Diabetes Insipidus for USMLE Step 1
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Diabetes Insipidus (DI) for the USMLE Step 1 Exam
- Pathophysiology
- Impaired ADH Activity: Diabetes insipidus (DI) is characterized by a deficiency of antidiuretic hormone (ADH) or renal resistance to its effects. This impairs water reabsorption in the renal collecting ducts, leading to excessive water loss.
- Polyuria and Polydipsia: The loss of free water results in large volumes of dilute urine (polyuria), leading to dehydration and compensatory thirst (polydipsia).
- Types of DI
- Central DI: Results from inadequate secretion of ADH.
- Causes:
- Idiopathic: The most common cause, likely related to autoimmune destruction of ADH-secreting neurons.
- Trauma or Surgery: Head trauma or neurosurgery can damage the hypothalamus or pituitary gland.
- Tumors: Pituitary adenomas, craniopharyngiomas, or metastases.
- Infiltrative Diseases: Conditions like sarcoidosis, tuberculosis, or histiocytosis affecting the hypothalamic-pituitary axis.
- Nephrogenic DI: Due to renal resistance to ADH, even though ADH secretion is normal or elevated.
- Causes:
- Genetic Mutations: Mutations in the V2 receptor or aquaporin-2 water channels.
- Medications: Lithium is a major cause of drug-induced nephrogenic DI.
- Electrolyte Imbalances: Hypercalcemia and hypokalemia can impair the kidney's ability to respond to ADH.
- Chronic Kidney Disease: Reduced ability to concentrate urine.
- Clinical Features
- Polyuria: Urine output exceeding 3 liters/day, sometimes reaching 20 liters/day in severe cases.
- Polydipsia: Excessive thirst as a compensatory mechanism to prevent dehydration.
- Nocturia: Frequent urination at night.
- Dehydration: If water intake is insufficient, symptoms of dehydration, such as dry mucous membranes, hypotension, and tachycardia, may develop.
- Hypernatremia: Can occur if fluid intake is inadequate, leading to high serum sodium levels.
- Diagnosis
- Clinical Suspicion: Polyuria and polydipsia should raise suspicion for DI.
- Water Deprivation Test:
- Purpose: Differentiates central and nephrogenic DI from primary polydipsia.
- Procedure: After water deprivation, the patient’s urine osmolality is measured, followed by desmopressin administration.
- Central DI: Low urine osmolality that improves with desmopressin.
- Nephrogenic DI: Urine remains dilute after desmopressin.
- Primary Polydipsia: Urine osmolality increases after water deprivation due to normal ADH function.
- Urine and Plasma Osmolality:
- Serum Osmolality: Increased (>295 mOsm/kg) due to water loss.
- Urine Osmolality: Decreased (<300 mOsm/kg) due to inability to concentrate urine.
- Serum Sodium: Hypernatremia may develop in cases of dehydration.
- Treatment
- Central DI:
- Desmopressin (DDAVP): A synthetic ADH analog used to replace the missing hormone. It can be administered intranasally, orally, or subcutaneously.
- Monitoring: Adjust desmopressin dosage to avoid water intoxication (hyponatremia).
- Treatment of Underlying Cause: Address tumors, trauma, or infiltrative diseases if present.
- Nephrogenic DI:
- Discontinue Offending Medications: Stop drugs like lithium that contribute to nephrogenic DI.
- Thiazide Diuretics: Paradoxically reduce urine output by inducing mild hypovolemia, which enhances proximal sodium and water reabsorption.
- Low-Sodium Diet: Helps to reduce urine output.
- Amiloride: Especially useful for lithium-induced nephrogenic DI, as it blocks lithium entry into renal cells.
- Complications
- Hypernatremia: If water intake does not compensate for water loss, patients may develop severe hypernatremia, which can cause confusion, seizures, or coma.
- Dehydration: Significant fluid loss without adequate replacement can result in hypotension, tachycardia, and potentially shock.
Key Points
- Pathophysiology:
- Central DI is caused by insufficient ADH production, while nephrogenic DI results from renal resistance to ADH.
- Both result in polyuria, polydipsia, and inability to concentrate urine.
- Causes:
- Central DI causes include head trauma, tumors, surgery, and idiopathic factors.
- Nephrogenic DI causes include lithium use, genetic mutations, and electrolyte imbalances.
- Diagnosis:
- Water deprivation test differentiates central DI from nephrogenic DI and primary polydipsia.
- Key findings include high serum osmolality and low urine osmolality.
- Treatment:
- Central DI is treated with desmopressin.
- Nephrogenic DI management includes thiazide diuretics, a low-sodium diet, and addressing underlying causes.
- Complications:
- Hypernatremia and dehydration are serious risks if DI is not managed properly.