How to manage a patient with both hypothyroidism and adrenal insufficiency, requiring hydrocortisone (corticosteroid) and levothyroxine (thyroid hormone replacement) therapy?

Management of Hypothyroidism with Concurrent Adrenal Insufficiency

Critical Safety Principle: Always Start Corticosteroids Before Thyroid Hormone

In patients with both adrenal insufficiency and hypothyroidism, steroids must always be started prior to thyroid hormone replacement to prevent life-threatening adrenal crisis. 1

This is the single most important principle in managing these coexisting conditions. Starting levothyroxine before adequate corticosteroid replacement can precipitate acute adrenal crisis by increasing cortisol metabolism, potentially leading to cardiovascular collapse and death 1, 2.

Step-by-Step Management Algorithm

Step 1: Confirm Both Diagnoses

For Adrenal Insufficiency:

• Obtain morning (8 AM) cortisol and ACTH levels before any treatment 2
• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH indicates primary adrenal insufficiency 2
• Morning cortisol <400 nmol/L with low or inappropriately normal ACTH suggests secondary adrenal insufficiency 2
• If cortisol is indeterminate (140-400 nmol/L), perform cosyntropin stimulation test: administer 0.25 mg IV/IM with cortisol measurements at 30 and 60 minutes 2
• Peak cortisol <500 nmol/L (<18 μg/dL) confirms adrenal insufficiency 2

For Hypothyroidism:

• Measure TSH and free T4 3
• TSH >10 mIU/L with low free T4 indicates overt hypothyroidism requiring treatment 3
• Check anti-TPO antibodies to identify autoimmune etiology 3

Step 2: Initiate Corticosteroid Replacement FIRST

Start hydrocortisone at least 1 week before initiating thyroid hormone replacement 1, 2

Dosing for Primary Adrenal Insufficiency:

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) 2
• Alternative: Prednisone 4-5 mg daily or cortisone acetate 25-37.5 mg daily 2
• Add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 2

Dosing for Secondary Adrenal Insufficiency:

• Same glucocorticoid doses as above 2
• Fludrocortisone is NOT needed (renin-angiotensin-aldosterone system remains intact) 2

Step 3: Monitor Corticosteroid Adequacy Before Starting Thyroid Hormone

Wait at least 1 week on stable corticosteroid replacement before initiating levothyroxine 1

Assess for adequate glucocorticoid replacement:

• Resolution of fatigue, nausea, and orthostatic symptoms 2
• Stable blood pressure without orthostatic hypotension 2
• Normalization of electrolytes (sodium, potassium) 2

For primary adrenal insufficiency, assess mineralocorticoid adequacy:

• Resolution of salt cravings 2
• No orthostatic hypotension 2
• Normal blood pressure in supine and standing positions 2
• Plasma renin activity in normal range 2

Step 4: Initiate Levothyroxine Replacement

Once corticosteroid replacement is stable, begin levothyroxine:

For patients <70 years without cardiac disease:

• Start levothyroxine 1.6 mcg/kg/day (full replacement dose) 3
• Target TSH 0.5-4.5 mIU/L with normal free T4 3

For patients >70 years or with cardiac disease:

• Start with lower dose of 25-50 mcg daily 3
• Titrate gradually by 12.5-25 mcg increments every 6-8 weeks 3
• Monitor closely for angina, palpitations, or cardiac decompensation 3

Step 5: Monitoring Protocol

Initial Phase (First 6-8 weeks):

• Check TSH and free T4 every 6-8 weeks while titrating levothyroxine 3
• Monitor blood pressure, electrolytes, and symptoms of adrenal insufficiency 2
• Adjust levothyroxine dose by 12.5-25 mcg increments based on TSH 3

Maintenance Phase:

• Once TSH is stable in target range (0.5-4.5 mIU/L), check TSH every 6-12 months 3
• Annual review for adrenal insufficiency with assessment of weight, blood pressure, and electrolytes 2
• Screen annually for other autoimmune conditions (both conditions are often autoimmune) 2

Critical Patient Education Requirements

All patients with adrenal insufficiency must receive:

