Diabetes insipidus. Diabetes insipidus: causes and symptoms, treatment in women and men

Diabetes insipidus is a pathology that is caused by vasopressin deficiency, its absolute or relative deficiency.

Vasopressin (antidiuretic hormone) is secreted in the hypothalamus and, among other functions, is responsible for normalizing the process of urination. According to the causes of origin, it is customary to distinguish three types of this disease: genetic, acquired, idiopathic.

Most patients who suffer from this rare disease still do not know the exact cause of its occurrence. This kind of diabetes insipidus is called idiopathic and affects about 70% of patients. Genetic diabetes insipidus is caused by a hereditary factor. In this case, it is present in several family members or in several generations in a row.

Prevalence

Diabetes insipidus is relatively rare. For example, in Uzbekistan, throughout the republic in 2012, 2,295 people were registered with this diagnosis, including 235 children. For every 100 thousand people of the total population of the republic in 2012, there were 7.7 people with this diagnosis. The majority of patients in the country were aged 40 - 49 years - 530 people (22.9%). This disease is rare in children and adolescents of Uzbekistan - in 2012, only 2.7 children per 100 thousand of the child population of the republic were registered.

Reasons for development

In approximately 30% of cases, the causes of diabetes insipidus remain unknown. This is due to the fact that no matter what diagnostic tests are performed, they do not show any diseases or factors that could cause the development of the disease.

The development of central diabetes insipidus is characterized by impaired levels of ADH secretion. This occurs due to the fact that an insufficient amount of vasopressin is produced in the hypothalamus, and it is the intermediate part of the brain that is responsible for the synthesis of ADH and the functioning of the urinary function. The causes of the disease may be the following factors:

  • a brain tumor;
  • head injuries;
  • postoperative complications (brain surgery);
  • syphilis;
  • sarcoidosis;
  • encephalitis;
  • multiple lesions in lung and breast tumors;
  • kidney disease;
  • anemia (sickle cell);
  • congenital pathologies;
  • renal failure;
  • use of medications that are toxic to the kidneys;
  • imbalance of potassium and calcium in the blood;
  • polycystic disease;
  • amyloidosis;
  • brain damage.

With the development of renal diabetes insipidus, the disease proceeds in the reverse order: the body produces vasopressin at a sufficient level, but the kidney tissues do not react to it.

Central diabetes insipidus

The development of central or hypothalamic-pituitary diabetes insipidus occurs due to the inability of the kidneys to accumulate fluid. This pathology occurs due to disturbances that occur in the functions of the distal tubules of the nephron. As a result, a patient with this form of diabetes insipidus suffers from frequent urination in combination with polydipsia (that is, unquenchable thirst syndrome).

It should be noted that if the patient has the opportunity to consume unlimited water, then there are no threats to his condition. If for one reason or another there is no such opportunity, and the patient cannot quench his thirst in time, he rapidly begins to develop dehydration (or hyperosmolar dehydration). Reaching the extreme stage of this syndrome is life-threatening for the patient, because the next stage is the transition to hypersomolar coma.

The long-term course of central diabetes insipidus for the patient develops into renal insensitivity to the antidiuretic hormone artificially administered for therapeutic purposes. For this reason, the sooner treatment for this form of diabetes insipidus begins, the more favorable the prognosis for the patient’s subsequent condition becomes.

It should also be noted that significant volumes of fluid consumed by the patient can cause the appearance of conditions accompanying this disease, such as biliary dyskinesia, the development of irritable bowel syndrome or gastric prolapse.

Renal diabetes insipidus

Diabetes insipidus in this form is provoked by organic or receptor pathologies of the kidneys, including enzymatic enzymes. The form is quite rare, and if it is observed in children, then, as a rule, in this case it is congenital. It is caused by mutations in the aquaporin-2 gene or mutations in the vasopressin receptor.

If we are talking about the acquired form of morbidity in adults, then it is advisable to note as the cause renal failure, which provokes this form of diabetes, regardless of the characteristics of its etiology. In addition, renal diabetes insipidus can also occur as a result of long-term therapy using lithium preparations and other specific analogues.

