12th April 2024

Diabetes insipidus (DI)

Diabetes insipidus is a metabolic disorder caused by either reduced production or response to ADH causing reduced water re-absorption. This manifests as polydipsia, polyuria (urinary volume greater than 50ml/kg/hr) and the formation of inappropriate hypotonic (dilute) urine, which reduces urine osmolality. This can be divided into two different types: central DI and nephrogenic DI. 

Central DI (relating to the hypothalamus and posterior pituitary gland) results when not enough ADH is produced or released. This can be due to pituitary surgery, craniopharyngioma, infiltrative pituitary stalk lesions, traumatic brain injury (TBI), subarachnoid haemorrhage, congenital hypothalamic-pituitary defects, alcohol, phenytoin and autoimmune disorders. (¹, ³)As central DI results from reduced ADH, it can be treated with a synthetic ADH analogue such as desmopressin. 

Nephrogenic DI is the result of renal insensitivity to ADH. This can be due to lithium treatment, chronic kidney disease (CKD), chronic hypercalcaemia or hypokalaemia. Nephrogenic DI can be treated with adequate fluid intake, salt restriction and diuretics to reduce polyuria. Both types of DI can be caused by genetic mutations, they may also be associated with hypernatraemia and present as a medical emergency. 

Diabetes insipidus can be confirmed by a serum osmolality above 293mOsm/kg, whereas the urine osmolality would be below 300mOsm/kg. A water deprivation test can be used to differentiate the type of DI. Water deprivation is carried out over 8 hrs with repeated measurements of urine and serum osmolality. A synthetic vasopressin analogue is given, if it is caused by central DI, the urine osmolality increases ≥ 750mOsm/kg. However, if there is no change in the urine osmolality after desmopressin is given or urine osmolality remains ≤ 750mOsm/kg, this indicates that the kidney is unable to use this synthetic vasopressin and points towards nephrogenic DI.