Diabetes Insipidus for USMLE Step 2
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Diabetes Insipidus (DI) for the USMLE Step 2 Exam
- Pathophysiology
- Impaired ADH Activity: Diabetes insipidus (DI) results from inadequate antidiuretic hormone (ADH) secretion or renal insensitivity to ADH, leading to impaired water reabsorption in the kidneys.
- Excessive Urine Output: Without the action of ADH, the renal collecting ducts cannot concentrate urine, leading to the excretion of large volumes of dilute urine.
- Polyuria and Polydipsia: Water loss causes significant polyuria, with compensatory polydipsia to maintain fluid balance.
- Types of DI
- Central DI: Caused by insufficient ADH secretion from the posterior pituitary.
- Causes:
- Idiopathic: Most common cause, likely autoimmune-mediated.
- Trauma or Surgery: Damage to the hypothalamus or pituitary from head injury or surgery (e.g., transsphenoidal pituitary surgery).
- Tumors: Craniopharyngiomas, pituitary adenomas, or metastatic lesions.
- Infiltrative Diseases: Sarcoidosis, Langerhans cell histiocytosis, or tuberculosis affecting the hypothalamus or pituitary.
- Nephrogenic DI: Caused by renal resistance to ADH.
- Causes:
- Genetic: Mutations in the V2 receptor or aquaporin-2 water channels.
- Medications: Lithium is the most common drug-related cause.
- Electrolyte Disorders: Hypercalcemia and hypokalemia impair the kidney’s ability to respond to ADH.
- Chronic Kidney Disease (CKD): Long-standing kidney disease can impair the concentrating ability of the renal tubules.
- Clinical Features
- Polyuria: Urine output often exceeds 3 liters/day, and in severe cases, it may reach 15-20 liters/day.
- Polydipsia: Intense thirst and excessive water intake to compensate for the water lost in urine.
- Nocturia: Frequent urination at night, which can disturb sleep.
- Dehydration: Signs include dry mucous membranes, hypotension, and tachycardia if water intake is insufficient.
- Hypernatremia: If fluid intake does not keep up with losses, serum sodium levels may increase, leading to hypernatremia.
- Diagnosis
- Water Deprivation Test:
- Used to differentiate between central DI, nephrogenic DI, and primary polydipsia.
- After water deprivation, urine osmolality is measured. Desmopressin is then administered.
- Central DI: Urine osmolality remains low after deprivation but increases significantly after desmopressin.
- Nephrogenic DI: Urine osmolality remains low after both water deprivation and desmopressin.
- Primary Polydipsia: Urine osmolality rises after water deprivation due to normal ADH function.
- Serum and Urine Osmolality:
- Serum Osmolality: Elevated (>295 mOsm/kg) due to free water loss.
- Urine Osmolality: Low (<300 mOsm/kg), indicating dilute urine despite dehydration.
- Serum Sodium: Hypernatremia (Na+ >145 mEq/L) can develop if the patient cannot compensate for water loss.
- Treatment
- Central DI:
- Desmopressin (DDAVP): Synthetic ADH analog that is the first-line treatment. It can be administered intranasally, orally, or parenterally.
- Monitoring: Careful monitoring of fluid balance and serum sodium to prevent water intoxication (hyponatremia).
- Nephrogenic DI:
- Discontinue Causative Medications: Stopping drugs like lithium may reverse nephrogenic DI.
- Thiazide Diuretics: Reduce urine output by promoting proximal tubular water reabsorption.
- Low-Sodium Diet: Reduces the osmotic load on the kidneys and decreases urine output.
- Amiloride: Especially beneficial in lithium-induced DI by inhibiting lithium entry into renal cells.
- Complications
- Hypernatremia: If water intake is insufficient, severe hypernatremia can develop, causing confusion, seizures, or coma.
- Dehydration: Can lead to hypotension, tachycardia, and shock if not treated adequately.
Key Points
- Pathophysiology: DI occurs due to insufficient ADH (central DI) or renal resistance to ADH (nephrogenic DI), leading to polyuria and dilute urine.
- Etiology: Central DI is often idiopathic or secondary to trauma or tumors, while nephrogenic DI may result from lithium use, genetic mutations, or electrolyte imbalances.
- Diagnosis: The water deprivation test helps distinguish central DI from nephrogenic DI and primary polydipsia. Key findings include elevated serum osmolality and low urine osmolality.
- Treatment: Central DI is treated with desmopressin, while nephrogenic DI may require thiazide diuretics, a low-sodium diet, and discontinuation of causative drugs.
- Complications: Hypernatremia and dehydration are serious risks if DI is not managed properly.