Why check Thyroid-Stimulating Hormone (TSH) and cortisol levels when evaluating a patient for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Why TSH and Cortisol Should Be Checked When Evaluating for SIADH

TSH and cortisol must be checked when evaluating for SIADH because hypothyroidism and adrenal insufficiency can present with nearly identical laboratory findings to SIADH, and failure to identify these conditions can lead to inappropriate treatment and increased morbidity and mortality. 1

Diagnostic Criteria for SIADH

SIADH is characterized by the following findings:

• Hyponatremia (serum sodium < 134 mEq/L) 2
• Hypoosmolality (plasma osmolality < 275 mOsm/kg) 2
• Inappropriately high urine osmolality (> 500 mOsm/kg) 2
• Inappropriately high urinary sodium concentration (> 20 mEq/L) 2
• Absence of hypothyroidism, adrenal insufficiency, and volume depletion 2

Why Thyroid Function Must Be Assessed

• Hypothyroidism can present with hyponatremia that mimics SIADH and must be excluded before diagnosing SIADH 2
• Thyroid dysfunction affects water metabolism and can lead to impaired free water clearance similar to SIADH 2
• TSH secretion can vary significantly (up to 50%) on a day-to-day basis, making serial measurements important for accurate diagnosis 3
• Medications commonly used in hospitalized patients (dopamine, glucocorticoids) can affect thyroid function during illness 3

Why Cortisol Must Be Assessed

• Adrenal insufficiency presents with hyponatremia in 90% of newly diagnosed cases and can be indistinguishable from SIADH if adrenal function is not specifically assessed 1
• Both adrenal insufficiency and SIADH present with euvolemic hypo-osmolar hyponatremia 1
• The standard 0.25 mg cosyntropin stimulation test with cortisol measurements at baseline and 30 minutes post-administration is necessary to rule out adrenal insufficiency 1
• Hyperkalemia is present in only about 50% of adrenal insufficiency cases, so its absence cannot rule out the condition 1

Diagnostic Algorithm for Hyponatremia Evaluation

1. Measure serum sodium, osmolality, and assess volume status 2

2. For hypo-osmolar hyponatremia (serum Na < 131 mmol/L), obtain: 2

   • Serum and urine osmolality
   • Urine electrolytes
   • Serum uric acid
   • TSH and free T4
   • Morning cortisol and ACTH (or perform cosyntropin stimulation test)

3. Categorize by volume status: 2

   • Hypovolemic: Consider CSW, diuretics, or adrenal insufficiency
   • Euvolemic: Rule out thyroid disease and hypocortisolism before diagnosing SIADH
   • Hypervolemic: Consider cirrhosis, heart failure, or renal failure

Treatment Implications

• Misdiagnosis can lead to inappropriate treatment: 1

  • SIADH requires fluid restriction and possibly vasopressin receptor antagonists
  • Adrenal insufficiency requires glucocorticoid replacement therapy
  • Hypothyroidism requires thyroid hormone replacement

• Treating secondary adrenal insufficiency with concurrent hypothyroidism requires starting corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 1

Common Pitfalls to Avoid

• Relying solely on electrolyte abnormalities for diagnosis of adrenal insufficiency, as hyponatremia may be only marginally reduced 1
• Failing to obtain TSH and cortisol levels before initiating treatment for presumed SIADH 2, 1
• Delaying treatment of suspected adrenal crisis for diagnostic testing when a patient is clinically unstable 1
• Diagnosing SIADH without excluding other causes of hyponatremia 4, 5
• Overlooking the possibility of corticotropin deficiency, which can mimic SIADH but requires completely different treatment 6

By checking both TSH and cortisol when evaluating for SIADH, clinicians can avoid misdiagnosis and ensure appropriate treatment, significantly reducing the risk of adverse outcomes in patients with hyponatremia.