Hi, all.
I agree that it is likely that the reason the orthostatic intolerance is worse first thing in the morning for many PWCs is that the diurnal cortisol variation is abnormal in many cases. If you want to check that, it is possible to get a 24-hour saliva cortisol test, even without a doctor's order. You can order the Saber Science test from
www.directlabs.com , take the saliva samples yourself, and send it in. They will send the results directly to you. This panel is the most complete saliva cortisol test, including samples every four hours around the clock. I think it will answer the question of whether your diurnal cortisol variation is shifted, and whether your cortisol levels are low, especially in the morning. If so, I think that will give you part of the answer.
In the GD--MCB hypothesis, the disruption of the normal cortisol levels and variation is caused by dysfunctional secretion of ACTH by the pituitary, due to glutathione depletion there. This occurs because glutathione is needed to control the redox state of cysteine molecules in the synthesis of secretory proteins.
Another part of the reason for the orthostatic intolerance in general, not just in the early part of the day, iis low total blood volume, another common feature of CFS. This results from a usually mild case of diabetes insipidus (not the same as diabetes mellitus, which involves blood sugar and insulin). Diabetes insipidus, as another poster has noted, is caused by insufficient production of the antidiuretic hormone. In the GD--MCB hypothesis, this is caused by glutathione depletion in the hypothalamus/pituitary. The biochemical mechanism for this problem is the same as for ACTH.
Compounding these problems is diastolic dysfunction of the heart, also commonly found in CFS (at least by Dr. Cheney, who runs echocardiograph studies on all his CFS patients). This results in low cardiac output of blood. In the GD--MCB hypothesis, this is due to glutathione depletion in the mitochondria of the heart muscle cells. In this case, the problem is partial blocks in enzymes in the Krebs cycle and the respiratory chain, which occur because the levels of oxidizing free radicals are allowed to rise when glutathione is low.
As you can see from the above, all three of the factors that I'm suggesting are involved in the orthostatic intolerance in CFS, especially early in the day, are ascribed in the GD--MCB hypothesis to glutathione depletion.
We've found that in order to correct the glutathione depletion in CFS, as in autism, it is necessary to lift the partial block in the methylation cycle. People are using several variations of a treatment to do that. These include the types of things that are done by the DAN! (Defeat Autism Now!) doctors for autism, Dr. Amy Yasko for autism, CFS, and adult neurological disorders, freddd's protocol as described in the B12 thread on this forum,andr the Simplified Treatment Approach that I extracted from the full Yasko treatment program. The last mentioned treatment has been described on this forum, and has been found to help at least two-thirds of those who have tried it.
For people who want to find out if they have a partial methylation cycle block and glutathione depletion, the best test to get is the Vitamin Diagnostics methylation pathways panel. This should be available again soon, as the lab is completing its move to a different building, and should be back in operation soon.
I'm working to understand why the simplified treatment did not work in the other one-third, and I think I am making progress in understanding that. Some of the factors in various cases I've studied seem to be comorbid Lyme disease or mold illness, lack of enough of the cofactor vitamins and minerals for the methylation cycle and related pathways, maldigestion of protein leading to malabsorption of amino acids, which are needed by this part of the biochemistry, and in some cases the presence of KPU, as noted by Dr. Klinghardt.
I hope this is helpful, and please note that I am not financially involved with either the tests or the treatment I've suggested. Also, please note that my position is that anyone who is on treatment to lift the methylation cycle block should be monitored by a licensed physician. Even though this treatment involves only a combination of certain targeted over-the-counter nutritional supplements, there have been a small number of serious adverse effects on this treatment, most apparently due to the presence of other comorbid conditions together with CFS, in a few cases.
Best regards,
Rich