Is Cushing's syndrome a concern with elevated cortisol levels, normal Free Thyroxine (FT4) and Free Triiodothyronine (FT3), and a Thyroid-Stimulating Hormone (TSH) level of 0.432?

From the Guidelines

Based on the provided lab values, there is insufficient evidence to diagnose Cushing's syndrome at this time, and further testing is needed to evaluate the clinical suspicion of Cushing's syndrome, as recommended by the most recent guideline update 1. Given the cortisol level of 25 and a TSH of 0.432 with normal free T4 and T3, the clinical picture is not conclusive for Cushing's syndrome. The slightly suppressed TSH could suggest subclinical hyperthyroidism rather than Cushing's syndrome.

Next Steps in Evaluation

To properly assess for Cushing's syndrome, the following tests are recommended as the first-line screening approach:

• 24-hour urinary free cortisol test
• Late-night salivary cortisol (collected at 11 PM-midnight on two separate occasions)
• Overnight 1mg dexamethasone suppression test These tests, as outlined in the consensus guideline for the diagnosis and management of Cushing's syndrome 1, offer better diagnostic accuracy than random cortisol measurements. The 24-hour urine collection assesses cortisol production throughout the day, salivary cortisol evaluates the loss of normal diurnal rhythm characteristic of Cushing's, and the dexamethasone test examines the hypothalamic-pituitary-adrenal axis feedback.

Considerations for Further Testing

If two of these screening tests are abnormal, further testing to determine the cause (pituitary, adrenal, or ectopic) would be warranted, including measuring ACTH levels to differentiate between ACTH-dependent and ACTH-independent Cushing's syndrome, as suggested by the guideline update 1. Additionally, evaluating for other causes of the mildly suppressed TSH is necessary, as thyroid dysfunction can sometimes mimic symptoms of cortisol excess.

Recent Guideline Recommendations

The most recent guidelines emphasize the importance of a systematic approach to diagnosing Cushing's syndrome, starting with clinical suspicion and proceeding through screening tests before moving to more specific diagnostic tests 1. The choice of initial tests should be based on their sensitivity, specificity, and the clinical context, with the understanding that no single test is definitive on its own.

From the Research

Concern for Cushing's Syndrome

• The patient's cortisol level is 25, and TSH is 0.432 with normal FT4 and FT3, which may indicate a concern for Cushing's syndrome 2, 3, 4.
• Cushing's syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology, and it can be caused by exogenous steroid use or endogenous overproduction of cortisol 2.

Next Steps in Diagnosis

• To confirm the diagnosis of Cushing's syndrome, further testing is needed, including:
  • 24-hour urinary free cortisol test 2, 3, 4, 5
  • Late-night salivary cortisol test 2, 3, 4
  • Dexamethasone suppression test 2, 3, 4
• These tests can help determine if the patient has endogenous Cushing's syndrome and if it is ACTH-dependent or ACTH-independent 4.

Laboratory Tests to Order Next

• Plasma corticotropin levels to help distinguish between adrenal causes of hypercortisolism and corticotropin-dependent forms of hypercortisolism 2
• Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging to help identify tumor sources of hypercortisolism 2
• Scalp-hair cortisol/cortisone analysis to assess long-term glucocorticoid exposure and detect transient periods of hypercortisolism 4