitation;

CCC disorder: tachycardia, hypotension up to collapse and coma;

blood clots: an increase in the amount of Hb, erythrocytes, Na + (N136-145 mmol / l, or meq / l) creatinine (N60-132 μmol / l, or 0.7-1.5 mg%);

the specific gravity of urine is low - 1000-1010, polyuria persists.

These phenomena of hyperosmolar dehydration are especially characteristic of congenital nephrogenic diabetes insipidus in children.

The diagnosis is made based on the classic signs of diabetes insipidus and laboratory and instrumental studies:

polydipsia, polyuria

low specific gravity of urine - 1000-1005

plasma hyperosmolarity, > 290 mosm/kg (N280-296 mosm/kg water, or mmol/kg water);

urine hypoosmolarity,< 100-200 мосм/кг;

hypernatremia, > 155 meq/l (N136-145 meq/l, mmol/l).

Conducted if necessary samples :

Dry eating test. This test is carried out in a hospital, its duration is usually 6-8 hours, with good tolerance - 14 hours. Liquid is not given. Food should be protein. Urine is collected every hour, the volume and specific gravity of each hourly portion are measured. Measure body weight after each 1 liter of urine.

Grade: the absence of a significant change in the specific gravity of urine in two subsequent portions with a loss of 2% of body weight indicates the absence of stimulation of endogenous vasopressin.

Sample with intravenous injection of 50 ml 2.5% solutionNaCl within 45 min. In diabetes insipidus, the volume and density of urine do not change significantly. In psychogenic polydipsia, an increase in plasma osmotic concentration rapidly stimulates the release of endogenous vasopressin, and the amount of urine excreted decreases, while its specific gravity increases.

A test with the introduction of vasopressin preparations - 5 units in / in or / m. With true diabetes insipidus, the state of health improves, polydipsia and polyuria decrease, plasma osmolarity decreases, urine osmolarity increases.

Differential diagnosis of diabetes insipidus

According to the main signs of diabetes insipidus - polydipsia and polyuria, this disease is differentiated from a number of diseases that occur with these symptoms: psychogenic polydipsia, diabetes mellitus, compensatory polyuria in chronic renal failure (chronic renal failure).

Nephrogenic vasopressin-resistant diabetes insipidus (congenital or acquired) is differentiated on the basis of polyuria with primary aldosteronism, hyperparathyroidism with nephrocalcinosis, malabsorption syndrome in chronic enterocolitis.

With diabetes

Table 22

With psychogenic polydipsia

Table 23

sign	diabetes insipidus	Psychogenic polydipsia
common cause	Infections, craniocerebral injuries (including surgical ones)	gradual Psychotrauma, psychogenic stress
The presence of a tumor	Tumors of the pituitary gland, sarcoma, lymphogranulomatosis, etc.	Is absent
Osmolarity:
Dry eating test (no more than 6-8 hours)	Without dynamics	The amount of urine decreases, the specific gravity and osmolality are normalized
Feeling good during this test	Deteriorating, thirst becomes excruciating	Condition and well-being are not violated
Test with / in the introduction 50 ml 2.5% NaCl	The amount of urine and its density without dynamics	The amount of urine decreases and the specific gravity 
	Feeling better, polydipsia and polyuria decrease	Feeling worse (headaches)

Central (hypothalamic-pituitary) with nephrogenic diabetes insipidus

Table 24

sign	Central diabetes insipidus	Diabetes insipidus, nephrogenic
	Cranial injuries, infections, tumors.	Family; hyperparathyroidism; taking drugs-lithium carbonate, demeclocycline, methoxyflurane
Sample with intravenous injection of 5 units of vasopressin	Feeling better, polydipsia and polyuria decrease. Plasma osmolality  and urine 	Without dynamics
Changes are found in the urine	Missing	Albuminuria, cylindruria
Creatine blood
arterial hypertension		BP often

Treatment of diabetes insipidus

Etiological : for tumors of the hypothalamus or pituitary gland - surgery, or radiation therapy, cryodestruction, the introduction of radioactive yttrium.

