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Diabetes Insipidus

Diabetes insipidus (DI), also known as arginine vasopressin deficiency (AVP-D) or arginine vasopressin resistance (AVP-R), is a condition characterised by the production of large amounts of dilute urine and increased thirst. Unlike diabetes mellitus, DI does not involve elevated glucose levels in the urine.

Vasopressin
3D structure of vasopressin, the hormone affected in diabetes insipidus

Types and Causes

There are four main types of DI, each with specific causes:

  1. Central DI: Caused by a deficiency in vasopressin production due to injury or damage to the hypothalamus or pituitary gland, or genetic factors.
  2. Nephrogenic DI: Occurs when the kidneys do not respond properly to vasopressin.
  3. Dipsogenic DI: Results from excessive fluid intake due to damage to the hypothalamic thirst mechanism, often associated with psychiatric disorders or certain medications.
  4. Gestational DI: Occurs during pregnancy due to the production of vasopressinase in the placenta, which breaks down antidiuretic hormone (ADH).

Signs and Symptoms

The hallmark symptoms of DI include excessive urination and extreme thirst, with a preference for cold water. Unlike diabetes mellitus, the urine in DI does not contain glucose. Other symptoms may include dehydration, blurred vision, and in severe cases, seizures. In children, DI can interfere with growth and development, presenting with fever, vomiting, or diarrhoea.

Pathophysiology

The regulation of urine production is managed by the hypothalamus, which produces ADH. ADH increases water permeability in the kidney's collecting ducts, allowing for water reabsorption and concentrated urine. In DI, this process is disrupted, leading to the excretion of large volumes of dilute urine.

Diagnosis

Diagnosis of DI involves several tests to distinguish it from other causes of excessive urination:

  • Urine and Blood Tests: To measure electrolyte levels, glucose, and urine osmolarity.
  • Fluid Deprivation Test: Measures changes in body weight, urine output, and composition when fluids are withheld. Desmopressin administration helps determine if DI is due to a defect in ADH production or kidney response.
  • Other Tests: Blood ADH levels and magnetic resonance imaging (MRI) may be necessary for central DI to investigate underlying causes.

Treatment

Central and Gestational DI

Treatment primarily involves the administration of desmopressin, which can be given intranasally or orally. Carbamazepine, an anticonvulsive medication, may also be effective. Gestational DI typically resolves postpartum but may recur in subsequent pregnancies.

Nephrogenic DI

Desmopressin is ineffective in nephrogenic DI. Treatment includes addressing the underlying cause and using thiazide diuretics to create mild hypovolaemia, encouraging salt and water uptake in the proximal tubule. Amiloride, a potassium-sparing diuretic, may be used alongside thiazides to prevent hypokalaemia. Lithium-induced nephrogenic DI can be managed with amiloride.

Etymology

The term "diabetes" derives from the Greek word meaning "syphon," reflecting the excessive discharge of urine. "Insipidus" means "tasteless" in Latin, indicating the absence of glucose in the urine, distinguishing it from diabetes mellitus. A survey among central DI patients suggested a preference for the term "vasopressin deficiency" to avoid confusion with diabetes mellitus.

Frequency and Prognosis

DI is relatively rare, with an incidence of 3 per 100,000 per year. With appropriate treatment, the prognosis for DI is good, although ongoing management is necessary to prevent complications such as dehydration and electrolyte imbalances.


Self-assessment MCQs (single best answer)

What is the primary hormone affected in diabetes insipidus?



Which type of diabetes insipidus is caused by a deficiency in vasopressin production?



What is the hallmark symptom of diabetes insipidus?



What test is used to measure changes in body weight, urine output, and composition when fluids are withheld?



Which medication is commonly used to treat central and gestational diabetes insipidus?



What is the primary treatment for nephrogenic diabetes insipidus?



Which of the following is NOT a symptom of diabetes insipidus?



What does the term "insipidus" mean in the context of diabetes insipidus?



Which of the following types of DI occurs due to excessive fluid intake?



What is the incidence rate of diabetes insipidus per year?



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