How can hypothyroidism (underactive thyroid) cause adrenal crisis?

How Hypothyroidism Can Precipitate Adrenal Crisis

Initiating thyroid hormone replacement in patients with unrecognized or untreated adrenal insufficiency can precipitate acute adrenal crisis because thyroid hormones accelerate the metabolic clearance of cortisol, rapidly depleting already insufficient glucocorticoid reserves. 1

Mechanism of Thyroid Hormone-Induced Adrenal Crisis

Increased Cortisol Clearance

• Thyroid hormones increase the metabolic clearance rate of glucocorticoids, creating a mismatch between cortisol demand and supply in patients with compromised adrenal function 1
• In patients with existing adrenal insufficiency (either primary or secondary), the adrenal glands cannot compensate for this accelerated cortisol degradation 2
• This metabolic acceleration can unmask previously compensated adrenal insufficiency or worsen subclinical disease 3

Clinical Scenarios Where This Occurs

Central (Secondary) Hypothyroidism with Hypopituitarism:

• Patients with hypophysitis commonly present with both central adrenal insufficiency (>75% of cases) and central hypothyroidism (>90% of cases) occurring simultaneously 2
• In these patients, low or normal TSH with low free T4 indicates pituitary dysfunction affecting multiple hormone axes 2
• Starting thyroid replacement without first addressing adrenal insufficiency is particularly dangerous in this population 2

Masked Adrenal Insufficiency:

• Hypothyroidism can mask symptoms of coexisting adrenal insufficiency because the reduced metabolic rate decreases cortisol requirements 3
• When thyroid hormone is replaced, the sudden increase in metabolic demand exposes the inability of failing adrenal glands to meet cortisol needs 4
• Studies demonstrate that subclinical hypothyroidism can reverse with glucocorticoid replacement alone, suggesting complex thyroid-adrenal interactions 3

Critical Management Principle

Always initiate corticosteroid replacement several days before starting thyroid hormone therapy when both deficiencies are present. 2

Specific Treatment Sequence:

• Start hydrocortisone first (15-20 mg daily in divided doses: 10-20 mg morning, 5-10 mg early afternoon) 2
• Wait several days to ensure adequate glucocorticoid coverage 2
• Only then initiate levothyroxine replacement 2
• This sequence prevents precipitating adrenal crisis by ensuring cortisol availability matches the increased metabolic demands created by thyroid hormone 2

Diagnostic Considerations

When to Suspect Combined Deficiency:

• Any patient with central hypothyroidism (low/normal TSH with low free T4) should be evaluated for concurrent adrenal insufficiency 2
• Measure morning ACTH and cortisol (ideally around 8 AM) before initiating thyroid replacement 2
• Consider ACTH stimulation testing if morning cortisol is indeterminate (between 3-15 mcg/dL) 2

Laboratory Patterns:

• Combined deficiency shows: low ACTH with low cortisol AND low/normal TSH with low free T4 2
• Approximately 50% of patients with hypophysitis present with panhypopituitarism (adrenal insufficiency plus hypothyroidism plus hypogonadism) 2
• Research shows 12% incidence of simultaneous hypothyroidism and adrenal insufficiency in critically ill patients 5

Common Pitfalls to Avoid

Primary Hypothyroidism Misdiagnosis:

• Do not assume all hypothyroidism is primary (thyroid gland failure) based solely on TSH elevation 6
• Some cases of secondary adrenal insufficiency can present with paradoxically elevated TSH that normalizes with glucocorticoid replacement 4, 6
• Always evaluate the full clinical context and consider screening for adrenal function in hypothyroid patients with atypical features 6

Failure to Recognize Central Hypothyroidism:

• TSH is not accurate for monitoring thyroid replacement in central hypothyroidism—use free T4 levels instead, targeting the upper half of the reference range 2
• Low or normal TSH with low free T4 should trigger immediate evaluation for hypopituitarism 2

Emergency Management:

• If adrenal crisis is suspected, use dexamethasone initially (does not interfere with subsequent ACTH stimulation testing) or hydrocortisone 100 mg IV if diagnosis is confirmed 2
• Provide stress-dose steroids (hydrocortisone 50-100 mg IV every 6-8 hours) and aggressive fluid resuscitation (3-4 L isotonic saline initially) 2

Patient Education Requirements

All patients with confirmed adrenal insufficiency require 2:

• Education on stress dosing during illness (doubling maintenance doses)
• Medical alert bracelet or necklace identifying adrenal insufficiency
• Emergency injectable hydrocortisone kit
• Clear instructions on when to seek immediate medical attention