Should overt hypothyroid (underactive thyroid) patients be screened for adrenal insufficiency?

Should Overt Hypothyroid Patients Be Screened for Adrenal Insufficiency?

No, routine screening for adrenal insufficiency is not recommended in all overt hypothyroid patients, but screening is critical in specific high-risk scenarios: suspected central hypothyroidism, autoimmune polyglandular syndrome, or when starting thyroid hormone replacement in patients with unexplained hypotension, hyponatremia, or hyperpigmentation.

Critical Safety Principle: Rule Out Adrenal Insufficiency Before Starting Levothyroxine

In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, always start corticosteroids before levothyroxine to prevent life-threatening adrenal crisis. 1, 2 Starting thyroid hormone replacement increases metabolic demand and can precipitate acute adrenal crisis in patients with undiagnosed adrenal insufficiency. 1

When to Screen for Adrenal Insufficiency in Hypothyroid Patients

High-Risk Scenarios Requiring Screening:

• Central (secondary) hypothyroidism: When TSH is low or inappropriately normal with low free T4, suggesting pituitary or hypothalamic disease 1, 3
• Autoimmune polyglandular syndrome: Patients with autoimmune hypothyroidism (positive TPO antibodies) have increased risk of concurrent autoimmune adrenal insufficiency (Addison's disease) 4, 5
• Unexplained clinical features: Hypotension, hyponatremia, hyperpigmentation, or hypoglycemia that cannot be fully explained by hypothyroidism alone 4, 6
• Acute presentation: Patients presenting with collapse, severe hypotension, or altered mental status 4, 6

Patients Who Do NOT Require Routine Screening:

• Primary hypothyroidism with elevated TSH and low free T4: These patients have intact pituitary-adrenal axis 1
• Subclinical hypothyroidism: Elevated TSH with normal free T4 in asymptomatic patients 1
• Isolated autoimmune thyroiditis: Without other autoimmune manifestations or suggestive symptoms 4

Diagnostic Approach When Screening Is Indicated

Initial Testing:

• Early morning (8 AM) serum cortisol and ACTH: Measured simultaneously before starting thyroid hormone 6, 2
• Primary adrenal insufficiency: Low cortisol (<5 µg/dL) with elevated ACTH 6
• Secondary adrenal insufficiency: Low or intermediate cortisol (5-10 µg/dL) with low or low-normal ACTH 6

Confirmatory Testing:

• Short cosyntropin stimulation test (250 µg): Gold standard for diagnosis, with peak cortisol <500 nmol/L diagnostic of adrenal insufficiency 4, 2, 7
• 21-hydroxylase antibodies: To identify autoimmune etiology in primary adrenal insufficiency 4, 2

Special Populations Requiring Heightened Vigilance

Autoimmune Polyglandular Syndrome:

• Patients with autoimmune hypothyroidism should be monitored for development of other autoimmune conditions, including adrenal insufficiency 4
• Annual screening includes monitoring for symptoms of adrenal insufficiency: unexplained fatigue, weight loss, hypotension, salt craving 4
• Consider measuring 21-hydroxylase antibodies in patients with multiple autoimmune conditions 5

Pregnant Women:

• Unexplained persistent nausea, fatigue, and hypotension in pregnancy warrant screening for adrenal insufficiency 2
• Both hypothyroidism and adrenal insufficiency can present with similar symptoms during pregnancy 2

Critical Pitfalls to Avoid

• Never start levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or hypophysitis 1, 2
• Do not assume all symptoms are due to hypothyroidism: Hypotension, hyponatremia, and hyperpigmentation suggest concurrent adrenal insufficiency 4, 6
• In autoimmune hypothyroidism, maintain surveillance for other autoimmune conditions: Regular monitoring every 12 months for associated autoimmune diseases is essential 4
• Recognize that TSH levels can be mildly elevated (4-10 IU/L) in primary adrenal insufficiency due to lack of cortisol's inhibitory effect on TSH production 4

Management When Both Conditions Coexist

• Always initiate corticosteroid replacement at least 1 week before starting thyroid hormone 1, 2
• Hydrocortisone 15-25 mg daily or prednisone 3-5 mg daily for adrenal insufficiency 6, 2
• Add fludrocortisone 0.05-0.3 mg daily for primary adrenal insufficiency 6, 2
• After stabilizing on corticosteroids, begin levothyroxine at standard doses 1

Evidence Quality and Guideline Consensus

The recommendation against universal screening is based on the low prevalence of adrenal insufficiency in the general hypothyroid population (affecting less than 279 per 1 million individuals) 6, while the recommendation for targeted screening in high-risk scenarios is strongly supported by consensus guidelines emphasizing the life-threatening consequences of missing this diagnosis 4, 2. The critical safety principle of starting corticosteroids before thyroid hormone in suspected cases is consistently emphasized across all major endocrine society guidelines 1, 2.