Idiopathic diabetes insipidus

The incidence of diabetes insipidus in this form accounts for a third of cases. Here, in particular, we are talking about the absence of any types of organic pathologies of the organ during diagnostic imaging of the pituitary gland. In other words, the reported incidence of diabetes insipidus is unknown. In some cases, it can be passed on by inheritance.

Symptoms

The earliest sign of diabetes insipidus is polyuria - increased urine output. On average, patients experience an increase in diuresis to five to six liters of urine per day. The urge to urinate occurs even at night. When water intake is limited, the patient's condition worsens: headache, increased heart rate, decreased blood pressure, fever, vomiting, and psychomotor agitation.

Against the background of excessive fluid loss, compensatory polydipsia occurs - thirst. Moreover, it is typical that thirst can be quenched only with the help of cool water. In addition, dry skin and mucous membranes are observed, as well as a decrease in salivation and sweating.

In infants, clinical symptoms differ from those in adults. This is due to the fact that if there is thirst, the child cannot report this, which means that the lost fluid is not fully restored. Children experience the following symptoms:

  1. Loss of body weight;
  2. Developmental delay;
  3. Paleness of the skin;
  4. Lack of appetite;
  5. No tears or sweat;
  6. Vomit;
  7. Increased body temperature.

Symptoms of diabetes insipidus in men are decreased libido and potency.

Symptoms of diabetes insipidus in women: menstrual irregularities up to amenorrhea, associated infertility, and if pregnancy does occur, an increased risk of spontaneous abortion.

Please note: in young children, due to dehydration, hypernatremia and hyperosmolarity of the blood quickly develop, accompanied by the appearance of seizures and the development of coma.

Diagnostics

If you suspect diabetes insipidus, you should consult an endocrinologist. Patients additionally visit a neurosurgeon, neurologist, and ophthalmologist. Women should consult a gynecologist.

Some research will need to be done. To detect diabetes insipidus:

  1. Examine the patient's urine and blood;
  2. Perform Zimnitsky's test;
  3. They do an ultrasound of the kidneys;
  4. A CT or MRI of the brain and echoencephalography are performed.

Laboratory tests will evaluate blood osmolarity, relative density, and urine osmolarity. A biochemical blood test makes it possible to obtain data on the levels of glucose, nitrogen, potassium, sodium and other substances.

Diagnostic indicators of the disease:

  • Low urine osmolarity (less than 100-200 mOsm/kg);
  • High sodium content in the blood (from 155 mEq/L);
  • Reduced relative density of urine (less than 1010);
  • Increased osmolarity of blood plasma (from 290 mOsm/kg).

Diabetes insipidus and diabetes mellitus are easy to distinguish. In the first case, sugar is not detected in the patient’s urine, and the level of glucose in the blood does not exceed the norm. The disease code according to ICD-10 is E23.2.

The main pathological conditions from which neurogenic diabetes insipidus should be distinguished are:

  • psychogenic polydipsia;
  • chronic renal failure;
  • diabetes;
  • nephrogenic diabetes insipidus.

Differential diagnosis

Common symptoms for diabetes insipidus and psychogenic polydipsia are increased thirst and frequent excessive urination. However, psychogenic polydipsia does not develop suddenly, but gradually, while the patient’s condition (yes, this disease is specific to women) does not change significantly. With psychogenic polydipsia, there are no signs of blood thickening, and symptoms of dehydration do not develop in the case of a test with fluid restriction: the volume of urine excreted decreases, and its density becomes greater.

Chronic renal failure may also be accompanied by thirst and excessive diuresis. However, this condition is also accompanied by the presence of urinary syndrome (the presence of protein, leukocytes and red blood cells in the urine, not accompanied by any external symptoms) and high diastolic (popularly referred to as “lower”) pressure. In addition, in case of renal failure, an increase in the blood levels of urea and creatinine is determined, which are within normal limits in diabetes insipidus.

In diabetes mellitus, unlike diabetes insipidus, a high level of glucose is determined in the blood, in addition, the relative density of urine is increased and glucosuria is noted (excretion of glucose in the urine).

Nephrogenic diabetes insipidus is similar in clinical manifestations to its central form: severe thirst, frequent heavy urination, signs of blood thickening and dehydration, low specific gravity of urine - all this is inherent in both forms of the disease. The difference between the peripheral form is the normal or even increased level of antidiuretic hormone (vasopressin) in the blood. In addition, in this case there is no effect from diuretics, since the cause of the peripheral form is the insensitivity of the receptors of renal tubular cells to ADH.

