Intended for healthcare professionals

Clinical Review Lesson of the week

Misinterpretation of serum cortisol in a patient with hyponatraemia

BMJ 2004; 328 doi: (Published 22 January 2004) Cite this as: BMJ 2004;328:215

When diagnostic confusion surrounds Addison's disease

Our thanks to Smith, Siddique and Corrall for their discussion of the
diagnostic confusion which surrounds Addison's disease, especially in
cases of atypical presentation. We would like to remind readers that:

1. An ACTH (synacthen) test is a simple, accurate predictor of
adrenal function.

2. Failure to conduct an ACTH (synacthen) test or begin treatment
promptly can be fatal.

3. Many cases of Addison's disease will present with only a few of
the textbook symptoms.

In 1996 and 1997 the BMJ reported three cases of Addison's disease
where failure to diagnose led to the deaths of two young adults and a
child (1). These cases were summed up by one of the authors: "Addison's
disease remains the master of unforgiving disguise".

In addition to the risks of death, a delayed diagnosis can also
result in permanent disability for a previously fit, young adult, due to
either the cardiac complications of severe hypovolaemia, or to cerebral
oedema. These problems, associated with a delayed diagnosis, have been
highlighted by a recent membership survey conducted by the UK Addison's
Disease Self-Help Group (ADSHG)(2). It is our hope that a higher level of
suspicion among medical professionals - particularly among GPs and ICU
staff - will reduce these preventable tragedies in future.

The ADSHG's 2003 membership survey includes information about the
individual's experiences in getting diagnosed. The key factor for a
successful, early diagnosis has been the GP's awareness of the possibility
of Addison's disease. One of our new members sums it up:

"When I got so weak I couldn't walk up stairs, my partner persuaded
me to visit the GP. My GP was brilliant. He arranged the relevant tests
and I was diagnosed soon after visiting him."

For the GP, the greatest challenges in early detection of Addison's
remain its rarity and the diffuse nature of its symptoms. The GP must be
able to distinguish between the psychological apathy of depression and the
physical exhaustion of adrenal failure. In some instances, this is
commendably handled. For example, our 2003 survey found that one GP
correctly identified Addison's disease in a patient who had been fit
enough to go mountain climbing one month earlier.

Few patients will present to their GP with the full complement of
textbook symptoms (see chart 1), thus compounding the challenges of
diagnosis. The possibility of Addison's is usually identified only after
more common causes of extreme fatigue have been excluded.

Nevertheless, the GP can conduct the basic screening tests for
Addison's on the spot: a physical examination will almost invariably
indicate weight loss with a weak hand-grip strength. If there is also
extra pigmentation (a seeming ski-holiday tan), with signs of postural
hypotension or reduced blood pressure in older patients, then referral for
an ACTH (synacthen) test is probably warranted - particularly if blood
tests reveal a low sodium level. Arlt and Allolio offer a helpful
discussion of the various laboratory tests for adrenal insufficiency (3).

Greater awareness of adrenal conditions seems to be leading to an
increase in diagnosed cases, and hopefully to a shorter period of pre-
diagnosis illness with fewer unnecessary deaths/disabilities (see Chart
2). The most recent research from Norway found that the rate of diagnosed
Addison's disease could be as high as 140 per million(4). This would
suggest more than 8,000 possible cases of Addison's disease in the UK.
However, The MedicAlert Foundation had only 2,279 registered members with
Addison's disease across the UK in 2003, equivalent to around 38 cases per
million total population.

We would like to encourage all GPs to remain alert to the possibility
of Addison's in cases of persistent, severe fatigue where there is
evidence of weight loss with a weak hand-grip, and extra pigmentation or


(1) C M Brosnan and N F C Gowing, Lesson of the week: Addison's
disease, BMJ 1996; 312: 1085-1087; Clare Dyer, News: court rules that
doctors do not have to tell parents the truth, BMJ 1997: 315: 75-80.

(2) International survey 2003 of Addison's group members in the UK,
Australia, Canada, New Zealand. Full results pending; provisional UK
data, drawn from 217 Addison's responses, cited in this letter.

(3) W Arlt W and Allolio B, Adrenal insufficiency, The Lancet 2003;
361: 1881-93.

(4) Lovas K, Husebye ES, High prevalence and increasing incidence of
Addison's disease in western Norway, Clinical Endocrinology 2002; 56: 787.

Competing interests:
None declared

Competing interests: No competing interests

08 April 2004
Katherine G White
Sarah Baker, Alyson Elliott, Deana Kenward, on behalf of the Addison¡¦s Disease Self-Help Group
Addison's Disease Self-Help Group