Diabetes Insipidus for PA

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Diabetes Insipidus (DI) for the Physician Assistant Licensing Exam

Impaired ADH Function: Diabetes insipidus (DI) is caused by either a deficiency in antidiuretic hormone (ADH) production (central DI) or resistance to ADH in the kidneys (nephrogenic DI). ADH normally promotes water reabsorption in the renal collecting ducts.
Polyuria and Polydipsia: Impaired ADH function leads to excessive water loss through urine (polyuria) and compensatory thirst (polydipsia) to maintain water balance.
Types of DI:
Central DI: Due to inadequate ADH secretion.
Nephrogenic DI: The kidneys fail to respond to normal or elevated ADH levels.

Central DI:
Idiopathic: The most common cause, often related to autoimmune destruction of ADH-producing neurons.
Head Trauma: Brain injury affecting the hypothalamus or pituitary gland.
Neurosurgery: Post-surgical complication from procedures near the pituitary gland (e.g., transsphenoidal surgery).
Tumors: Craniopharyngiomas, pituitary adenomas, or metastatic lesions.
Infiltrative Diseases: Sarcoidosis, tuberculosis, and histiocytosis affecting the hypothalamus or pituitary.
Nephrogenic DI:
Medications: Lithium is the most common drug-related cause of nephrogenic DI, impairing ADH signaling.
Genetic: Mutations in the V2 receptor or aquaporin-2 water channels.
Electrolyte Disorders: Hypercalcemia and hypokalemia reduce renal responsiveness to ADH.
Chronic Kidney Disease (CKD): Impairs the kidney’s ability to concentrate urine.

Polyuria: Patients typically have urine output exceeding 3 liters/day, which can reach 15–20 liters/day in severe cases.
Polydipsia: Excessive thirst due to water loss, leading to large fluid intake.
Nocturia: Frequent nighttime urination, which can disturb sleep.
Dehydration: Dry mucous membranes, hypotension, and tachycardia if fluid intake does not compensate for water loss.
Hypernatremia: Elevated serum sodium levels if water intake is insufficient, causing confusion, irritability, or neurological symptoms.

Water Deprivation Test:
Used to differentiate central DI from nephrogenic DI and primary polydipsia.
After water deprivation, urine osmolality is measured. Desmopressin (synthetic ADH) is administered to determine the response.
Central DI: Urine osmolality remains low after water deprivation but increases significantly after desmopressin.
Nephrogenic DI: Urine osmolality remains low after water deprivation and does not respond to desmopressin.
Primary Polydipsia: Urine osmolality increases after water deprivation due to intact ADH function.
Serum and Urine Osmolality:
Serum Osmolality: Typically elevated (>295 mOsm/kg) due to free water loss.
Urine Osmolality: Low (<300 mOsm/kg) because of the kidney’s inability to concentrate urine.
Serum Sodium: Hypernatremia (Na+ >145 mEq/L) may develop in patients who do not adequately compensate for fluid loss.

Central DI:
Desmopressin (DDAVP): A synthetic ADH analog is the treatment of choice, administered intranasally, orally, or parenterally.
Monitoring: Monitor serum sodium and fluid balance to avoid hyponatremia and water intoxication.
Treat Underlying Causes: Address tumors, trauma, or infiltrative diseases as needed.
Nephrogenic DI:
Correct the Cause: Discontinue offending medications (e.g., lithium) and address electrolyte imbalances.
Thiazide Diuretics: Thiazides paradoxically reduce urine output by inducing mild volume depletion, promoting proximal sodium and water reabsorption.
Amiloride: Beneficial in lithium-induced nephrogenic DI, as it reduces lithium entry into renal cells.
Low-Sodium Diet: Reduces the osmotic load on the kidneys, decreasing urine volume.

Hypernatremia: If fluid intake does not compensate for water loss, hypernatremia may cause confusion, seizures, or coma.
Dehydration: Severe dehydration can lead to hypotension, tachycardia, and shock.

Key Points

Pathophysiology: Central DI results from insufficient ADH secretion, while nephrogenic DI occurs due to renal resistance to ADH.
Etiology: Common causes of central DI include trauma, tumors, and idiopathic factors, while nephrogenic DI may be due to lithium use, electrolyte imbalances, or genetic defects.
Diagnosis: The water deprivation test differentiates central DI from nephrogenic DI and primary polydipsia. Elevated serum osmolality and low urine osmolality are key findings.
Treatment: Central DI is treated with desmopressin, while nephrogenic DI management includes thiazide diuretics, low-sodium diet, and correction of underlying causes.
Complications: Hypernatremia and dehydration are major risks if DI is not managed effectively.