How to treat diabetes insipidus?

The treatment of diabetes insipidus is based on replacement therapy with synthetic analogues of vasopressin. Drugs that can compensate for the level of antidiuretic hormone in the body include Desmopressin or Adiuretin. They come in the form of tablets or nasal sprays. In the treatment of diabetes insipidus with Desmopressin tablets, dosages of up to 0.4 mg 3-4 times a day are used. Injecting liquid with synthetic vasopressin into the nose should also be carried out at least 3 times a day.

In the treatment of diabetes insipidus, drugs with a longer-lasting effect are also used, for example, Pitressin Tanat. It can be used once every 3-5 days. Diet therapy plays an important role in the treatment of diabetes insipidus. All patients with a deficiency of antidiuretic hormone in the body are recommended to eat smaller meals and increase the amount of complex carbohydrates in the diet (potatoes, vegetables, grains, legumes, meat, nuts).

Stimulation of the production of natural vasopressin in incomplete diabetes insipidus is carried out with the drugs Chlorpropamide and Carbamazepine.

Patients with a pituitary tumor are advised to undergo surgical treatment of diabetes insipidus - removal of the tumor and, if necessary, radiation exposure.

Diet and nutrition

The main goal of diet therapy is to reduce urination, and in addition, to replenish the body with vitamins and minerals that they “lose” due to frequent urge to go to the toilet.

It is worth giving preference to cooking in these particular ways:

  • boil;
  • steamed;
  • stew food in a saucepan with olive oil and water;
  • bake in the oven, preferably in a sleeve, to preserve all the beneficial substances;
  • in a slow cooker, except for the “fry” mode.

When a person has diabetes insipidus, the diet should exclude those categories of foods that increase thirst, for example, sweets, fried foods, spices and seasonings, and alcohol.

The diet is based on the following principles:

  • reduce the amount of protein consumed, leaving the norm of carbohydrates and fats;
  • reduce salt concentration by reducing its consumption to 5 g per day;
  • food should consist mainly of vegetables and fruits;
  • to quench your thirst, use natural juices, fruit drinks and compotes;
  • eat only lean meat;
  • include fish and seafood, egg yolks in the diet;
  • take fish oil and phosphorus;
  • eat small meals often.

Sample menu for the day:

  • first breakfast – omelet (steamed) of 1.5 eggs, vinaigrette (with vegetable oil), tea with lemon;
  • second breakfast – baked apples, jelly;
  • lunch - vegetable soup, boiled meat, stewed beets, lemon drink;
  • afternoon snack – rosehip decoction, jam;
  • dinner - boiled fish, boiled potatoes, sour cream, tea with lemon.

Drinking plenty of fluids is necessary - after all, the body loses a lot of water during dehydration and needs to be compensated.

Folk remedies

To improve sleep and reduce irritability, sedatives are used:

  1. Take equal parts of crushed valerian roots, fennel and caraway fruits, motherwort herbs and mix everything thoroughly. Then, from the resulting mixture, take two tablespoons of the raw material and pour 400 ml of boiling water, let it brew until cool and decant. Take half a glass if you feel irritable or nervous.
  2. Take equal parts of crushed valerian roots, hop cones, motherwort herbs, rose hips, mint leaves and mix everything thoroughly. From the resulting mixture, take one tablespoon of raw material and pour a glass of boiling water. Let it sit for an hour and then express. Take 1/3 glass at night for insomnia or increased nervous agitation.

To reduce thirst:

  1. Take 60 grams of crushed burdock root, place it in a thermos and pour one liter of boiling water. Leave it overnight and express in the morning. Take two-thirds of a glass three times a day.
  2. 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.
  3. Take 5 grams (one teaspoon) of crushed young walnut leaves and pour a glass of boiling water. Let it brew and take it like tea.

What's the forecast?

The prognosis of diabetes insipidus mainly depends on what form is diagnosed in the patient. The majority of patients with diabetes insipidus have a favorable prognosis for life, but not for recovery. Diabetes insipidus does not affect performance or life expectancy, but can significantly reduce its quality.