In infectious processes - antibiotic therapy.

With hemoblastoses - cytostatic therapy.

Replacement therapy - drugs that replace vasopressin:

Adiuretin(a synthetic analogue of vasopressin) intranasally, 1-4 drops in each nostril 2-3 times a day; available in 5 ml vials, 1 ml - 0.1 mg of the active substance;

Adiurecrine(extract of the posterior pituitary gland of cattle). Available in powder form. Inhale 0.03-0.05 2-3 times a day. The duration of one inhalation is 6-8 hours. In inflammatory processes in the nasal cavity, the absorption of adiurecrin is disrupted and its effectiveness is sharply reduced;

RP: adiurecrini 0.05 Dsd No. 30.S. inhale through the nose, ampoules 1 ml;

Pituitrin. Release form 5 units of activity. Water-soluble extract of the posterior pituitary gland of cattle. It is administered in 5 units (1 ml) 2-3 times a day / m. Often causes symptoms water intoxication(headaches, abdominal pain, diarrhea, fluid retention) and allergies;

DDAVP(1 deamino-8D-arginine-vasopressin) - a synthetic analogue of vasopressin;

diuretics of the thiazide group(Hypothiazid and others). Hypothiazide 100 mg per day reduces glomerular filtration, excretion of Na + with a decrease in the amount of urine. The effect of thiazide diuretics is not detected in all patients with diabetes insipidus and weakens over time;

Chlorpropamide(an oral antidiabetic drug) is effective in some patients with diabetes insipidus. Tablets of 0.1 and 0.25. Assign a daily dose of 0.25 in 2-3 doses. The mechanism of antidiuretic action has not been fully elucidated, it is assumed that it potentiates vasopressin, at least at its minimum amounts in the body.

In order to avoid hypoglycemia and hyponatremia, it is necessary to control the level of glucose and Na + in the blood.

The antidiuretic hormone vasopressin is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. By binding to the carrier protein neurophysin, the ADH-neurophysin complex in the form of granules is transported to the terminal extensions of the axons of the neurohypophysis and the median eminence. ADH accumulates in the axon endings in contact with the capillaries. Secretion of ADH is dependent on plasma osmolality, circulating blood volume, and BP levels. Osmotically sensitive cells located in the periventricular regions of the anterior hypothalamus respond to changes in the electrolyte composition of the blood. Increased activity of osmoreceptors with an increase in blood osmolality stimulates vasopressinergic neurons, from the endings of which vasopressin is released into the general circulation. Under physiological conditions, plasma osmolality is in the range of 282-300 mOsm/kg. Normally, the threshold for ADH secretion is plasma osmolality starting at 280 mOsm/kg. Lower values for ADH secretion can be observed during pregnancy, acute psychoses, and oncological diseases. The decrease in plasma osmolality caused by the intake of large amounts of liquid suppresses the secretion of ADH. At a plasma osmolality level of more than 295 mOsm/kg, an increase in ADH secretion and activation of the thirst center are noted (Fig. 1). Controlled by the osmoreceptors of the choroid plexus of the anterior part of the hypothalamus, the activated center of thirst and ADH prevents dehydration of the body.

The regulation of vasopressin secretion also depends on changes in blood volume. When bleeding, vasopressin secretion is significantly affected by volomoreceptors located in the left atrium. In blood vessels, blood pressure acts through V1-baroosmoreceptors, which are located on the smooth muscle cells of blood vessels. The vasoconstrictor effect of vasopressin in blood loss is due to the contraction of the smooth muscle layer of the vessel, which prevents the fall in blood pressure. With a decrease in blood pressure by more than 40%, an increase in the level of ADH is noted, 100 times higher than the value of its basal concentration. Baroreceptors located in the carotid sinus and aortic arch respond to an increase in blood pressure, which ultimately leads to a decrease in ADH secretion. In addition, ADH is involved in the regulation of hemostasis, the synthesis of prostaglandins, and promotes the release of renin.

