This is a real-world medical entrance exam question, please give the true answer based on the question and selection. Topic name: None, Subject name: Pediatrics
Which one of the following is the earliest manifestation of Cushing's syndrome : 
Select and explain. 
A. Loss of diurnal variation, B. Increased ACTH, C. Increased plasma cortisol, D. Increased urinary metabolites of cortisol
A: Loss of diurnal variation
Answer: A: Loss of diurnal variation 
Explanation: Nelson writes :
"Laboratoiy .findings (for Cushing Syndrome)"
Cortisol levels in blood are normally elevated at 8 AM and decrease to less than 50% by midnight except in infants and young children in whom a diurnal rhythm is not always established. In patients with cushing syndrome this circadium rhythm is lost, and cortisol levels at midnight and 8 AM are usually comparable. Obtaining diurnal blood samples present logistical difficulties as part of an outpatient evaluation, but cortisol can be measured in saliva samples, which can be obtained at home at the appropriate times of day. Night time salivary cortisol levels are elevated and may be a screening test in obese children.