Brief overview
- Definition: hormonally induced disturbance of water-electrolyte balance due to excessive excretion of urine. Kidneys are unable to concentrate urine and retain water.
- Causes: either deficiency of antidiuretic hormone, ADH (diabetes insipidus centralis) or deficient renal response to ADH (diabetes insipidus renalis).
- Symptoms: excessive urine output (polyuria), highly diluted 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 condition, with medication (desmopressin as an ADH substitute, possibly also other drugs) and, if possible, elimination of the cause. Sometimes, in addition to treating the cause, a low-salt, low-protein diet and adequate fluid intake are sufficient.
Diabetes insipidus: definition
Disease forms
The hormone disorder behind diabetes insipidus involves antidiuretic hormone (ADH). Also called vasopressin, this hormone is produced in the hypothalamus, a part of the diencephalon. However, it is stored and released as needed by the adjacent pituitary gland (hypophysis).
ADH is involved in the regulation of 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 urine more – that is, to retain more water.
In diabetes insipidus, this regulatory mechanism is disturbed. Depending on the exact location of the disorder, physicians distinguish between the following forms of the disease:
- Diabetes insipidus centralis: In this case, a disorder in the area of the hypothalamus or pituitary gland causes an ADH deficiency – the hormone is completely absent or is present in insufficient quantities. In both cases, the body cannot (sufficiently) signal the kidneys when they should retain water in the body. Central diabetes insipidus is also called “diabetes insipidus neurohormonalis”.
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 name “diabetes”. The term means “flow” and indicates the pathologically increased urine excretion in both diseases.
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”.
In contrast, the frequent urination in diabetes mellitus is due to the pathologically elevated blood glucose level. The body tries to get rid of the excess sugar (glucose) through the urine. And because sugar physically binds water, a lot of water is also lost: the patient therefore excretes large amounts of sugar-containing urine – hence the term “honey-sweet flow”.
Diabetes insipidus: symptoms
The leading symptoms of diabetes insipidus are:
- Polydipsia: increased thirst and fluid intake (often ice-cold water is preferred).
- Asthenuria: inability of the kidney to concentrate urine, so it is diluted (measurable as decreased osmolality = decreased solute concentration)
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, diabetes insipidus is accompanied by additional neurological symptoms: Increased urine output raises blood sodium levels (hypernatremia). This can be reflected, for example, in confusion, muscle weakness and lethargy. Lethargy is a disturbance of consciousness with drowsiness and physical and mental slowing (sluggishness).
In some patients, diabetes insipidus is the result of another disease (see below: Causes). Then symptoms of the underlying disease are added.
Diabetes insipidus: diagnostics
Blood and urine tests
To clarify possible diabetes insipidus, the physician orders blood and urine tests:
- Blood: In diabetes insipidus, elevated levels of sodium and other salts (electrolytes) can be detected. Sodium levels are particularly markedly elevated in patients who do not (cannot) consume enough fluids to compensate for water loss.
- Urine: Urine over 24 hours is collected and then analyzed. In diabetes insipidus, it is diluted (decreased solute concentration = decreased osmolality). The specific gravity of urine is decreased, the content of sugar in urine is normal (distinguishing feature from diabetes mellitus – there the sugar in urine is increased).
Thirst test
The suspected diagnosis of diabetes insipidus can be confirmed with a thirst test (water deprivation test). The exact test procedure may vary. However, it basically works as follows:
Despite lack of fluid intake, patients with diabetes insipidus continue to excrete urine, and this urine is diluted unchanged (unchanged urine osmolality), while blood serum osmolality increases. In healthy individuals, on the other hand, the amount of urine would decrease and the urine osmolality would increase during the thirst test.
The test is terminated either after the planned duration or earlier if the patient’s blood pressure drops, heart rate increases, or body weight decreases by more than five percent.
Differentiating between central and renal diabetes insipidus
If the measurements taken during the thirst test confirm diabetes insipidus, the physician can find out which form of the disease is present by administering a hormone preparation before stopping the test:
For this purpose, he injects the patient with ADH, i.e. vasopressin (or its synthetic derivative desmopressin, which is alternatively available as a nasal spray). Subsequently, the urine emitted is again analyzed:
- Diabetes insipidus renalis: Despite vasopressin intake, excessive urine excretion continues, and the urine is only slightly less dilute (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.
It would also be possible to distinguish between the two forms by direct measurement of ADH in the blood, 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 elevated. However, this measurement is difficult and is not part of the routine program. In addition, the thirst test provides sufficiently accurate results.
Differential diagnosis of psychogenic polydipsia
When someone drinks and excretes many liters of fluid per day, it is not always due to a form of diabetes. Thirst and subsequent urination may also be increased beyond normal levels as a result of a mental illness such as schizophrenia.
