Diagnostic value of salivary cortisol in 1-mg dexamethasone suppression test

BACKGROUND: Late-night salivary cortisol and serum cortisol measurements after 1-mg Dexamethasone Suppression Test (1-mg DST) are routinely used to diagnose Cushing’s syndrome (CS). Measuring morning salivary instead of serum cortisol after 1-mg DST would make the diagnostics of CS fully non-invasive.

AIM: To evaluate the diagnostic accuracy of salivary cortisol in 1-mg DST as measured by electrochemiluminescence assay (ECLIA).

MATERIALS AND METHODS: We combined a cohort diagnostic study, including 164 participants (132 females, 32 males) aged from 18 to 77 years: 110 were overweight or obese as increased BMI is the most common sign of Cushing’s Syndrome (CS), and 54 healthy volunteers. In each cohort late-night salivary cortisol was measured (at 23:00) followed by 1-mg DST and blood and salivary sampling for cortisol measurement the next morning at 08:00-09:00. Cortisol in saliva and serum were measured on automatic analyzer Cobas е 601 by F. Hoffmann-La Roche Ltd, using ECLIA. The final diagnosis was confirmed by the histological evaluation after surgery or using a follow-up observation in patients with obesity to exclude Cushing’s syndrome manifestation.

RESULTS: Among 110 patients, 54 subjects were finally confirmed as having Cushing's syndrome. Reference interval for salivary cortisol after 1-mg DST was estimated to be 0,5–12,7 nmol/l (5–95 procentile). Maximal salivary cortisol level in 1-mg DST registered in healthy person was 29,6 mmol/l. Areas under the curve (AUC) were as following: for salivary cortisol in 1-mg DST – 0,838 (95% СI 0,772–0,905), for blood cortisol in 1-mg DST – 0,965 (95% CI 0,939–0,992) and for late-night salivary cortisol – 0,925 (95% CI 0,882–0,969). The optimal cut-off point for salivary cortisol after 1-mg DST was estimated as 12.1 nmol/l (sensitivity 60%, specificity 92,9%) among CS versus healthy subjects; 12,6 (sensitivity 58,2%, specificity 96,2%) among patients with obesity and CS; and – 12,2 nmol/l (sensitivity 60,7%, specificity 93,4%) among CS and both obese and healthy control subjects. Considering small difference between cut-off points, the recommended cut-off value for salivary cortisol after 1-mg DST is recommended to be 12,0 nmol/l if measured by ECLIA.

CONCLUSION: Although salivary cortisol after 1-mg DST is inferior to serum cortisol after 1-mg DST in the diagnostic performance and diagnostic accuracy, it can be used as a low-invasive screening test with superior specificity.

Cushing syndrome, salivary cortisol, electrochemiluminescence immunoassay, 1-mg dexamethasone suppression test

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17. Патент РФ на изобретение №2695798 / 06.06.18. Белая Ж.Е, Малыгина А.А, Гребенникова Т.А, Ильин А.В, Рожинская Л.Я, Фадеев В.В, Мельниченко Г.А, Дедов И.И. Способ ранней диагностики вторичной плацентарной недостаточности. [Patent RUS №2695798 / 06.06.18. Belaya ZHE, Malygina AA, Grebennikova TA, Ilyin AV, Rozhinskaya LYA, Fadeev VV, Mel’nichenko GA, Dedov I.I. Sposob rannej diagnostiki vtorichnoj placentarnoj nedostatochnosti. (In Russ).] Доступно по: https://new.fips.ru/registers-doc-view/fips_servlet?DB=RUPAT&DocNumber=0002695798&TypeFile=html. Ссылка активна на 14.04.2020.