Should a patient with a history of Hashimoto's thyroiditis, high thyroid antibodies, bipolar 1 disorder, hypogonadism, and hyperlipidemia be tested for adrenal insufficiency?

Should This Patient Be Tested for Adrenal Insufficiency?

Yes, this patient with Hashimoto's thyroiditis and high thyroid antibodies should undergo screening for adrenal insufficiency with a morning cortisol and ACTH measurement, followed by ACTH stimulation testing if results are indeterminate. 1

Rationale for Screening in Autoimmune Thyroid Disease

• Patients with autoimmune thyroid disease require continuous surveillance for other autoimmune disorders, particularly primary adrenal insufficiency (Addison's disease). 1

• The presence of one autoimmune endocrine disorder substantially increases the risk of developing additional autoimmune endocrinopathies, including primary adrenal insufficiency, which occurs in the context of autoimmune polyglandular syndromes. 1, 2

• Thyroid autoantibodies followed by development of hypothyroidism is frequently seen in patients with primary adrenal insufficiency, and the reverse association also occurs—patients with established autoimmune thyroid disease are at increased risk for developing adrenal insufficiency. 1

• Asymptomatic or subclinical adrenal insufficiency can occur in patients with autoimmune thyroid disease, where elevated ACTH with normal or borderline cortisol indicates compensated adrenal hypofunction. 2

Specific Diagnostic Approach

Initial Testing

• Obtain paired early morning (8 AM) serum cortisol and plasma ACTH measurements as the first-line diagnostic test. 3, 4

• Include a basic metabolic panel to assess for hyponatremia (present in 90% of newly diagnosed cases) and hyperkalemia (present in ~50% of primary adrenal insufficiency cases). 3, 4

Interpretation of Initial Results

• Basal cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in the presence of acute illness is diagnostic of primary adrenal insufficiency. 3

• Basal cortisol <400 nmol/L with elevated ACTH raises strong suspicion and warrants confirmatory testing. 3

• If morning cortisol is indeterminate (neither clearly normal nor clearly low), proceed with ACTH stimulation testing. 3

Confirmatory ACTH Stimulation Test

• Administer 0.25 mg cosyntropin (tetracosactide) intramuscularly or intravenously. 3

• Measure serum cortisol at baseline and 30 minutes (and/or 60 minutes) post-administration. 3

• A peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency, while >550 nmol/L is considered normal. 3, 4

Etiologic Workup if Positive

• Measure 21-hydroxylase (anti-adrenal) autoantibodies to identify autoimmune etiology, which accounts for ~85% of primary adrenal insufficiency cases in Western populations. 3, 4

• If autoantibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, tumor, tuberculosis, or other structural causes. 3, 4

Critical Clinical Considerations

Important Caveats About Negative Findings

• Neither negative adrenal autoantibodies nor normal plasma renin activity can exclude asymptomatic adrenocortical insufficiency in patients with autoimmune thyroid disease. 2

• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only approximately 50% of cases. 3

• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—some patients may have normal electrolytes at presentation. 3

Timing Considerations with Thyroid Treatment

• If both adrenal insufficiency and hypothyroidism are present, corticosteroids must be started several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis. 3

• Starting thyroid hormone in a patient with undiagnosed adrenal insufficiency can unmask or worsen adrenal crisis by increasing metabolic demands. 3

Annual Surveillance Protocol

• Regular monitoring of thyroid function every 12 months is important in patients with primary adrenal insufficiency, including serum TSH, FT4, and TPO antibodies. 1

• The annual screening should also include plasma glucose levels, HbA1c, complete blood count, and B12 levels to screen for other associated autoimmune conditions. 1

When to Suspect Acute Adrenal Crisis

• Unexplained collapse, hypotension, and gastrointestinal symptoms (vomiting or diarrhea) should immediately raise suspicion for adrenal insufficiency. 3

• Treatment of suspected acute adrenal insufficiency should NEVER be delayed for diagnostic procedures—give 100 mg IV hydrocortisone immediately plus 0.9% saline infusion if adrenal crisis is suspected. 3

• Blood samples for cortisol and ACTH should be obtained before treatment if possible, but treatment must not be delayed. 3

Additional Context for This Patient

Given this patient's multiple comorbidities (bipolar disorder, hypogonadism, hyperlipidemia), screening is particularly important because:

• Fatigue and other nonspecific symptoms could be attributed to these conditions, potentially masking early adrenal insufficiency. 1

• Subclinical thyroid disease can contribute to fatigue, making it important to detect both thyroid and adrenal dysfunction. 1

• The patient may be on medications that could interact with glucocorticoid or mineralocorticoid replacement if adrenal insufficiency is diagnosed. 3