What causes Diabetes Insipidus (DI)?

From the Guidelines

Diabetes insipidus is caused by problems with either the production or action of antidiuretic hormone (ADH), also called vasopressin, which can be due to various factors including genetic disorders, certain medications, or kidney diseases. The exact cause of diabetes insipidus can vary depending on the type, with central diabetes insipidus occurring when the brain's pituitary gland doesn't produce enough ADH, typically due to damage from surgery, tumors, head injuries, or infections 1. Nephrogenic diabetes insipidus happens when the kidneys don't respond properly to ADH, often because of genetic disorders, certain medications (like lithium), or kidney diseases 1.

Types of Diabetes Insipidus

• Central diabetes insipidus: occurs when the brain's pituitary gland doesn't produce enough ADH
• Nephrogenic diabetes insipidus: happens when the kidneys don't respond properly to ADH
• Gestational diabetes insipidus: develops during pregnancy when an enzyme produced by the placenta destroys the mother's ADH
• Dipsogenic diabetes insipidus: results from damage to the thirst mechanism in the hypothalamus, causing excessive thirst and fluid intake

Key Factors

• Genetic testing can provide an early and definite diagnosis, with important implications for clinical management and outcome 1
• An early diagnosis also prevents prolonged, unrecognized periods of severe hypertonic dehydration, which can result in seizures, developmental delay and cognitive impairment
• Treatment depends on the specific type but may include desmopressin (DDAVP) for central and gestational forms, modification of medications for nephrogenic forms, or addressing underlying causes when possible 1

Recommendations

• Free access to fluid in all children with nephrogenic diabetes insipidus (NDI) is recommended 1
• Normal-for-age milk intake (instead of water) in infants with NDI to guarantee adequate caloric intake is recommended
• Considering tube feeding in infants and children with repeated episodes of vomiting and dehydration and/or failure to thrive is recommended
• Dietetic counselling from a dietitian who has experience with the disease is recommended for every patient with NDI

From the Research

Causes of Diabetes Insipidus

The causes of diabetes insipidus can be categorized into two main types:

• Central diabetes insipidus, which is caused by inadequate or impaired secretion of antidiuretic hormone (ADH) from the posterior pituitary gland 2, 3, 4, 5
• Nephrogenic diabetes insipidus, which is caused by impaired or insufficient renal response to ADH 2, 3, 4, 6

Subtypes of Diabetes Insipidus

There are also less common subtypes of diabetes insipidus, including:

• Dipsogenic diabetes insipidus, characterized by excessive thirst due to a low osmotic threshold 3
• Gestational diabetes insipidus, characterized by increased concentration of placental vasopressinase during pregnancy 3

Underlying Conditions

Diabetes insipidus can be caused by various underlying conditions, such as:

• Hypothalamic neurons conditions that affect the secretion of ADH 5
• Pituitary surgery or traumatic brain injury 5
• Systemic diseases 5
• Mutations in the genes that encode key proteins in the AVP signaling pathway 6
• Specific drug exposure, especially lithium, and hydroelectrolytic disorders 6