Diabetes Insipidus

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Contents


Introduction

Diabetes insipidus is a condition in which large volumes of dilute urine are produced due to either a deficiency of antidiuretic hormone (neurogenic diabetes insipidus), a lack of responsiveness of the kidney (nephrogenic), damage to the hypothalamus (dipsogenic) or as a rare complication of pregnancy (gestational) or hypothalamic dysfunction (dipsogenic).

The list of neurogenic causes is considerable and reflects a variety of intracranial diseases. As a general rule, anything that can produce hypopituitarism may induce diabetes insipidus, either as part of generalised hypopituitarism, or in some cases as an isolated disorder.

The list of causes of nephrogenic diabetes insipidus is shorter

Dipsogenic diabetes insipidus is a rare disease in which the hypothalamus malfunctions and induces a permanent state of thirst. This results in excessive fluid intake which suppresses the secretion of ADH.

Gestational diabetes insipidus is a much rarer complication of pregnancy than its better known diabetic counterpart, diabetes mellitus. The placenta produces vasopressinase, which degrades ADH (vasopressin is another name for ADH). Very rarely, the synthesis of vasopressinase by the placenta is sufficient to interfere with the function of ADH.

Psychiatric disorders may rarely include excessive water ingestion (psychogenic polydipsia), despite normal hypothalamic, pituitary and renal function. This form of abnormally high water intake can be confused with diabetes insipidus because the body will respond to the excessive water load by producing lots of urine and thus the patient has polyuria and polydipsia.


Pathology and Clinical Features

Patients present with polyuria and nocturia. The urine output can reach 15L per day (the normal minimum urine ouput is 0.5ml/kg/hour, which gives a daily minimum urine output of around 840ml per day in a 70kg person). This polyuria can have a huge impact on the patient's quality of life.

The unbalanced water loss which occurs in diabetes insipidus produces an increase in the serum osmolality and this induces a sense of thirst. Thus, patients also have polydipsia.

Providing that the patient has access to a sufficient quantity of water electrolyte disturbances and established hyperosmolality will not result because the patient can drink enough water to compensate. However, if the thirst mechanism is disrupted or the patient is unable to drink enough, hyperosmolarity and hypernatraemia develop.


Investigations

The water deprivation test is the central diagnostic procedure. The test is begun in the morning following a light breakfast. The patient is then not allowed any fluids for eight hours. The weight, plasma electrolytes and plasma osmolality, urine output and urine osmolality are measured at frequent intervals during the course of the test. A normal person would respond by engaging their ADH mechanism and thus producing less urine in order to conserve urine. The urine becomes more concentrated. The plasma osmolarity and electrolyte concentrations remain normal.

A patient who has an excessive fluid intake (psychogenic polydipsia) or dipsogenic diabetes insipidus, will respond as a normal person.

A person who has diabetes insipidus will be unable to respond to the water deprivation and will continue to lose water. Their urine output will remain high and the urine will still be dilute, even if though their plasma osmolarity is rising. Their weight will also drop. If these features become established the patient can then be given a synthetic ADH analogue, desmopressin. This should correct neurogenic diabetes insipidus but will not affect nephrogenic diabetes insipidus.

Patients who have diabetes insipidus will usually produce a positive test before the eight hours are finished. It is not necessary to continue the test to eight hours if the diagnosis has been made. Indeed, if the plasma osmolarity is becoming disturbed or significant weight loss (over 3%) occurs, the test should be halted for safety reasons.


Treatment

Neurogenic diabetes insipidus can be treated by giving desmopressin. Although this is a peptide hormone is it sufficiently small that it can be absorted through the nasal mucosa if administered as a nasal spray. Any underlying cause for the diabetes insipidus should be addressed.

Treating the underlying cause is also important in the management of nephrogenic diabetes insipidus but desmopressin may not be very ineffective. Instead, a low salt, low protein diet is used, in conjuction with thiazide diuretics and non-steroidal anti-inflammatory drugs.

The low salt, low protein diet gives kidney fewer solutes to excrete. This reduces the volume of urine the kidney is obliged to make, particularly given that the poor kidney cannot vary the concentration of the urine. However, the diet can be difficult to follow and may be impossible to implement in children.

The use of a diuretic to treat a disease that is characterised by the production of bucketloads of urine may seem bizarre, but the rational is to employ the diuretic to induce a state of volume depletion. This provokes the body into using other systems (that do not use ADH) to increase sodium and water retention by the kidney.

Non-steroidal anti-inflammatory drugs inhibit the synthesis of prostaglandins by the kidney. Prostaglandins oppose the actions of ADH so blocking them reduces natural diuretic processes.

Although nephrogenic diabetes insipidus is secondary to the kidney failing to respond to ADH, the failure may not be absolute and high doses of desmopressin may nevertheles yield some degree of improvement in the symptoms.

Desmopressin should not be employed in dispogenic diabetes insipidus because the abnormal thirst drive will cause the patient to keep drinking. Administering an ADH agonist in this situation will cause fluid retention and hypoosmolarity and can result in a situation that is similar to the syndrome of inappropriate ADH secretion.