Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis.
BACKGROUND
The diagnostic value of tests for detecting hypothalamic-pituitary adrenal insufficiency (HPAI) is controversial.


OBJECTIVE
Our objective was to compare standard-dose and low-dose corticotropin tests for diagnosing HPAI.


METHODS
We searched the PubMed database from 1966-2006 for studies reporting diagnostic value of standard-dose or low-dose corticotropin tests, with patient-level data obtained from original investigators.


METHODS
Eligible studies had more than 10 patients. All subjects were evaluated because of suspicion for chronic HPAI, and patient-level data were available. We excluded studies with no accepted reference standard for HPAI (insulin hypoglycemia or metyrapone test) if test subjects were in the intensive care unit or if only normal healthy subjects were used as controls.


METHODS
We constructed receiver operator characteristic (ROC) curves using patient-level data from each study and then merged results to create summary ROC curves, adjusting for study size and cortisol assay method. Diagnostic value of tests was measured by calculating area under the ROC curve (AUC) and likelihood ratios.


RESULTS
Patient-level data from 13 of 23 studies (57%; 679 subjects) were included in the metaanalysis. The AUC were as follows: low-dose corticotropin test, 0.92 (95% confidence interval 0.89-0.94), and standard-dose corticotropin test, 0.79 (95% confidence interval 0.74-0.84). Among patients with paired data (seven studies, 254 subjects), diagnostic value of low-dose corticotropin test was superior to standard-dose test (AUC 0.94 and 0.85, respectively; P<0.001).


CONCLUSIONS
Low-dose corticotropin test was superior to standard-dose test for diagnosing chronic HPAI, although it has technical limitations.
Kazlauskaite
Rasa
R
John H. Stroger Jr. Hospital of Cook County and Rush Medical College, M.Sc., 1900 West Polk Street, Room 806, Chicago, Illinois 60612, USA. rasa_kazlauskaite@rush.edu
Evans
Arthur T
AT
Villabona
Carmen V
CV
Abdu
Tariq A M
TA
Ambrosi
Bruno
B
Atkinson
A Brew
AB
Choi
Cheung Hei
CH
Clayton
Richard N
RN
Courtney
C Hamish
CH
Gonc
E Nazli
EN
Maghnie
Mohamad
M
Rose
Susan R
SR
Soule
Steven G
SG
Tordjman
Karen
K
D000307:Adrenal Gland Diseases / Q000175:diagnosis*; D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000378:metabolism; D000328:Adult; D002648:Child; D003366:Cosyntropin / Q000494:pharmacology; D005215:Fasting; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007027:Hypothalamic Diseases / Q000175:diagnosis*; D007030:Hypothalamo-Hypophyseal System; D010900:Pituitary Diseases / Q000175:diagnosis*; D012372:ROC Curve; D015203:Reproducibility of Results
D005938:Glucocorticoids; D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone