Chapter 61: Diabetes Insipidus & Syndrome of Inappropriate Antidiuretic Hormone

DIABETES INSIPIDUS (DI)

• Uncontrolled free water losses lead to severe hypernatremia and significant dehydration

NORMAL WATER HOMEOSTASIS

• Normal plasma osmolality: 275 to 295 mOsm/L

• Controlled via thirst and arginine vasopressin

• Arginine vasopressin (AVP): Produced in supraoptic and paraventricular nuclei of hypothalamus, released in posterior pituitary

  • Vasopressin receptors

    • V1: liver, vasculature – contributes to vasoconstriction, hepatic gluconeogenesis

    • V2: kidney – functions to increase renal tubule water permeability

  • AVP mechanism

    • Binds V2 in renal collecting ducts: increases permeability via aquaporin-2 channels – allows diffusion of water from tubules to plasma

    • Release regulated by osmoreceptors near anterior hypothalamus

    • Nonosmotic factors affecting AVP release: volume depletion, hypotension, pain, nausea, medications

    • Desmopressin (DDAVP) – lacks smooth muscle contraction effects; more specific for V2 receptor

PATHOPHYSIOLOGIC MECHANISMS

• Central DI: defect in secretion or synthesis of vasopressin → decreased free water reabsorption in renal collecting tubules

  • Genetic

  • Injury/damage to pituitary gland and/or hypothalamus

    • Post–hypothalamic-pituitary surgery; may be transient (permanent if transection of pituitary stalk)

    • Central nervous system (CNS) infections

    • CNS tumors (e.g., craniopharyngioma)

    • Traumatic brain injury

    • Hypoxic ischemic injury

    • Brain death

• Nephrogenic DI: impaired ability to concentrate urine

  • Genetic

  • Drugs: lithium, amphotericin B, rifampin

  • Neoplasm

  • Sickle cell

  • Metabolic derangements

  • Obstructive uropathy

DIAGNOSIS

• Hallmarks:

  • Polyuria and polydipsia

  • Urine specific gravity <1.005

  • Urine output (UOP) >4 mL/kg/hr

  • Serum Na >145 mEq/L

  • Serum osmolality >285 mOsm/L

  • Urine osmolality <100 to 200 mOsm/L

• Serum sodium and osmolality depend on hydration status

CLINICAL MANIFESTATIONS

• Thirst, polyuria, dilute urine, hypovolemia, tachycardia, poor perfusion, shock

• CNS abnormalities – lethargy, irritability, seizure, coma

• Hyperosmolar state – risk of venous sinus thrombosis

TREATMENT

• Fluid resuscitation to reverse hypovolemic shock if necessary

• Then hypotonic fluid to replace urine losses in addition to maintenance requirements

• Avoid hyperglycemia if giving large volumes of dextrose-containing fluids – risk of osmotic diuresis worsening dehydration

• If vasopressin sensitive (central DI), initiation of vasopressin administration

• Avoid rapid correction of hypernatremia – correct over 48 to 72 hours to avoid cerebral edema

SYNDROME OF INAPPROPRIATE ANTIDIURECTIC HORMONE SECRETION (SIADH)

• Relative hypersthenuria (increased urine osmolality) and hyponatremia

PATHOPHYSIOLOGIC MECHANISMS

• Pituitary hypersecretion of vasopressin → excess of water in extracellular and intracellular compartments → renin/aldosterone activity reduced → increased natriuresis due to expansion of extracellular volume

• Causes of SIADH

  • CNS: brain injury, tumors, infections

  • Adrenal insufficiency

  • Drugs: vincristine, cyclophosphamide, carbamazepine, barbiturates

  • Malignancy

  • Hypothyroidism

  • Guillan-Barre

  • Infant botulism

  • Pulmonary diseases: tuberculosis, cystic fibrosis

  • Positive end-expiratory pressure (PEEP)

DIAGNOSIS

• Hypotonic hyponatremia

• Serum sodium <125 mEq/L

• Serum osmolality <260 mOsm/L

• Urine sodium >18 mEq/L

• Inappropriate urine concentration at some level of serum hypo-osmolality

• Elevated urinary sodium excretion with normal salt and water intake

• Signs of hypovolemia or ...