Help needed interpreting elevated ACTH. Related to methylation issues?

[seadanc]

Hello all

Ive been watching this section of the forums for a while curious whether my CFS symptoms may be related to methylation issues and trying to learn (on a very simplified level) the biochemistry involved. Unfortunately gaps in my education and brain fog are proving to be major hurdles.

Ive only recently started to work with a CFS aware doctor who ordered a number of new tests. Im struggling a bit to interpret the results and Richs recent post referencing ACTH and pituitary really piqued my interest. Among my results are high IGF-1 and ACTH levels. I believe some of the other results may point toward methylation issues but I was assuming that the ACTH level was unrelated. Ive been referred to an endocrinologist for investigation of a possible pituitary tumor but it is fascinating to learn that there is a relationship between ACTH levels and methylation problems / glutathione depletion. Any insight Rich or others can provide on the results below would be hugely appreciated!

These results were either out of range or might be related to methylation problems...

MTHFR homozygous C677TT
IGF-1, 292 (94 252)
ACTH, 191.7 (7.2 63.3)
Homocysteine, 13.4 (0.0 15.0)
Thrombin Antithrombin Complex, 12.3 (high no range given)
B-12, 375 (211 946)
Folate RBC, 400 (468 1258)
IgG Subclass 1, 632 (700 1600)
IgG Subclass 2, 376 (422 1292)

Thank you to all for the time and energy devoted to making these forums such an amazing resource. Happy holidays! Dan C

 

[richvank]

Hi, Dan.

Have you been diagnosed as having ME/CFS? The reason I ask is that high IGF-1 and high ACTH are not usually found in ME/CFS. You may indeed have a methylation issue, but I'm glad you are being checked for a pituitary tumor. Usually ACTH is somewhat low and not properly regulated, and usually IGF-1 is normal in ME/CFS. To test for a partial methylation cycle block, it's best to take the Health Diagnostics and Research Institute methylation pathways panel. You do have high-normal homocysteine, which could be due to a partial block of methionine synthase, or due to low flow down the transsulfuration pathway, or both. The MTHFR polymorphism will make it more difficult for your cells to produce methylfolate. Your blood serum B12 is low-normal, which suggests that you have a low absolute B12 status. Measuring urine methylmalonate is a more sensitive indicator for a functional B12 deficiency. Low red blood cell folate suggests oxidative stress damage to the cell membranes. I agree that checking for a pituitary tumor is a good idea. I hope the endocrinologist is able to help you.

Best regards,

Rich

 

[seadanc]

Hi Rich -

Thanks so much for your reply! I have indeed been diagnosed with ME/CFS. I meet the criteria quite nicely - thank you very much . I have had symptoms for 20+ years. I do fall under the "wired and tired" subset. I wonder if the elevated ACTH is a contributor there. Cortisol levels are normal though.

The doctor I'm working with has been unwilling to order the methylation pathways panel (although she has a copy of your study with Dr. Nathan on her desk). She believes that the existence of the homozygous MTHFR polymorphism is enough to have me start the methylation protocol. I will revisit the idea of running the panel.

Regarding the ACTH level - I'm still trying to understand the relationship with the methylation cycle. I see your quote from a recent thread,

"As you probably know, I have suggested that in ME/CFS this is usually due to abnormal secretion of ACTH, because of glutathione depletion in the pituitary. If your glutathione is depleted, and you are able to bring it up by lifting the partial methylation cycle block, your diurnal cortisol variation should become more normal."

So...Is the relationship such that, all other things being equal, low glutathione from a partial methylation cycle block would reduce ACTH? In my case then, either I don't have low glutathione or I have another factor (i.e. pituitary tumor) offsetting?

Lastly, with the possibility of a pituitary tumor (even though likely benign) is there a worry that taking folinic acid or methylfolate would provoke tumor growth?

Thanks again!!! Dan

 

[richvank]

Hi, Dan.

O.K., so you do have ME/CFS. Then it does seem that something else must be going on. After 20 years, I would expect that the HPA axis would be at least "blunted," as the literature describes it. In other words, in ME/CFS it usually does not respond normally. ACTH is usually somewhat low and also does not have its usual diurnal regulation, and that usually causes cortisol to have an abnormal diurnal variation, also. Have you had a 24-hour saliva cortisol test, or just a one-time-only cortisol measurement, such as in the morning?

The advantage of running the methylation pathways panel is that it not only gives you concrete data to evaluate your methylation cycle, folate metabolism and glutathione, but it also gives you baseline data for comparison later, if you do go onto a methylation protocol, so you can gauge progress on the treatment. Symptoms alone are not always a good guide, because they can be a little rocky at first, even though good things are happening for the long run.

There is always the possibility that my hypotheses are invalid, and there is also the possibility that they will not apply to a particular case, but yes, I have suggested that glutathione depletion in ME/CFS causes the hypothalamus and the pituitary to go low in glutathione, and that affects their ability to produce certain hormones at normal levels and with normal regulation. In the case of ACTH, my hypothesis predicts that it will be low, and that it will not be secreted with normal regulation. So yes, I suspect that something else is going on in your case. A pituitary tumor would cause increased secretion of one or more pituitary hormones, depending on the cell type in the tumor.

There are some published papers that indicate that folate plays a role in at least some types of pituitary tumors, so I think it would be wise to check out the possibility of a tumor before supplementing this.

Best regards,

Rich

 

[seadanc]

Hi Rich -

I have had a 24 hour saliva cortisol test (although it was a number of months before the recent ACTH test) which came back within the normal range for each collection time. Not quite understanding the HPA axis I would have guessed that (in a healthy individual) the high ACTH would result in high cortisol levels. Maybe my cortisol would be blunted if not for the elevated ACTH and will fall when the ACTH is brought under control?

Anyway... sounds like step one is pituitary investigation and then on to methylation issues.

Best regards and happy holidays!

Dan