Diabetes Insipidus

Depending on the diabetes insipidus cause, 4 distinct diabetes insipidus types exist - 

Central Diabetes Insipidus

The body does not produce sufficient ADH and water is continuously lost through the urine. Even if the person becomes dehydrated, due to the deficiency of vasopressin, the body is unable to claim fluid back from the urine in the kidneys. Hormone production can be affected due to infections, tumors, trauma, or surgery of the hypothalamus or the pituitary gland. Central diabetes insipidus is the most common type. 

Nephrogenic Diabetes Insipidus

Certain substances (including drugs and imbalanced electrolytes) can cause malfunctioning of the receptors that recognize and bind with the ADH to reabsorb water. Sometimes, nephrogenic diabetes insipidus can also be genetically inherited and present since birth. The most common cause of nephrogenic diabetes insipidus is the use of lithium (used to treat mania and bipolar disorder). 

Dipsogenic Diabetes Insipidus

This is also called primary polydipsia (increased oral fluid intake) and generally occurs not due to the absence or insensitivity of kidney receptors towards vasopressin, but due to damage to the thirst-regulating mechanism. The center in the brain that regulates thirst, and thus oral fluid intake, is present in the hypothalamus. Any injury, infection, or damage to it, or due to other associated mental health problems, primary polydipsia can set in.

Gestational Diabetes Insipidus

Gestational diabetes insipidus is the term used to exclusively refer to the disease that occurs during pregnancy and in the immediate postpartum period. It may occur due to a few reasons, the first being the production of an enzyme (vasopressinase) by the placenta, which breaks down vasopressin and prevents its action. In some women, this enzyme may not get cleared and gestational diabetes insipidus can set in. However, sometimes the presence of diabetes insipidus may be related to other more complex disorders seen in pregnancy like gestational hypertension, preeclampsia, or HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome.

Further, you will read about diabetes insipidus symptoms.

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The following diabetes insipidus symptoms can be seen in adults -

• Severe thirst and increased fluid intake
• Urinating a lot and more frequently
• Waking up at night to empty the bladder
• Preference for cold drinks
• Dehydration:
  • Fatigue
  • Feeling sluggish
  • Dizziness
  • Confusion
  • Nausea
• Weakness
• Muscle pain
• Irritability

The following diabetes insipidus symptoms can be seen in infants -

• Crankiness
• Slow growth
• Poor feeding
• Dehydration in newborns: 
  • Sunken soft spot on the top of the head (called the anterior fontanelle in medical terms)
  • Sleeping too much (more than usual for a baby)
  • Sunken eyes
  • Crying with little or no tears
  • Fussiness
  • Cold or discolored hands and feet
  • Wrinkly skin
• Dehydration in older infants and toddlers: 
  • Tired or cranky
  • Not playful
  • A dry diaper for 6 hours or longer
  • Sunken eyes
  • Crying with few or no tears
  • A dry mouth
  • Constipation or hard and few bowel movements 
  • Cold hands
  • Fast breathing
  • Fast heart rate

The following diabetes insipidus symptoms can be seen in children -

• Drinking a lot of water
• Frequent voiding of the bladder, sometimes every hour
• New bedwetting habit or waking up at night to urinate
• Dehydration:
  • Fatigue
  • Feeling sluggish
  • Dizziness
  • Confusion
  • Nausea

Now, please check out diabetes insipidus causes in the next section of this article.

The possible diabetes insipidus causes vary depending on the type -

Central Diabetes Insipidus

• Idiopathic (due to unknown causes)
• Genetic
• Post-surgery (especially transfrontal and transsphenoidal)
• Traumatic brain injury
• Tumors
  • Craniopharyngioma
  • Pituitary tumors (Read more: Prolactinoma)
  • Hypothalamus tumors
  • Metastasis (tumors spread from cancer elsewhere in the body, like lungs, etc.)
• Infections
  • Meningitis (tubercular, viral, etc)
  • Toxoplasmosis
• Autoimmune disease
  • Systemic lupus erythematosus (SLE)
  • Sarcoidosis
  • Scleroderma, and more. 
• Infractions
  • Aneurysm (dilated ballooned-out blood vessel) rupture
  • Sheehan’s syndrome (after childbirth, sometimes the pituitary gland can lose its blood supply and its tissue can die)
• Toxins (like snake venom)

Nephrogenic Diabetes Insipidus

• Genetic
  • Autosomal dominant 
  • Autosomal recessive 
  • X-linked
• Drug-induced
  • Lithium (used in the treatment of bipolar disorder and mania; important cause of nephrogenic diabetes insipidus)
  • Demeclocycline
  • Amphotericin B
  • Loop diuretics (furosemide, etc)
• Electrolyte imbalance
  • Hypokalaemia
  • Hypercalcemia 
• Kidney diseases affecting the kidney medulla
  • Pyelonephritis (purulent kidney infection)
  • Hydronephrosis 
  • NSAID-induced kidney damage (nephropathy)
  • Amyloidosis
  • Sarcoidosis
  • Polycystic kidney disease
  • Multiple myeloma
  • Fanconi syndrome
• Infections
  • HIV
• Sickle cell anemia, etc. 

