Cortisol is an essential hormone produced by the adrenal glands. It exhibits circadian rhythm, with the highest levels seen soon after waking. Symptoms of cortisol deficiency (adrenal insufficiency) are typically non-specific and include fatigue, muscle weakness/aching, dizziness on standing, anorexia, nausea, vomiting, diarrhoea, abdominal pain and weight loss. Primary (adrenal gland pathology) and secondary (pituitary gland pathology) causes of adrenal insufficiency are rare. The commonest cause of adrenal insufficiency is suppression with steroids, which is usually a transient phenomenon, but it can take months or years for recovery of adrenal function.
Due to the circadian nature of cortisol production, random cortisol measurements are rarely helpful, and screening for adrenal insufficiency relies on assessing adrenal gland function as close to waking as possible. Traditionally this has been done by bringing the patient to hospital as early as feasible, ideally 8-9 AM, however this may be some considerable time after the patient has woken, so false positive rates are high, resulting in many patients requiring dynamic adrenal gland function testing with a Short Synacthen Test (SST).
Waking Salivary Cortisone is a new screening test for adrenal insufficiency. Using saliva, taken at home shortly after waking, to measure adrenal function provides a patient friendly, non-invasive screening test. It is more accurate than an early morning cortisol blood test, reducing the need for Synacthen testing, and should be used as the first line screening test (Debono et al NEJM Evid 2023; 2:2, DOI: 10.1056/EVIDoa2200182). Salivary cortisol and cortisone correlate very closely with serum cortisol (JCEM 2016; 101:1469). In saliva, serum cortisol is rapidly converted to cortisone, which, being more abundant and more sensitive at low levels, is the preferred biomarker. There are other advantages over blood cortisol testing including interpretable results in patients on oestrogen containing medication and with hypoproteinaemic conditions e.g. liver disease.
The test has a proven safety record and has been in routine in Sheffield Teaching Hospitals for the past four years without a case of adrenal insufficiency being missed, however if there is high clinical suspicion that a patient is in adrenal crisis, current protocols should still be followed.
- Samples can be collected using Salivette devices (www.sarstedt.com, part number 51.1534.500) or via passive drool if the devices are not available. Samples are stable for five days at room temperature therefore patients can return them to the laboratory when convenient. The assay is run twice weekly, and requests can be made via HIVE.