An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome, 2020, Lee et al

In other words, you're saying that the fact of there being 100 possible models is what suggests none of them are on target because the volume of ideas would indicate they're all shots in the dark?

 

In a way yes, but there is also the statistical argument.

Say 99 models have been published. A.N. Other publishes a new model - no. 100. If A.N.is right then 100% of 99 models were wrong. So the going rate for validity in this field was zero, and being out of 99 the p value or whatever the number is will be small. The reader can conclude that model no.100 is pretty unlikely to be right, just as no. 47 is unlikely to be right, and so on.

 

If there is lower cortisol, there isn't so much resistance, rather increased sensitivity. But results in patients have been equivocal on both cortisol levels and glucocorticoid receptor sensitivity.

The levels are rarely pathologically low in CFS (which would indicate an adrenal disorder). The basal levels in saliva or blood compared to healthy participants are also subject to a wide variety of influences, least of which are different sleep rhythms and different activity patterns (less activity in the morning, lower intensity of activity and so on). The key point is that cortisol is not primarily a "stress" hormone, but a feed-forward metabolic hormone that forms daily cycles based on sleep/activity patterns as well as psychological anticipation of higher levels of exertion.