Sodium ions and mannitol are powerful stimulators of vasopressin secretion. Urea does not affect the secretion of the hormone, and glucose leads to inhibition of its secretion.

Mechanism of action of antidiuretic hormone

ADH is the most important regulator of water retention and mediates fluid homeostasis in conjunction with atrial natriuretic hormone, aldosterone, and angiotensin II.

The main physiological effect of vasopressin is to stimulate water reabsorption in the collecting ducts of the cortical and medulla of the kidneys against the osmotic pressure gradient.

In renal tubular cells, ADH acts through V2 baroreceptors (type 2 vasopressin receptors), which are located on the basolateral membranes of collecting duct cells. The interaction of ADH with V2 receptors leads to the activation of vasopressin-sensitive adenylate cyclase and an increase in the production of cyclic adenosine monophosphate (AMP). Cyclic AMP activates protein kinase A, which in turn stimulates the incorporation of water channel proteins, aquaporin-2, into the apical membrane of cells. This ensures the transport of water from the lumen of the collecting ducts into the cell and further: through the water channel proteins aquaporin-3 and aquaporin-4 located on the basolateral membrane, water is transported into the intercellular space, and then into the blood vessels. The result is concentrated urine with high osmolality (Fig. 2).

Osmotic concentration is the total concentration of all dissolved particles. It can be interpreted as osmolarity and measured in osmol / l or as osmolality - in osmol / kg. The difference between osmolarity and osmolality lies in the way this value is obtained. For osmolarity, this is a calculation method for the concentration of basic electrolytes in the measured liquid. Osmolarity formula:

Osmolarity = 2 x (Na (mmol/l) + K (mmol/l)) + glucose (mmol/l) + urea (mmol/l) + 0.03 x total protein (g/l) .

The osmolality of plasma, urine and other biological fluids is an osmotic pressure that depends on the amount of ions, glucose and urea, which is determined using an osmometer device. Osmolality is less than osmolarity by the value of oncotic pressure.

With normal secretion of ADH, urine osmolarity is always above 300 mOsm/L and can even increase to 1200 mOsm/L and higher. In ADH deficiency, urine osmolarity is below 200 mosm/L.

Etiological factors of central diabetes insipidus

Among the primary causes of the development of CND, there is a hereditary familial form of the disease transmitted by autosomal dominant or autosomal recessive inheritance. The presence of the disease can be traced back to several generations and may affect a number of family members, it is due to mutations that lead to changes in the structure of ADH (DIDMOAD-syndrome). Congenital anatomical defects in the development of the midbrain and diencephalon can also be the primary causes of the development of CDI. In 50-60% of cases, the primary cause of CND cannot be established - this is the so-called idiopathic diabetes insipidus.

Among the secondary causes leading to the development of CDI are called traumatic brain injury (brain concussion, orbital injury, fracture of the base of the skull).

The development of secondary NSD may be associated with conditions after transcranial or transsphenoidal operations on the pituitary gland for such brain tumors as craniopharyngioma, pinealoma, germinoma, leading to compression and atrophy of the posterior pituitary gland.

Inflammatory changes in the hypothalamus, supraoptic-hypophyseal tract, infundibulum, pedicle, posterior pituitary gland are also secondary causes of CND.

The leading factor in the occurrence of the organic form of the disease is infection. Among acute infectious diseases, influenza, encephalitis, meningitis, tonsillitis, scarlet fever, whooping cough are distinguished; among chronic infectious diseases - tuberculosis, brucellosis, syphilis, malaria, rheumatism.

Among the vascular causes of CDI are Shien's syndrome, circulatory disorders of the neurohypophysis, thrombosis, aneurysms.

