From the Guidelines
Congenital nephrogenic diabetes insipidus (NDI) is a rare but significant advanced cause of polydipsia, characterized by insensitivity of the distal nephron to antidiuretic hormone (ADH), leading to polyuria, polydipsia, and the risk of hypertonic dehydration. This condition is often diagnosed in older children and adults, with polydipsia being the predominant symptom at diagnosis 1. The exact incidence and prevalence of congenital NDI are unknown, but it is considered a rare disease. Secondary forms of NDI are more frequent and can be caused by other inherited kidney diseases or medications.
Some key characteristics of congenital NDI include:
- Polyuria, failure to thrive, and signs of dehydration as typical presenting symptoms
- Serum osmolality usually >300 mOsm/kg H2O owing to hypernatraemia
- Urine is inappropriately diluted, with osmolality usually <200 mOsm/kg H2O (urine osmolality < plasma osmolality)
- Infants are particularly at risk of dehydration due to lack of free access to fluid
Other advanced causes of polydipsia may include:
- Diabetes mellitus, leading to osmotic diuresis and subsequent thirst
- Central or nephrogenic diabetes insipidus, preventing proper water reabsorption in the kidneys
- Medications like lithium, demeclocycline, and certain antipsychotics, which can induce polydipsia as a side effect
- Psychogenic polydipsia, often seen in psychiatric disorders like schizophrenia
- Hypercalcemia, hypokalemia, and certain kidney diseases, which can impair water conservation
Diagnosis of these conditions typically involves blood and urine tests to measure electrolytes, glucose, kidney function, and hormone levels, with water deprivation tests sometimes needed to differentiate between diabetes insipidus types 1. Treatment must target the underlying cause rather than just managing the symptom of excessive thirst, and clinicians should be aware of the clinical practice recommendations for the diagnosis, treatment, and genetic counseling of NDI, as outlined in the international expert consensus statement 1.
From the FDA Drug Label
Desmopressin acetate is contraindicated in patients with ... excessive fluid intake (e.g., polydipsia) Patients with conditions associated with fluid and electrolyte imbalance ... and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
The advanced causes of polydipsia mentioned in the label include:
- Habitual or psychogenic polydipsia: drinking excessive amounts of water
- Conditions associated with fluid and electrolyte imbalance, such as: + Cystic fibrosis + Heart failure + Renal disorders 2
From the Research
Advanced Causes of Polydypsia
The causes of polydypsia can be complex and varied. Some of the advanced causes include:
- Diabetes Insipidus (DI): a disorder characterized by the excretion of large amounts of hypotonic urine, which can be caused by a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, or by resistance to AVP in the kidneys 3, 4, 5.
- Primary Polydipsia: a condition characterized by excessive intake of fluids, which can be caused by a dysfunction in the thirst mechanism, involvement of the hippocampus, stress-reducing behavior, or lesion occurrences in specific areas of the brain 6.
- Dipsogenic DI: a condition characterized by an abnormally low thirst threshold, which can be caused by a variety of factors, including genetic abnormalities or acquired defects in the thirst mechanism 3, 4.
- Nephrogenic DI: a condition characterized by resistance to AVP in the kidneys, which can be caused by a variety of factors, including genetic abnormalities or acquired defects in the kidneys 3, 4, 5.
- Central DI: a condition characterized by a deficiency of AVP in the pituitary gland or the hypothalamus, which can be caused by a variety of factors, including genetic abnormalities, head trauma, or tumors 3, 4, 5.
Diagnostic Approaches
The diagnosis of polydypsia can be challenging and requires a comprehensive approach, including:
- Water Deprivation Test: a test used to differentiate between DI and primary polydipsia, which involves measuring urine osmolality and serum sodium levels after a period of water deprivation 3, 6, 5.
- Hypertonic Saline Stimulation: a test used to measure the response of the kidneys to AVP, which can help differentiate between central and nephrogenic DI 3.
- Copeptin Measurement: a test used to measure the levels of copeptin, a surrogate marker of AVP, which can help diagnose DI and differentiate between central and nephrogenic DI 3, 6, 5.
- Pituitary MRI: a test used to visualize the pituitary gland and diagnose lesions or tumors that may be causing central DI 5.