How to evaluate for adrenal insufficiency in a patient with hypothyroidism before starting thyroid hormone replacement therapy?

Evaluation for Adrenal Insufficiency in Hypothyroidism Before Starting Thyroid Hormone Replacement

All patients with hypothyroidism should be evaluated for adrenal insufficiency before starting thyroid hormone replacement therapy, as initiating thyroid hormone without adequate adrenal function can precipitate an adrenal crisis. 1

Diagnostic Approach

Initial Screening

1. Morning (8 AM) cortisol and ACTH levels 1, 2

   • Low cortisol with high ACTH: Primary adrenal insufficiency
   • Low cortisol with low/normal ACTH: Secondary adrenal insufficiency

2. Laboratory findings suggestive of adrenal insufficiency:

   • Hyponatremia
   • Hyperkalemia (in primary adrenal insufficiency)
   • Hypoglycemia

Confirmatory Testing

• ACTH stimulation test (gold standard) 1
  • Administer 250 μg synthetic ACTH (Synacthen/cosyntropin)
  • Measure cortisol at baseline, 30 minutes, and 60 minutes
  • Normal response: Peak cortisol >18 μg/dL (500 nmol/L)
  • Inadequate response confirms adrenal insufficiency

Special Considerations in Hypothyroidism

• Thyroid dysfunction can affect cortisol metabolism and HPA axis function 3, 4
• Patients with primary hypothyroidism may have falsely low cortisol levels due to altered metabolism
• Secondary hypothyroidism may coexist with secondary adrenal insufficiency if pituitary dysfunction is present

Clinical Indicators Warranting Evaluation

• Unexplained fatigue, weakness, or lethargy beyond typical hypothyroid symptoms
• Postural hypotension or hypotension unresponsive to volume repletion
• Hyponatremia disproportionate to hypothyroidism
• History of pituitary disease or radiation
• Recent cessation of glucocorticoid therapy
• Presence of other autoimmune conditions (increased risk of polyglandular autoimmune syndrome)

Management Algorithm

1. If adrenal insufficiency is suspected or confirmed:

   • Start glucocorticoid replacement before thyroid hormone
   • Preferred: Hydrocortisone 15-25 mg/day in 2-3 divided doses 1
   • Alternative: Prednisone 5 mg daily (equivalent to hydrocortisone 20 mg) 5

2. Timing of thyroid hormone initiation:

   • Begin thyroid hormone replacement 3-5 days after starting glucocorticoid therapy
   • Start with low dose levothyroxine and titrate gradually

3. Patient education (essential):

   • Stress dosing instructions for illness or surgery
   • Emergency injectable glucocorticoids
   • Medical alert identification for adrenal insufficiency 5

Common Pitfalls to Avoid

1. Starting thyroid hormone without assessing adrenal function

   • Can precipitate adrenal crisis by increasing cortisol clearance

2. Misinterpreting thyroid function tests in adrenal insufficiency

   • Adrenal insufficiency can cause elevated TSH with normal/low T4 4
   • May mimic primary hypothyroidism

3. Inadequate glucocorticoid coverage

   • Underdosing can lead to adrenal crisis when thyroid hormone is initiated
   • Failure to provide stress dosing education

4. Overlooking secondary causes

   • Failing to investigate pituitary pathology when central adrenal insufficiency is present
   • Consider MRI of pituitary in cases of multiple hormone deficiencies 5

5. Delaying endocrinology consultation

   • Early endocrinology consultation is recommended for complex cases 5

By systematically evaluating adrenal function before initiating thyroid hormone replacement, clinicians can prevent potentially life-threatening adrenal crises and optimize treatment outcomes for patients with hypothyroidism.