Salivary Cortisone in AI

• Research type

  Research Study

• Full title

  Salivary Cortisone as an Adrenal Insufficiency Test (SCAIT)

• IRAS ID

  262618

• Contact name

  Miguel Debono

• Contact email

  m.debono@sheffield.ac.uk

• Sponsor organisation

  Sheffield Teaching Hospitals

• Duration of Study in the UK

  1 years, 11 months, 30 days

• Research summary

  Research Summary

  Background
  Adrenal insufficiency (AI) occurs when the body is unable to produce cortisol, an essential hormone for overcoming stress, including illness and injury. Low cortisol levels lead to fatigue, weakness and low blood pressure. Left untreated, the body can no longer regulate blood sugar, control blood pressure or reduce inflammation, increasing the risk of emergency admission, cardiac arrest and eventually death (if symptoms worsen). AI occurs in patients with hormonal disorders (Addison’s and Pituitary disease) and temporarily in up to 50% patients on steroids used to treat inflammation.

  AI is currently diagnosed in hospital by a Short Synacthen Test (SST) by taking blood to measure cortisol before and 30 minutes after an injection of a synthetic form of the pituitary hormone ACTH, Synacthen. Misdiagnosis and delayed diagnosis of AI are common as symptoms are non-specific.

  Aims
  The aim is to provide a patient friendly, more convenient, cheaper salivary test to reduce and replace the use of the SST for the majority of patients. As cortisol is converted to cortisone in the saliva, the new test measures waking salivary cortisone in saliva collected at home. Potential benefits are:
   No blood test
   No hospital visit for testing
   It costs £13 per patient compared with £156 for the SST

  Design/methodology
  Around 200 individuals being tested for AI will be recruited. We will ask patients to chew a cotton bud or “salivette” for one minute as soon as they first wake up at home to start their day. Although the new test wouldn’t require a hospital visit, for the purpose of research, we need to compare salivary cortisone levels with blood cortisol levels taken during the routine hospital SST. The study will confirm whether the measurement of salivary cortisone (new test) can replace the standard SST based on how accurate it is and whether it is acceptable to patients.

  Summary of Results

  BACKGROUND Worldwide, adults and children are at risk of adrenal insufficiency as a result of adrenal suppression from use of anti-inflammatory glucocorticoids and opiates, as well as infectious diseases. The adrenocorticotropin (ACTH) stimulation test is the reference standard for diagnosis of adrenal insufficiency but requires clinic attendance and venesection. Salivary cortisone reflects free serum cortisol, and samples can be collected at home and posted to a laboratory. We tested whether home waking salivary cortisone level could be used to screen for adrenal insufficiency.
  METHODS
  A prospective, diagnostic accuracy study was performed in patients at high risk of adrenal insufficiency. Patients collected a home salivary sample on waking and then attended the clinical facility for an ACTH stimulation test. Salivary cortisone was measured by liquid chromatography–tandem mass spectrometry. Receiver-operating characteristic curves were computed, and positive and negative predictive values were calculated.
  RESULTS
  Two hundred twenty patients were recruited. As measured by an ACTH stimulation test, the prevalence of adrenal insufficiency was 44%. The area under the receiver-operating characteristic curve for waking salivary cortisone as a predictor of adrenal insufficiency was 0.95 (95% confidence interval [CI], 0.92 to 0.97). Cutoffs to ensure a minimum of 95% sensitivity and specificity gave a negative predictive value of 96% (95% CI, 90 to 99) and a positive predictive value of 95% (95% CI, 87 to 99) to exclude and confirm adrenal insufficiency, respectively. Waking salivary cortisone data provided information similar to that of an ACTH stimulation test in 70% of participants. Eighty-three percent of patients preferred home salivary collection to clinic attendance.
  CONCLUSIONS
  Home waking salivary cortisone sampling has accuracy for the diagnosis of adrenal insufficiency similar to that of a standard ACTH stimulation test. Patients found the at-home test to be more convenient than the hospital-based test. (Funded by the National Institute for Health Research.)

• REC name

  Yorkshire & The Humber - South Yorkshire Research Ethics Committee

• REC reference

  19/YH/0333

• Date of REC Opinion

  4 Oct 2019

• REC opinion

  Favourable Opinion