Diabetes insipidus is a rare condition where the kidneys cannot retain the appropriate quantity of water. This occurs due to a lack of production of sufficient quantities of the antidiuretic hormone (ADH) or arginine vasopressin (AVP). This hormone is produced in the hypothalamus and released by the pituitary gland, a small gland at the base of the brain that releases several other hormones as well. The condition affects individuals of all age groups. Diabetes insipidus that occurs during pregnancy
is called gestational diabetes insipidus.
Normally, the kidneys secrete excess of water during urine formation, most of which is then reabsorbed. Antidiuretic hormone regulates the kidneys to reabsorb the water into the body; thus, the body releases concentrated urine. However, in the absence of ADH, the kidneys are unable to reabsorb the water and dilute urine is excreted in large quantities.
There are 2 forms of diabetes insipidus. Central diabetes insipidus is a condition that develops in the presence of insufficient quantities of ADH. Nephrogenic diabetes insipidus results when the ducts in the kidney are unable to reabsorb water in the presence of ADH.
Causes of Diabetes Insipidus
Central diabetes insipidus is caused mainly due to decrease in production of the ADH hormone. Some of the causes of central diabetes mellitus are:
- Head injury
- Infections (e.g., meningitis, encephalitis)
- Stroke affecting blood supply to the hypothalamus or the pituitary gland
- Inflammatory conditions affecting the brain which include sarcoidosis, systemic lupus erythematosus and so on
; for example, familial neurohypophyseal diabetes insipidus is a condition caused by mutation in the ADH gene Nephrogenic diabetes insipidus can be due to genetic or acquired causes. Genetic nephrogenic diabetes mellitus commonly manifests in children and could be due to mutation in the aquaporin-2 water channel protein, known as AQP2, or vasopressin V2 receptor (AVPR2).Causes of acquired nephrogenic diabetes insipidus are as follows:
- Kidney disorders, such as polycystic kidney disease
- Use of drugs (e.g., lithium, ofloxacin, demeclocyline, aminoglycosides etc.)
- Severe hypercalcemia (excess quantities of calcium) or hypokalemia (low levels of potassium)
- Formation of inflammatory granulomas in the kidney e.g. sarcoidosis
Symptoms of Diabetes Insipidus
The main symptoms of diabetes insipidus are as follows:
- Increased thirst and craving for iced water (polydipsia) – An individual can drink between 2 to 20 L of water a day
- Increased frequency of urination (polyuria), with production of large volumes of urine
- Symptoms due to dehydration and loss of electrolytes like dry mouth, low blood pressure, fatigue and muscle pains–Seizure – observed in infants and the elderly
- Changes in mental state - observed in infants and the elderly
- Lethargy – observed in infants and the elderly
Diagnosis of Diabetes Insipidus
Diabetes insipidus may be diagnosed in the following ways:
- Analyzing the concentration of the urine, urine output
- Testing the blood for Osmolality of the plasma, electrolyte concentration, levels of blood glucose, levels of plasma AVP
- Scanning the brain using MRI
- Restricting the intake of water – This is a defining test to indicate the cause of excess urination.
- Genetic screening
It is difficult to clearly diagnose diabetes insipidus in children. The neurophysiological changes in children are monitored on a regular basis with MRI. In children with nephrogenic diabetes insipidus, the electrolyte concentrations are measured.
Treatment for Diabetes Insipidus
Treatment for diabetes insipidus differs based on the severity of the condition. Consuming adequate quantities of water may treat mild diabetes insipidus. The drugs used to treat central diabetes insipidus, include carbamezapine
, desmopressin, indapamide, chlorpropamide, among others. These drugs improve the water retention capability of the kidneys. Children are favorably treated with vasopressin or desmopressin (the synthetic analogue of vasopressin).
Maintaining the sodium levels in the body, and thus, the water content in the body, are ways to treat nephrogenic diabetes. Nonsteroidal anti-inflammatory drugs are also used for the treatment.
Indomethacin and chlorothiazide are also used to treat children with nephrogenic diabetes insipidus.
Other therapeutic strategies to treat patients with nephrogenic diabetes insipidus are also being investigated. These include the use of phosphodiesterase (PDE) inhibitors, statins, heat shock proteins (HSP90) and prostaglandins.
Regular monitoring of the patient during treatment should be carried out by which one can identify water intoxication and electrolyte imbalance.
Patients are monitored on a regular basis to understand the cause and severity of the condition, and to watch for any complications. Patients are encouraged to drink large quantitites of water to avoid dehydration.