With severe diabetes insipidus, most patients are assigned disability group 3. If diabetes insipidus is symptomatic, then when the cause is eliminated, recovery occurs. If the disease was caused by an injury, then after treatment it is possible to restore the functions of the pituitary gland. If diabetes insipidus is not treated, dehydration will cause the development of stupor and subsequent coma.

Diabetes insipidus is a disease resulting from a deficiency of antidiuretic hormone (vasopressin) or impaired sensitivity of the kidney tissue to it. The main symptoms of the disease are excessive urine production (which is why this condition is called “diabetes”, and the word “insipidus” indicates that there are no problems with blood sugar levels in this disease) and extreme thirst. Diabetes insipidus can be a congenital or acquired disease and affects both men and women. There are many causes of diabetes insipidus. Treatment of the disease consists of replacement therapy with a synthetic analogue of the hormone. From this article you will learn basic information about diabetes insipidus.

Antidiuretic hormone is produced by the cells of the hypothalamus, and then travels through special fibers to the pituitary gland and accumulates there. The hypothalamus and pituitary gland are components of the brain. From the pituitary gland, the hormone is released into the bloodstream, reaching the kidneys with the bloodstream. Normally, antidiuretic hormone ensures that fluid in the kidneys is absorbed back into the bloodstream. That is, not everything that is filtered through the renal barrier is excreted and is urine. Most of the fluid is reabsorbed back. With diabetes insipidus, everything that is filtered is excreted from the body. This results in liters and even tens of liters per day. Naturally, this process creates a strong thirst. A sick person is forced to drink a lot of fluid in order to somehow compensate for its deficiency in the body. Endless urination and the constant need for fluid exhaust a person, which is why the term “diabetes” 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 females and males. 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 occurs in the second or third decade of life. The disease is multifactorial, that is, it has many causes. Let's take a closer look at this point.


Causes of diabetes insipidus

Doctors divide all cases of diabetes insipidus into central and renal. This classification is based on the causes of its occurrence.

Central diabetes insipidus is associated with problems in the hypothalamus and pituitary gland in the brain (that is, “in the center”), where antidiuretic hormone is formed and accumulates; the renal one is caused by 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, and its blockade by antibodies. Such situations may arise when:

  • genetic disorders (defects of genes responsible for the synthesis of vasopressin, defects of the skull 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). Anatomical damage occurs 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 for 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 sella turcica;
  • 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 accumulated, or block the hormone itself, rendering it inoperative). This situation is possible with sarcoidosis, tuberculosis, granulomatous lung diseases;
  • use of Clonidine (Clonidine);
  • for no apparent reason. In such situations they speak 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 symptoms may go away after pregnancy.

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

  • renal failure;
  • mutations in the gene responsible for receptors for vasopressin in the kidneys;
  • amyloidosis;
  • increasing 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 large amounts of urine (more than 3 liters per day) and severe 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);
  • free from pathological impurities (for example, increased levels of leukocytes, the presence of red blood cells).

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

Even if a person is not allowed to drink, a lot of urine will still be produced, leading to dehydration. A diagnostic test is based on this phenomenon to confirm the presence of diabetes insipidus in a patient. This is the so-called dry food test. For 8-12 hours the patient is not given any liquid (including with food). Moreover, 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 expansion of the renal pelvis system, ureters and even the bladder. Of course, this does not happen immediately, but over a certain period of illness.

Thirst in diabetes insipidus is a consequence of the loss of huge amounts of fluid in the urine. The body tries to find ways to restore the contents of the bloodstream, and therefore thirst arises. I want to drink almost constantly. A person drinks water in liters. Due to such water overload of the gastrointestinal tract, the stomach is stretched, the intestines are irritated, digestive problems and constipation arise. At first, with diabetes insipidus, the fluid supplied through drinking compensates for losses in the urine, and the cardiovascular system does not suffer. However, over time, fluid deficiency still occurs, blood flow becomes insufficient, and the blood thickens. Then symptoms of dehydration occur. Severe general weakness, dizziness, headache appear, 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 include dry and flabby skin, an almost complete absence of sweat, and a small amount of saliva. Weight is invariably lost. I am concerned about the feeling of nausea and periodic vomiting.

In women, the menstrual cycle is disrupted, 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 treatment for diabetes insipidus is replacement 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, nasal drops) and oral (tablets) use. The most commonly used are spray, nasal drops and tablets. Injectable forms are required only in severe cases or, for example, when treating mentally ill people.

