In a patient evaluated for Cushing's disease, cortisol was high on several days but Day 4 cortisol was lower. What is the most likely reason for the Day 4 result?

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Multiple Choice

In a patient evaluated for Cushing's disease, cortisol was high on several days but Day 4 cortisol was lower. What is the most likely reason for the Day 4 result?

Cortisol has a strong daily rhythm: it peaks in the early morning and is lowest at night. When evaluating for Cushing’s, you’re looking for loss of that diurnal variation or an inappropriately high level at night. If a sample is collected at the wrong time, you can miss the abnormal pattern and get a result that looks normal. In this case, taking Day 4 cortisol as an early morning specimen instead of a late-night one could make the value appear normal or lower than the true nocturnal excess seen on other days. The nocturnal rise that helps reveal Cushing’s would not be captured, so the Day 4 result wouldn’t reflect the underlying hypercortisolism. Other possibilities—such as an elevated ACTH baseline, a dexamethasone suppression test error, or a laboratory unit issue—don’t specifically explain why a single day would appear falsely normal due to timing. The key idea is that timing relative to the circadian rhythm is what can mask the abnormality.

Cortisol has a strong daily rhythm: it peaks in the early morning and is lowest at night. When evaluating for Cushing’s, you’re looking for loss of that diurnal variation or an inappropriately high level at night. If a sample is collected at the wrong time, you can miss the abnormal pattern and get a result that looks normal.

In this case, taking Day 4 cortisol as an early morning specimen instead of a late-night one could make the value appear normal or lower than the true nocturnal excess seen on other days. The nocturnal rise that helps reveal Cushing’s would not be captured, so the Day 4 result wouldn’t reflect the underlying hypercortisolism.

Other possibilities—such as an elevated ACTH baseline, a dexamethasone suppression test error, or a laboratory unit issue—don’t specifically explain why a single day would appear falsely normal due to timing. The key idea is that timing relative to the circadian rhythm is what can mask the abnormality.

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