People with diabetes insipidus excrete excessive amounts of urine and suffer from increased thirst – just like diabetics, i.e. patients with diabetes mellitus. In contrast to diabetes, however, diabetes insipidus is based on a hormone-related disruption of the water-salt balance. Read here what can cause this disorder, which symptoms can occur in addition to increased urination and drinking and treatment for diabetes insipidus!
ICD codes for diabetes insipidus: N25 | E23
• Definition : hormonal imbalance in the water-electrolyte balance caused by excessive urinary excretion. The kidneys are unable to concentrate urine and retain water.
• Causes : either lack of antidiuretic hormone, ADH (diabetes insipidus centralis) or poor kidney response to ADH (diabetes insipidus renalis).
• Symptoms : Excessive urine output (polyuria), very dilute urine, excessive thirst and increased fluid intake (polydipsia), possibly neurological symptoms (such as confusion, weakness).
• Diagnostics : blood and urine tests, thirst test.
• Treatment for diabetes insipidus : depending on the type and severity of the disease with medication (desmopressin as an ADH substitute, possibly also other medication) and if possible eliminating the cause. Sometimes, in addition to treating the cause, a low-salt and low-protein diet and adequate fluid intake are sufficient.
Definition of diabetes insipidus
Diabetes insipidus (“water urinary dysentery”) is a rare disease caused by a hormonal imbalance. This throws the water-electrolyte balance (water-salt balance) out of 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!).
Types of diabetes insipidus
The hormone imbalance behind diabetes insipidus involves antidiuretic hormone (ADH). The hormone, also known as vasopressin, is formed in the hypothalamus, a part of the diencephalon. However, it is stored and released as required by the neighboring pituitary gland (pituitary gland).
ADH is involved in the regulation of water balance. When the body is dehydrated, the pituitary gland secretes ADH into the blood. It causes the kidneys to concentrate urine more – so retain more water.
In diabetes insipidus, this regulatory mechanism is disrupted. Depending on where exactly the disorder is, doctors differentiate between the following forms of the disease:
• Diabetes insipidus centralis : Here, a disorder in the area of the hypothalamus or pituitary gland causes an ADH deficiency – the hormone is either missing completely or is present in too small a quantity. 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 insipidus renalis : In renal diabetes insipidus, there is sufficient ADH, but the kidneys do not respond or do not respond sufficiently. So there is ADH resistance. Doctors also refer to this form of the disease as nephrogenic diabetes insipidus (“nephrogenic” means “starting from the kidneys “).
Diabetes mellitus: similarities and differences
Despite a different disease mechanism, diabetes insipidus and diabetes mellitus 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 output in both diseases.
As mentioned, diabetes insipidus is caused by the kidneys’ inability to concentrate urine. So this is diluted – hence the name diabetes insipidus = ” tasteless flow “.
In contrast, the frequent urination in diabetes mellitus is due to the abnormally high blood sugar level. The body tries to get rid of excess sugar (glucose) through urine. And because sugar physically binds water, a lot of water is also lost: the patient excretes large amounts of sugary urine – hence the term ” honey-sweet flow “.
Symptoms of diabetes insipidus
The main symptoms of diabetes insipidus are:
• Polyuria : Excessive urination of more than 2.5 liters in 24 hours (in young children sometimes diarrhea instead of polyuria ). The increased urination is particularly noticeable at night – the need to urinate at night (nocturia) repeatedly wakes up those affected.
• Polydipsia : increased thirst and fluid intake (ice-cold water is often preferred).
• Asthenuria : inability of the kidneys to concentrate urine, causing it to be dilute (measurable as decreased osmolality = decreased concentration of dissolved particles).
If the patient cannot compensate for the increased water loss by drinking more, the body dries out. Medical professionals refer to this as dehydration.
Neurological symptoms sometimes also occur with diabetes insipidus : increased urine excretion increases the sodium level in the blood (hypernatremia). This can manifest itself, for example, in confusion, muscle weakness and lethargy. Lethargy is a disorder of consciousness with drowsiness and physical and mental slowdown (sluggishness).
