What is the connection between adrenal insufficiency and hypothyroidism?

The Connection Between Adrenal Insufficiency and Hypothyroidism

Adrenal insufficiency and hypothyroidism are interconnected endocrine disorders that frequently coexist, with adrenal insufficiency requiring treatment before hypothyroidism to prevent precipitating an acute adrenal crisis. 1

Pathophysiological Connections

Central (Secondary) Adrenal Insufficiency and Hypothyroidism

• Hypophysitis (pituitary inflammation) can cause both central hypothyroidism and central adrenal insufficiency simultaneously 2
  • Central hypothyroidism occurs in >90% of hypophysitis cases
  • Central adrenal insufficiency occurs in >75% of hypophysitis cases
  • Approximately 50% of patients present with panhypopituitarism (adrenal insufficiency + hypothyroidism + hypogonadism)

Primary Hypothyroidism and Adrenal Function

• Primary hypothyroidism can be associated with secondary adrenal insufficiency 3
• Subclinical hypothyroidism can be reversible when present alongside adrenal insufficiency 4
  • Thyroid function tests may normalize with adrenal hormone replacement alone, without requiring thyroid hormone replacement

Diagnostic Challenges

• Serum TSH levels may be misleading in cases of combined hypothalamic hypothyroidism and secondary adrenal insufficiency 5
  • TSH levels can be in ranges typically associated with primary hypothyroidism even when the condition is secondary

Clinical Implications

Treatment Priority

• When both adrenal insufficiency and hypothyroidism coexist, glucocorticoid replacement must be initiated before thyroid hormone therapy 1
• Failure to treat adrenal insufficiency first can precipitate an acute adrenal crisis 1
  • Thyroid hormone increases metabolic clearance of glucocorticoids
  • Starting thyroid hormone first can deplete already limited cortisol reserves

Diagnostic Approach

• Morning serum cortisol and ACTH levels should be measured alongside thyroid function tests when evaluating patients with suspected endocrine disorders 6
• Interpretation thresholds for morning serum cortisol:
  • ≥300 nmol/L (≥10.8 μg/dL): excludes adrenal insufficiency
  • <110 nmol/L (<4 μg/dL): suggests adrenal insufficiency
  • 110-300 nmol/L: further testing required

Management Considerations

• Proper glucocorticoid replacement is essential for patients with adrenal insufficiency 6
  • Typical hydrocortisone dosing: 15-25 mg daily in divided doses
  • Alternative: prednisone 5-7.5 mg daily
• Mineralocorticoid replacement (fludrocortisone 50-200 μg daily) is necessary for primary adrenal insufficiency 6
• DHEA replacement (25-50 mg daily) may be considered for persistent symptoms 6

Critical Situations

Acute Adrenal Crisis Prevention

• All patients with adrenal insufficiency should:
  • Wear medical alert identification
  • Carry a steroid alert card
  • Have an emergency hydrocortisone injection kit 6

Stress Dosing Protocol

• Minor illness/stress: double or triple usual daily dose
• Moderate stress: hydrocortisone 50-75 mg/day in divided doses
• Severe stress: hydrocortisone 100 mg IV immediately, followed by 100-300 mg/day 6

Special Populations

Critical Illness

• Combined hypothyroidism and adrenal insufficiency occurs in approximately 12% of critically ill patients with sepsis or hemorrhagic shock 7
• Routine testing for both conditions may be indicated in critically ill patients

Unusual Presentations

• Adrenal insufficiency can sometimes present with elevated thyroid hormone levels and elevated TSH 8
• These abnormalities typically correct with corticosteroid replacement

Monitoring

• Annual follow-up should include:
  • Assessment of well-being
  • Weight and blood pressure measurement
  • Serum electrolyte testing
  • Screening for other autoimmune disorders
  • Bone mineral density assessment every 3-5 years 6

Remember that the connection between these two endocrine disorders is bidirectional and complex, requiring careful diagnostic evaluation and treatment sequencing to prevent serious complications.