JenniferJuniper

Thanks for posting this! I've been diagnosed with PCOS, but I believe there is something else that's causing my symptoms... it's very possible that this is it. I've been tested for an 11-hydroxylase deficiency (test was normal), but I don't think that's related to 11beta-Hydroxysteroid Dehydrogenase, so I will definitely ask about testing for this. I find this part interesting: Circulating glucocorticoid levels are not elevated in persons with the metabolic syndrome; however, could it be possible that the corticosteroid action occurs at a local level, giving rise to the effects of excess glucocorticoid receptor stimulation in a tissue-restricted manner without elevating plasma levels of glucocorticoids? To paraphrase (from a completely layman's perspective, of course), I think this means one can have the effect of excess cortisol, but not have this excess show up in blood tests. I don't understand what is meant by "tissue-restricted manner"... I assume that such an effect would also not be picked up in a urine test? In any case, they present this as a question, so I don't know whether this has progressed any further than the hypothesis stage. (Side note... just read a bit more and I think the "tissue-restricted manner" they refer to has to do with the liver and adipose tissues. Click here for more about adipose tissues.) I also thought this was interesting: Overexpression of 11beta-HSD1 in the liver resulted in transgenic mice that had fatty livers and elevations in serum cholesterol and triglycerides, but only mild insulin resistance (normal glucose tolerance with mildly elevated plasma insulin levels). Interestingly, these mice developed hypertension, a key component of the metabolic syndrome. The mechanism likely to be responsible for the development of hypertension is increased intrahepatocyte glucocorticoid activity, which leads to increased expression of the angiotensinogen gene, which would upregulate the activity of the angiotensin-aldosterone system. Personally, I believe my insulin is fairly mild, considering I've been on Metformin since December 2005 and haven't seen much of an effect (other than the "Metformin's Revenge" side-effects, which I won't go into at this point as I don't want to gross anyone out!). I have suffered from mild hypertension (usually in the 140/80 range, though it can go higher and lately has been just fine), but my serum cholesterol and triglycerides are actually quite LOW (my last total cholesterol was 136... it has been lower. The range for the test was 140-200). I'm going to look into the "intrahepatocyte glucocorticoid activity" part... not sure what that means, but "hepatic" has to do with the liver, so I guess it has something to do with cortisol activity in the liver? Other stuff... I have had hypokalemia (low potassium) in the past, but it was fine this last round of tests. Therefore, the section titled "From Curiosity to Central Player" could apply, especially the following: ...11beta-HSD2 normally converts cortisol to its biologically inactive congener cortisone in the kidney and placenta, thus protecting the mineralocorticoid receptor in renal tubules from excess stimulation by cortisol. (The mineralocorticoid receptor can be activated by glucocorticoids as well.) With a nonfunctional 11beta-HSD2 enzyme, patients with the mutation or consumers of potent licorice had excess stimulation of mineralocorticoid receptors by glucocorticoids, resulting in a syndrome of "apparent mineralocorticoid excess (AME)." I wonder if excess cortisol stimulating the renal tubules could cause kidney stones? I know kidney stones are often part of Cushing's, so this makes sense. My stones didn't present themselves until after I began to gain weight, experience fatigue, etc... anyway, kind of an interesting point. All in all, definitely something to check out if your symptoms don't seem to line up with the "classic" symptoms of Cushing's. Will let y'all know if I manage to get myself tested for this... Jennifer