Hypocortisolism in survivors of severe acute respiratory syndrome (SARS), 2005. Khee Shing-Leow et al

Publication date: 2005

https://pmc.ncbi.nlm.nih.gov/articles/pmid/16060914/
Summary
Objective
Following the severe acute respiratory syndrome (SARS) outbreak, many survivors were observed to suffer from psychosomatic symptoms reminiscent of various endocrine disorders. Hence, we sought to determine the existence of any chronic endocrine sequelae in SARS survivors.

Design, patients, measurements
Sixty-one survivors of SARS prospectively recruited were analysed for hormonal derangements 3 months following recovery. Patients with pre-existing endocrine disorders were excluded. Any endocrine abnormalities diagnosed were investigated and treated where indicated up to a year. Serial evaluation facilitated characterization of trends and prognostication of any endocrinological aberrations.

Results
Twenty-four (39·3%) patients had evidence of hypocortisolism. The hypothalamic–pituitary–adrenal (HPA) axis dysfunction of the majority resolved within a year. Two (3·3%) of the hypocortisolic cohort had transient subclinical thyrotoxicosis. Four (6·7%) were biochemically hypothyroid, being comprised of three with central hypothyroidism and one with primary hypothyroidism. Two of the three with central hypothyroidism had concomitant central hypocortisolism. Eight had subnormal DHEAS levels.

Conclusions
These preliminary findings highlight a possible aetiologic role of SARS-associated coronavirus in causing a reversible hypophysitis or direct hypothalamic effect, with the HPA axis affected more frequently than the HPT axis.

 

I've put this thread in Long Covid research, although it relates to the SARS-CoV-1 outbreak in Singapore, not the latest Corona virus.
This paper has been cited as evidence of hypocortisolism in survivors of SARS-CoV infections.

There were 238 people infected with SARS and 33 of them died. People with pre-existing endocrine disorders were excluded form this study. They studied 6 1 survivors. 8 of the participants had had severe SARS and had been in ICU.

There's a bit to unpick there.

24 of the 61 patients are reported as having hypocortolism.

10 of the patients had been given corticosteroids during their acute care and the authors note that some of the cases are likely to be a result of steroid-induced suppression.

It is possible that some of the patients had an underlying issue before becoming unwell (perhaps it made them more susceptible to infection), and that it is just the subsequent investigations that have identified it.

There's also the possibility that the illness has perturbed hormone systems.

 

Six of the 24 patients termed as having hypocortolism were given systemic glucocorticoids during the SARS infection and one was taking inhaled corticosteroids for asthma.

 

Hopefully, I can have a look at this a bit more tomorrow. I note though that a significant proportion of the patients with a normal 'HPA axis' reported fatigue and orthostatic issues:

 

I'm not sure if the authors understood 'psychosomatic' in the same way that I do. If an endocrinological basis resulting from a disease process accounts for psychosomatic manifestations, are they really psychosomatic manifestations? It all gets quite circular, but I think one bit of semi-solid ground is 'can the problem be fixed by thinking about things differently?

 

238 people infected with SARS, 33 died.
205 people survived, 2 with pre-existing hypothyroidism excluded
Of the 203, 60 met inclusion criteria and agreed to participate, enrolled at 3 months post-discharge

So, quite a lot of people did not participate. I suspect that the authors would have known the endocrinological status of some of the infected people, and probably would have encouraged those with 'interesting' endocrinology to participate. People who participated got followup treatment if needed.

The 60 enrolled people includes 8 who had severe SARS (admitted to ICU), 10 used corticosteroids during the acute illness

 

So, actually only three had 8 am cortisol levels below the cut-off level. Also, I don't believe an 8 am cortisol level less than 138 mol/l necessarily means that the person is hypocortisolic. As we have discussed elsewhere, cortisol levels vary a lot over a day, and someone who is not working, who has disrupted sleep and who may be napping during the day may well not have a pronounced morning peak cortisol level.

I don't think we have enough evidence here to conclude that the SARS-CoV-1 survivors had unusually low serum cortisol, especially with the complication of steroid medicines.

So, 7 of the 24 'patients with hypocortisolism' had been exposed to steroids.

Of the 21 people whose data is given in Table 2 (because they underwent ACTH testing), only 4 out of 17 patients with 24-hour urinary free cortisol results had low levels. I can't tell if these patients had been treated with steroids.

I'm finding the ACTH testing results harder to understand, or explain away.

So, 4 had mildly raised ACTH. Of those, 1 had been given systemic steroids during their illness. All the others had ACTH in the normal range.

How do you know if someone has 'inappropriately normal' ACTH?
The stimulated ACTH levels in the first test (shown in Table 2) do look low, with the figures in later tests increasing substantially.


A severe illness might indeed cause hypocortisolism, as might the steroids or other medicines the patients were given. That doesn't mean hypocortisolism is part of ME/CFS symptomology. I wonder if there are other studies that measured cortisol in SARS-Cov-1 and MERS.