Using the dosage form in the form of a spray or nasal drops allows you to get by with significantly 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 generally accepted that 10 mcg of the intranasal form is equivalent to 0.2 mg of the tablet form.

Another nuance of using nasal drops or spray is that it works faster. For colds or allergic diseases, when the nasal mucosa swells and adequate absorption of the drug is impossible, spray or drops can be applied to the oral mucosa (the dose is doubled).

The dose of the drug depends on how much antidiuretic hormone the patient produces and how severe its deficiency is. If the hormone deficiency is, for example, 75%, this is one dose, if 100% (complete absence of the hormone) is another. The selection 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 drugs is justified in partial diabetes insipidus.

Adequate replacement therapy for diabetes insipidus with Desmopressin allows a person to lead a normal lifestyle with few restrictions (this applies to diet and drinking). In this case, complete 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 hypothiazide in large doses, non-steroidal anti-inflammatory drugs, but such treatment does not always give a positive result.

With diabetes insipidus, patients should adhere to a certain diet. It is necessary to limit protein intake (to reduce the load on the kidneys), and increase the content of foods rich in fats and carbohydrates in the diet. The diet is divided: it is better to eat more often and in smaller portions to ensure the absorption of food.

Separately, the water load should be noted. Without adequate fluid replacement, diabetes insipidus causes complications. But it is not recommended to replenish fluid loss with plain water. 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 using 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 as possible to normal. And this is no longer enough.

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


Diabetes mellitus is a disease that everyone hears. However, in addition to metabolic syndrome, which is associated with pancreatic abnormalities, obesity and other disorders, there is another form of the disease. It occurs much less frequently, but is more difficult to diagnose and more often leads to dangerous complications. Treatment for diabetes insipidus is also more difficult than for the more common glucoid form of the disease.

What is diabetes insipidus

In order to understand what diabetes insipidus is, you should remember what the more common form is. Diabetes is a word from Greek that translates to "permeable" because ancient scientists, starting with Hippocrates, primarily noted increased urination and increased thirst in their patients. Such symptoms are characteristic of diabetes mellitus, however, another form, not associated with disorders of the pancreas, manifests itself in much the same way.

Diabetes insipidus is also an endocrine disease, but depends on non-lifestyle factors. As a rule, it is provoked by various genetic disorders affecting the brain, kidneys or other organs.

The term can be translated as “diabetes”. Unlike diabetes, this type of disease immediately affects the kidneys and can sometimes develop against the background of severe damage to these organs.

The mechanism of the disease in pathogenesis is as follows:

  1. Often the disease is congenital, but each time there is a certain “trigger” that provokes the active development of the pathology.
  2. The production of the hormones oxytocin and vasopressin is disrupted - these substances are responsible for the normal regulation of fluid entering the body.
  3. Normally, fluid should be retained for a short time; the kidneys remove not just water, but also waste substances that are toxic to the body.
  4. Against the background of hormonal imbalance in the body, the normal elimination of harmful substances is disrupted.
  5. At the same time, dehydration increases, although it is compensated by thirst and the need to drink plenty of fluids.

Diagnosis is somewhat difficult because the disease differs from the usual form. Glucose tests are ineffective and are used solely to exclude a more common form of the disease. Diabetes insipidus in women should also be distinguished from cystitis and inflammation in the urogenital area, which can also provoke an increased urge to urinate.

The most effective diagnostic test is a fluid restriction test for 10-12 hours. This is a rather unpleasant procedure, since the patient may experience severe thirst and suffer from poor health. It is advisable to carry out the analysis under the supervision of the attending physician and only after all other possible diagnoses have been excluded. A characteristic feature of diabetes insipidus is that in the absence or limitation of the flow of water into the body, frequent urination persists, and the person quickly loses weight due to the fact that water leaves all tissues and cells. Loss of up to 5% of body weight during the test is possible.

Additional diagnostics include a full examination, necessarily with an MRI of the brain, since sometimes the condition develops against the background of severe diseases in the central nervous system.

A complete kidney examination along with consultation with a nephrologist is also necessary. In general, we can say that diabetes insipidus is a more complex disease fraught with unforeseen complications than the more common “sugar” form.