Depending on the anatomical localization, CND can be permanent or transient. If the supraoptic and paraventricular nuclei are damaged, ADH function is not restored.

The development of nephrogenic ND is based on congenital receptor or enzymatic disorders of the distal tubules of the kidneys, leading to resistance of receptors to the action of ADH. At the same time, the content of endogenous ADH can be normal or elevated, and taking ADH does not eliminate the symptoms of the disease. Nephrogenic ND can occur with long-term chronic urinary tract infections, urolithiasis (UCD), and prostate adenoma.

Symptomatic nephrogenic ND can develop in diseases accompanied by damage to the distal tubules of the kidneys, such as sickle cell anemia, sarcoidosis, amyloidosis. Under conditions of hypercalcemia, sensitivity to ADH decreases and water reabsorption decreases.

Psychogenic polydipsia develops on a nervous basis mainly in women of menopausal age (Table 1). The primary occurrence of thirst is due to functional disorders in the center of thirst. Under the influence of a large amount of fluid and an increase in the volume of circulating plasma through the baroreceptor mechanism, a decrease in the secretion of ADH occurs. Urinalysis according to Zimnitsky in these patients reveals a decrease in relative density, while the sodium concentration and blood osmolarity remain normal or low. With the restriction of fluid intake, the well-being of patients remains satisfactory, while the amount of urine decreases, and its osmolarity rises to physiological limits.

Clinical picture of central diabetes insipidus

For the manifestation of ND, it is necessary to reduce the secretory capacity of the neurohypophysis by 85%.

The main symptoms of ND are profuse frequent urination and intense thirst. Often the volume of urine exceeds 5 liters, it can even reach 8-10 liters per day.

Hyperosmolarity of the blood plasma stimulates the thirst center. The patient cannot go without fluid intake for more than 30 minutes. The amount of fluid drunk with a mild form of the disease usually reaches 3-5 liters, with moderate severity - 5-8 liters, with a severe form - 10 liters or more. Urine is discolored, its relative density is 1000-1003 g/l. In conditions of excessive fluid intake in patients, appetite decreases, stomach overdistension occurs, gastrointestinal secretion decreases, gastrointestinal motility slows down, and constipation develops. When the hypothalamic region is affected by an inflammatory or traumatic process, along with ND, other disorders can be observed, such as obesity, growth pathology, galactorrhea, hypothyroidism, and diabetes mellitus (DM). With the progression of the disease, dehydration leads to dryness of the skin and mucous membranes, a decrease in salivation and sweating, the development of stomatitis and nasopharyngitis. With a sharp dehydration, general weakness, palpitations begin to increase, a decrease in blood pressure is noted, a headache quickly intensifies, and nausea appears. Patients become irritable, there may be hallucinations, convulsions, collaptoid states.

Diagnosis of central diabetes insipidus

To confirm the diagnosis, the most common causes of nephrogenic ND (diabetes mellitus, hypercalcemia, hypokalemia, inflammatory kidney disease) should be excluded at the first stage of the examination. If plasma hyperosmolarity (more than 3000 mOsm / kg), hypernatremia and urine hypoosmolarity (100-200 mOsm / kg) are detected, they proceed to the second stage of the examination.

At this stage of the examination, a test with dehydration (test with a dry diet) is performed to rule out primary polydipsia and a test with desmopressin to rule out nephrogenic ND.

The classic test with a dry diet consists in prohibiting the use of any liquid for 6-14 hours. Before and during the test (every 1-2 hours), body weight, blood pressure, pulse are measured, blood plasma osmolality, sodium content in blood plasma, volume and osmolality of urine. The dry eating test is terminated when the patient loses more than 5% body weight, unbearable thirst, an increase in sodium content and an increase in blood osmolality above the normal range. If during the test blood osmolality > 300 mOsm/kg, sodium level >145 mmol/l, while urine osmolality<300 мОсм/кг, для дальнейшей дифференциальной диагностики центрального и нефрогенного НД проводят тест с десмопрессином. Для этого пациент принимает 10 мкг или 0,1 мг десмопрессина или п/к, в/м или в/в вводится эквивалентная доза, равная 2 мкг десмопрессина. Пациенту разрешается выпить жидкости, по объему не превышающей 1, 5-кратный объем выделенной мочи во время пробы с сухоедением. Через 2 и 4 ч собирается моча для определения объема и осмоляльности.

