OVERVIEW
• Diabetes insipidus (DI) is a condition where the body loses too much fluid through excess urination, resulting in a significant risk of dangerous dehydration and other illnesses
• It is a rare condition affecting the regulation of body fluid levels.
• Patients with diabetes insipidus produce large amounts of urine, causing frequent urination and thirst.
• There are two main forms of DI namely central DI (brain condition) and nephrogenic DI (kidney disorder) and the underlying mechanism of the disease varies in the two forms
• Other rare forms include gestational DI and primary polydipsia (psychogenic polydipsia)

NORMAL FLUID REGULATION
• Fluids make up nearly 60 percent of our total body mass. Maintaining the correct amount of fluid is key to overall health.
• Drinking water and consuming food throughout the day provides the required fluid while urinating, sweating and breathing eliminates fluid from the body.
• Fluid regulation is carried out by certain organ systems with the aid of hormones. The kidney and the brain are the two main organs involved in fluid regulation
• The kidneys produce urine to remove the extra fluid in the body. Consequently, the kidneys make less urine to conserve fluid lost to sweating , or make more urine to remove excess fluid in your body.
• On the other hand, the brain regulates this process in various ways. The hypothalamus regulates the feeling of thirst and the need to drink water as well as producing an antidiuretic hormone (ADH), (vasopressin) by the pituitary gland.
• When our body needs to conserve water, the pituitary gland secretes vasopressin into the blood stream. However, when we need to excrete excess water, the hormone is secreted in smaller quantities or not at all to increase urination.

CAUSES OF DIABETES INSIPIDUS
CENTRAL DI
• Central diabetes insipidus is caused by low or absent levels of vasopressin.
• The condition can be primary i.e present at birth, or secondary if it is acquired later in life.
• The cause of primary central diabetes insipidus is not clear. Some cases are believed to be due to a genetic disorder
• Secondary conditions that affect vasopressin production include brain lesions resulting from head injuries, brain surgery and cancers.

NEPHROGENIC DI
• Nephrogenic diabetes insipidus can also be inherited or acquired and once again affect response of the kidneys to vasopressin.
• In nephrogenic DI, the kidneys’ ability to concentrate urine i.e. when water needs to be conserved, is reduced and excess urine is produced.
• Inherited nephrogenic DI presents at birth and usually affects males although women can pass on the gene to their offspring
Causes of secondary (acquired) nephrogenic diabetes insipidus include
? Renal cysts due to various conditions, such as autosomal dominant polycystic kidney disease (ADPKD), medullary cystic disease complex, nephronophthisis, and medullary sponge kidney
? Kidney infection
? Drugs – especially lithium, amphotericin B, dexamethasone, demeclocycline, dopamine, ofloxacin, and orlistat
? Cancers
? High blood calcium levels (hypercalcemia)
? Rare disorders – amyloidosis, Sjögren’s syndrome, and Bardet-Biedl syndrome
? Chronic hypokalemic nephropathy
? Cardiopulmonary bypass, which may influence vasopressin levels and may require
desmopressin treatment

GESTATIONAL DI
Gestational diabetes insipidus is rare and only occurs during pregnancy when an enzyme made by the placenta destroys ADH produced by the mother.

PRIMARY POLYDIPSIA
Another name for this form is dipsogenic diabetes insipidus, and is caused by drinking an excessive amount of fluids. It can be caused by disruption of the thirst-regulating mechanism in the hypothalamus, but has also been linked to mental conditions, such as schizophrenia.

CLINICAL FEATURES OF DI
• Extreme thirst
• Passing large amounts of dilute colorless urine
• Frequent urge to get up at night to pass urine
• Preference for cooler drinks
• In severe cases urine output may be upto 20 liters a day especially if the person is drinking plenty of fluids (normal adult typically produces about 1-2 liters of urine a day).

SUSPECT/RULE OUT POSSIBLE DI IN AN INFANT
• Unusually heavy, wet diapers and frequent need to change
• Frequent bed-wetting
• Fever
• Vomiting
• Constipation
• Sleeping issues
• Delayed growth
• Weight loss

COMPLICATIONS OF DI
• Dehydration – Dry mouth, lethargy, excessive thirst, changes in skin elasticity
• Electrolyte imbalance – Weakness, nausea and vomiting, confusion, muscle cramps and loss of appetite

DIAGNOSIS OF DI
Urine examination – Urine will be colorless and have low specific gravity with a high concentration of water and a low concentration of solutes

Water deprivation test – It is a reliable test to help diagnose diabetes insipidus, but has to be performed by a specialist, as it can be dangerous if performed unsupervised. The test involves withholding fluid intake and allowing the person to become increasingly dehydrated and taking off blood and urine samples

The test can help conclusively rule out psychogenic polydipsia since persons with this condition may try to drink some water during this test, despite strict instructions to the contrary.

Under normal circumstances, dehydration triggers vasopressin release from the pituitary gland, telling the kidneys to conserve water and concentrate the urine.
In diabetes insipidus, either vasopressin is not released, or the kidneys become resistant to the hormone.
The two forms of DI can be further pinpointed if the urine concentration responds to injection or nasal spray of vasopressin.
Improvements in urine concentration indicate that the kidneys are responding to the hormone’s instruction to conserve water, suggesting that the diabetes insipidus is central. If the kidneys fail to respond to the synthetic vasopressin, the cause is likely to be nephrogenic.

Magnetic resonance imaging (MRI) – Diagnostic MRI scan can identify abnormalities in or near the pituitary gland. It is a non-invasive test and uses a powerful magnetic field and radio waves to produce detailed images of brain tissues.

Genetic screening – If there is a family history of excess urination, the doctor may recommend a genetic screening.

TREATMENT OF DI
CENTRAL DI
Mild central DI responds to increasing fluid intake
Abnormalities or tumors in the brain must be treated
A drug called desmopressin (synthetic vasopressin) is given as injection, tablet or nasal spray to replace the deficient ADH
Other medications such as indomethacin and chlorpropamide make ADH more available in the body.

NEPHROGENIC DI
Desmopressin will not help since kidneys are resistant to vasopressin
Low salt diet is recommended
Diuretic such as hydrochlorothiazide can improve symptoms of nephrogenic DI

Drug induced DI – Stop the offending drug

GESTATIONAL DI is treated with desmopressin

PRIMARY POLYDIPSIA is treated by reducing fluid intake and treating any concurrent mental illness

RAPID REVIEW
• Diabetes insipidus is a condition characterized by improper fluid regulation, resulting in excessive urination.
• DI is often accompanied by increased thirst and high water intake.
• As diabetes insipidus is not a common condition, it is usually a diagnosis of exclusion
• Type of DI is confirmed by the water deprivation test
• If not treated or patient fails to drink sufficient water, dangerous dehydration and electrolyte imbalance can occur