Variety

There are several types of the disease, depending on the factors that influenced the manifestation of the pathology.

There are two main types, as with diabetes mellitus:

  1. Neurogenic form means that the disease arose as a result of brain disorders of the subcortical zone. This subtype implies that the disturbances occurred in the hypothalamus, pituitary gland, or both parts of the subcortical zone. It is characterized by a violation of the release of hormones into the blood, which guarantee the normal distribution of fluid in the tissues.
  2. The nephropathological or renal form is considered less common, although it can occur for many different reasons. It lies in the fact that the kidneys are affected, the ability of these organs to normally filter fluid is impaired, releasing only the minimum that is truly excessive for the body.
  3. Diabetes insipidus also occurs in pregnant women. It gives a worse prognosis compared to “ordinary” gestational diabetes, since it indicates abnormalities that have developed against the background of the woman’s altered hormonal status. If the gestational form passes spontaneously, then insipidus during pregnancy remains after the birth of the child, while simultaneously increasing the risk of developing a similar condition in the baby.

Congenital forms make themselves felt either in the first months after birth - parents begin to pay attention to the fact that the child looks dehydrated and urinates too often - but can appear much later. It all depends on the underlying causes and characteristics of the pathogenesis.

Causes of the disease

The development of diabetes insipidus, on the one hand, is more difficult to predict than diabetes mellitus; on the other hand, it manifests itself only in cases of serious endocrine disorders affecting all regulatory functions.

Doctors point to the following prerequisites for the disease:

  1. Brain tumors affecting the hypothalamus and pituitary gland. The disease can manifest itself equally in malignant and benign courses.
  2. Metastases of cancer that are found in the brain - they act similarly to the primary tumor formation. Any undesirable effect on human hormonal centers - the pituitary gland and hypothalamus - can provoke a huge number of endocrine disorders, including. Diabetes insipidus.
  3. Impaired blood supply to the brain - we are again talking about the same centers. The causes of the anomaly sometimes lie in the consequences of a stroke, but sometimes the development of a dangerous pathology can be provoked by such a “harmless” disease as osteochondrosis.
  4. Traumatic brain injuries are always a risk factor for any disorders affecting humoral activity.
  5. Hereditary forms manifest themselves very early, as a rule, they are detected during the mother’s pregnancy. Dangerous from the point of view of kidney failure in infants and other serious complications.
  6. Renal dysfunction - renal failure, atherosclerosis of the excretory system, lithium poisoning.

In general, we can say that the prerequisites for the development of diabetes insipidus are more serious than those of the common form of decreased sensitivity to glucose. If with glucoresistance a person can be healthy, with the exception of poor eating habits, increased body weight and other characteristics, then diabetes insipidus always indicates severe damage to the brain or kidneys.

Symptoms

The symptoms of the disease are quite specific and almost always attract the patient’s attention. It must be remembered that other diseases may occur in the background, including those that provoked the development of pathology. The clinical picture depends on the general health of the person.

Typically, the following signs are found:

  1. Increased thirst. A person can drink up to 3-5 liters of water per day. Thirst is felt specifically: a dry mouth, lips that from the outside look crusty and swept away.
  2. Increased amount of urine excreted. A person goes to the toilet every half hour to an hour, and urinates a lot each time. The urge feels urgent, and the person is unable to tolerate it.
  3. If you examine urine visually, it will be colorless and devoid of a characteristic odor due to the fact that the kidneys cannot remove substances that poison the body with liquid.
  4. General weakness, fatigue, and poor health are almost always associated. There is a sharp loss of body weight, mainly due to cellular fluid, which is why the person looks exhausted.
  5. In children with congenital brain pathologies and the manifestation of diabetes insipidus, enuresis is almost always detected - involuntary urination at night. The urgency increases as the disease progresses.

People with diabetes insipidus are characterized by dysfunction of the liver and biliary tract. They are often tormented by constant nausea. Patients with this pathology appear painful, their emotional background is reduced, and neuroses and depressive states often occur. In men, potency decreases; in women, menstrual irregularities and infertility occur.

Treatment

The best way to treat diabetes insipidus is to correct the factor that influenced the development of this disease. This is more of a syndrome than a disease, that is, when the main cause is eliminated, the negative symptoms of a particular pathology also go away.

