Disorders of Water Balance: Understanding Arginine Vasopressin Deficiency and Arginine Vasopressin Resistance

Dr U. Srirangalingam outlines the symptoms, causes, diagnostic pathways, and treatment options for disorders of water balance, including arginine vasopressin deficiency and arginine vasopressin resistance.

Maintaining stable water balance is central to overall health, as even small disturbances can affect blood volume, concentration, and kidney function. The body relies on a hormone called arginine vasopressin (AVP), also known as antidiuretic hormone, to regulate how much water the kidneys retain. When this system does not work as expected, patients often experience excessive thirst and the passing of unusually large volumes of urine. These symptoms can be disruptive, and early assessment helps clarify whether the issue relates to hormone secretion, kidney response, or another underlying cause.

At the London Lauriston Clinic, a private health clinic in London, patients have rapid access to specialist assessment, modern diagnostic testing, and coordinated care within a multidisciplinary team. This approach ensures that both diagnosis and management are delivered with accuracy and clarity, supported by shared decision-making.

Updated Terminology for These Water-balance Disorder

The traditional terms cranial diabetes insipidus and nephrogenic diabetes insipidus have been replaced by more precise and clinically helpful names:

• Arginine vasopressin deficiency (AVP-D) – formerly cranial diabetes insipidus
• Arginine vasopressin resistance (AVP-R) – formerly nephrogenic diabetes insipidus

These terms reduce confusion with diabetes mellitus, which is an entirely different condition caused by raised blood sugar levels. In diabetes mellitus, the high glucose concentration in the urine draws water with it, leading to large urine volumes and significant thirst. 

Using updated terminology helps patients understand whether their symptoms relate to hormone dysfunction, kidney response, or blood glucose levels.

What Symptoms Should Prompt Assessment?

Common symptoms include:

• Feeling very thirsty (polydipsia)
• Passing large volumes of urine (polyuria)
• Waking repeatedly at night to drink or urinate
• A strong preference for cold water
• Persistent symptoms of dehydration

These features often appear gradually, which means they can be overlooked until daily routines are noticeably affected.

Defining Polyuria and Polydipsia

A helpful threshold is:

• Polyuria: more than 3 litres of urine in 24 hours
• Polydipsia: excessive thirst leading to high fluid intake

Some patients urinate frequently but pass normal total volumes. This is often related to bladder irritation or urgency symptoms rather than a disorder of water balance. Distinguishing these patterns is an important first step in planning the right investigations.

Several Conditions Can Lead to Increased Thirst and High Urine Output

Before diagnosing an AVP-related disorder, more common causes need to be excluded, including:

• Diabetes mellitus – where raised glucose levels cause high urine volumes
• High calcium levels (hypercalcaemia)
• Low potassium levels (hypokalaemia)
• Dry mouth related to mouth breathing, Sjögren’s syndrome, or similar conditions
• Excessive habitual drinking (primary polydipsia), which can impair the kidney’s ability to concentrate urine

Ruling out these possibilities ensures that investigations are focused and evidence based. If these conditions are excluded, a disorder of arginine vasopressin secretion or kidney response becomes more likely.

Understanding Antidiuretic Hormone (Vasopressin)

Arginine vasopressin is produced in the hypothalamus and stored and released by the posterior pituitary gland. Its role is to help the kidneys conserve water by concentrating the urine. 

When the posterior pituitary cannot release AVP properly, or when the kidneys cannot respond to it, the body struggles to maintain normal water balance. This often leads to increased urine output and an ongoing drive to drink.

For this reason, patients may require:

• Pituitary hormone testing
• Assessment of pituitary function
• MRI imaging of the pituitary gland

These investigations help identify whether symptoms are due to structural changes, hormonal disruption, or a kidney-related response.

How AVP-related Disorders Are Diagnosed

Historically, diagnosis relied on the water deprivation test, which was lengthy, uncomfortable, and difficult for many patients to tolerate. Advances in endocrinology have improved diagnostic accuracy and patient comfort.

Arginine-copeptin Test 

This modern 60-minute test uses arginine stimulation to measure copeptin, a reliable and stable marker of vasopressin release. It accurately differentiates between:

• Arginine vasopressin deficiency (AVP-D)
• Arginine vasopressin resistance (AVP-R)
• Primary polydipsia

This diagnostic method offers clear, actionable results and is among the most patient-friendly endocrine tests currently in clinical practice. The London Lauriston Clinic also offers the arginine-copeptin test.

Treatment Options for Water-balance Disorders

Management depends on the underlying diagnosis and the patient’s overall health.

1. Arginine vasopressin deficiency (AVP-D)

Most patients are treated with desmopressin, an effective analogue of vasopressin that helps restore normal water balance.

2. Arginine vasopressin resistance (AVP-R)

Treatment focuses on careful fluid regulation and addressing the underlying cause. Several medications can reduce urine volume depending on the mechanism involved, and ongoing monitoring is important to maintain electrolyte stability.

3. Primary polydipsia

Managed through structured fluid-intake strategies and, where relevant, behavioural or psychological support. Education is often key, as patients may not recognise how drinking patterns affect kidney function.

4. Metabolic causes

Correction of high calcium, low potassium, or raised blood glucose is essential to restore normal water balance.

At the London Lauriston Clinic, these conditions are managed within a multidisciplinary team that ensures patients understand their diagnosis, what drives their symptoms, and how treatment choices align with long-term health.

When to Seek Specialist Evaluation for Water-balance Symptoms

Persistent changes in thirst or urine output may indicate an underlying endocrine issue, which is why timely specialist input is advised. A focused specialist evaluation helps determine whether the symptoms relate to hormone function, kidney response, or another medical cause.

Specialist assessment is recommended for:

• Persistent excessive thirst
• Passing more than 3 litres of urine daily
• Night-time drinking or urination
• Unexplained dehydration
• A history of pituitary disease or pituitary surgery
• Uncertain or fluctuating water-balance symptoms

Timely evaluation helps prevent dehydration, protect kidney function, and reduce the risk of long-term complications. Patients in London who experience these symptoms can arrange rapid-access appointments at the London Lauriston Clinic, which provides dedicated endocrine assessment for disorders of water balance such as arginine vasopressin deficiency and arginine vasopressin resistance.

This article was written by Dr Umasuthan Srirangalingam, consultant endocrinologist at the London Lauriston Clinic, where he specialises in pituitary, thyroid, adrenal, and water-balance conditions. He is also recognised for his expertise in polycystic ovarian syndrome and hormone replacement therapy for both men and women. Dr Srirangalingam delivers comprehensive endocrine care supported by advanced hormonal testing and imaging, offering patients a clear and evidence-based path to diagnosis and treatment.