What is the etiology, diagnosis, and management of Diabetes Insipidus (DI)?

From the Guidelines

Diabetes insipidus (DI) is a rare endocrine disorder characterized by the inability to regulate fluids in the body, resulting in excessive thirst and urination.

Etiology

The etiology of DI can be central, due to a deficiency in antidiuretic hormone (ADH), or nephrogenic, resulting from renal insensitivity to ADH 1.

Diagnosis

Diagnosis is typically made through a comprehensive family history and pedigree construction, measuring serum sodium, serum osmolality and urine osmolality 1.

• The detection of inappropriately diluted urine (that is, urinary osmolality <200 mOsm/kg H2O), in combination with high–normal or elevated serum sodium is pathognomonic for the diagnosis of diabetes insipidus (nephrogenic or central) and warrants early genetic testing if NDI is suspected 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 1.

Management

Management of central DI involves treatment with desmopressin, typically administered intranasally at a dose of 5-20 mcg daily, divided into 2-3 doses, for an indefinite duration 1,

• while nephrogenic DI may require treatment with hydrochlorothiazide, a thiazide diuretic, at a dose of 25-50 mg daily, in combination with a low-sodium diet and potassium supplementation as needed 1.
• In symptomatic infants and children with NDI, treatment with a thiazide and prostaglandin synthesis inhibitors is recommended 1.
• Fluid intake should be ad libitum, with access to fluid in all patients with NDI to prevent dehydration, hypernatraemia, growth failure and constipation 1.
• Dietary modifications, including a low-sodium diet, can help reduce renal osmotic load and minimize urine volume 1.
• Genetic counselling is crucial for patients with NDI, particularly for female carriers of X-linked NDI, to inform reproductive options and family planning 1.

From the FDA Drug Label

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. Laboratory tests for monitoring the patient include urine volume and osmolality In some cases, plasma osmolality may be required.

The etiology of Diabetes Insipidus (DI) is not directly addressed in the provided drug labels. The diagnosis of DI involves laboratory tests, including:

• Urine volume and osmolality
• Plasma osmolality (in some cases) The management of central (cranial) DI involves antidiuretic replacement therapy with desmopressin acetate injection 4 mcg/mL. 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. Fluid restriction should be observed to prevent possible hyponatremia and water intoxication. 2, 2, 2

From the Research

Etiology of Diabetes Insipidus (DI)

• Diabetes insipidus (DI) is a rare endocrine disease involving antidiuretic hormone (ADH) deficiency, encompassing both central and nephrogenic causes 3
• The two main classifications of DI are central diabetes insipidus (CDI), characterized by a deficiency of the posterior pituitary gland to release ADH, and nephrogenic diabetes insipidus (NDI), characterized by the terminal distal convoluted tubule and collecting duct resistance to ADH 4
• Other less common classifications include dipsogenic DI, characterized by excessive thirst due to a low osmotic threshold, and gestational DI, characterized by increased concentration of placental vasopressinase during pregnancy 4

Diagnosis of Diabetes Insipidus (DI)

• The gold standard for diagnosis is a water deprivation test followed by desmopressin administration 3
• A detailed medical history, physical examination, and imaging studies are needed to detect the etiology of diabetes insipidus 5
• Differentiation between the various forms of hypotonic polyuria is then done by the classical water deprivation test or the more recently developed hypertonic saline or arginine stimulation together with copeptin (or AVP) measurement 5
• Baseline plasma copeptin measurement is a stable surrogate biomarker of AVP release and can be used in the diagnosis of NDI 6

Management of Diabetes Insipidus (DI)

• Treatment of DI is dependent on the disease classification, but severe complications may arise if not tended to appropriately 4
• The most important step in symptom management is maintaining fluid intake ahead of fluid loss with emphasis placed on preserving the quality of life 4
• The most common treatment of CDI and gestational DI is the administration of synthetic ADH, desmopressin (DDAVP) 4
• Nephrogenic treatment, although more challenging, requires discontinuation of medications as well as maintaining a renal-friendly diet to prevent hypernatremia 4
• Therapeutic options for NDI include nonpharmacological interventions, such as sufficient water intake and a low-sodium diet, and pharmacological treatment with thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride 6