For me - I lean strongly toward poor internal regulation of endocrine/hormonal function.
In essence, if you look at everyones' theories above, it is apparent that everything - stress, metabolic issues (poor liver function), illness/virus, rigorous exercise/training, impact of certain toxins/drugs on the body, etc. (except for direct nerve damage, which is hard for me to buy, as none of the diagnostics on our nerve function EVER come back irregular, but I'd never say never) all of it has a direct cause and effect on the endocrine system.
Endocrinology and the myriad of bodily systems, chemicals, physiological functions and the like that are associated with that field is SO complex and SO poorly understood by medicine at large, that we are fighting an uphill battle if we are suffering from anything other than diabetes and/or thyroid disease. And even those are not so well understood and/or managed. Do you realize how common it is for diabetics to suffer from severe and wide-ranging NEUROLOGICAL and other effects (such as parasthesia, numbness, anciliarry nerve damage, etc.)? Likewise, how thyroid conditions cause anxiety, pain, twitching, fatigue, cramps, etc.? So for every area we do know about, consider how many others we don't - cortisol, DHEA, testosterone, epinephrine, norepinephrine, etc. etc. etc. Do you know there is a whole subculture of post-menopausal and PCOS women out there (all over the internet), who are TWITCHING away and blaming it on hormones and menopause, not even AWARE that BFS exists? And how many of us aren't even aware that twitching and fatigue are COMMONLY REPORTED symptoms of these conditions? What's particularly interesting to me is that it is SO rare for any of us that race off to neuros to get tested EVER have a truly "abnormal" result on the gold standard neurological tests, yet very few if any have had cortisol or a full hormone panel done, and we wouldn't even think of seeing an endocrinologist for this unless we suspect thyroid problems. Yet even with that small subset of us, I've seen MANY ON HERE get abnormal thyroid results, high blood pressure, abnormal liver enzymes, abnormal ANA (which is much more rheumatic, but has endocrine associations) and the like...of course, none of this means much to a neuro, because these findings do not point to problems with a neurological origin, but because it's our muscles and nerves thump thump thumping away, there we are.
That's my long-winded theory, but no matter how you slice it and dice it, what goes on in the roots of the tree causes what's happening on the branches, yet I've always suspected most of us are focusing squarely on the branches when we chase down neurological origins for our problems.
Interesting conversation for sure!
JG
I have had above normal bilirubin (liver enzyme) levels measured several times in the past and so have a couple family members. Some scientific studies have shown that this high normal or a bit above actually seems to protect against heart disease. Who knows? maybe it increases the likeliehood of BFS.