If, after the administration of desmopressin, the level of urinary osmolality increases by more than 50%, the central form of ND is diagnosed. If the effect of the administered drug is less than 50% or absent, this indicates a nephrogenic form of ND.

Difficulties in diagnosis are partial forms of CND, nephrogenic ND, primary polydipsia, since in these cases there is no clear clinical picture. After a dry eating test, urine osmolality in these patients is determined in the range from 300 to 750 mOsm / kg, after taking desmopressin, urine osmolality is<750 мОсм/кг. Дальнейшее обследование пациентов на фоне приема низких доз десмопрессина (10 мкг х 1-2 р./сут, 0,1 мг х 1-2 р./сут) в течение 7 дней включает определение суточного диуреза, осмоляльности крови и мочи. У пациентов с первичной полидипсией на фоне приема препаратов десмопрессина общее самочувствие не улучшается.

Patients with a confirmed diagnosis of CDI undergo magnetic resonance imaging of the brain to establish the cause of the disease and identify pathological changes in the hypothalamic-pituitary region.

Treatment

Replacement therapy of CND is carried out with a synthetic analogue of ADH - desmopressin. Features of the chemical structure of desmopressin are the replacement of L-arginine in the 8th position of the chain with D-arginine, as well as additional deamination of cysteine in the 1st position. The drug acts only on the V2 receptors of the renal tubules and does not act on the V1 receptors of the smooth muscles of the blood vessels. In this regard, while taking the drug, there is a minimal vasoconstrictive activity and a more pronounced and prolonged antidiuretic effect.

Among the dosage forms of desmopressin, there are: a tablet oral form, a tablet sublingual form, and an intranasal spray (Table 2). With CND, the average therapeutic doses of desmopressin tablets vary from 0.1 mg to 1.6 mg / day, the frequency of administration is 2-3 times / day. When using the tablet sublingual form, the initial dose of the drug is 60 mcg 2-3 times / day, the average daily dose is from 60 to 360 mg / day. With intranasal administration of the drug, the daily dose is from 10 μg to 40 μg / day, which is due to individual sensitivity to the drug; multiplicity of reception - 2 rubles / day.

When taking the tablet form, the antidiuretic effect is observed after 1-2 hours. Intranasal administration provides a faster onset of action after 15-30 minutes, since the administration of the drug is not associated with food intake, which ensures greater bioavailability. Also, a rapid therapeutic effect is noted when using the sublingual form of the drug, the onset of action of which is 15-45 minutes after administration. The interval between taking the drug and eating is 5-10 minutes.

It should be borne in mind that food intake reduces the absorption of the drug and its effectiveness, therefore it is recommended to take the tablet form of the drug on an empty stomach 30-40 minutes before a meal or 2 hours after it. Intranasal spray can be used regardless of food intake in patients with various diseases of the gastrointestinal tract, in patients in intensive care units. At the same time, catarrhal phenomena in patients significantly complicate the treatment with this form of desmopressin. The sublingual form of administration of the drug is practically not associated with food intake, it is easily titrated. This form of desmopressin allows you to more accurately select the required dose of the drug.

When replacing or when switching from one form of desmopressin to another, the dose taken is recalculated (Table 3).

Conclusion

Currently, various forms of desmopressin are used to effectively treat patients with CDI. Only individual selection of the drug and titration of its dose can achieve clinical and laboratory compensation of the disease.

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