Diabetes insipidus, central E23.2

Synonyms

Water urine dysentery; diabetes spurius; neurohypophyseal D.i.; pituitary D.i.;

First describer

The Dutch anatomist Pieter Pauw (1564 - 1617) was the first to describe the clinical picture of diabetes insipidus in an 18-year-old girl in 1590, who died during the course of the disease (Kivelä 1998).

Central diabetes insipidus (ZDI) is a disease in which there is reduced ADH secretion in the posterior lobe of the pituitary gland (Brochert 2005). As a result, the kidneys are unable to produce concentrated urine when dehydrated (Herold 2021).

In ZDI, the urine volume comprises > 50 ml / kg bw per day (corresponds to > 3500 ml at 70 kg).

(Kasper 2015)

ZDI is a form of diabetes insipidus, which also includes:

• nephrogenic diabetes insipidus (NDI)
• gestational diabetes insipidus
• primary polydipsia (see diabetes insipidus)

(Kasper 2015)

ZDI is divided into permanent ZDI and partial ZDI (Siegenthaler 2006).

Diabetes insipidus is one of the rare diseases and affects both sexes equally often (Lehnert 2010). ZDI is found more frequently than nephrogenic diabetes insipidus (Herold 2021).

Causes of ZDI can be:

• idiopathic

The idiopathic form occurs in about 1/3 of cases. On the one hand, it is dominantly inherited and on the other hand, autoantibodies are found against cells that produce vasopressin (Herold 2021).

In genetic ZDI, 5 different forms are now known. These include the so-called Wolfram syndrome, in the context of which - together with diabetes mellitus, neural deafness and optic atrophy - a ZDI can occur (Kasper 2015).

• Secondary

The secondary form is found in about 2/3 of cases. It results from trauma, tumors, inflammatory diseases such as encephalitis, meningitis, etc. (Herold 2021), post-neurosurgical, aneurysms, hypoxia, drugs that interfere with AVP release such as phenytoin, etc. (Kuhlmann 2015).

Secondary D. i. can also occur:

• in the course of pregnancy due to a primary plasma ADH deficiency as so-called partial gestational diabetes insipidus

(Kasper 2015)

• in the case of excessive fluid intake due to an inhibition of secretion. One differentiates between 3 forms:
• 1. dipsogenic D.i.

In this case, the inadequate increase in thirst is caused by a reduction of the target value in the osmoreceptor regulatory mechanism (can occur in the context of meningitis, neurosarcoidosis, multiple sclerosis, etc.).

• 2. Psychogenic polydipsia

In psychogenic polydipsia, there is primarily no increased feeling of thirst; polydipsia rather occurs in the context of psychoses or obsessive-compulsive neuroses.

• 3. Iatrogenic polydipsia

This form of polydipsia arises from recommendations (medical or tabloid) that one should drink a lot because it has preventive or therapeutic benefits.

(Kasper 2015)

Due to the lack of antidiuretic hormone of the posterior lobe of the pituitary gland, the ADH-dependent urine concentration, which takes place in the distal renal tubules and the collecting tubes, is not (sufficiently) possible. There is increased excretion of a dilute urine, polyuria with a urine osmolality of < 300 mosmol / µg (Herold 2021).

At the same time, there is an inability to concentrate the urine (so-called asthenuria). This causes osmoregulatory compulsive polydipsia (Herold 2021). If the patient has only a limited amount of fluid available, dehydration occurs very quickly (Borchert 2005).

The ZDI only becomes clinically apparent when > 80 % of the ADH-secreting neurons have failed (Herold 2021).

ZDI due to genetic defects typically does not manifest itself immediately after birth, but rather develops - depending on the mutation - at different rates over months or years and then remains manifest.

In middle age, there may be a spontaneous improvement in symptoms. The cause of this is as yet unknown (Kasper 2015).

• Polydipsia
• Polyuria (in 50 % of patients urine output is between 4 - 8 l / d, in 25 % > 12 l / d and in individual cases up to 40 l / d [Siegenthaler 2006])
• Enuresis

[Kasper 2015)

• nocturia (if this is absent, a D.i. is practically excluded)
• Daytime sleepiness due to nocturnal polyuria (Kasper 2015)
• Asthenuria (the ability of the urine to concentrate is absent)

(Herold 2021)

• Symptoms of pituitary gland stylet transection:

In a ZDI caused by trauma or postoperatively, in which there is a transection of the pituitary stalk (Siegenthaler 2006), there are 3 different phases:

• 1st phase, so-called initial phase:

In this phase, polyuria occurs and lasts for about 4 - 5 days. It is assumed that the lack of ADH release is due to a dysfunction of the hypothalamus.

• 2nd phase, so-called antidiuretic phase:

It lasts for about 6 - 11 days and is caused by the release of residual ADH from the pituitary gland.

• 3rd phase, so-called permanent ZDI:

After the first two phases, a permanent ZDI then sets in.

(Kuhlmann 2015)

• Symptoms of destruction above the eminentia mediana:

A permanent ZDI occurs in patients who experience destruction above the eminentia mediana (Siegenthaler 2006).

• Symptoms of destruction below the eminentia mediana:

In this case, both a permanent and a transient ZDI can occur (Siegenthaler 2006).