In some patients, diabetes insipidus is the result of another disease (see Causes below). Then there are the symptoms of the underlying disease.
Causes of diabetes Insipidus
Both types of the disease – central and renal diabetes insipidus – can be hereditary or acquired (e.g. due to various diseases). There are also cases in which no cause of the disease can be found. They are referred to as ” idiopathic “.
Causes of central diabetes insipidus
Physicians refer to the hereditary variant as primary diabetes insipidus centralis. Often there is a change (mutation) in the vasopressin gene on chromosome 20.
Secondary diabetes insipidus centralis is acquired. It can have the following triggers, among others:
- Skull injuries (esp. skull base fracture).
- Tumors above or within the Turk’s saddle (a saddle-shaped part of the skull bone in which the pituitary gland is located).
- Nodular new tissue formation (granulomas), such as can occur in sarcoid or tuberculosis.
- Malformations (such as aneurysms) of the arteries supplying the brain.
- Infection-related inflammation of the brain or meninges (encephalitis, meningitis).
- Total removal of the pituitary gland (hypophysectomy), eg 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 increased breakdown of ADH. The hormone level can then drop so much that the kidneys can no longer retain enough water in the body.
Causes of renal diabetes insipidus
In some patients, renal diabetes insipidus is hereditary. The cause is usually a gene change (gene mutation) on the X chromosome, i.e. the female sex chromosome. Affected men always develop renal diabetes insipidus because they only have one X chromosome. However, in women with two X chromosomes, the mutation can have different effects: some women have no symptoms, others develop polydipsia and polyuria to varying degrees, and still others develop renal diabetes insipidus with the same severity as men with this mutation.
More rarely, hereditary diabetes insipidus renalis is caused by a gene mutation on another chromosome (not a sex chromosome, but a non-sex-determining 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 medications 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.
- Inflammation of the renal pelvis.
- Sickle cell anemia : an inherited disorder in which red blood cells (erythrocytes) are formed that are sickle-shaped rather than disc-shaped. These can block blood vessels and damage the kidneys, among other things.
- Amyloidosis : rare disease with abnormally folded proteins (proteins are made up of long chains of amino acids that are normally folded in a specific way). The abnormal proteins can be deposited in the kidneys, among other things, and damage them as a result.
- Sjogren’s Syndrome.
- Certain cancers (such as myeloma, sarcoma).
- Various medications : mainly lithium (for mental disorders), but also others such as demeclocycline and ofloxacin (antibiotics), amphotericin B (antifungal medication), dexamethasone (a cortisone), ifosfamide (cancer medication), orlistat (for obesity).
Diagnosis of diabetes insipidus
In a conversation with the patient (or in the case of children with the parents), the doctor first collects the medical history. Among other things, he inquires about the symptoms that occur and any known underlying diseases. A general physical exam 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 orders blood and urine tests:
• Blood : Elevated levels of sodium and other salts (electrolytes) can be detected in diabetes insipidus. The sodium level is particularly significantly increased in patients who do not (or cannot) drink enough fluids to compensate for the loss of water.
• Urine : The urine over 24 hours is collected and then analyzed. In diabetes insipidus it is diluted (decreased concentration of dissolved particles = decreased osmolality). The specific urine weight is reduced, the sugar content in the urine is normal (distinguishing feature from diabetes mellitus – there the sugar in the urine is increased).
The suspected diagnosis of diabetes insipidus can be confirmed with a thirst test (water deprivation test). The exact test procedure may vary. Basically it works like this:
The patient must not drink anything for several hours (eg 12 hours). During this time he will be under constant medical surveillance in case he becomes dangerously dehydrated. Various parameters are regularly measured, such as the amount of urine passed, the amount of dissolved particles (osmolality) in the urine and blood, and the patient’s body weight.
Despite lack of fluid intake, patients with diabetes insipidus continue to excrete urine, and this urine remains diluted (unchanged urine osmolality) while blood serum osmolality increases. In healthy people, on the other hand, the amount of urine would decrease and the urine osmolality would increase when they tried to drink thirst.
The test is terminated either after the scheduled run time or earlier if the patient’s blood pressure falls, heart rate increases, or body weight decreases by more than five percent.
