Addison’s disease

In a rapid response to our paper, Gabriel Antony comments that a
paired measurement of random serum cortisol and plasma
adrenocorticotrophin (ACTH), and not the short synacthen test, is the
investigation of choice for the diagnosis of Addison’s disease (1).
Although we agree that a low random cortisol together with a raised ACTH
level suggests the diagnosis, we would still advocate a short synacthen
test to diagnose hypoadrenalism. There are several reasons why:

• The short synacthen test has been extensively studied in both
healthy individuals as well as in patients with primary and secondary
hypoadrenalism, which have allowed to derive validated cut-off levels for
normal response (2). In contrast, there are no validated cut-off levels
are for a paired random cortisol and ACTH. Extreme cases of low cortisol
and high ACTH may be diagnostic, but more subtle changes may lead to
confusion. Accepting that the symptoms of Addison’s disease are non-
specific, it is important to have clear diagnosis before committing a
patient to lifelong glucocorticoid replacement.

• A short-synacthen test is a quick, easy test. Analysing an ACTH
level is more complicated – requiring the sample to be taken immediately
(on ice) to the laboratory and having a much longer turn-around time for
the results. As well as practical difficulties in performing the test in
primary care, it may lead to an inappropriate delay in diagnosis and thus
treatment.

• A low random cortisol with a normal ACTH could represent
secondary hypoadrenalism. A patient or clinician could thus be falsely
reassured that these tests are normal.

Regarding the question of glucocorticoid replacement at times of
physiological stress in patients with Addison’s disease, treatment
strategy should vary according to the nature and severity of the illness.
We agree that it is important for patients with Addison’s disease and
their next of kin to learn when and how to inject intramuscular
hydrocortisone as timely parenteral administration of hydrocortisone at
the time of a serious illness particularly if the patient is unable to
tolerate oral medication could be life-saving. However, there is no
justification to recommend hydrocortisone injections during every minor
illnesses or stress. The optimum balance can be achieved through patient
education.

References:

1. Vaidya B, Chakera AJ, Dick C. Easily Missed? Addison’s disease.
BMJ 2009; 339:b2385

2. Dorin RI, Qualls CR, Crapo LM. Diagnosis of Adrenal
Insufficiency. Annals of Internal Medicine. 2003; 139(3):194-204

Competing interests:
None declared