Diabetes insipidus: Treatment
Treatment of diabetes insipidus depends on the form, cause and severity of the disease. It aims to reduce urine output to the point where the patient can lead a normal life and is no longer awakened at night by excessive urination.
Therapy of diabetes insipidus centralis
In diabetes insipidus centralis, hormone substitution is usually necessary – the missing hormone ADH must be replaced by medication, namely by regular administration of desmopressin. This artificial derivative of antidiuretic hormone has the same effect as its natural counterpart, but has a longer duration of action. It can be administered in different ways. Many patients administer desmopressin as a nasal spray. However, the active ingredient is also available as a tablet and as an injection under the skin or into a vein. In all cases, the dosage is adjusted individually.
Desmopressin is also often used to treat children (and adults) who wet the bed at night (bedwetting, enuresis) – it suppresses the urge to urinate at night.
- Thiazide diuretics: These are dehydrating drugs that paradoxically can reduce urine output in patients with diabetes insipidus centralis (and diabetes insipidus renalis).
- ADH-releasing drugs: these increase ADH production and are thus suitable for patients with partial ADH deficiency (i.e., when the body can still provide small amounts of ADH). These agents 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 (an anti-inflammatory and painkiller from the NSAID group) can reduce the amount of urine, albeit usually only slightly. The effect can be increased, however, if the patient also takes a thiazide diuretic and eats a low-sodium diet.
Regardless of whether the ADH deficiency is complete or partial, the cause of central diabetes insipidus is always eliminated if possible. For example, a brain tumor causing the ADH deficiency can often be surgically removed.
Therapy of diabetes insipidus renalis
- Drinking an adequate amount of water
- diet low in salt and protein
- if possible elimination of the cause of the disease
If the diabetes insipidus symptoms persist despite these measures, the physician prescribes medications that reduce the amount of urine. Drugs that are sometimes given for diabetes insipidus centralis are considered: diuretic drugs (thiazide diuretics or the potassium-saving diuretic amiloride) or NSAIDs (such as indomethacin).
Sufficient drinking is extremely important in 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 be hereditary or acquired (for example, due to various diseases). In addition, there are cases in which no cause of the disease can be found. They are referred to as “idiopathic”.
Causes of diabetes insipidus centralis
Physicians refer to the hereditary variant as primary diabetes insipidus centralis. It is often caused by a mutation of the vasopressin gene on chromosome 20.
- skull injuries (especially skull base fracture)
- tumors above or inside the saddle of the skull (a saddle-shaped part of the skull bone, in whose depression the pituitary gland is located)
- Nodular tissue neoplasms (granulomas), such as those that can occur in sarcoidosis or tuberculosis
- malformations (such as aneurysms) of the arteries supplying the brain
- infectious brain or meningitis (encephalitis, meningitis)
- total removal of the pituitary gland (hypophysectomy), e.g. in the case of a pituitary tumor
Diabetes insipidus centralis may also develop temporarily in the second half of pregnancy: The placenta may produce an enzyme (vasopressinase) that causes 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
More rarely, hereditary diabetes insipidus renalis is due to a gene mutation on a different chromosome (not a sex chromosome, but a non-sex-determining autosome). This mutation can then lead to disease onset regardless of sex.
Acquired forms of diabetes insipidus renalis are the result of diseases or medications that affect the kidneys. Examples include:
- Polycystic kidney disease: inherited disease in which numerous fluid-filled cavities (cysts) form in the kidneys – at the expense of intact kidney tissue.
- Renal pelvic inflammation
- Sickle cell anemia: Hereditary disease in which sickle-shaped instead of disc-shaped red blood cells (erythrocytes) are formed. These can clog vessels and thus damage the kidneys, among other things.
- Amyloidosis: rare disease involving abnormally folded proteins (proteins consist of long chains of amino acids that are normally folded in a certain way). The abnormal proteins can be deposited in the kidneys, among other places, causing damage to them.
- Sjögren’s syndrome
- certain cancers (such as myeloma, sarcoma)
Diabetes insipidus: Prognosis
In most cases, diabetes insipidus can be treated without any problems. Acquired forms of the disease are sometimes even curable – provided that the cause (e.g. a brain tumor) can be eliminated. If not, however, those affected can usually lead a normal life with the appropriate therapy and good medical care.
There is no cure for congenital (hereditary) diabetes insipidus. However, with proper treatment and care, the disease can be kept under control, so that a normal life is generally possible. However, early treatment is important! For example, if babies are born with hereditary diabetes insipidus renalis but it is not recognized and treated right away, there is a risk of permanent brain damage with reduced intelligence.
Diabetes insipidus that develops during pregnancy returns to normal on its own within one to two weeks after birth.
