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Diabetes Insipidus

Dr. Suvansh Raj NirulaMBBS

January 27, 2021

January 27, 2021

Diabetes Insipidus
Diabetes Insipidus

In diabetes insipidus (DI), due to the decreased secretion or reduced sensitivity to the effects of antidiuretic hormone (ADH), excessive fluid is lost in urine and the patient experiences increased thirst. Most prominent symptoms of diabetes insipidus are polyuria (increased frequency and output of urine) and polydipsia (increased thirst and water intake). The other signs and symptoms are dehydration and electrolyte imbalance, which can also prove fatal. The underlying cause influences the presentation. Diagnosis is made by taking a thorough medical history, conducting a physical examination, laboratory investigations, radiological imaging and some special tests. Treatment includes fluid and electrolyte correction followed by desmopressin in some cases of central diabetes insipidus. The overall outlook is good; however, electrolyte imbalance can be deadly. 

(Read more: Syndrome of inappropriate antidiuretic hormone secretion)

Diuresis is the technical term that refers to excessive production of urine by the kidneys due to filtration of extra body fluids. ADH, also known as arginine vasopressin (AVP), is synthesised by the hypothalamus and is released by the pituitary gland, along with oxytocin, through its posterior lobe. Vasopressin, by binding with V2 receptors in the distal convoluted tubules (DCT) of the kidneys, increases water permeability and resorption of extra fluid. Thus, by reducing the urine output, it exerts an antidiuretic effect. When a person is dehydrated or thirsty, the vasopressin level is raised by the central nervous system (hypothalamus and pituitary gland) and this causes more water to be absorbed back from the urine (which becomes more concentrated and dark) in the kidneys. Similarly, when a person is adequately hydrated and has had enough to drink, the vasopressin levels are down-regulated by the same organs and more water is allowed to leave the body through urine (which becomes diluted and pale). 

Certain conditions can produce central diabetes insipidus (DI), where the synthesis or secretion of ADH is reduced significantly. In other cases, due to underlying causes, the V2 vasopressin (ADH) receptors in the distal convoluted tubules (DCT) of the kidney can become insensitive to the hormone. That is to say, the receptor molecules do not bind with the hormone molecule and the physiological change necessary for the fluid to be absorbed back into the circulatory system of the body does not occur. 

Types of diabetes insipidus

Depending on the cause, four distinct types of diabetes insipidus (DI) 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, tumours, 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 recognise 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 centre 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 presentation of diabetes insipidus may be related to other more complex disorders seen in pregnancy like gestational hypertensionpreeclampsia or HELLP (haemolysis, elevated liver enzymes, low platelet count) syndrome. 

Signs and symptoms of diabetes insipidus

Following signs can be seen in adults:

Following signs 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 the usual for a baby)
    • Sunken eyes
    • Crying with little or no tears
    • Fussiness
    • Cold or discoloured 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

Following signs 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

Causes of diabetes insipidus

The possible causes vary depending on the type of diabetes insipidus: 

Central Diabetes Insipidus:

  • Idiopathic (due to unknown causes)
  • Genetic
  • Post surgery (especially transfrontal and transsphenoidal)
  • Traumatic brain injury
  • Tumours
    • Craniopharyngioma
    • Pituitary tumours (Read more: Prolactinoma)
    • Hypothalamus tumours
    • Metastasis (tumours spread from cancer elsewhere in the body, like lungs, etc.)
  • Infections
  • Autoimmune disease
  • 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) 

(Read more: Snake bite

Nephrogenic Diabetes Insipidus: 

  • Genetic
    • Autosomal dominant 
    • Autosomal recessive 
    • X-linked
  • Drug-induced
  • Electrolyte imbalance
  • 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
  • Sickle cell anaemia, etc. 

Dipsogenic diabetes insipidus:  

Gestational Diabetes Insipidus:

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

Diagnosis of diabetes insipidus

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 the 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 diagnosis for diabetes insipidus: 

  • 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: Inability to control the urine at night is not necessarily due to 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. 

Tests for diabetes insipidus

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, 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:
    • Physical appearance of urine: The colour 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: 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.
    • Presence of glucose or ketone bodies in urine also indicate 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 anaemia.
  • Radiological imaging studies: Various modalities can be used to diagnose the possible underlying cause of central or dipsogenic diabetes insipidus. Tumours or injury to the hypothalamus or pituitary gland can be visualised 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. 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). If the urine volume reduces and

Treatment of diabetes insipidus

Treatment would depend on which type of diabetes insipidus the patient has. 

Central diabetes insipidus:

  • Mild cases can be managed by fluid replacement by increasing oral intake. Dehydration can be corrected with intravenous fluids and electrolytes. (Read more: What is fluid therapy)
  • 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 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. Combination of a thiazide diuretic and an NSAID can be given to further reduce urine volume.  
  • Intermittent catheterisation is needed in severe cases to prevent bladder back flow complications. 

Complications of diabetes insipidus

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. (Read more: Sleep disorders)

Prognosis of diabetes insipidus

In cases where treatment along with fluid and electrolyte correction is started on time, the outlook is good. 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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Doctors for Diabetes Insipidus

Dr. Tanmay Bharani Dr. Tanmay Bharani Endocrinology
15 Years of Experience
Dr. Sunil Kumar Mishra Dr. Sunil Kumar Mishra Endocrinology
23 Years of Experience
Dr. Parjeet Kaur Dr. Parjeet Kaur Endocrinology
19 Years of Experience
Dr. M Shafi Kuchay Dr. M Shafi Kuchay Endocrinology
13 Years of Experience
Consult a Doctor

Medicines for Diabetes Insipidus

Medicines listed below are available for Diabetes Insipidus. Please note that you should not take any medicines without doctor consultation. Taking any medicine without doctor's consultation can cause serious problems.