Establishment and Clinical Application of Reference Intervals of Salivary Cortisol

NCT07168122 | Recruiting DMC

• 1 other identifier: 20250811
• Study Type: observational
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to establish the normal reference intervals of salivary cortisol and optimal cut-offs for Cushing's sydrome and adrenal insufficiency.

Conditions

Healthy Adult; Cushing Syndrome; Adrenal Insufficiency

Outcome Measures

Primary Outcomes (4)

• Reference intervals of salivary cortisol

  Salivary cortisol levels were evaluated by immunomagnetic-bead-based LC-MS assay and fluorescence immunoassay system to establish its reference intervals according to the 2.5th and 97.5th percentiles.

  8:00, 16:00 and 23:00 on the day of sample collection

• Optimal cut-off and diagnostic accuracy of salivary cortisol in Cushing's syndrome

  The diagnostic cut-off for each analysis method was defined as either the calculated upper reference interval (97.5th percentile) or the optimal value determined by the Youden index. The sensitivity, specificity and area under curve for Cushing's syndrome was calculated using samples from all available healthy controls and cases.

  23:00 on the day of sample collection

• Optimal cut-off and diagnostic accuracy of salivary cortisol in adrenal insufficiency

  The diagnostic cut-off for each analysis method was defined as either the calculated lower reference intervals (2.5th percentile) or the optimal value determined by the Youden index. The sensitivity, specificity and area under curve for adrenal insufficiency was calculated using samples from all available healthy controls and cases.

  8:00 on the day of sample collection

• Comparison of diagnostic accuracy of salivary cortisol in Cushing's syndrome and adrenal insufficiency

  The diagnostic accuracies of the fluorescence immunoassay system and the immunomagnetic-bead-based LC-MS assay were compared by analyzing their areas under the receiver operating characteristic (ROC) curves using DeLong's test for paired statistics.

  8:00 or 23:00 on the day of sample collection

Secondary Outcomes (4)

• Agreement in assessment of salivary cortisol

  8:00, 16:00 and 23:00 on the day of sample collection

• Between-groups differences in salivary cortisol of healthy volunteers with different age ranges

  8:00, 16:00 and 23:00 on the day of sample collection

• Between-groups differences in salivary cortisol of healthy volunteers with different sex

  8:00, 16:00 and 23:00 on the day of sample collection

• Between-groups differences in salivary cortisol of healthy volunteers with different body mass index ranges

  8:00, 16:00 and 23:00 on the day of sample collection

Study Arms (3)

Heathy Volunteers

120 Healthy Volunteers for the establishment of reference intervals of salivary cortisol

Cushing's sydrome

50 cases diagnosed with Cushing's sydrome

Adrenal insufficiency

50 cases diagnosed with adrenal insufficiency

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The participants are enrolled from Shanghai Sixth People's Hospital, Shanghai.

You may qualify if:

• Age ≥ 18 and ≤ 60 years old;
• Body mass index (BMI) ≥ 18.5 and ≤ 24.9 kg\*m\^-2;
• No previous history of chronic diseases such as hyperglycemia, hypertension, dyslipidemia, coronary heart disease and stroke;
• Normal glucose regulation, defined as: fasting blood-glucose \< 5.6 mmol/L, 2-hour blood-glucose after glucose load \< 7.8 mmol/L, and glycated hemoglobin (HbA1c) \< 5.7%.

You may not qualify if:

• Liver or kidney dysfunction, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or direct bilirubin higher than 1.5 times the upper limit of normal, or serum creatinine \>115 μmol/L;
• Pregnancy or lactation women, or people with cancer or mental illness;
• Factors affecting cortisol levels, including hypothalamus-pituitary-adrenal axis disease, autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, etc.), diagnosed mental disease, Alzheimer's disease, alcoholism (alcohol \> 60 g/d for male, \>40 g/d for women) and corticosteroid therapy in the past 3 months (females with contraceptives or estrogen);
• Factors affecting saliva collection, such as serious oral problems (oral ulcers, gingival bleeding);
• Night shift workers, who are awake from 11:00 PM to 7:00 AM;
• Acute infection (body temperature ≥ 37.3 ℃ or C-reactive protein \> 50 mg/L).
• Cases:
• Aged 18 to 80 years old;
• Patients with suspected Cushing's syndrome or adrenal insufficiency.
• Corticosteroid therapy within the last 6 weeks;
• Acute infection;
• Severe oral conditions;
• Severe liver and kidney dysfunction;
• Alcoholism, depression, or other psychiatric disorders.

Sponsors & Collaborators

• Shanghai 6th People's Hospital: lead

Study Sites (1)

Shanghai Sixth People's Hospital

Shanghai, Shanghai Municipality, 200233, China

RECRUITING

MeSH Terms

Conditions

Cushing Syndrome; Adrenal Insufficiency

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Central Study Contacts

Jian Zhou, Doctor

CONTACT

+86-021-64369181; zhoujian@sjtu.edu.cn

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Professor, Chief Physician, Deputy Director

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: September 11, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)