Therapy depends entirely on the precipitating circumstances and may include:

  1. Removal of a brain tumor. It is recommended not to touch benign ones if they do not affect a person’s quality of life, but disorders in the pituitary gland and hypothalamus are a direct indication for neurosurgical intervention.
  2. A replacement hormone is prescribed, which helps the body not immediately remove fluid, but use it “correctly”. Desmopressin-based drugs do an excellent job of this task.
  3. Pituitrin oil solution- a long-acting medicine that ensures the normal functioning of the endocrine system for some time.
  4. Chlorpropamide, Carbamazepine- prescribed to replace antidiuretic hormone. These medications also help retain fluid so that it can cleanse the kidneys of toxins and be released as normal urine.
  5. Nephrological therapy is often prescribed, which is aimed at restoring normal organ function, along with water-salt balance.

The most dangerous symptom of the disease is polyuria. Therefore, maintaining water-salt balance becomes an important part of therapy. Dehydration affects children, the elderly, and those who do not take care of their condition. With diabetes insipidus, severe complications can occur, including coma caused by dehydration.

ethnoscience

Additional traditional therapy for diabetes insipidus is acceptable if basic basic treatment is carried out. It acts as an additional treatment and helps improve the patient’s general condition and quality of life.

Popular recipes:

  1. Take 70 g of dried blueberry leaves. Pour a liter of boiling water and let it brew. Drink two tablespoons every day before each meal.
  2. Dandelion is good for treating illness. You need to take 10 g of dry roots, pour a glass of boiling water, steam in a steam bath without boiling, and then leave for another hour. Drink a tablespoon of the decoction before meals.
  3. Drink chicory regularly. The drink is a good substitute for coffee, which is contraindicated in case of illness. Chicory has a beneficial effect on the kidneys and genitourinary system.
  4. Walnut leaves in a small amount - about 5 g - pour 200 ml of boiling water, leave for half an hour. Contraindicated if a person is prone to constipation.

Folk remedies are aimed at general improvement of the condition, healing the body and eliminating unpleasant symptoms. In no case should they completely replace drug, surgical or other indicated therapy.

Diet for diabetes insipidus

Dietary restrictions are less strict than for diabetes. It must be remembered that patients almost always experience a decrease or complete absence of appetite, they are prone to exhaustion, so food should be sufficiently high in calories.

The following principles are also important:

  1. Maximum protein restriction - in order to reduce the load on the kidneys. It is recommended to remove from the diet not only animal, but also plant protein, including beans, peas, and mushrooms.
  2. It is prohibited to use diuretics, which include coffee, tea, and sweet drinks containing caffeine from everyday foods.
  3. It is advisable to limit fats, especially in the form of broths and soups.
  4. Alcohol, fast food, and any potentially toxic products, such as store-bought sausages, are strictly prohibited.
  5. Excess salt is not recommended. Meals should be frequent, small, and sufficiently nutritious.

Dietary regimen is important for the treatment of diabetes insipidus, since proper nutrition is the key to normal functioning of the body and reducing the load on damaged organs.

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 neurohypophysis and median eminence axons. ADH accumulation occurs in axon endings in contact with capillaries. ADH secretion depends on plasma osmolality, circulating blood volume, and blood pressure 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 bloodstream. Under physiological conditions, plasma osmolality is in the range of 282-300 mOsm/kg. Normally, the threshold for ADH secretion is the osmolality of blood plasma starting from 280 mOsm/kg. Lower values ​​for ADH secretion can be observed during pregnancy, acute psychosis, and cancer. A decrease in plasma osmolality caused by large amounts of fluid intake suppresses ADH secretion. At a plasma osmolality level of more than 295 mOsm/kg, an increase in ADH secretion and activation of the thirst center are observed (Fig. 1). Controlled by the osmoreceptors of the choroid plexus in the anterior part of the hypothalamus, the activated thirst center and ADH prevent dehydration of the body.

Regulation of vasopressin secretion also depends on changes in blood volume. During bleeding, volume receptors located in the left atrium have a significant effect on the secretion of vasopressin. 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 during blood loss is due to contraction of the smooth muscle layer of the vessel, which prevents a drop in blood pressure. When blood pressure decreases by more than 40%, an increase in the level of ADH is observed, 100 times higher than its basal concentration. Baroreceptors located in the carotid sinus and aortic arch respond to increased 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, but glucose leads to inhibition of its secretion.