Dipsogenic diabetes insipidus

• Psychogenic
  • Obsessive Compulsive Disorder (OCD)
  • Schizophrenia
• Infections
  • Tubercular meningitis 
• Trauma or head injury
• Sarcoidosis
• Multiple Sclerosis (MS)
• Idiopathic 

Gestational Diabetes Insipidus

• Due to the vasopressinase enzyme secreted by the placenta during pregnancy that deactivates vasopressin or ADH.

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The doctor will begin by taking a proper medical history with an emphasis on recent brain surgery, brain infection, head trauma, mental illnesses, autoimmune diseases, or pregnancy. Any new psychiatric or neurological manifestations are also sought out. Usually, suspicion of diabetes insipidus (DI) is raised due to complaints of unexplained polyuria (excessive urination) and/or polydipsia (excessive thirst and water intake). 

A clinical examination is conducted with a focus on neurological testing. A psychiatric evaluation might also be needed to rule out psychogenic causes. After ruling out the other differential diagnoses, with the help of various investigations and tests, the underlying cause of diabetes Insipidus is elucidated and treated accordingly. 

The differential diabetes insipidus diagnosis -

• Diabetes mellitus: Both diseases present with polyuria and polydipsia but are caused due to different reasons. Furthermore, the other presenting features set the two apart. 
• Enuresis or bedwetting in older children: The inability to control the urine at night is not necessarily due to the overproduction of urine. 
• Urinary tract infection (UTI): While a patient complains of increased urgency to urinate in a UTI, urine volume itself is not increased.

Following are the tests you might be asked to get done -

Blood tests

• Blood sugar test: Elevated blood glucose levels can indicate diabetes mellitus, which also presents with polyuria and polydipsia
• Kidney function tests: To rule out kidney diseases, and kidney failure and check the serum electrolyte levels. Electrolyte imbalance due to diabetes Insipidus can prove fatal.
• Serum antibody tests: Autoimmune diseases can be ruled out by testing for their specific indicative antibodies.
• HIV test

Urine tests

• The physical appearance of urine: The color of urine (dark or pale) indicates the hydration status of the individual.
• 24-hour urine output: Urine output is more than 3L per day in diabetes insipidus.
• Urine osmolality: This informs about the concentration of the urine and also helps grade the results of the water deprivation test described later. 
• Urinalysis (urine routine) gives information about the loss of electrolytes and indication for imbalance.
• The presence of glucose or ketone bodies in urine also indicates uncontrolled diabetes mellitus.

Other investigations

• Lumbar puncture and cerebrospinal fluid analysis, culture, and sensitivity testing: They can rule out infection of the brain (encephalitis) or the brain covering (meningitis).
• Peripheral blood smear test: It can show sickle red blood cells in case of sickle cell anemia.

Radiological imaging studies

Various modalities can be used to diagnose the possible underlying cause of central or dipsogenic diabetes insipidus. Tumors or injuries to the hypothalamus or pituitary gland can be visualized using:

• X-ray of the skull
• CT scan
• MRI of the brain 
• Kidney diseases can also require radiological imaging investigations and at times biopsies as well for diagnosis. 

Special tests

Some special tests are carried out to confirm the diagnosis of diabetes insipidus and to differentiate between central and nephrogenic types. These tests are:

• Water deprivation test: A special test in which the patient does not consume water or other fluids for a prolonged period (of at least 6 to 8 hours). The urine output is measured after this. If there is a decrease in the volume from the previously recorded output, the cause of polyuria was most likely excessive water intake. However, if the urine output volume remains unchanged the patient is likely suffering from diabetes insipidus. A water deprivation test is followed up by an antidiuretic hormone test. 
• Antidiuretic hormone test: A medicine called desmopressin, similar to the naturally occurring vasopressin, is given to the patient after a period of water deprivation (6 to 8 hours).

Keep reading this article to know more about diabetes insipidus treatment.

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Diabetes insipidus treatment would depend on type - 

Central diabetes insipidus

• Mild cases can be managed by fluid replacement by increasing oral intake. Dehydration can be corrected with intravenous fluids and electrolytes.
• ADH replacement by desmopressin can be done. However, this increases the risk of hyponatremia and should be prescribed judiciously. 

Nephrogenic diabetes insipidus

• Cases with less than 4L per day of urine output do not need definitive management.
• In the case of drug-induced diabetes insipidus (very common with lithium use), the drug dose should be stopped or reduced.
• Mild to moderate diabetes insipidus can be treated with desmopressin. A combination of a thiazide diuretic and an NSAID can be given to further reduce urine volume.
• Intermittent catheterization is needed in severe cases to prevent bladder backflow complications.

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Some of the complications that can occur because of diabetes insipidus are: 

Dehydration

Dehydration can set in due to unchecked loss of water through urine and an imbalance in ADH, which regulates the water balance of the body. Along with water, other electrolytes like sodium can also be lost.

Electrolyte imbalance

Loss of the body's electrolytes can impact the overall functioning of the body. Vital organs can be affected and death can also occur in severe cases. 

Sleep disturbance

Repeated waking at night to urinate can disrupt the sleep-wake cycle.

In cases where diabetes insipidus treatment along with fluid and electrolyte correction is started on time, the outlook is good. The elderly, children and those with acute illnesses are at greater risk of dehydration, hypernatraemia, cardiovascular collapse, and even death. The underlying cause significantly determines the overall outcome.

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