Ensuring Absence of Adrenal Crisis Before Levothyroxine Initiation

Critical Pathophysiology and Diagnostic Approach

The American College of Endocrinology recommends screening for adrenal insufficiency before levothyroxine in patients with central hypothyroidism, as this suggests pituitary or hypothalamic disease that may also affect ACTH production 1, 2
Patients with hypophysitis or pituitary disease from any cause, including immune checkpoint inhibitor therapy, should be screened for adrenal insufficiency 3, 1
The Endocrine Society suggests that patients with autoimmune hypothyroidism (Hashimoto's thyroiditis) have increased risk of concurrent autoimmune adrenal insufficiency (Addison's disease) 2
Unexplained hypotension, hyponatremia, or hyperpigmentation that cannot be fully explained by hypothyroidism alone should prompt screening for adrenal insufficiency 2
A history of prolonged glucocorticoid use (≥20 mg/day prednisone or equivalent for ≥3 weeks) can cause iatrogenic secondary adrenal insufficiency 2

Morning diagnostic tests, including serum cortisol, plasma ACTH, basic metabolic panel, and DHEAS, should be measured before administering any corticosteroids 1, 2, 3
The cosyntropin (Synacthen) stimulation test should be performed if morning cortisol is between 5-18 μg/dL (140-500 nmol/L) 2
A normal response to the cosyntropin stimulation test is defined as a peak cortisol >500-550 nmol/L (>18-20 μg/dL) 2
Adrenal insufficiency is diagnosed if peak cortisol <500 nmol/L (<18 μg/dL) 2

If adrenal insufficiency is confirmed or strongly suspected clinically, do not start levothyroxine, and initiate glucocorticoid replacement first, waiting at least 1 week before starting thyroid hormone 1, 2
Physiologic glucocorticoid dosing, such as hydrocortisone 15-25 mg daily, should be used 2
In cases of suspected adrenal crisis, treatment must never be delayed for diagnostic testing, and IV hydrocortisone 100 mg bolus should be administered immediately 2
The American College of Emergency Physicians recommends infusing 0.9% saline at 1 L/hour (at least 2L total) in cases of adrenal crisis 3, 2

Patients diagnosed with adrenal insufficiency must receive stress dosing instructions, an emergency injectable hydrocortisone kit, a medical alert bracelet or necklace, and education on warning signs of impending adrenal crisis 2, 3