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Original Article Usefullness of Urinary Free Cortisol Measurement in Diagnosis of Iatrogenic Cushing Syndrome.
Yong Hyun Kim, Sang Jin Kim, Dong Seop Choi
Endocrinology and Metabolism 2000;15(2):162-169

Published online: January 1, 2001
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Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

BACKGROUND
Although insulin induced hypoglycemia test is a standard diagnostic method in assessment of hypothalamo-pituitary-adrenal axis, rapid ACTH stimulation test using 250microgram has been used as a first line diagnostic test especially in secondary adrenal insufficiency due to iatrogenic Cushing syndrome because it is easy and safe. However, it was suggested that a maximal cortisol response can be achieved with a much lower ACTH dose and 1microgram ACTH enhances the sensitivity without decreasing specificity of test. Also recently, there was a report that midnight to morning urine cortisol increment is more accurate, noninvasive method can be used for measurement of hypothalmo-pituitary-adrenal axis. In this study, we compared the 1microgram ACTH stimulation test with midnight to morning urinary free cortisol increment in secondary adrenal insufficiency due to iatrogenic Cushing syndrome to study the agreement of two test and accuracy of increment of urinary free cortisol in diagnosis of adrenal insufficiency. METHODS: Double voided urine sample were collected at midnight and 8 A.M. in 12 patients who have Cushing-like feature and history of taking glucocorticoids and in 12 normal controls. Urinary free cortisol was measured and cortisol increment was defined as the morning urine free cortisol minus the midnight urine free cortisol. The 1microgram ACTH stimulation test was performed in 12 iatrogenic Cushing syndrome patients at the same day and compard with the result of cortisol increment. RESULTS: Using the results of 12 controls, normal urine free cortisol increment was defined as greater than 165.5nmol/L(6.0microgram/dL). Subnormal cortisol response in 1microgram ACTH stimulation test was noted in 8 out of 12 patients group and urinary free cortisol increment was not observed in 7 out of 8 subnormal response group. Normal cortisol response in 1microgram ACTH stimulation test was noted in 4 out of 12 patients group and urinary free cortisol increment was observed in 3 out of 4 normal response group. So 83% of concordance rate between 1microgram ACTH stimulation test and urine free cortisol increment was recorded. CONCLUSION: Urinary free cortisol increment has high concordance rate with 1microgram ACTH stimulation test and simple, easy test in diagnosing secondary adrenal insufficiency due to iatrogenic Cushing syndrome. Further study including more patients will be helpful to know the adequacy and reliability of test in evaluation of hypothalamo-pituitary-adrenal axis.

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