Regarding cortisol in Cushing's syndrome, which statement is true?

In Cushing's syndrome, the regulation and measurement of cortisol levels is crucial for diagnosis. The statement indicating that twenty-four-hour urinary free cortisol is a more sensitive test than plasma total cortisol is true because urinary free cortisol reflects total cortisol production over a full day, which can capture the hypercortisolism that characterizes Cushing's syndrome. Plasma cortisol levels, on the other hand, can vary throughout the day due to their natural diurnal pattern, making them potentially less reliable for diagnosis when taken at a single point in time.

In patients with Cushing's syndrome, particularly Cushing's disease (which is caused by a pituitary adenoma), there is typically a loss of normal diurnal variation of cortisol secretion, leading to elevated levels throughout the day. Therefore, the idea that patients show pronounced diurnal variation is incorrect.

Additionally, while high serum cortisol-binding protein concentrations can influence total cortisol measurements, they do not increase the amount of free cortisol, which is the biologically active form. Thus, options regarding free cortisol levels influenced by serum binding proteins do not apply accurately to the context of Cushing's syndrome.

Finally, while an elevated serum total cortisol level may suggest issues with cortisol production, it is not diagnostic of Cushing's