From the Guidelines
Diabetes insipidus should be managed with a comprehensive approach that includes genetic testing, proper diagnosis, and treatment tailored to the specific type of the disorder, with the goal of reducing morbidity, mortality, and improving quality of life. The condition occurs in two main forms: central diabetes insipidus, caused by insufficient production of antidiuretic hormone (ADH) by the pituitary gland, and nephrogenic diabetes insipidus, where the kidneys don't respond properly to ADH 1.
Diagnosis and Treatment
For central diabetes insipidus, desmopressin (DDAVP) is the primary medication, available as nasal spray, oral tablets, or sublingual tablets 1. For nephrogenic diabetes insipidus, thiazide diuretics like hydrochlorothiazide may be prescribed along with a low-salt diet and NSAIDs like indomethacin in some cases 1. Genetic testing is strongly recommended for early and definite diagnosis, especially in cases of congenital nephrogenic diabetes insipidus, to identify the genetic cause and guide clinical management 1.
Genetic Testing
The use of a massively parallel sequencing-based multigene panel that includes at least AQP2, AVPR2, and AVP is highly recommended for genetic testing, as it can identify the genetic cause of NDI at a reasonable cost while limiting incidental findings 1. Genetic testing should be performed in a laboratory accredited for diagnostic genetic testing, and it is crucial for precise genetic counselling, family planning, and identifying patients who may be eligible for future genetically stratified clinical trials 1.
Diagnostic Approach
A comprehensive family history and pedigree construction are essential to identify family cases, and the initial work-up consists of measuring serum sodium, serum osmolality, and urine osmolality 1. The detection of inappropriately diluted urine, in combination with high–normal or elevated serum sodium, is pathognomonic for the diagnosis of diabetes insipidus and warrants early genetic testing if NDI is suspected 1. Patients should monitor fluid intake and output, maintain electrolyte balance, and be aware of symptoms of dehydration or water intoxication. Proper diagnosis and treatment can significantly improve the quality of life for patients with diabetes insipidus, and early genetic diagnosis can prevent prolonged, unrecognized periods of severe hypertonic dehydration, which can result in seizures, developmental delay, and cognitive impairment 1.
From the FDA Drug Label
Desmopressin Acetate Injection is indicated as antidiuretic replacement therapy in the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Desmopressin acetate injection is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus. Diabetes Insipidus: Desmopressin acetate injection 4 mcg/mL is indicated as antidiuretic replacement therapy in the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region.
Diabetes Insipidus Treatment: Desmopressin acetate is indicated for the treatment of central (cranial) diabetes insipidus.
- It is not effective for nephrogenic diabetes insipidus.
- The dosage must be determined for each patient and adjusted according to the pattern of response 2, 3.
- Key considerations:
- Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover.
- Fluid restriction should be observed.
- The usual dosage range in adults is 0.5 mL (2 mcg) to 1 mL (4 mcg) daily, administered intravenously or subcutaneously, usually in two divided doses 3.
From the Research
Definition and Types of Diabetes Insipidus
- Diabetes insipidus (DI) is a disorder characterized by excretion of large amounts of hypotonic urine 4.
- Central DI results from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, whereas nephrogenic DI results from resistance to AVP in the kidneys 4.
- Central and nephrogenic DI are usually acquired, but genetic causes must be evaluated, especially if symptoms occur in early childhood 4.
Diagnosis of Diabetes Insipidus
- Distinguishing between the different types of DI can be challenging and is done either by a water deprivation test or by hypertonic saline stimulation together with copeptin (or AVP) measurement 4.
- A detailed medical history, physical examination, and imaging studies are needed to ensure an accurate DI diagnosis 4.
Treatment of Central Diabetes Insipidus
- Desmopressin (DDAVP) is the first line agent for outpatient treatment of central diabetes insipidus due to its ease of administration, safety, and tolerability 5.
- The major complication of DDAVP therapy is water intoxication and hyponatremia, which can be reduced by careful dose titration and close monitoring of serum osmolality 5.
- Alternative treatments for central diabetes insipidus include indapamide, chlorpropamide, and carbamazepine 6, 7, 8.
- Indapamide has been shown to be effective in reducing 24-hour urinary volume and increasing urinary osmolality, with minimal adverse effects 6.
- Chlorpropamide and carbamazepine can be used in combination to achieve a good antidiuretic effect while minimizing side effects 8.