What is the next recommended test for a 27-year-old woman with fatigue, myalgia, intermittent dizziness, abdominal pain, unintentional weight loss, mild hyponatremia, mildly elevated Thyroid-Stimulating Hormone (TSH), and low morning cortisol level?

From the Guidelines

The next recommended test for this 27-year-old woman is an ACTH stimulation test (also called cosyntropin stimulation test or short Synacthen test). This test should be performed to confirm suspected adrenal insufficiency, which is strongly suggested by her low morning cortisol level along with her constellation of symptoms, including fatigue, myalgia, intermittent dizziness, abdominal pain, unintentional weight loss, mild hyponatremia, and mildly elevated Thyroid-Stimulating Hormone (TSH) 1. During this test, synthetic ACTH (250 mcg) is administered intravenously, and cortisol levels are measured at baseline, 30 minutes, and 60 minutes after administration. A normal response would show cortisol rising to >18-20 μg/dL. If her cortisol fails to appropriately increase, this confirms adrenal insufficiency. Following confirmation, additional testing including ACTH level measurement would help differentiate between primary adrenal insufficiency (Addison's disease) and secondary adrenal insufficiency. Her clinical presentation is classic for adrenal insufficiency, and the mildly elevated TSH may indicate early thyroid dysfunction, which can coexist with adrenal insufficiency, particularly in autoimmune polyglandular syndromes 1. Prompt diagnosis is essential as untreated adrenal insufficiency can progress to life-threatening adrenal crisis. It's also crucial to note that if there's a clinical suspicion of impending acute adrenal crisis, the patient should be given intravenous hydrocortisone immediately, and a physiologic saline infusion, without delaying treatment for diagnostic procedures 1.

Some key points to consider in the management and diagnosis of adrenal insufficiency include:

• The importance of measuring cortisol levels after ACTH stimulation to confirm the diagnosis of adrenal insufficiency 1.
• The need to differentiate between primary and secondary adrenal insufficiency through ACTH level measurement after confirming adrenal insufficiency 1.
• The potential for coexisting thyroid dysfunction, particularly in autoimmune polyglandular syndromes, and the necessity of starting corticosteroids before thyroid hormone replacement to avoid precipitating an adrenal crisis 1.
• The role of education on stress dosing, use of emergency steroid injectables, and the importance of a medical alert bracelet for patients with adrenal insufficiency 1.

Given the most recent and highest quality evidence, the ACTH stimulation test is the next logical step in diagnosing and managing this patient's condition, considering her symptoms and laboratory findings 1.

From the Research

Next Recommended Test

The patient's symptoms, including fatigue, myalgia, intermittent dizziness, abdominal pain, unintentional weight loss, mild hyponatremia, mildly elevated Thyroid-Stimulating Hormone (TSH), and low morning cortisol level, suggest the possibility of adrenal insufficiency.

• The diagnosis of adrenal insufficiency should be suspected in the presence of non-specific symptoms such as fatigue, anorexia, weight loss, hypotension, hyponatremia, and hyperkalemia 2.
• Given the patient's low morning cortisol level, the next step would be to confirm the diagnosis using biochemical tests, such as the adrenocorticotropic hormone (ACTH) stimulation test 3.
• If the ACTH stimulation test is inconclusive, a Synacthen test should be carried out 2.
• The choice of test may depend on the clinical context, with the low-dose ACTH stimulation test being more sensitive and specific than the high-dose test for diagnosing secondary adrenal insufficiency in non-stressed patients 4.
• Morning serum cortisol (MSC) may also be used as a screening test for adrenal insufficiency, with a cutoff value of 234.2 mmol/L having a sensitivity of 83.3% and a specificity of 89.1% 5.

Considerations

• The patient's mildly elevated TSH level may indicate primary hypothyroidism, which can be associated with secondary adrenocortical insufficiency 6.
• The diagnosis of adrenal insufficiency can be challenging, and clinicians should have a high index of suspicion, especially in patients with non-specific symptoms and laboratory findings such as hyponatremia and hypotension 3.