In the case of the above-mentioned symptoms, a D.i. is suspected after glucosuria has been ruled out.

The following diagnostic procedure is recommended:

• 24 h urine

If there is an excretion volume of > 50 ml / kg bw (corresponds to 70 kg > 3500 ml) and a serum osmolality of > 300 mosmol / l, this confirms the diagnosis of a D.i. (Kasper 2015).

For further diagnostic specification see "Laboratory".

MRI

The posterior pituitary lobe appears on cerebral MRI in healthy adults and children as a hyperintense signal, the so-called "bright spot". This is reduced in size or absent in patients with cerebral D.i. (Kasper 2015).

In addition, MRI can also provide evidence of the cause of a ZDI (e.g. tumours) (Kasper 2015).

• Sodium in urine decreased
• Sodium in plasma increased
• specific gravity ≤ 1004 g / l (normal value 1010 - 1030 g / l)
• Osmolality in serum higher than in urine (in healthy individuals 270 - 303 mosmol / l in serum and 500 - 1170 mosmol / l in urine)

(Striebel 2014)

• Osmolality in urine < 300 mosmol / l (Herold 2021).

• 24 h urine:

If here an excretion volume of > 50 ml / kg bw (corresponds to 70 kg > 3500 ml) and a serum osmolality of > 300 mosmol / l, this confirms the diagnosis of D.i. (Kasper 2015).

To further specify the type of D.i., further diagnostic measures are required.

• Measurement of Copeptin:

Measurement of copeptin is best for further differentiation. This test method has higher sensitivity and specificity than the thirst test with ADH- measurement performed so far.

Test procedure:

The determination of copeptin can be performed as a stress test with hypertonic NaCl solution or as a measurement after dehydration.

• Stress test with NaCl:

Here, copeptin is determined first, followed by infusion of a hypertonic 3% NaCl solution, and copeptin is measured again.

Result at ZDI:

• Urine osmolality remains low
• Plasma osmolality increases
• Copeptin i. S. remains low

NaCl- test is more reliable than dehydration test with 95%.

(Herold 2021)

• Dehydration:

Copeptin level is measured after 8 hours of dehydration in the morning fasting.

In central diabetes insipidus, the copeptin level is < 2.6 pmol / l.

If the determined value is between 2.6 - 20 pmol / l, a further fasting blood sample is required after 16 h of dehydration, in which serum sodium is determined in addition to copeptin. The copeptin index is calculated from these values. If this is < 20, it is a case of central diabetes insipidus partialis and if the value is > 20, it is a case of primary polydipsia.

(Kasper 2015)

The above-mentioned stress test with NaCl has taken the place of the so-called "Hickey-Hare test" still mentioned in the older literature (Nawroth 2013).

• nephrogenic diabetes insipidus
• primary polydipsia (see diabetes insipidus)
• diabetes mellitus (in this case there is osmotic diuresis)
• diuretic abuse
• hypercalcemic crisis
• Dry mouth (indicated by medications such as anticholinergics).

(Herold 2021)

Causal treatment of ZDI consists of therapy of the underlying condition, if this is possible.

Symptomatic therapy can be given with desmopressin, a vasopressin analogue, which is available for i. v., s. c. intranasal or oral use (Herold 2021). The normal dose is

• approx. 2 - 3 x 100 - 400 µg / d orally
• approx. 2 - 3 x 10 - 20 µg / d as a nasal spray

(Kasper 2015)

The amount of the dose depends on the urine volume and serum sodium values (Fassnacht 2019).

An uncomplicated ZDI can be completely eliminated with this (Kasper 2015).

If some ADH is still present, additional medications that include

• enhance the release of ADH are used such as:
  • Clofibrate
  • Carbamazepine
• Drugs that complement the action of ADH such as:
  • Chlorpropamide
  • Carbamazepine

(Kuhlmann 2015)

• Gestational diabetes insipidus:

Gestational diabetes insipidus does not respond to ADH. Treatment in this case is with desmopressin (Lehnert 2010).

Dosage recommendation: 0.05 - 0.02 ml (5 - 20 µg) of solution (100 µg / ml) intranasally (Paumgartner 2013). The exact dosage depends on the urine volume and serum sodium (Fassnacht 2019).

• Postoperative ZDI:

Neurosurgical patients should be educated about the symptoms of possible ZDI preoperatively. It is also recommended to have serum electrolytes determined regularly until the 10th p. o. day (Fassnacht 2019).

The treatment of p.o. diabetes insipidus consists in administrations of desmopressin i. v. or s. c.,

Recommended dosage: 0.25 - 1.0 µg every 12 - 24 hours.

The primary goal of treatment is normalization of urine volume and serum sodium.

If the ZDI persists at discharge, oral or intranasal administration can be switched to.

The patient should be informed about possible side effects of the medication (such as nausea, vomiting, headache and, in the case of progressive hyponatremia, unconsciousness or even coma), as immediate consultation with the treating physician may be necessary due to pausing the medication.

(Fassnacht 2019)

The prognosis of ZDI depends primarily on the underlying disease, and if it is a tumorous disease, on the histology (Lentze 2014).

An uncomplicated ZDI can be completely eliminated with appropriate treatment (Kasper 2015).

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