What Is Central Diabetes Insipidus?

  • Afsheen Hidayat MSc in Clinical Microbiology, Queen Mary University of London, UK

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Central diabetes insipidus (CDI) is a rare disorder resulting from insufficient production or release of vasopressin. It causes the fluids in the body to become out of balance and is characterized by excessive thirst (polydipsia) and excessive urination (polyuria).

Overview

CDI is caused by impairment of vasopressin secretion. Vasopressin or arginine vasopressin (AVP) is known as the anti-diuretic hormone. Vasopressin is produced by the hypothalamus and stored in the posterior pituitary gland before being released to regulate body fluid levels. Vasopressin regulates fluid levels by inducing water reabsorption in the kidneys.2 A deficiency of vasopressin causes the body to make large amounts of urine and causes a feeling of intense thirst even after having something to drink.  CDI is often caused by damage to the hypothalamus or pituitary gland due to the growth of tumours, head injuries, infections, or other factors.It is mainly diagnosed by a fluid deprivation test.

Causes of central diabetes insipidus 

When the exact cause of CDI  is unknown, it is called idiopathic central diabetes insipidus. In other cases, the deficiency in vasopressin can occur due to various underlying factors, some of which include:4 

  • Head trauma: As the pituitary gland is located at the base of the skill, it can be damaged by an injury to the head. The damage can lead to disruption in the production of vasopressin leading to CDI.
  • Tumours: Tumours in the brain, particularly in the hypothalamus or pituitary gland, can affect the cells responsible for vasopressin production by damaging the cells directly or compressing the surrounding tissue that is responsible for vasopressin release.
  • Infections and inflammation: conditions such as encephalitis or meningitis can affect the brain and damage the hypothalamus or pituitary gland, causing a disruption in vasopressin production and release.
  • Surgery or radiation therapy: procedures that target the brain or pituitary gland can also damage the structures responsible for vasopressin production or release.
  • Autoimmune disorders: Certain autoimmune conditions, where the immune system attacks the body's own tissues, can affect the hypothalamus or pituitary gland, causing CDI.
  • Genetic factors: While rare, there are genetic conditions that can cause central diabetes insipidus. These genetic mutations can affect the development or functioning of the hypothalamus or pituitary gland.
  • Other factors: Certain medications, such as lithium (used to treat bipolar disorder), can lead to central diabetes insipidus. Additionally, some cases of CDI might be related to congenital (present at birth) issues or metabolic disorders.

Signs and symptoms of Central diabetes insipidus 

Central diabetes insipidus is characterized by excessive thirst and the production of large volumes of diluted urine. The signs and symptoms of central diabetes insipidus can vary from person to person, but here are some common ones:

  • Excessive thirst (Polydipsia): People with central diabetes insipidus often experience intense and constant thirst. They may feel the need to drink large amounts of water throughout the day to quench their thirst.
  • Frequent and large urination (Polyuria): Central diabetes insipidus leads to the excretion of large volumes of diluted urine. This can result in frequent trips to the bathroom, both during the day and night (nocturia).
  • Diluted urine: The urine produced by individuals with central diabetes insipidus is typically very diluted and lacks the usual yellow colour and concentrated appearance. This is due to the reduced ability of the kidneys to reabsorb water.
  • Dehydration: Despite drinking large amounts of water, individuals with central diabetes insipidus can still experience dehydration. This is because the excessive urine output causes them to lose more water than they can take in, leading to a fluid imbalance in the body.
  • Dry mouth and dry skin: Dehydration can cause dry mouth and dry skin. Individuals may feel thirsty even after drinking water and may experience discomfort due to the lack of moisture.
  • Fatigue and weakness: Dehydration and the disruption of fluid balance can lead to fatigue and weakness. Electrolyte imbalance resulting from the excessive loss of fluids can contribute to these symptoms.
  • Irritability: Dehydration and the body's attempts to compensate for fluid imbalances can lead to irritability and mood changes.
  • Weight loss: Excessive fluid loss can lead to weight loss if the condition is not managed correctly.
  • Increased heart rate: Dehydration can cause an increase in heart rate (tachycardia) as the body tries to maintain blood pressure and circulation.
  • Low blood pressure (hypotension): In severe cases of dehydration, blood pressure may drop, leading to feelings of light-headedness or dizziness.
  • Headache: Dehydration can cause headaches as the brain lacks adequate hydration.

Management and treatment for central diabetes insipidus 

The management of central diabetes insipidus is mainly by identifying the root cause of CDI and regulating fluid balance. If a specific underlying cause, such as a tumour or head injury, is identified, addressing that cause may alleviate the central diabetes insipidus symptoms. Other management and treatment options include.

Synthetic vasopressin replacement

The primary treatment of CDI is replacing the missing vasopressin with synthetic forms. Desmopressin (DDAVP) is a synthetic vasopressin that can be administered either by a nasal spray, an oral tablet, or an injection. This helps regulate water balance and reduces excessive urination and thirst.

Hydration and fluid intake

Maintaining adequate fluid intake is crucial to prevent dehydration. It is essential to drink water according to their doctor's recommendations to balance their fluid needs and prevent overhydration.

Regular monitoring

People with central diabetes insipidus require regular medical check-ups to monitor the condition and hydration level to adjust treatment as needed. 

Diagnosis

The diagnosis of central diabetes insipidus involves a combination of clinical evaluation, medical history, physical examination, and specific tests to assess the body's ability to regulate water balance and vasopressin levels. 

