How to assess adrenal function in patients with suspected central hypothyroidism (underactive thyroid gland due to pituitary hormone deficiency)?

Assessment of Adrenal Function in Central Hypothyroidism

For patients with suspected central hypothyroidism, adrenal function should be assessed with morning serum ACTH and cortisol levels, with consideration of an ACTH stimulation test (cosyntropin test) prior to initiating thyroid hormone replacement to prevent precipitating an adrenal crisis. 1, 2

Diagnostic Algorithm for Adrenal Assessment in Central Hypothyroidism

Initial Laboratory Evaluation

• Morning (8 AM) serum cortisol and ACTH levels 1, 2
• Complete thyroid function tests (TSH, free T4) 1
• Comprehensive metabolic panel to assess electrolytes and glucose 1
• Gonadal hormones (testosterone in men, estradiol in women, FSH, LH) 1

Interpretation of Initial Results

• Suggestive of central adrenal insufficiency: Morning cortisol <250 nmol/L (9 μg/dL) 2
• Suspicious for adrenal insufficiency: Morning cortisol <400 nmol/L (14.5 μg/dL) with inappropriately low or normal ACTH 2
• Indeterminate: Morning cortisol in intermediate range (250-400 nmol/L) 2

Confirmatory Testing

• ACTH stimulation test (gold standard): 1, 2
  • Administer 250 μg synthetic ACTH (cosyntropin)
  • Measure cortisol at baseline, 30 minutes, and 60 minutes
  • Peak cortisol <500 nmol/L (18 μg/dL) indicates adrenal insufficiency
  • Perform prior to initiating thyroid hormone replacement

Imaging

• MRI of the sella with pituitary cuts for all patients with suspected central hypothyroidism 1
• Look for pituitary abnormalities such as:
  • Stalk thickening
  • Suprasellar convexity
  • Heterogeneous enhancement
  • Increased height of the gland 1

Clinical Significance and Management

Prevalence and Importance

• Central adrenal insufficiency occurs in >75% of patients with hypophysitis 1
• Approximately 17-62% of patients with nonfunctioning pituitary adenomas have adrenal insufficiency 1
• Adrenal insufficiency must be identified and treated before thyroid hormone replacement 1, 2, 3

Management Sequence

1. Confirm adrenal status before initiating thyroid hormone replacement 1, 2
2. If adrenal insufficiency present: Start glucocorticoid replacement first
   • Hydrocortisone 15-20 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon) 2
3. Then initiate thyroid hormone replacement after adequate cortisol replacement 1, 4
   • Target free T4 in the upper half of normal range 5, 6

Critical Considerations and Pitfalls

Potential Complications

• Adrenal crisis risk: Thyroid hormone increases cortisol metabolism and clearance 1, 2
• Starting thyroid hormone without addressing adrenal insufficiency can precipitate life-threatening adrenal crisis 1, 3

Monitoring Considerations

• Assess both free T4 and free T3 levels to evaluate adequacy of thyroid replacement 5
• Monitor for signs of under or over-replacement of both hormones 2, 5
• Consider biochemical indices of thyroid hormone action for optimal replacement 5

Special Situations

• Reversible hypothyroidism: Some cases of subclinical hypothyroidism may resolve with glucocorticoid replacement alone 3
• Glucocorticoid functional reserve: May improve after achieving euthyroidism in primary hypothyroidism 7

Follow-up Protocol

• Regular assessment of adrenal function during first year: 1, 2
  • Monthly for first 6 months
  • Every 3 months for next 6 months
  • Every 6 months thereafter
• All patients with adrenal insufficiency should obtain and carry a medical alert bracelet 1

By systematically assessing adrenal function before initiating thyroid hormone replacement, clinicians can prevent potentially life-threatening adrenal crises in patients with central hypothyroidism.