How long have you had diabetes
- definition: hormone-related disturbance of the water-electrolyte balance through excessive excretion of urine. The kidneys are unable to concentrate urine and hold back water.
- causes: either lack of antidiuretic hormone, ADH (diabetes insipidus centralis) or poor response of the kidneys to ADH (diabetes insipidus renalis)
- Symptoms: excessive urine excretion (polyuria), very dilute urine, excessive feeling of thirst and increased fluid intake (polydipsia), possibly neurological symptoms (such as confusion, weakness)
- Diagnosis: Blood and urine tests, thirst test
- treatment: depending on the form and severity of the disease with medication (desmopressin as an ADH replacement, possibly also other medication) and, if possible, removal of the cause. Sometimes, in addition to treating the cause, a low-salt and low-protein diet and sufficient fluid intake are sufficient.
Diabetes insipidus: definition
Diabetes insipidus is a rare disease that is caused by a hormonal disorder. This unbalances the water-electrolyte balance (water-salt balance): the kidneys are unable to concentrate the urine and retain water in the body. As a result, those affected excrete large amounts of diluted urine (up to 20 liters a day!).
Forms of disease
The hormonal disorder behind diabetes insipidus affects that Antidiuretic Hormone (ADH). That too Vasopressin This hormone is produced in the hypothalamus, part of the diencephalon. However, it is stored and released as needed by the neighboring pituitary gland (pituitary gland).
ADH is involved in regulating the water balance. When there is a lack of water in the body, the pituitary gland releases ADH into the blood. It causes the kidneys to concentrate the urine more - that is, to hold back more water.
In diabetes insipidus, this regulating mechanism is disturbed. Depending on where exactly the disorder is, doctors differentiate between the following forms of disease:
- Diabetes insipidus centralis: Here, a disorder in the area of the hypothalamus or pituitary gland causes an ADH deficiency - the hormone is either completely absent or present in insufficient quantities. In both cases, the body cannot (sufficiently) signal the kidneys when they are supposed to retain water in the body. Central diabetes insipidus is also called "diabetes insipidus neurohormonalis".
- Diabetes insipidus renalis: In renal diabetes insipidus there is sufficient ADH, but the kidneys do not respond or do not respond adequately. So there is an ADH resistance. Doctors also refer to this form of disease as nephrogenic diabetes insipidus ("nephrogenic" stands for "starting from the kidney").
Diabetes mellitus: similarities and differences
Despite a different disease mechanism, diabetes insipidus and diabetes mellitus (diabetes) have one thing in common, which is reflected in the common part of the name "diabetes". The term means "flow" and indicates the pathologically increased urine excretion in both diseases down.
As mentioned, the underlying cause of diabetes insipidus is the inability of the kidneys to concentrate urine. This is therefore diluted - hence the name Diabetes insipidus = "tasteless flow".
On the other hand, the increased urination in diabetes mellitus is due to the pathologically increased blood sugar level. The body tries to get rid of excess sugar (glucose) through the urine. And because sugar physically binds water, a lot of water is lost: the patient excretes large amounts of urine containing sugar - hence the name "honey flow".
Diabetes insipidus: symptoms
The main symptoms of diabetes insipidus are:
- Polyuria: excessive urine excretion of more than 2.5 liters in 24 hours (sometimes diarrhea instead of polyuria in small children). The increased urination is particularly noticeable at night - the need to urinate at night (nocturia) repeatedly wakes those affected.
- Polydipsia: increased thirst and increased fluid intake (ice-cold water is often preferred)
- Asthenuria: Inability of the kidney to concentrate the urine, which is why it is diluted (measurable as decreased osmolality = decreased concentration of dissolved particles)
If patients cannot compensate for the increased water loss by drinking more, the body becomes dehydrated. Medical professionals refer to this as Dehydration (or dehydration).
Sometimes insipidus also occurs in diabetes neurological symptoms on: The increased urine excretion increases the sodium level in the blood (hypernatremia). This can result in, for example, confusion, muscle weakness and lethargy. Lethargy is a disorder of consciousness with drowsiness and physical and psychological slowdown (sluggishness).
In some patients, diabetes insipidus is the result of another disease (see below: causes). Then come Symptoms of the underlying disease added.
Diabetes insipidus: diagnostics
When talking to the patient (or, in the case of children, the parents), the doctor first collects the Medical history (Anamnese). To do this, he asks about the symptoms and any known underlying diseases, among other things. A general physical examination It is also part of the routine when someone comes to the doctor with unexplained symptoms such as increased urination.
