What are the symptoms of anti-diuretic hormone (ADH) imbalance?

Symptoms of Anti-Diuretic Hormone Imbalance

The symptoms of anti-diuretic hormone (ADH) imbalance primarily manifest as hyponatremia with neurological symptoms including confusion, lethargy, headache, nausea, muscle cramps, gait instability, and in severe cases, seizures and coma. 1

Excess ADH (SIADH)

Pathophysiology

• Excess ADH activates vasopressin V2 receptors in renal tubules, increasing water reabsorption and causing impaired free water clearance 2
• Results in dilutional hyponatremia despite normal or expanded extracellular fluid volume
• Common in small cell lung cancer (SCLC) due to ectopic production of ADH by tumor cells 1, 2

Clinical Presentation by Severity

1. Mild hyponatremia (126-135 mEq/L):

   • Often asymptomatic or subtle symptoms
   • Nausea
   • Muscle cramps
   • Headache
   • Mild neurocognitive deficits 2, 3

2. Moderate hyponatremia (120-125 mEq/L):

   • Weakness
   • Gait instability
   • Headache
   • Dizziness
   • Nausea and vomiting 1, 2

3. Severe hyponatremia (<120 mEq/L):

   • Confusion
   • Delirium
   • Lethargy
   • Seizures
   • Coma
   • Brain herniation (rare)
   • Death (if untreated) 1, 2, 3

Laboratory Findings in SIADH

• Hyponatremia (serum sodium <135 mEq/L)
• Hypoosmolality (plasma osmolality <275 mOsm/kg)
• Inappropriately concentrated urine (urine osmolality >500 mOsm/kg relative to serum)
• High urinary sodium concentration (>20 mEq/L)
• Normal adrenal and thyroid function 2

ADH Deficiency (Diabetes Insipidus)

Central Diabetes Insipidus (ADH deficiency)

• Polyuria (excessive urination)
• Polydipsia (excessive thirst)
• Dehydration
• Hypernatremia
• Production of large volumes of dilute urine 1

Nephrogenic Diabetes Insipidus (ADH resistance)

• Insensitivity of the distal nephron to ADH
• Polyuria and polydipsia
• Risk of hypertonic dehydration
• Failure to thrive (in infants)
• Hypernatremia with inappropriately dilute urine 1

Special Considerations

SIADH in Specific Populations

• Children: More prone to hypoglycemia, even hypoglycemic seizures 1
• Elderly: More susceptible to falls due to gait and attention disorders even with moderate hyponatremia 4
• Athletes: Marathon runners with SIADH risk hypotonic encephalopathy with potentially fatal cerebral edema 4

Common Causes of ADH Imbalance

1. SIADH:

   • Malignancies (especially small cell lung cancer)
   • CNS disorders (meningitis, encephalitis, stroke)
   • Medications (antipsychotics, antidepressants, carbamazepine)
   • Pulmonary diseases
   • Post-surgical states 1, 2

2. Diabetes Insipidus:

   • Genetic mutations
   • Head trauma
   • Pituitary surgery
   • Infiltrative diseases
   • Idiopathic 1

Clinical Pitfalls and Caveats

1. Diagnostic challenges:

   • Not all hyponatremia is due to SIADH - evaluate volume status carefully
   • Consider other causes of hyponatremia (adrenal insufficiency, hypothyroidism, medications)
   • Hyperglycemia and hypertriglyceridemia can cause pseudo-hyponatremia 4

2. Treatment considerations:

   • Overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome
   • Treatment should be based on symptom severity and chronicity
   • Fluid restriction alone is often sufficient for mild cases 1, 3

3. Monitoring:

   • Improvement in hyponatremia is associated with reduced brain edema, improved cognition, quality of life, and complex information processing 1
   • ADH levels and hyponatremia usually improve after successful treatment of underlying causes (e.g., SCLC) 1

Remember that symptoms of ADH imbalance can be subtle initially but may progress rapidly to life-threatening complications if not recognized and treated appropriately.