What is Diabetes Insipidus (DI)?

From the Guidelines

Diabetes insipidus is a rare disorder characterized by the inability to regulate fluids due to problems with antidiuretic hormone (ADH), leading to excessive urine production and thirst, with two main types: central and nephrogenic diabetes insipidus. This condition occurs when the body can't properly regulate fluids, resulting in symptoms such as producing large amounts of dilute urine, extreme thirst, and frequent urination day and night 1. The exact incidence and prevalence of congenital nephrogenic diabetes insipidus are unknown, but it is considered a rare disease 1.

Key Characteristics

• Insensitivity of the distal nephron to antidiuretic hormone (ADH) or arginine vasopressin (AVP) 1
• Inability of the kidney to concentrate urine, leading to polyuria, polydipsia, and the risk of hypertonic dehydration 1
• Symptoms include polyuria, failure to thrive, and signs of dehydration, with serum osmolality usually >300 mOsm/kg H2O and urine osmolality usually <200 mOsm/kg H2O 1

Diagnosis and Management

• Diagnosis requires blood and urine tests, and sometimes a water deprivation test 1
• Treatment depends on the type of diabetes insipidus, but may include desmopressin (DDAVP) for central diabetes insipidus, and thiazide diuretics like hydrochlorothiazide, a low-salt diet, and NSAIDs for nephrogenic diabetes insipidus 1
• Free access to fluid is recommended for all children with nephrogenic diabetes insipidus, along with normal-for-age milk intake and consideration of tube feeding in infants with repeated episodes of vomiting and dehydration 1

Recommendations for Treatment and Follow-up

• Monitoring dietary salt and protein intake to reduce renal osmotic load and minimize urine volume 1
• Starting treatment with a thiazide and prostaglandin synthesis inhibitors in symptomatic infants and children 1
• Adding amiloride to thiazide in patients with hypokalaemia induced by thiazides 1
• Ongoing drug treatment should be based on the balance of apparent efficacy and concern over development of side effects 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.

Desmopressin acetate injection is ineffective for the treatment of nephrogenic diabetes insipidus

Diabetes Insipidus is a condition that can be managed with desmopressin acetate injection, specifically central (cranial) diabetes insipidus and temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. However, it is ineffective for the treatment of nephrogenic diabetes insipidus 2.

From the Research

Definition of Diabetes Insipidus

Diabetes insipidus is a disorder characterized by the excretion of large amounts of hypotonic urine, leading to excessive thirst and craving for cold water 3, 4, 5. It is an endocrine condition involving the posterior pituitary peptide hormone, antidiuretic hormone (ADH) 4.

Types of Diabetes Insipidus

There are two main types of diabetes insipidus:

• Central diabetes insipidus (CDI), characterized by a deficiency of the posterior pituitary gland to release ADH 3, 4, 6
• Nephrogenic diabetes insipidus (NDI), characterized by the terminal distal convoluted tubule and collecting duct resistance to ADH 3, 4, 6 Additionally, there are two less common classifications:
• Dipsogenic DI, characterized by excessive thirst due to a low osmotic threshold 4, 5
• Gestational DI, characterized by increased concentration of placental vasopressinase during pregnancy 4

Causes and Symptoms

Diabetes insipidus can be caused by inadequate or impaired secretion of ADH from the posterior pituitary gland or impaired renal response to ADH 3. Symptoms include expelling excessive quantities of highly dilute urine, extreme thirst, and craving for cold water 4.

Diagnosis and Treatment

Diagnosis of diabetes insipidus involves a water deprivation test or hypertonic saline stimulation together with copeptin (or AVP) measurement, as well as a detailed medical history, physical examination, and imaging studies 5. Treatment depends on the underlying aetiology and differs in central DI, nephrogenic DI, and primary polydipsia 4, 5, 6. Common treatments include:

• Administration of synthetic ADH, desmopressin (DDAVP) for CDI and gestational DI 4
• Discontinuation of medications and maintaining a renal-friendly diet to prevent hypernatremia for NDI 4
• Behavioral therapy aimed at regulating water intake and/or administration of antipsychotic pharmaceutical therapy for dipsogenic DI 4