• Medical alert bracelet or necklace indicating adrenal insufficiency 1, 2
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training 2
• Stress dosing instructions: double or triple dose during illness, fever, or physical stress 2
• Warning signs of adrenal crisis: severe weakness, vomiting, hypotension, confusion 2

Specific instructions for combined therapy:

• Take hydrocortisone first thing in morning (can wake early, take dose, return to sleep) 2
• Take levothyroxine 30-60 minutes before breakfast, at least 4 hours apart from calcium or iron 3
• Never skip hydrocortisone doses—this is life-sustaining medication 2

Common Pitfalls and How to Avoid Them

Pitfall #1: Starting levothyroxine before or simultaneously with corticosteroids

• This is the most dangerous error and can precipitate fatal adrenal crisis 1, 2
• Always wait at least 1 week after starting hydrocortisone before initiating levothyroxine 1

Pitfall #2: Forgetting mineralocorticoid replacement in primary adrenal insufficiency

• Primary adrenal insufficiency requires BOTH glucocorticoid and mineralocorticoid replacement 2
• Fludrocortisone 0.05-0.1 mg daily is essential for blood pressure control and electrolyte balance 2
• Adjust dose based on blood pressure, salt cravings, and plasma renin activity 2

Pitfall #3: Overtreating hypothyroidism

• Approximately 25% of patients on levothyroxine are unintentionally overtreated with TSH suppression 3
• TSH suppression (<0.1 mIU/L) increases risk of atrial fibrillation, osteoporosis, and fractures 3
• Target TSH 0.5-4.5 mIU/L, not suppressed levels 3

Pitfall #4: Inadequate stress dosing education

• Patients must understand to double or triple hydrocortisone during illness 2
• Failure to increase dose during stress can precipitate adrenal crisis 2
• All patients need emergency injectable hydrocortisone kit 2

Pitfall #5: Missing the diagnosis of adrenal insufficiency in hypothyroid patients

• Both conditions can present with fatigue, weakness, and hypotension 4, 5
• Adrenal insufficiency occurs in 12% of critically ill patients with hypothyroidism 5
• Always screen for adrenal insufficiency before treating hypothyroidism, especially in autoimmune thyroid disease 2, 6

Special Clinical Scenarios

Acute Presentation/Adrenal Crisis:

• If patient presents with hypotension, vomiting, or altered mental status, treat immediately 2
• Give IV hydrocortisone 100 mg bolus immediately—do NOT delay for diagnostic testing 2
• Infuse 0.9% saline at 1 L/hour (at least 2L total) 2
• Draw blood for cortisol and ACTH before treatment if possible, but never delay treatment 2

Pregnancy or Planning Pregnancy:

• Optimize both conditions before conception 3
• Levothyroxine requirements increase 25-50% during pregnancy 3
• Hydrocortisone requirements may also increase during pregnancy 2
• Target TSH <2.5 mIU/L in first trimester 3

Perioperative Management:

• Stress-dose hydrocortisone is mandatory for any surgery or procedure 2
• Minor stress: double usual daily dose for 1-2 days 2
• Moderate stress: hydrocortisone 50-75 mg daily 2
• Major stress: hydrocortisone 100-150 mg daily 2
• Continue levothyroxine throughout perioperative period 3

Why This Sequence Matters: The Pathophysiology

Thyroid hormone increases the metabolic clearance of cortisol 1. In patients with intact adrenal function, the adrenal glands compensate by increasing cortisol production. However, in patients with adrenal insufficiency, this compensatory mechanism is absent. Starting levothyroxine increases cortisol metabolism without the ability to increase production, rapidly depleting already insufficient cortisol stores and precipitating acute adrenal crisis 1, 2.

This is not a theoretical concern—case reports document fatal outcomes when this principle is violated 4, 7, 6. The coexistence of these conditions is not rare: 12% of critically ill patients with hypothyroidism have concurrent adrenal insufficiency 5, and both conditions frequently occur together in autoimmune polyglandular syndromes 8.

The bottom line: When managing hypothyroidism with concurrent adrenal insufficiency, always prioritize morbidity and mortality prevention by starting corticosteroids first, waiting at least one week, confirming adequate replacement, and only then initiating thyroid hormone replacement. 1, 2