Normal ranges and diagnostic cut-offs for salivary cortisol

Study for Reference Intervals and Optimal Cut-offs for Salivary Cortisol

This project will test two saliva cortisol methods — a lab LC‑MS assay and a rapid fluorescence immunoassay — to find normal ranges and the best diagnostic cut-offs for adults with suspected Cushing syndrome or adrenal insufficiency.

Quick facts

• Study type: Observational
• Enrollment: 220 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shanghai 6th People's Hospital (Academic / other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07168122 on ClinicalTrials.gov

What this trial studies

Saliva testing offers a non-invasive way to measure biologically active free cortisol but is challenged by very low concentrations and limited detection methods. This observational work will apply an immunomagnetic‑bead LC‑MS assay with simplified preparation and a fluorescence immunoassay designed for point‑of‑care use. The team will establish reference intervals in a healthy adult population and determine optimal diagnostic cut-offs using samples from patients with Cushing syndrome and adrenal insufficiency. Comparing the two methods aims to support clinical adoption by defining reliable thresholds and practical workflows.

Who should consider this trial

Good fit: Ideal candidates include healthy adults aged 18–60 with BMI 18.5–24.9 for establishing reference ranges, and adults with confirmed or suspected Cushing syndrome or adrenal insufficiency for determining diagnostic cut-offs.

Not a fit: People outside the age or BMI criteria, pregnant or lactating women, those with chronic diseases, heavy alcohol use, or conditions/medications that alter cortisol levels are unlikely to benefit from the study findings.

Why it matters

Potential benefit: If successful, clinicians could use accurate, non-invasive saliva tests — including a rapid point-of-care option — to help diagnose and screen for Cushing syndrome and adrenal insufficiency.

How similar studies have performed: Salivary cortisol measured by LC‑MS is already used in research and some clinical settings, but the simplified LC‑MS workflow and the fluorescence point‑of‑care immunoassay are newer and less broadly validated.

Eligibility criteria

Healthy Volunteers:

Inclusion Criteria:

1. Age ≥ 18 and ≤ 60 years old;
2. Body mass index (BMI) ≥ 18.5 and ≤ 24.9 kg\*m\^-2;
3. No previous history of chronic diseases such as hyperglycemia, hypertension, dyslipidemia, coronary heart disease and stroke;
4. 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%.

Exclusion Criteria:

1. 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;
2. Pregnancy or lactation women, or people with cancer or mental illness;
3. 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);
4. Factors affecting saliva collection, such as serious oral problems (oral ulcers, gingival bleeding);
5. Night shift workers, who are awake from 11:00 PM to 7:00 AM;
6. Acute infection (body temperature ≥ 37.3 ℃ or C-reactive protein \> 50 mg/L).

Cases:

Inclusion Criteria:

1. Aged 18 to 80 years old;
2. Patients with suspected Cushing's syndrome or adrenal insufficiency.

Exclusion Criteria:

1. Corticosteroid therapy within the last 6 weeks;
2. Acute infection;
3. Severe oral conditions;
4. Severe liver and kidney dysfunction;
5. Alcoholism, depression, or other psychiatric disorders.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Sixth People's Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jian Zhou, Doctor

Conditions Healthy Adult; Cushing Syndrome; Adrenal Insufficiency