Diabetes insipidus is characterized by greatly increased urine excretion (polyuria), which can reach 20 liters or more in some cases. The consequence is intense thirst and increased drinking (polydipsia). There are two types: central diabetes insipidus and nephrogenic diabetes insipidus.

Central Diabetes Insipidus:

The hormone ADH (Antidiuretic Hormone), normally produced in the hypothalamus, is released through the posterior pituitary gland. ADH acts on the collecting ducts of the kidneys, promoting water reabsorption. In the kidney, a significant amount of fluid is filtered through the glomeruli and then reabsorbed in the subsequent collecting ducts, a process mediated by ADH. The absence of ADH leads to substantial fluid loss through the kidneys, resulting in polyuria. ADH deficiency can be caused by reduced production in the hypothalamus or by tumors and other processes affecting the hypothalamus or pituitary gland.

Diagnosis:

The diagnosis of diabetes insipidus is performed through a water deprivation test. Patients are not allowed to drink fluids during the test. Since ADH is unstable and difficult to measure directly, Copeptin (CT-proAVP), which is released alongside ADH and more stable, is used for testing. At regular intervals, Copeptin levels, plasma osmolality, urine volume, urine osmolality, and specific gravity are measured. In diabetes insipidus, plasma osmolality is <300 milliosmol/kg, and urine osmolality is <250 milliosmol/kg. An increase of more than 300 milliosmol/kg rules out diabetes insipidus. Specific gravity does not increase in the presence of diabetes insipidus.

Nephrogenic Diabetes Insipidus:

In rare cases, there is a defect in the kidney’s response to ADH. This defect can be congenital or acquired. In congenital cases, the gene responsible for the condition is located on the X-chromosome, so typically only males exhibit symptoms. Females can pass the gene to their sons. Certain medications, like lithium, can also block the effects of ADH. Nephrogenic diabetes insipidus can also occur in conditions such as polycystic kidney disease, sickle cell disease, severe infections of the renal pelvis, amyloidosis, Sjögren’s syndrome, and certain tumors.

ADH is present in normal or even elevated concentrations in nephrogenic diabetes insipidus. The symptoms of polyuria and polydipsia are similar to those in central diabetes insipidus. Diagnosis involves a water deprivation test, followed by a Desmopressin (ADH analog) test. In central diabetes insipidus, Desmopressin administration leads to an increase in urine osmolality and specific gravity and reduces urine output. If the patient does not respond to Desmopressin, it indicates nephrogenic diabetes insipidus.