Abstract
The measurement of cortisol in saliva is becoming more widely accepted as a screening
test for the diagnosis of hypercortisolism. Since 1986, cortisol measurement in saliva
has been continuously used in our department. In this study we compared salivary cortisol
profiles from proven Cushing's disease patients with profiles from healthy subjects
and obese children. The purpose was to evaluate the predictive value of the method
for the diagnosis of hypercortisolism and to define cut-off levels to exclude or identify
hypercortisolism. Cortisol in saliva was measured in 150 Cushing's disease patients
(30 children, 120 adults, ranging from age 4 - 70), 100 healthy subjects (55 children,
45 adults, ranging from age 6 - 60), and 31 children (age 7 - 15) with an age-related
body-mass-index above the 90th percentile. Generally, five saliva samples were taken
over the day at 6 : 00 - 8 : 00 a.m., 11 : 00 - 12 : 00 a.m., 4 : 00 - 6 : 00 p.m.,
7 : 00 - 8 : 00 p.m., and 10 : 00 p.m. The samples were measured using a radioimmuno-assay
(INCSTAR Corporation, Stillwater, Minnesota, USA). For healthy subjects, morning levels
of cortisol in saliva between 3 - 19 µg/l were found. These levels dropped to levels
in between < 1 - 11 µg/l at 11 : 00 - 12 : 00 a.m., < 1 - 6 µg/l at 4 : 00 - 6 : 00
p.m., < 1 - 4.5 µg/l at 7 : 00 - 8 : 00 p.m., and < 1 - 2.9 µg/l at 10 : 00 p.m. The
measured values showed a correlation with age, height, and weight. In Cushing's disease
patients, the circadian salivary cortisol rhythm was missing, compared to healthy
subjects. There was no significant difference in salivary cortisol levels or circadian
rhythm between healthy or obese children. We found a high sensitivity for the detection
of hypercortisolism at the 10 : 00 p.m. salivary cortisol measurement. The following,
age dependent cut-off levels for salivary cortisol at 10 : 00 p.m. were calculated
for the exclusion of hypercortisolism. Age 6 - 10: 1.0 µg/l (sensitivity 100 %, specificity
87.5 %); age 11 - 15: 1.7 µg/l (sensitivity 100 %, specificity 100 %); age 16 - 20:
1.9 µg/l (sensitivity 94.7 %, specificity 90.5 %); age 21 - 60: 1.6 µg/l (sensitivity
100 %, specificity 90.9 %). For the proof of Cushing's syndrome, the following age
dependent cut-off levels at 10 : 00 p.m. were found: age 6 - 10: 1.9 µg/l (sensitivity
100 %, specificity 80 %); age 11 - 15: 1.7 µg/l (sensitivity 100 %, specificity 100
%); age 16 - 20: 2.5 µg/l (sensitivity 100 %, specificity 84.2 %); age 21 - 60: 1.9
µg/l (sensitivity 100 %, specificity 87.6 %). The cortisol assessment in saliva is
a sensitive and reliable method to discriminate normocortisolemic from hypercortisolemic
patients. From our view, the major advantages of this method are the reliability,
non-invasiveness, and use in ambulatory patients.
Key words
Cushing's disease - Cushing's syndrome - cortisol - saliva - RIA
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Dr. Jörg Flitsch
Bereich Hypophysenchirurgie (Leiter: Dr. D.K. Lüdecke)
Neurochirurgische Klinik
Universitätskrankenhaus Hamburg-Eppendorf
Martinistraße 52
20246 Hamburg
Germany
Telefon: + 4940428032765
Fax: + 49 4 04 28 03 59 82
eMail: flitsch@uke.uni-hamburg.de