Letter to the editor
Adrenal insufficiency is caused by failure of the adrenal glands to produce physiological amounts of cortisol and sometimes aldosterone (in the case of Addison’s Disease). Adrenal insufficiency can be a consequence of pituitary / adrenal insufficiency or suppression of endogenous cortisol production as a result of taking exogenous steroids for a prolonged period of time.
The short synacthen test (SST) is the most commonly performed investigation to assess adrenal function (1,2) as it is more practical than the ‘gold standard’ insulin tolerance test (ITT) (3).
In some, but far from all centres a 60-minute serum cortisol post-synacthen is still checked as part of the STT protocol, while in other centres it is not deemed necessary to do this. In the light of these differences in practice, we investigated whether the 60-minute serum cortisol adds value to interpretation of the SST.
All patients attended a single centre, Salford Royal Foundation Trust (SRFT) for their tests. Data from 207 consecutive SSTs were obtained from the Hospital Electronic Patient Record (EPR). All tests were performed before midday. We looked at a period of 12 months from mid-June 2017 to mid-June 2018. Where a patient had more than one SST, the first of the SSTs was analysed.
Serum cortisol was measured by immunoassay on the Siemens Centaur XP analyser (Erlangen, Germany). The analytical range of this assay is 13.8–2069 nmol/L.
Whenever possible, an individual on oral corticosteroids was changed to oral hydrocortisone for 48 hours prior to the SST being performed (if they were not already on this) with omission of hydrocortisone on the evening before and the morning of the test or omission on the morning of the test if on daily prednisolone/dexamethasone. A 30-60-minute cortisol concentration of ≥450nmol/L defined a pass; 350-449nmol/L defined borderline.
Our findings were that in relation to the laboratory assay post-synacthen cortisol pass cut-off of ≥450nmol/L, in 16/207 (7.2%) of cases the 60-minute cortisol was ≥450nmol/L (adequate adrenocortical function) but the 30-minute cortisol was below this. Importantly in all cases where the 30-minute cortisol did indicate a pass (i.e. was ≥450nmol/L) the 60-minute cortisol was also ≥450nmol/L. Thus the 60-minute cortisol measurement resulted in 7.2% of patients being deemed to have adequate adrenocortical function when the 30-minute cortisol would not have done so.
The 60-minute cortisol therefore retains utility in ruling out adrenocortical insufficiency. Determination of the 60-minute cortisol is done in some endocrine centres and was supported by the work of Chitale et al (4). The authors of that paper stated that individuals passing the SST only at 60 min tend to exhibit a ‘delayed response’ to exogenous adrenocorticotrophic hormone (ACTH) but in essence have normally functioning adrenal glands. This conclusion was supported in a recent paper by Butt et al (5) who looked at 849 people undergoing SSTs and reported that 9.5% of patients had a suboptimal response at 30 minutes, but reached the threshold value at 60 minutes. There is also the possibility that the 60-minute serum cortisol level may actually be more representative of physiological adrenocortical function than the 30-minute serum cortisol (6).
If patient management is based solely on the 30-min sample, the individual have to undergo further tests or may be commenced on unnecessary, long-term steroid replacement therapy.
To conclude, we propose that the 60-minute cortisol should be part of the SST as relying on 30-minute cortisol level alone may falsely ascribe individuals to having adrenocortical insufficiency. It would surely be sensible to work towards an international consensus in relation to whether or not the 60-minute cortisol should be part of all SST protocols.