Distinguishing between central and renal diabetes insipidus
If the measurements during the thirst test confirm diabetes insipidus, the doctor can find out which form of the disease is present before the end of the test by administering a hormone preparation:
To do this, he injects the patient with ADH, i.e. vasopressin (or its synthetic derivative desmopressin, which is also available as a nasal spray). Then the urine is analyzed again:
• Diabetes insipidus centralis : The administration of vasopressin reduces urine excretion and the urine is less diluted – recognizable by an increase in urine osmolality: It is 50 to 100 percent if the disease is based on a complete ADH deficiency, and still still 15 to 45 percent with partial ADH deficiency (lower ADH level).
• Diabetes insipidus renalis : Despite vasopressin intake, 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 hormones, but a missing or poor kidney response to the hormone.
A direct measurement of ADH in the blood at the end of the thirst experiment (before vasopressin injection) could also distinguish between the two forms. ADH levels would be low in central diabetes insipidus and appropriately elevated in renal diabetes insipidus. 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
If someone drinks many liters of liquid a day and then passes it out again, it is not always due to a form of diabetes. Thirst and, as a result, urination can also be increased beyond normal as a result of a mental illness such as schizophrenia.
When clarifying suspected diabetes insipidus, the doctor must rule out such psychogenic polydipsia, which is not always easy. But there are some clues. For example, unlike people with diabetes insipidus, people with psychogenic polydipsia do not suffer from nighttime urges to urinate (nocturia) that repeatedly wake them up.
Treatment for diabetes insipidus
The treatment for diabetes insipidus depends on the type, cause and severity of the disease. It aims to reduce urine output to such an extent that the patient can lead a normal life and are no longer woken up by excessive urination at night.
Therapy of diabetes insipidus centralis
With diabetes insipidus centralis, hormone substitution is usually necessary – the missing hormone ADH must be replaced with medication, namely through the regular administration of desmopressin. This artificial derivative of the antidiuretic hormone works the same as its natural counterpart, but has a longer duration of action. It can be applied in different ways. Many patients administer desmopressin as a nasal spray. The active ingredient is also available as a tablet and as an injection under the skin or in a vein. The dosage is adjusted individually in all cases.
Children (and adults) who wet themselves at night (bedwetting, enuresis) are often treated with desmopressin – it suppresses the urge to urinate at night.
In addition to or as an alternative to desmopressin, other medications can be useful for diabetes insipidus centralis:
• Thiazide diuretics : These are diuretics that, paradoxically, can reduce urine output in patients with central diabetes insipidus (and renal diabetes insipidus).
• 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 reducer chlorpropamide and the epilepsy drug carbamazepine. They can be combined with thiazide diuretics.
• Prostaglandin inhibitors : Drugs such as indomethacin (an NSAID medicine used to reduce pain and inflammation) can decrease the amount of urine produced, although usually only slightly. However, the effect can be increased if the patient also takes a thiazide diuretic and eats a low-sodium diet.
Regardless of whether the ADH deficiency is complete or partial – if possible, the cause of central diabetes insipidus is always 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, eliminate the cause of the disease.
If the diabetes insipidus symptoms persist despite these measures, the doctor prescribes drugs that reduce the amount of urine produced. Drugs that can be used are those that are sometimes given in diabetes insipidus centralis: draining drugs (thiazide diuretics or the potassium-sparing diuretic amiloride) or NSAIDs (such as indomethacin).
Sufficient drinking is extremely important in diabetes insipidus renalis: Even several hours without drinking water can cause severe dehydration!
Prognosis of diabetes insipidus
In most cases, diabetes insipidus can be treated without any problems. Acquired forms of the disease are sometimes even curable – provided the cause (eg 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. However, with the right treatment and care, the disease can be kept under control and a normal life is generally possible. However, early treatment is important! For example, if babies are born with hereditary diabetes insipidus renalis, but this is not recognized and treated immediately, there is a risk of permanent brain damage with intellectual disability.
Diabetes insipidus that develops during pregnancy returns to normal on its own within a week or two after birth.