Faculty Collaboration Database

High variability in baseline urinary free cortisol values in patients with Cushing's disease. Clin Endocrinol (Oxf) 2014 Feb;80(2):261-9

Date

06/12/2013

Pubmed ID

23746264

Pubmed Central ID

PMC4231220

DOI

10.1111/cen.12259

Scopus ID

2-s2.0-84891858213 (requires institutional sign-in at Scopus site)   103 Citations

Abstract

OBJECTIVE: Twenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate-to-severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data.

DESIGN: Observational study (enrolment phase of Phase III study).

METHODS: Patients (n = 152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) ≥1·5×ULN (normal: 30-145 nmol/24 h) were included. Mean UFC level was calculated from four 24-h urine samples collected over 2 weeks.

RESULTS: Over 600 24-h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000 nmol/24 h (SD 1872) and 940 nmol/24 h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48-56). The intrapatient CV was 51% (95% CI: 44-58) for samples 1 and 2, 49% (95% CI: 43-56) for samples 3 and 4 and 54% (95% CI: 49-59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism.

CONCLUSIONS: There is intrapatient variability of approximately 50% in 24-h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24-h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity.

Author List

Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Sen K, Salgado LR, Colao A, Biller BM, Pasireotide B2305 Study Group

Author

James W. Findling MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Cushing Syndrome
Double-Blind Method
Female
Humans
Hydrocortisone
Male
Middle Aged
Pituitary ACTH Hypersecretion
Recurrence
Reference Values
Severity of Illness Index
Somatostatin
Time Factors
Treatment Outcome