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.