Mechanism of action of antidiuretic hormone

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

The main physiological effect of vasopressin is to stimulate the reabsorption of water in the collecting ducts of the renal cortex and medulla against an 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 tubule cells. The interaction of ADH with V2 receptors leads to activation of vasopressin-sensitive adenylate cyclase and increased 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 cell membrane. 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 method of obtaining this value. For osmolarity, this is a calculation method based on the concentration of the main electrolytes in the measured liquid. Formula for calculating osmolarity:

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

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

With normal ADH secretion, urine osmolarity is always above 300 mOsm/L and can even increase to 1200 mOsm/L and higher. With 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 an autosomal dominant or autosomal recessive type of inheritance. The presence of the disease can be traced in several generations and can affect a number of family members; it is caused by mutations leading to changes in the structure of ADH (DIDMOAD syndrome). Congenital anatomical defects in the development of the midbrain and diencephalon may also be the primary causes of the development of CND. In 50-60% of cases, the primary cause of CDI cannot be determined - this is the so-called idiopathic diabetes insipidus.

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

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

Inflammatory changes in the hypothalamus, supraopticohypophyseal tract, infundibulum, stalk, and posterior lobe of the pituitary gland are also secondary causes of the development of CND.

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

Among the vascular causes of CDI can be called Sheehan's syndrome, disorders of the blood supply to the neurohypophysis, thrombosis, and aneurysms.

Depending on the anatomical location, CDI can be permanent or transient. If the supraoptic and paraventricular nuclei are damaged, the 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 receptor resistance to the action of ADH. In this case, the content of endogenous ADH may be normal or increased, 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 DI 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 thirst center. Under the influence of a large amount of fluid and an increase in the volume of circulating plasma, a decrease in ADH secretion occurs through the baroreceptor mechanism. Urine examination according to Zimnitsky in these patients reveals a decrease in relative density, while the sodium concentration and osmolarity of the blood remain normal or reduced. By limiting fluid intake, patients' health remains satisfactory, while the amount of urine decreases and its osmolarity increases to physiological limits.

Clinical picture of central diabetes insipidus

To manifest ND, a decrease in the secretory capacity of the neurohypophysis by 85% is necessary.

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

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

Diagnosis of central diabetes insipidus

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

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

The classic test with dry eating consists of prohibiting the consumption 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 urine osmolality. The dry food test is stopped when the patient loses more than 5% of body weight, unbearable thirst, an increase in sodium content and an increase in blood osmolality above normal limits. If during the test the blood osmolality is > 300 mOsm/kg, the sodium level is > 145 mmol/l, and the 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 urine 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 presented by partial forms of CDI, nephrogenic DI, primary polydipsia, since in these cases there is no clear clinical picture. After a test with a dry diet, the urine osmolality in these patients is determined in the range from 300 to 750 mOsm/kg; after taking desmopressin, the 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 CND undergo magnetic resonance imaging of the brain to determine the cause of the disease and identify pathological changes in the hypothalamic-pituitary region.

Treatment

Replacement therapy for CND is carried out with a synthetic analogue of ADH - desmopressin. Features of the chemical structure of desmopressin include the substitution 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, minimal vasoconstrictor activity and a more pronounced and prolonged antidiuretic effect are observed.

Among the dosage forms of desmopressin there are: oral tablet form, sublingual tablet form and intranasal spray (Table 2). For CND, the average therapeutic doses of tableted desmopressin 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. When administering the drug intranasally, the daily dose is from 10 mcg to 40 mcg/day, which is due to individual sensitivity to the drug; dosage frequency: 2 times per 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 observed 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 must be taken into account 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. The intranasal spray can be used regardless of food intake in patients with various gastrointestinal diseases and in patients in intensive care units. At the same time, catarrhal symptoms in patients significantly complicate treatment with this form of desmopressin. The sublingual form of administration of the drug is practically not associated with food intake and is easily titrated. This form of desmopressin allows you to more accurately select the required dose of the drug.

When replacing or 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 CND. Only individual selection of the drug and titration of its dose make it possible to achieve clinical and laboratory compensation for the disease.

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