Diabetes Insipidus: Types, Causes, and Treatment Options

Diabetes insipidus (DI), by definition, is a polyureic disorder resulting from the insufficient production of antidiuretic hormone (ADH) (central/neurogenic DI) or due to the unresponsiveness of the renal tubules to ADH (nephrogenic DI).

•  In short, this condition results in an imbalance of salt and water metabolism.
•  which results in intense thirst and heavy urination.
•  Diabetes insipidus is a rather rare disorder.
• This condition was recently renamed as:
  • Arginine Vasopressin Deficiency
  • Arginine Vasopressin Resistance (AVP-R)
• Diabetes insipidus is of 4 types:
  • Central DI (CDI)
  • Nephrogenic DI (NDI)
  • Dipsogenic DI
  • Gestational DI

Aetiology

• The cause of diabetes insipidus varies depending upon its type.
• There is no particular cause for about one-third of all cases of central diabetes insipidus. These cases are known as idiopathic.
• Idiopathic cases appear to be related to the immune system attacking the normal healthy cells and producing AVP.
• CDI is a rare form of DI.

Types & Causes of Diabetes Insipidus

Risk factors of Diabetes Insipidus

• Having a family history of DI.
• Taking medications (lithium, demeclocycline, and heavy metals) that can cause kidney problems.
• History of a brain surgery or major head injury.
• Having certain metabolic disorders such as:
  • High blood calcium levels
  • Low blood potassium levels
• In cases of pregnancy, the risk of developing gestational diabetes insipidus is high with:
  • Multi-fetal gestation
  • Conditions affecting liver function, such as preeclampsia and HELLP syndrome.

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Epidemiology

• When considering the general population, DI affects 1 in 25,000 people (0.004%). Hence, it can be said that diabetes insipidus is a rather rare disease.
• Even though it can affect people of any age group, adults are likely to be more susceptible to this ailment.
• Due to its rare occurrence, it must be addressed in medical education and any research setting to improve clinical management.
• Diabetes insipidus is more prevalent among males. But the gene can be passed on to the next generation by women.
• There is no racial predilection for DI.
• The incidence of nephrogenic diabetes insipidus caused by AQP2 mutations is about 1 in 20 million births.
• Inherited causes for nephrogenic and central diabetes insipidus account for only 1 to 2% of the cases.
• Pathophysiology
• In DI, urine osmolality of less than 300 mOsmol/kg is seen.
• In most cases of diabetes insipidus, urine volume usually exceeds 3 to 3.5 liters in 24 hours.
• The posterior pituitary produces ADH, one of the main determinants regarding water homeostasis within the body, and is the principal hormone of diabetes insipidus.
• The physiology of water balance in humans is achieved mainly by three interrelated determinants:
  • Thirst
  • ADH synthesis and secretion
  • Proper kidney function

• If ADH mechanisms are disrupted, a wide range of changes take place in the body.
• Diabetes insipidus is involved with the release of ADH and the sensitivity to ADH in the distal convoluted tubule and the collecting duct.
• During DI, the following changes take place in the body:
  • Electrolyte imbalances
  • Water loss
  • Changes in serum and urine osmolality

• The baroreceptor negative feedback loop responds to changes in blood pressure and volume.
• The hypothalamus responds to the baroreceptor changes in the following ways:
  • Suppressing the ADH synthesis
  • Increasing the ADH synthesis
  • Suppressing or increasing the release of ADH from the posterior pituitary gland.

• ADH release can be stimulated even by slight changes in blood volume (5 to 10% decrease) or mean arterial pressure (5% decrease).
• Hence, the body initially regulates the ADH secretion in response to osmoregulation.
• In cases of severe volume depletion, baroreceptor stimulation of ADH overweighs osmoregulation. 

Central diabetes insipidus

• Absent or reduced production from the hypothalamus or secretion of ADH from the posterior pituitary causes central DI.
• Mostly, this is due to any damage that might happen to the pituitary gland.
• This ultimately results in dilute urine.

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Nephrogenic diabetes insipidus

• Caused due to any defect that might happen to the renal tubules.
• This leads to a decreased response of the tubules to ADH.
• This ultimately leads to dilute urine.

Dipsogenic diabetes insipidus

• Caused by excessive fluid intake or damage to the thirst regulating mechanism of the hypothalamus.
• This results in dilute urine.

