From the Guidelines
The workup for diabetes insipidus should begin with measuring serum sodium, serum osmolality, and urine osmolality to identify inappropriately diluted urine and high-normal or elevated serum sodium, which is pathognomonic for the diagnosis of diabetes insipidus. This initial step is crucial as it helps in differentiating diabetes insipidus from other causes of polyuria and polydipsia. According to the international expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus 1, a comprehensive family history and pedigree construction are essential to identify family cases, especially when suspecting nephrogenic diabetes insipidus.
Key Diagnostic Steps
- Measuring serum sodium, serum osmolality, and urine osmolality to confirm the diagnosis of diabetes insipidus
- Comprehensive family history and pedigree construction to identify potential familial cases of nephrogenic diabetes insipidus
- Early genetic testing if nephrogenic diabetes insipidus is suspected based on the initial workup and family history
Differential Diagnoses
The differential diagnoses for diabetes insipidus include acquired nephrogenic diabetes insipidus, central diabetes insipidus, primary polydipsia, poorly controlled diabetes mellitus, and other secondary forms of inherited nephrogenic diabetes insipidus, as outlined in Table 1 of the international expert consensus statement 1. Each of these conditions has distinguishing characteristics that can guide further diagnostic testing and management. For instance, central diabetes insipidus responds to desmopressin (DDAVP), whereas nephrogenic diabetes insipidus does not.
Further Testing
Further testing may include the water deprivation test, which is considered the gold standard for diagnosing diabetes insipidus, followed by the administration of desmopressin to differentiate between central and nephrogenic forms. Additional tests such as plasma vasopressin levels, MRI of the brain for central diabetes insipidus, genetic testing for familial forms of nephrogenic diabetes insipidus, and comprehensive metabolic panels are important for a thorough evaluation and to rule out other causes of polyuria.
Given the complexity and the need for precise diagnosis to guide treatment, a systematic approach that includes a combination of clinical evaluation, laboratory tests, and sometimes genetic testing is essential for accurately diagnosing diabetes insipidus and determining the appropriate treatment strategy 1.
From the FDA Drug Label
Laboratory tests for monitoring the patient include urine volume and osmolality In some cases, plasma osmolality may be required.
The workup for diabetes insipidus includes monitoring urine volume and osmolality, and in some cases, plasma osmolality may be required 2.
- Key components of the workup:
- Urine volume
- Urine osmolality
- Plasma osmolality (in some cases)
From the Research
Diagnosis of Diabetes Insipidus
The diagnosis of diabetes insipidus (DI) is challenging and relies on laboratory values, urine output, and physical examination of the patient 3. A high clinical suspicion of DI should be enough to initiate treatment.
Types of Diabetes Insipidus
DI is either due to deficient secretion of arginine vasopressin (central) or to tubular unresponsiveness (nephrogenic) 3. 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.
Diagnostic Tests
Distinguishing between the different types of DI can be challenging and is done either by:
- A water deprivation test
- Hypertonic saline stimulation together with copeptin (or AVP) measurement 4
- A detailed medical history
- Physical examination
- Imaging studies are needed to ensure an accurate DI diagnosis 4
Key Features for Diagnosis
Key features for diagnosis include:
- Polyuria, generally defined as urine output exceeding 3 liters per day in adults 3
- Excretion of large amounts of hypotonic urine 4
- Electrolyte imbalance that can affect the normal physiology of different organ systems 3
Differentiation from Primary Polydipsia
Central or nephrogenic DI must be differentiated from primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action 4. Primary polydipsia is most common in psychiatric patients and health enthusiasts, but the polydipsia in a small subgroup of patients seems to be due to an abnormally low thirst threshold, a condition termed dipsogenic DI 4.
Drug-Induced Diabetes Insipidus
Drug-induced DI is a well-known entity with an extensive list of medications 3. Drug-induced nephrogenic diabetes insipidus is not a common disorder except in patients receiving treatment with lithium salts for affective disorders, where it may affect about 10% of patients treated long term 5.
Treatment
Treatment of DI or primary polydipsia depends on the underlying aetiology and differs in central DI, nephrogenic DI, and primary polydipsia 4. Symptomatic treatment is often used, and the offending drug should be stopped if drug-induced 5. In some cases, treatment with thiazides and amiloride, or nonsteroidal anti-inflammatory drugs like indomethacin, may be tried 5, 6, 7.