Does a patient with primary hypothyroidism and potential autoimmune thyroiditis need to be checked for adrenal insufficiency if other laboratory tests are normal?

Should Adrenal Insufficiency Be Checked in Primary Hypothyroidism with Normal Labs?

Yes, adrenal insufficiency must be actively screened for in patients with primary hypothyroidism and suspected autoimmune thyroiditis, even when other routine laboratory tests appear normal, because autoimmune adrenal insufficiency frequently coexists with autoimmune thyroid disease and can be life-threatening if missed. 1, 2

Why Screening Is Critical

The presence of one autoimmune endocrine disorder substantially increases the risk of developing others, particularly in the context of autoimmune polyglandular syndromes. 1 Specifically:

• Autoimmune thyroid disease and primary adrenal insufficiency commonly occur together, with thyroid autoantibodies frequently preceding the development of hypothyroidism in patients with established adrenal insufficiency. 1
• "Normal" routine labs do not exclude adrenal insufficiency. Patients can have compensated or subclinical adrenal insufficiency with normal electrolytes, normal plasma renin activity, and even negative adrenal autoantibodies. 3
• Starting thyroid hormone replacement before confirming adequate adrenal function can precipitate adrenal crisis, as thyroid hormone increases cortisol metabolism and can unmask previously compensated adrenal insufficiency. 2, 4

The Dangerous Clinical Pitfall

Never initiate levothyroxine therapy in a patient with suspected autoimmune thyroiditis without first excluding adrenal insufficiency. 2 This is a critical error that has resulted in life-threatening adrenal crises. 4 One case report documented a patient with polyglandular syndrome who was initially treated for hypothyroidism alone and developed severe hypotension, hyponatremia, and hypoglycemia—symptoms that only resolved after hydrocortisone and fludrocortisone were added. 4

Specific Screening Algorithm

Step 1: Measure Morning Cortisol and ACTH

• Draw paired early-morning (8 AM) serum cortisol and plasma ACTH levels. 2, 5
• If morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH: Primary adrenal insufficiency is confirmed. 2
• If morning cortisol is intermediate (140-400 nmol/L or 5-14.5 μg/dL): Proceed to cosyntropin stimulation test. 5
• If morning cortisol >400 nmol/L (>14.5 μg/dL) with normal ACTH: Adrenal insufficiency is effectively ruled out. 5

Step 2: Cosyntropin Stimulation Test (If Needed)

• Administer 0.25 mg cosyntropin (Synacthen) intramuscularly or intravenously. 1, 6
• Measure serum cortisol at 30 and 60 minutes post-administration. 1, 7
• Peak cortisol <550 nmol/L (<18-20 μg/dL) confirms adrenal insufficiency. 1, 7, 6

Step 3: Determine Etiology

• Test for 21-hydroxylase autoantibodies (21OH-Ab) to confirm autoimmune Addison's disease, which accounts for approximately 85% of primary adrenal insufficiency cases in Western populations. 1, 2, 6
• If 21OH-Ab is positive, the diagnosis of autoimmune adrenal insufficiency is established and no further etiologic workup is needed. 1, 5

Who Needs Screening?

Screen for adrenal insufficiency in patients with:

• Primary hypothyroidism with positive thyroid peroxidase antibodies (TPO-Ab), indicating autoimmune thyroiditis. 1, 2
• Unexplained persistent fatigue, salt craving, postural dizziness, or hyperpigmentation, even with normal electrolytes. 2, 3
• Hyponatremia (present in 90% of new cases), hyperkalemia (50% of cases), or mild hypercalcemia (10-20% of cases). 2
• Elevated ACTH levels on routine testing, which should prompt immediate cortisol measurement and cosyntropin testing. 3

What "Normal Labs" Can Miss

Two case reports illustrate this danger: 3

• Both patients had normal plasma renin activity and plasma aldosterone concentration, suggesting intact mineralocorticoid function.
• Both had negative adrenal autoantibodies initially.
• Both had normal baseline cortisol but elevated ACTH, with impaired cortisol response to ACTH stimulation testing.
• Both were associated with autoimmune thyroid disease (Graves' disease in one, early Hashimoto's thyroiditis in the other).

The key finding was elevated ACTH despite "normal" cortisol—a compensated state that would decompensate under stress or with thyroid hormone replacement. 3

Ongoing Surveillance After Initial Screening

If initial screening is negative but the patient has confirmed autoimmune thyroiditis:

• Recheck thyroid function tests (TSH, FT4, TPO-Ab) annually. 1, 2
• Monitor for new symptoms of adrenal insufficiency (fatigue, salt craving, postural hypotension, hyperpigmentation). 2
• Repeat adrenal function testing if new symptoms develop or if the patient requires increased thyroid hormone doses without symptomatic improvement. 1