The literature pointing to the endocrine & metabolic effects of opioids not necessarily extending to the thyroid seems to have been pretty consistent for many years saying there was no solid evidence or a suggestion of what form the effect would take, and I for one have not really detected any trend away from that in my reading on this. The extreme fatigue is a part of the withdrawal syndrome which has been one of the worst in my experience and I have actually suspected a relatively benign and transient cardiac and circulatory cause for it, one separate from anything that destabilises and triggers angina pectoris or worse, as they seem to start and peak in different stages of withdrawal and only very rarely have I had them simultaneously. I first discovered the fatigue during a transportation mess caused by a blizzard back in the 1970s during a slog from almost one end to the other of Montréal-Dorval airport when I was 12 hours late for my dose of morphine and was huffing and puffing but for some reason nowhere near as blue, purple, or green as I would have expected, just white as a ghost . . . it took this huge storm with a 95 kPa central pressure and hurricane force winds half the size of North America to do that whereas this kind of clusterfuck was happening at least south of the border 10 to 30 times a year it seems by 2004 or so . . . often with no meteorological cause at all . . .
I have been very interested in opioids and the endocrine system for a long time since I have always had a labile metabolism that seems to be made so mainly by the thyroid and opioids seem to have narrowed the scope of oscillation; opioids slow down metabolism in general it seems, resulting in the possible (positive) effects on longevity caeteris paribus . . . my experience has been a slight decline in where my body temperature naturally settles from 36.7 to 36.4°C and blood pressure at 95/60 mmHg or so . . . The one thing the doctors do advise me about this is to keep supplementing calcium, Vitamin D, phosphorous, and strontium to stave off osteomalacia and osteoporosis, which I started in the early 1980s. The thought is that hypogonadism causes that, but I have not been bedeviled by that touch wood. Supplementing iodine and making sure there is fish in the diet is also a very good idea just on general principle.
There are a third and fourth effect to which I can attest, but the literature is thinner and the theories all over the board, though opium, morphine, codeine, dihydrocodeine and hydromorphone were used for these purposes at least through the end of the 1930s -- whatever diabetes or other cause of anomalous blood sugar tests and beta thalassaemia minor I may have is obliterated by morphine, whole opium and codeine, morphine esters, 14-dihydromorphinones, and some open-chain opioids like dipipanone (phenadoxone could have too -- I was never on it very long) with blood glucose always in the 115-125 range.
Add all this together, and that all could very well be why there are people on morphine and other opioids for many decades and living to well past 100 years old. Year 50 is coming up for me somewhat soon and it runs in the family.
I also started with low blood pressure naturally, so I'm also mulling around the idea that less contractility=insufficient profusion.