How should a patient with hypothyroidism and Addison's disease be treated?

Treatment of Hypothyroidism and Addison's Disease

In patients with both hypothyroidism and Addison's disease, corticosteroid replacement must be initiated first and stabilized before starting thyroid hormone replacement, as initiating levothyroxine before adequate cortisol replacement can precipitate a life-threatening adrenal crisis. 1, 2

Critical Treatment Sequence

Step 1: Initiate Corticosteroid Replacement First

• Start hydrocortisone 15-20 mg daily in divided doses (typically two-thirds in the morning, one-third in early afternoon to mimic diurnal rhythm) for primary adrenal insufficiency 1
• Most patients with primary adrenal insufficiency also require fludrocortisone 0.05-0.1 mg daily, adjusted based on volume status, sodium levels, and renin response (target upper half of reference range) 1
• Stabilize the patient on corticosteroid replacement for at least 1 week before introducing thyroid hormone 1, 3
• Titrate hydrocortisone to a maximum of 30 mg daily total dose for residual symptoms of adrenal insufficiency 1

Step 2: Initiate Thyroid Hormone Replacement Only After Corticosteroid Stabilization

• Begin levothyroxine only after the patient is stabilized on adequate corticosteroid replacement 1, 3
• For patients under 60 years without cardiac disease: start levothyroxine at 1.6 mcg/kg/day (typically 75-100 mcg for women, 100-150 mcg for men) 3, 4, 5
• For patients over 60 years or with cardiac disease: start at a lower dose of 25-50 mcg daily and titrate gradually 1, 3, 4
• Monitor TSH and free T4 every 6-8 weeks during dose titration, targeting TSH in the reference range (0.5-4.5 mIU/L) 3, 4

Physiological Rationale for Treatment Sequence

The mechanism behind this critical sequencing is that thyroid hormone accelerates cortisol clearance and increases metabolic demands. 1, 6 In patients with untreated or inadequately treated adrenal insufficiency, initiating levothyroxine can unmask the cortisol deficiency by increasing cortisol metabolism, precipitating acute adrenal crisis with hypotension, shock, and potentially death 1, 3.

• Interestingly, steroid replacement alone can normalize thyroid function tests in some Addison's disease patients with primary hypothyroidism through both autoimmune and non-autoimmune mechanisms 6
• However, this normalization does not occur in all patients, so thyroid function should be reassessed after corticosteroid stabilization 6

Ongoing Monitoring and Patient Education

Essential Patient Education

• All patients need education on stress dosing for sick days, surgery, or high-stress situations (typically doubling or tripling maintenance dose) 1
• Provide emergency injectable hydrocortisone supplies (100 mg) with instructions for self-injection or administration by family members 1
• Patients must wear a medical alert bracelet or necklace identifying adrenal insufficiency to trigger stress-dose corticosteroids by emergency personnel 1
• Advise patients to take salt and salty foods ad libitum and avoid licorice and grapefruit juice (which can affect mineralocorticoid activity) 1

Long-term Monitoring Schedule

• Review patients at least annually with assessment of health, well-being, weight, blood pressure, and serum electrolytes 1
• Monitor for development of new autoimmune disorders, particularly hypothyroidism progression if initially subclinical 1
• Once thyroid replacement is stable, monitor TSH every 6-12 months or with symptom changes 3, 4
• Assess for complications of glucocorticoid therapy including bone mineral density every 3-5 years 1

Common Pitfalls to Avoid

• Never start thyroid hormone before ruling out and treating adrenal insufficiency in patients with suspected or known Addison's disease—this is the most critical error and can be fatal 1, 3
• Avoid using long-acting steroids like prednisone as first-line therapy; hydrocortisone allows recreation of diurnal cortisol rhythm and reduces risk of over-replacement 1
• Do not assume hypothyroidism is permanent without reassessment after corticosteroid stabilization, as some cases normalize with steroid replacement alone 6
• Approximately 25% of patients on levothyroxine are unintentionally maintained on excessive doses that suppress TSH, increasing risks for atrial fibrillation, osteoporosis, and fractures—regular monitoring prevents this 3, 4
• Failing to provide stress-dosing education and emergency supplies is a dangerous oversight that leaves patients vulnerable to adrenal crisis during intercurrent illness 1