From the Guidelines
Diabetes insipidus is primarily caused by problems with either the production or action of antidiuretic hormone (ADH), also known as vasopressin, with central diabetes insipidus resulting from insufficient ADH production and nephrogenic diabetes insipidus resulting from the kidneys' inability to respond to ADH. The etiology of diabetes insipidus can be complex, involving various factors such as genetic mutations, acquired conditions, or medications. According to the most recent expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus 1, this condition is characterized by insensitivity of the distal nephron to antidiuretic hormone (ADH), leading to polyuria, polydipsia, and the risk of hypertonic dehydration.
Key Causes of Diabetes Insipidus
- Central diabetes insipidus: results from insufficient ADH production by the hypothalamus or inadequate release from the posterior pituitary gland, which can occur due to damage from surgery, head trauma, tumors, infections, infiltrative diseases, autoimmune conditions, or genetic mutations 1.
- Nephrogenic diabetes insipidus: develops when the kidneys cannot respond properly to ADH, which can be inherited through genetic mutations affecting the ADH receptor (AVPR2) or water channel proteins (aquaporin-2), or acquired from conditions like chronic kidney disease, hypercalcemia, hypokalemia, or medications (particularly lithium) 1.
- Gestational diabetes insipidus: can temporarily occur during pregnancy due to increased vasopressinase activity.
- Dipsogenic diabetes insipidus: is rare and results from excessive fluid intake that suppresses ADH secretion.
Importance of Genetic Testing
Genetic testing can provide an early and definite diagnosis of congenital nephrogenic diabetes insipidus, with important implications for clinical management and outcome 1. We strongly recommend performing genetic testing in a laboratory accredited for diagnostic genetic testing, using a massively parallel sequencing-based multigene panel that includes at least AQP2, AVPR2, and AVP. This approach can help identify the genetic cause of NDI, determine the genetic risk status of the extended family, and support patient decision-making regarding family planning.
From the Research
Aetiology of Diabetes Insipidus
The aetiology of diabetes insipidus can be attributed to two main defects:
- Inadequate or impaired secretion of antidiuretic hormone (ADH) from the posterior pituitary gland, resulting in central or neurogenic diabetes insipidus 2, 3, 4, 5
- Impaired or insufficient renal response to ADH, leading to nephrogenic diabetes insipidus 2, 3, 4, 5
Classification of Diabetes Insipidus
Diabetes insipidus can be classified into four main types:
- Central diabetes insipidus (CDI): characterized by a deficiency of ADH secretion from the posterior pituitary gland 3, 4, 5
- Nephrogenic diabetes insipidus (NDI): characterized by resistance to ADH in the kidneys 3, 4, 5
- Dipsogenic diabetes insipidus: characterized by excessive thirst due to a low osmotic threshold 3, 4
- Gestational diabetes insipidus: characterized by increased concentration of placental vasopressinase during pregnancy 3
Causes of Nephrogenic Diabetes Insipidus
Nephrogenic diabetes insipidus can be caused by various factors, including:
- Lithium intake, which is the most common cause of acquired NDI 6
- Genetic mutations affecting the ADH receptor or aquaporin-2 channels 4
- Kidney damage or disease 5
Diagnosis and Treatment
Diagnosis of diabetes insipidus involves a water deprivation test or hypertonic saline stimulation together with copeptin (or AVP) measurement, as well as a detailed medical history, physical examination, and imaging studies 4. Treatment depends on the underlying aetiology and type of diabetes insipidus, and may include: