title: Incidence of Cushing's syndrome in patients with significant hypercortisoluria.
abstract: OBJECTIVE
  To investigate the incidence of Cushing's syndrome (CS) in patients with significant hypercortisoluria and the performance of urinary free cortisol (UFC) screening.
  
  
  METHODS
  Retrospective file review.
  
  
  METHODS
  The computerized database of a publicly funded health maintenance organization (HMO) in Israel was searched for all patients who underwent 24-h UFC testing in 2005-2014 with a result of more than twice the upper limit of normal (ULN). The patients' medical files were reviewed for a subsequent diagnosis of CS by an expert endocrinologist. Findings were evaluated for patterns in CS diagnosis and UFC testing over time.
  
  
  RESULTS
  Of 41 183 individuals tested, 510 (1.2%) had UFC >2× ULN (214 >3× ULN). Eighty-five (16.7%) individuals were diagnosed with CS (63 female and mean age 47.2 ± 15.1 years), mainly Cushing's disease (55.3%) or adrenal Cushing's syndrome (37.6%). The number of UFC tests increased steadily, from 1804 in 2005 to 6464 in 2014; yet, the resultant detection rate of CS remained generally stable. The calculated incidence of CS in the general HMO-insured population based only on the patients identified in the present cohort was 4.5 new cases/million/year (median 4.9/million/year, range 1.7-5.9/million/year), which was also relatively stable. The most common reason for referral for UFC screening was obesity. Of the 148 patients before bariatric surgery with UFC >2× ULN, 2 were diagnosed with CS.
  
  
  CONCLUSIONS
  The incidence of CS is higher than previously suggested. The consistently increasing number of UFC tests being performed has not been accompanied by a similar increase in CS detection rate. The expected yield of routine UFC testing before bariatric surgery is low.
authors.affiliation: Institute of EndocrinologyRabin Medical Center-Beilinson Hospital, Petach Tikva, Israel daniaron@netvision.net.il.|Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel.|Maccabi Health Care Services.
authors.forename: Dania
authors.initials: D
authors.lastname: Hirsch
authors.affiliation: Institute of EndocrinologyRabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.|Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel.|Maccabi Health Care Services.
authors.forename: Gloria
authors.initials: G
authors.lastname: Tsvetov
authors.affiliation: Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel.|Maccabi Health Care Services.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Manisterski
authors.affiliation: Maccabi Health Care Services.
authors.forename: Nirit
authors.initials: N
authors.lastname: Aviran-Barak
authors.affiliation: Central LaboratoryMaccabi Healthcare Services, Rehovot, Israel.
authors.forename: Varda
authors.initials: V
authors.lastname: Nadler
authors.affiliation: Central LaboratoryMaccabi Healthcare Services, Rehovot, Israel.
authors.forename: Sandra
authors.initials: S
authors.lastname: Alboim
authors.affiliation: Central LaboratoryMaccabi Healthcare Services, Rehovot, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Kopel
mesh_terms: D000328:Adult; D003480:Cushing Syndrome / Q000652:urine*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D006854:Hydrocortisone