Diabetes Insipidus for USMLE Step 3

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Diabetes Insipidus (DI) for the USMLE Step 3 Exam

Impaired ADH Activity: Diabetes insipidus (DI) occurs when there is insufficient antidiuretic hormone (ADH) secretion or renal resistance to ADH, leading to excessive free water loss.
Polyuria and Polydipsia: The inability to concentrate urine results in polyuria (excessive urination) and compensatory polydipsia (excessive thirst) to maintain hydration.
Types of DI:
Central DI: Characterized by deficient ADH production or release from the hypothalamus or pituitary.
Nephrogenic DI: The kidneys do not respond to normal ADH levels due to a defect in the renal tubules.

Central DI:
Idiopathic: Most common cause, likely autoimmune in origin.
Head Trauma: Trauma affecting the hypothalamus or pituitary gland.
Neurosurgery: Surgery near the pituitary (e.g., transsphenoidal surgery) can lead to transient or permanent DI.
Tumors: Pituitary or hypothalamic tumors (e.g., craniopharyngiomas) may impair ADH secretion.
Infiltrative Diseases: Conditions such as sarcoidosis or tuberculosis affecting the hypothalamic-pituitary axis.
Nephrogenic DI:
Medications: Lithium is a common cause of nephrogenic DI, as it interferes with ADH signaling.
Electrolyte Imbalances: Hypercalcemia and hypokalemia can impair the kidney’s ability to concentrate urine.
Genetic Mutations: Mutations in the V2 receptor or aquaporin-2 water channels cause congenital nephrogenic DI.

Polyuria: Urine output exceeding 3 liters/day, with extreme cases reaching 15–20 liters/day.
Polydipsia: Excessive thirst due to water loss, with patients consuming large amounts of water.
Nocturia: Frequent urination at night, disrupting sleep.
Dehydration: Signs include dry mucous membranes, hypotension, and tachycardia if water intake is insufficient.
Hypernatremia: Increased serum sodium if fluid losses are not adequately replaced.

Water Deprivation Test:
Used to differentiate central DI, nephrogenic DI, and primary polydipsia.
After a period of water deprivation, the patient's urine osmolality is measured, followed by administration of desmopressin (a synthetic ADH).
Central DI: Urine osmolality remains low after water deprivation but increases with desmopressin.
Nephrogenic DI: Urine osmolality remains low after both water deprivation and desmopressin.
Primary Polydipsia: Urine osmolality increases after water deprivation due to intact ADH secretion.
Serum and Urine Osmolality:
Serum Osmolality: Elevated (>295 mOsm/kg) due to free water loss.
Urine Osmolality: Low (<300 mOsm/kg) due to inability to concentrate urine.
Serum Sodium: Hypernatremia (Na+ >145 mEq/L) may occur, especially if fluid intake is insufficient.

Central DI:
Desmopressin (DDAVP): A synthetic ADH analog, desmopressin is the mainstay of treatment. It can be administered intranasally, orally, or parenterally.
Monitoring: Monitor serum sodium to avoid overcorrection, which could lead to water intoxication and hyponatremia.
Address Underlying Cause: Surgical intervention for tumors or discontinuation of causative agents may be necessary.
Nephrogenic DI:
Correct Underlying Causes: Discontinuing lithium or correcting electrolyte imbalances may improve symptoms.
Thiazide Diuretics: Thiazides reduce polyuria by inducing mild volume depletion, leading to increased sodium and water reabsorption in the proximal tubules.
Amiloride: Particularly useful in lithium-induced DI, as it inhibits lithium's effect on the kidneys.
Low-Sodium Diet: Reduces the osmotic load on the kidneys, decreasing urine output.

Hypernatremia: If fluid intake does not match water loss, hypernatremia can develop, leading to neurological symptoms like confusion, seizures, and coma.
Dehydration: Severe dehydration can result in hypotension, tachycardia, and circulatory shock.

Key Points

Pathophysiology: Central DI results from inadequate ADH production, while nephrogenic DI involves renal resistance to ADH.
Etiology: Causes of central DI include trauma, tumors, and neurosurgery, while nephrogenic DI can be due to medications (e.g., lithium), genetic mutations, or electrolyte imbalances.
Diagnosis: The water deprivation test differentiates between central DI, nephrogenic DI, and primary polydipsia. Key diagnostic findings include elevated serum osmolality and low urine osmolality.
Treatment: Central DI is treated with desmopressin, while nephrogenic DI requires thiazide diuretics, low-sodium diet, and correction of underlying causes.
Complications: Hypernatremia and dehydration are serious risks in untreated or inadequately managed DI.