Blood and urine tests
To clarify possible diabetes insipidus, the doctor will order blood and urine tests:
- blood: In diabetes insipidus, increased levels of sodium and other salts (electrolytes) can be detected. The sodium level is particularly significantly increased in patients who (cannot) drink enough fluids to compensate for the water loss.
- urine: The urine over 24 hours is collected and then analyzed. In diabetes insipidus it is diluted (reduced concentration of dissolved particles = reduced osmolality). The specific urine weight is reduced, the sugar content in the urine is normal (differentiating factor from diabetes mellitus - there the sugar in the urine is increased).
The suspected diagnosis of diabetes insipidus can be made with a Thirst test (dehydration test) to confirm. The exact test procedure can vary. Basically, however, it works as follows:
The patient is not allowed to drink anything for several hours (e.g. 12 hours). During this time he will be continuously monitored by a doctor if he dries up dangerously. Various parameters are measured regularly, such as the amount of urine released, the amount of dissolved particles (osmolality) in the urine and blood, and the patient's body weight.
In spite of lack of fluid intake, patients with diabetes insipidus continue to pass urine, and this urine is diluted unchanged (unchanged urine osmolality), while the osmolality in the blood serum increases. In healthy people, on the other hand, the amount of urine would decrease and urine osmolality would increase when attempting thirst.
The test is either canceled after the planned duration or earlier if the patient's blood pressure drops, the heart rate increases or the body weight drops by more than five percent.
Differentiation between central and renal diabetes insipidus
If the measurements in the thirst test confirm diabetes insipidus, the doctor can find out which form of the disease is present by administering a hormone preparation before ending the test:
To do this, he injects ADH, i.e. vasopressin (or its synthetic derivative desmopressin, which is alternatively also available as a nasal spray) into the patient. The urine released is then analyzed again:
- Diabetes insipidus centralis: The administration of vasopressin reduces the amount of urine excreted and the urine is less diluted - recognizable by an increase in urine osmolality: it is 50 to 100 percent if the disease is due to a complete ADH deficiency, and at least it is 15 to 45 percent with partial ADH deficiency (lowered ADH level).
- Diabetes insipidus renalis: Despite the supply of vasopressin, the excessive urine excretion continues and the urine is only slightly less diluted (slight increase in urine osmolality) - after all, the problem here is not a lack of hormone, but a lack of or inadequate response of the kidneys to the hormone.
A direct measurement of the ADH in the blood could also distinguish between the two forms, namely at the end of the thirst test (before vasopressin injection). In diabetes insipidus centralis the ADH level would be low, in diabetes insipidus renalis it would be appropriately increased. However, this measurement is difficult and is not part of the routine program. In addition, the thirst test gives sufficiently accurate results.
Differential diagnosis of psychogenic polydipsia
If someone drinks many liters of fluids a day and then excretes it, it is not always due to some form of diabetes. The thirst and, as a result, urination can also be increased beyond the normal level as a result of a mental illness such as schizophrenia.
When investigating suspected diabetes insipidus, the doctor must rule out such a psychogenic polydipsia, which is not always easy. But there are some pointers. For example, people with psychogenic polydipsia do not suffer from the need to urinate at night (nocturia), which repeatedly wakes them up - in contrast to people with diabetes insipidus.
Diabetes insipidus: treatment
Treatment for diabetes insipidus depends on the form, cause and severity of the disease. It aims to reduce the amount of urine produced so that the patient can lead a normal life and is no longer awakened by excessive urination at night.
Therapy of diabetes insipidus centralis
In diabetes insipidus centralis there is usually one Hormone replacement necessary - the missing hormone ADH must be replaced with medication, through regular administration of desmopressin. This artificial derivative of the antidiuretic hormone has the same effect as its natural counterpart, but has a longer duration of action. It can be applied in different ways. Many patients give themselves desmopressin as a nasal spray. The active ingredient is also available as a tablet and as an injection under the skin or into a vein. The dosage is adjusted individually in all cases.
Desmopressin is also often used to treat children (and adults) who wet themselves at night (bed-wetting, enuresis) - it suppresses the nocturnal urge to urinate.
In addition or as an alternative to desmopressin, diabetes insipidus centralis can also be used other drugs be useful:
- Thiazide diuretics: These are dehydrating drugs that paradoxically can reduce the amount of urine in patients with diabetes insipidus centralis (and diabetes insipidus renalis).
- ADH-releasing drugs: They increase ADH production and are therefore suitable for patients with partial ADH deficiency (i.e. when the body can still provide small amounts of ADH). These active ingredients include the blood sugar lowering drug chlorpropamide and the epilepsy drug carbamazepine. They can be combined with thiazide diuretics.