Gestational diabetes insipidus

• Caused by an increased concentration of placental vasopressin.
• The placental vasopressin negatively inhibits the mother's ADH, resulting in its deficiency.
• Large amounts of dilute urine are produced as a result of this.

Diagnosis of Diabetes Insipidus

Clinical features in adults

• Urinating more than 3 liters a day (polyuria)
• Bed-wetting
• Severe thirst
• The low-measured concentration of urine
• Dehydration, which might come along with:
  • Loss of consciousness
  • Confusion
  • Dizziness
  • Nausea
  • Fatigue
  • Extreme thirst: often drinking more than 1 gallon of liquid per day.
  • Feeling sluggish

• Weakness
• Muscle pains
• Preference for cold drinks
• Pale, colorless urine
• Crankiness

Clinical features in children and infants

• In the case of infants, the signs and symptoms include:
  • Crankiness
  • Slow growth
  • Vomiting
  • Fever
  • Loss of body weight
  • Poor feeding
• In children, the signs and symptoms include:
  • Urge to urinate more often.
  • Drinking a lot of water
  • New bed-wetting habit
  • Low energy
  • Dehydration

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Complications of diabetes insipidus

• Dehydration and electrolyte imbalance are the main complications of diabetes insipidus.
• This can be compensated by consuming more liquid.
• Dehydration can be dangerous and life-threatening.
• Other complications include:
  • Tachycardia
  • Hypotension
  • Weight loss
  • Fatigue
  • Kidney damage
  • Brain damage
  • Decreased temperature.
  • Headaches

Investigations of Diabetes Insipidus

• A fluid or water deprivation test is the most reliable and simplest method for diagnosing diabetes insipidus.
• The test includes not drinking fluid for several hours to see how the body responds.
• In the case of diabetes insipidus, the patients will continue to urinate large amounts of dilute/watery urine (light coloured urine).
• In the normal case, one would only urinate small amounts of concentrated urine (dark yellow).
• Other tests that help to diagnose diabetes insipidus include:
  • Blood tests check the levels of antidiuretic hormone (ADH).
  • Blood tests check glucose levels, which helps to rule out diabetes mellitus.
  • Urinalysis to check osmolality (the concentration of the urine) and for ketones, which would indicate diabetes mellitus.
  • Imaging tests such as MRI check for any issues with the pituitary gland or hypothalamus, which can lead to diabetes insipidus.

Management of Diabetes Insipidus

Central and gestational diabetes insipidus management:

• Desmopressin is considered the first-line treatment for central diabetes insipidus.
• It works like an antidiuretic hormone.
• Desmopressin can be taken as
  • Injection
  • Pill
  • Nasal spray

• Desmopressin is also sometimes used to treat gestational diabetes insipidus.
• Dipsogenic diabetes insipidus management
• An effective way to treat dipsogenic diabetes insipidus management has not been discovered yet.
• If any underlying condition causes this, the treatment is usually directed towards that particular cause.

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Side effects of desmopressin

• Nosebleeds
• Abdominal pain
• Headache
• Nausea
• A blocked or runny nose
• Water retention (If too much desmopressin is taken or if the patient drinks too much water while taking it). This leads to the following symptoms:
  • Hyponatremia
  • Headaches
  • Feeling bloated
  • Dizziness

Symptoms of hyponatremia

• Severe and prolonged headache.
• Confusion
• Nausea and vomiting

Nephrogenic diabetes insipidus management

• Thiazide diuretics
• Amiloride
• NSAIDS (indomethacin)

Prognosis of Diabetes Insipidus

• The outlook for DI is generally good.
• As long as the proper treatment is taken and if the individual makes sure they consume enough water, DI can be managed and is not considered a serious ailment.
• The risk of any complications that might lead to mortality is more among the following:
  • Infants
  • Seniors
  • People with any mental health conditions (because they may have trouble recognizing thirst and cannot do anything about it).

Also read: Pulmonary Alveolar Proteinosis : Types, Risk Factors

Points to Remember 

• The indirect water deprivation test is not used in pregnancy as prolonged water restriction could lead to:
  • Foetal and maternal dehydration
  • Hypernatremia
  • Increase the risk of uteroplacental insufficiency.

• The literal meaning of diabetes insipidus means passing lots of insipid or 'tasteless' urine.
• Thiazides decrease the urine volume in both central and nephrotic DI. But they also produce an antidiuretic effect, which remains paradox.

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