From the Guidelines
Diabetes insipidus should be suspected in patients presenting with polyuria, polydipsia, failure to thrive, and hypernatremic dehydration, with a comprehensive diagnostic approach including measurement of serum sodium, serum osmolality, and urine osmolality, as well as genetic testing for early and definite diagnosis. The diagnostic criteria for diabetes insipidus include:
- Polyuria of more than 3 liters per day
- Polydipsia
- Dilute urine with a specific gravity less than 1.005 or osmolality less than 200 mOsm/kg
- Elevated plasma osmolality (>295 mOsm/kg) with inappropriately low urine osmolality The initial work-up consists of measuring serum sodium, serum osmolality, and urine osmolality, with the detection of inappropriately diluted urine (urinary osmolality <200 mOsm/kg) in combination with high–normal or elevated serum sodium being pathognomonic for the diagnosis of diabetes insipidus (nephrogenic or central) 1.
Genetic testing can provide an early and definite diagnosis, with important implications for clinical management and outcome, and can avoid unpleasant, challenging, and potentially harmful diagnostic procedures, including the desmopressin (DDAVP) test or the water deprivation test 1. A massively parallel sequencing-based multigene panel that includes at least AQP2, AVPR2, and AVP should be used to identify the genetic cause of NDI at the most reasonable cost while limiting incidental findings 1.
The use of genetic testing is highly recommended, even for females with overt NDI, as overt NDI in females can be caused by biallelic pathogenic variants in AQP2, but some females with AVPR2 pathogenic variants also develop the complete NDI phenotype 1. Genetic testing in a laboratory accredited for diagnostic genetic testing is strongly recommended, particularly in male offspring of heterozygote AVPR2 mutation carriers, to prevent primary manifestations of the disorder by facilitating early treatment and monitoring.
From the FDA Drug Label
Diabetes Insipidus: This formulation is administered subcutaneously or by direct intravenous injection. Desmopressin acetate injection 4 mcg/mL dosage must be determined for each patient and adjusted according to the pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover.
The criteria for Diabetes Insipidus treatment with desmopressin acetate injection include:
- Determining the dosage for each patient
- Adjusting the dosage according to the pattern of response
- Estimating response by two parameters:
- Adequate duration of sleep
- Adequate, not excessive, water turnover 2
From the Research
Criteria for Diabetes Insipidus
The criteria for diabetes insipidus (DI) include:
- High hypotonic urinary output of more than 50ml per kg body weight per 24 hours 3
- Associated polydipsia of more than 3 liters a day 3
- Urine osmolality remains below 250 mOsmol/kg and serum sodium greater than 145 mmol/L in severe forms of DI 4
- Urine osmolality between 250 and 750 mOsmol/kg in partial forms of DI 4
Diagnostic Tests
Diagnostic tests for DI include:
- Water deprivation test 4, 5, 6
- Measurement of plasma arginine vasopressin (AVP) levels 5
- Measurement of plasma copeptin (CP) levels 5
- Pituitary magnetic resonance imaging (MRI) 4
- Desmopressin test 4
Differential Diagnosis
Differential diagnosis of DI includes:
- Central DI: characterized by inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland 3
- Nephrogenic DI: characterized by the inability to concentrate urine despite having normal or elevated plasma concentrations of AVP 7
- Primary polydipsia: characterized by excessive intake of large amounts of fluid leading to polyuria in the presence of intact AVP secretion and appropriate antidiuretic renal response 3