- Prostaglandin inhibitors: Active ingredients such as indomethacin (a pain reliever and anti-inflammatory drug from the NSAID group) can reduce the amount of urine, albeit usually only slightly. The effect can be increased if the patient also takes a thiazide diuretic and a low-sodium diet.
Regardless of whether the ADH deficiency is complete or partial - if possible, central diabetes insipidus will always also be The cause eliminated. For example, a brain tumor that causes the ADH deficiency can often be surgically removed.
Therapy of diabetes insipidus renalis
Therapy for this form of diabetes insipidus is more difficult. It consists of several components:
- Drinking an adequate amount of water
- low-salt and low-protein diet
- if possible, elimination of the cause of the disease
If diabetes insipidus symptoms persist despite these measures, the doctor will prescribe drugs that reduce the amount of urine. Active substances such as those given in diabetes insipidus centralis are possible: dehydrating drugs (thiazide diuretics or the potassium-sparing diuretic amiloride) or NSAIDs (such as indomethacin).
Sufficient drinking is extremely important with diabetes insipidus renalis: Even several hours without fluid intake can cause severe dehydration!
Diabetes insipidus: causes
Both forms of the disease - central and renal diabetes insipidus - can hereditary or acquired be (for example through various diseases). There are also cases in which no cause of the disease can be found. They are called "idiopathic" designated.
Causes of diabetes insipidus centralis
As primary Diabetes insipidus centralis is what doctors call the hereditary variant. Often there is a change (mutation) in the vasopressin gene on chromosome 20 behind it.
A secondary Diabetes insipidus centralis is acquired. Among other things, it can have the following triggers:
- Skull injuries (especially fracture of the base of the skull)
- Tumors above or inside the Turkish saddle (a saddle-shaped part of the skull bone in the recess of which the pituitary gland lies)
- Nodular tissue growth (granulomas), such as those that can arise in sarcoid or tuberculosis
- Malformations (such as aneurysms) of the arteries supplying the brain
- Infectious inflammation of the brain or meninges (encephalitis, meningitis)
- Total removal of the pituitary gland (hypophysectomy), e.g. in the case of a pituitary tumor
Diabetes insipidus centralis can also develop temporarily in the second half of pregnancy: the placenta can produce an enzyme (vasopressinase) that ensures an increased breakdown of ADH. The hormone level can then drop so much that the kidneys can no longer retain sufficient water in the body.
Causes of diabetes insipidus renalis
In some patients, the diabetes is insipidus renalis hereditary. Usually the cause is a gene change (gene mutation) on the X chromosome, i.e. the female sex chromosome. Affected men always get renal diabetes insipidus because they only have one X chromosome. In women with their two X chromosomes, however, the mutation can have different effects: some women have no symptoms at all, others develop polydipsia and polyuria to different degrees, and still others develop diabetes insipidus renalis with the same severity as men with this mutation.
More rarely, hereditary diabetes insipidus renalis is based on a gene mutation on another chromosome (not a sex chromosome, but a non-sexing autosome). This mutation can then lead to the outbreak of the disease regardless of gender.
Acquired forms of diabetes insipidus renalis are the result of diseases or drugs that affect the kidneys. Examples are:
- Polycystic Kidney Disease: Hereditary disease in which numerous fluid-filled cavities (cysts) form in the kidneys - at the expense of intact kidney tissue.
- Pelvic inflammation
- Sickle cell anemia: Hereditary disease in which sickle-shaped instead of disc-shaped red blood cells (erythrocytes) are formed. These can clog blood vessels and thus damage the kidneys, among other things.
- Amyloidosis: a rare disease with abnormally folded proteins (proteins are made up of long chains of amino acids that are usually folded in a certain way). The abnormal proteins can be deposited in the kidneys, among other things, and thereby damage them.
- Sjogren's syndrome
- certain cancers (such as myeloma, sarcoma)
- various drugs: mainly lithium (for mental disorders), but also others such as demeclocycline and ofloxacin (antibiotics), amphotericin B (anti-fungal agents), dexamethasone (a cortisone), ifosfamide (cancer drug), orlistat (against obesity)
Diabetes insipidus: prognosis
In most cases, diabetes insipidus can be treated without any problems. Acquired forms of the disease are sometimes even curable - provided the cause (e.g. a brain tumor) can be eliminated. If not, those affected can usually lead a normal life with the right therapy and good medical care.
There is no cure for congenital (hereditary) diabetes insipidus. With the right treatment and care, however, the disease can be kept under control so that a normal life is generally possible. However, early treatment is important! If, for example, babies are born with inherited diabetes insipidus renalis, but this is not recognized and treated immediately, there is a risk of permanent brain damage with intellectual impairment.
Diabetes insipidus that develops during pregnancy normalizes on its own within one to two weeks after the birth.
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