Objectives: Primary adrenal insufficiency AI is regarded as a progressive disease needing lifelongreplacement therapy, but this may not always be the case.
Material and methods: A non-acute presentation of AI following a hypotensive episode caused by blood loss was investigated.
Results: Adrenal function fully recovered without treatment.
Conclusions: There should be a high index of suspicion and a low threshold for performing tests of adrenal function in survivors of criticalillness and severe hypotensive episodes.
Adrenal insufficiency, transient adrenal ischaemia, reversible adrenal dysfunction
The diagnosis of primary adrenal insufficiency (AI) is not synonymous with thelabel of Addison's disease. However, Addison's disease caused by autoimmune adrenalitis remains by far the most common cause of primary AI. The prevalence of primary AI is reported to be 93–140 per million andsecondary insufficiency has a prevalence of 125–280 per million[1].
Primary AI caused by autoimmune adrenalitis leading to Addison's disease is regarded as a progressive disease needing lifelongglucocorticoid and mineralocorticoid replacement therapy. However, a single case report documents partial recovery from autoimmune primary AI[2]. Hence AI may not always be an incurable disease with a need for life-long steroid replacement therapy.
Acute primary AI and acute secondary AI have also been reported following shock aftera surgical procedure or trauma[3]. Changes implicating AI as a cause of death or co-morbidity have also been documented in post mortemfindings[4]. AI has also been reported after cardiac arrest, but its prognostic significance and the value of pre-emptiveintervention are unclear[5].
Post-operative or critical illness-related primary AI has been reported as having an acuteonset in adrenal crisis and as being persistent[3-5]. A chronic or sub-acute presentation does not appear to be common.
We report the case of a non-acute presentation of AI following a hypotensiveepisode caused by blood loss with subsequent full recovery of adrenal function.
A 38-year-old woman was referred to the endocrine service as she was tired andher family doctor could not identify a cause apart from low cortisol. Her symptoms were of progressively increasing tiredness. She had no posturalsymptoms. She was known to have experienced a significant period of post-operative prolonged hypotension 4 months before presentation. Atpresentation to the endocrinology service, physical examination was unremarkable and she had no physical signs to suggest an endocrine illness.Haematological and biochemical indices were all within reference ranges. Prolactin was 326, LH 4.6, FSH 5.0 and ACTH 18 (08:40 h). She had a sub-optimalcortisol response to stimulation with tetracosactrin (Table 1).
| Time | >0 | Week 6 | Week 12 | Week 18 |
|---|---|---|---|---|
| 0 | 193 | 178 | 394 | 376 |
| 30 min | 408 | 529 | 624< | 738 |
Table 1 - Results of corticotrophin stimulation test
Adrenal antibodies were negative. The diagnosis was diminished adrenal reserve due to primary AI butunlikely to be caused by autoimmune adrenalitis. In the absence of evidence to suggest other causes of primary AI, the most likelycause was thought to be post-hypotensive AI.
The diagnosis was discussed with the patient and surgeons. The patient wished to avoid replacement therapywith steroids. She received sick day rule advice as for primary AI and was given a stock of steroids for use in an emergency and emergency contact numbersbut did not receive replacement therapy. Further elective surgery was deferred pending resolution of her adrenal function. She underwent serial corticotropin stimulation tests, which showed improving adrenal response leading to full recovery. She later underwent an electivesurgical procedure without steroid cover uneventfully with no haemodynamic instability during or after surgery.
Our patient's findings suggest that some patients may progress to have absolute AIwith a prolonged period of recovery which may not have been evident in previous intensive therapy unit-based case series as they were not designed to assesslong-term effects on hypothalamic-pituitary-adrenal (HPA) function.
Our patient's presentation was unusual in that it was of a more insidious naturemimicking that of autoimmune adrenalitis. However, in the absence of antibodies, co-existence of other autoimmune disease and theoccurrence following massive blood loss suggest that the mechanism of causation was hypotension and ischaemia of the adrenal glands, although adrenal haemorrhage cannot be ruled out as imaging was carried outsome time after the acute insult and in the recovery phase. The absence of clinical signs and biochemical evidence of other pituitary dysfunction and thepresence of detectable ACTH suggests primary AI although we did not perform a CRH test or dynamic pituitary function tests to establish normal pituitaryreserve.
Our patient's symptoms were non-specific and she did not have the classic signs ofprimary AI such as pigmentation and postural hypotension although she did have tiredness. We conclude that symptoms of AI following critical illness may be missed asthey may be attributed to anaemia, post-operative symptoms or the effects of post-traumatic stress disorder following life-threatening critical illness.Transient reversible AI may be more common than previously thought as it may present without adrenal crisis.
Our case shows that such patients may have a non-acute presentation. Theidentification of potential risk factors such as recent critical illness, shock, sepsis or blood loss should be an integral part of the investigation of suspected AI, which should be considered as a diagnosisif other causes seem unlikely. Furthermore, there may be a case for extending traditional studies of adrenal function in patients treated in critical careunits to study the long-term effects of adrenal function in survivors of critical illness and severe hypotensive episodes. Until reliable data areavailable, treatment plans should take into account individual circumstances and patient preference stated as an informed empowered choice.