  • Clinical evaluation: a detailed medical history is taken by a healthcare professional. This includes information about symptoms, fluid intake, urination patterns, and any underlying medical conditions or medications. It is important to provide accurate information about the frequency and volume of urination, as well as the frequency and duration of experiencing excessive thirst.
  • Physical examination: This is conducted to assess overall health and identify signs of dehydration, such as dry mouth, rapid heartbeat, and low blood pressure.
  • Water deprivation test: the standard test used most commonly to diagnose diabetes insipidus is the indirect water deprivation test.  This test involves monitoring the patient's fluid intake, urine output, and changes in body weight over a specific period while they are restricted from drinking water. In cases of central diabetes insipidus, the urine will remain diluted despite being dehydrated. The inability to produce sufficient vasopressin leads to the excretion of large volumes of diluted urine. A person with normal vasopressin function will have concentrated urine when they become dehydrated.5
  • Desmopressin (DDAVP) challenge test: a desmopressin challenge test can be performed to confirm the diagnosis of CDI and determine the severity of the condition. During this test, a dose of desmopressin is given, and the urine output and urine concentration are monitored. If the urine output decreases and the urine becomes more concentrated after desmopressin administration, it indicates a positive test and confirms the diagnosis of CDI.
  • MRI imaging: In some cases, an MRI (magnetic resonance imaging) scan of the brain may be required to visualize the hypothalamus and pituitary gland. This can help identify structural abnormalities, such as the presence of tumours or damage to the hypothalamus and pituitary gland that might be causing central diabetes insipidus. Another finding that can be used for the diagnosis of central diabetes insipidus is the absence of the pituitary bright spot in MRI images.2 
  • Blood tests: Blood tests may be conducted to measure electrolyte levels, such as sodium and potassium, as well as hormone levels, including vasopressin and other pituitary hormones.

FAQs

How common is central diabetes insipidus? 

Central diabetes insipidus is a rare condition. According to the NHS, it affects about 1 in 25,000 people in the general population.

Who is at risk of central diabetes insipidus?

The individuals that are at risk of central diabetes insipidus include those with head trauma, brain tumours, infections affecting the brain, a history of brain surgery or radiation therapy, genetic factors, autoimmune disorders, and certain medications. These conditions can affect the pituitary gland which can hinder t the release of vasopressin.

When should I see a doctor?

Diabetes insipidus is characterised by a sudden onset of symptoms of frequent urination and excessive thirst. Other symptoms include a preference for cold drinks, drinking more fluids at night and the presence of nocturia. Contact your doctor immediately if you develop these symptoms.2

Summary

Central diabetes insipidus is a rare condition where the body lacks vasopressin, leading to excessive thirst, frequent urination and the production of diluted urine. The causes of CDI can include head trauma, tumours, infections, and genetics. It is characterized by the Symptoms of extreme thirst, frequent urination, diluted urine, dehydration, dry mouth, fatigue, irritability, and weight loss. Diagnosis involves tests like water deprivation and desmopressin challenge. Treatments include synthetic vasopressin and managing underlying causes of CDI. Early medical intervention is crucial for accurate diagnosis and effective management of CDI.

References:

  1. Christ-Crain M, Gaisl O. Diabetes insipidus. La Presse Médicale [Internet]. 2021 Dec 1 [cited 2023 Aug 17];50(4):104093. Available from: https://www.sciencedirect.com/science/article/pii/S0755498221000300
  2. Refardt J. Diagnosis and differential diagnosis of diabetes insipidus: Update. Best Practice & Research Clinical Endocrinology & Metabolism [Internet]. 2020 Sep 1 [cited 2023 Aug 17];34(5):101398. Available from: https://www.sciencedirect.com/science/article/pii/S1521690X20300257
  3. Tomkins M, Lawless S, Martin-Grace J, Sherlock M, Thompson CJ. Diagnosis and management of central diabetes insipidus in adults. The Journal of Clinical Endocrinology & Metabolism [Internet]. 2022 Sep 28 [cited 2024 Mar 14];107(10):2701–15. Available from: https://academic.oup.com/jcem/article/107/10/2701/6623615
  4. Verbalis JG. Acquired forms of central diabetes insipidus: Mechanisms of disease. Best Practice & Research Clinical Endocrinology & Metabolism [Internet]. 2020 Sep 1 [cited 2023 Aug 17];34(5):101449. Available from: https://www.sciencedirect.com/science/article/pii/S1521690X20300762
  5. Garrahy A, Moran C, Thompson CJ. Diagnosis and management of central diabetes insipidus in adults. Clin Endocrinol [Internet]. 2019 Jan [cited 2023 Aug 17];90(1):23–30. Available from: https://onlinelibrary.wiley.com/doi/10.1111/cen.13866

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Afsheen Hidayat

M.B.B.S, MSc in Clinical Microbiology

Afsheen possesses a strong background in both the medical and scientific disciplines and is a highly educated health researcher. She is a medical expert who is eager to pursue a career in clinical research and medical writing because she believes that it is crucial to improve patient outcomes and provide better medical care. After working as a clinician in Dubai, she came to realise that her goal was to use her extensive research skills to raise the standard of healthcare. She obtained an MSc in Clinical Microbiology from Queen Mary University of London to advance her research career, and she is currently working as a medical writer.

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