Posted by Elroy on May 19, 2005, at 21:45:06
In reply to Re: Urine Test to Measure Neurotransmitter Levels? » Elroy, posted by 4WD on May 19, 2005, at 15:33:06
OK, will try to provide sufficient detail but keep it simple enough to insure that the main points are covered.
By the way, do you have any of your actual numbers AND the reference range that your lab uses (for example, cortisol is at 276 with a reference range of 20 - 100 for normal range)???
The dex suppression test being borderline is enough evidence to raise suspicions (obviously in combination with the known high cortisol). But the dex suppression test itself does not have a high degree of absolute reliability.
The CRH test is an older test that was done to (hopefully) determine Cushings or not - and to give some degree of an indication whether or not it is pituitary related or adrenal related.
QUOTE: The differentiation between mild Cushing’s syndrome and pseudo-Cushing’s syndrome can prove extremely difficult and poses a considerable challenge to the physician. A pseudo-Cushing’s state may be defined as some or all of the clinical features that resemble true Cushing’s syndrome together with some evidence of hypercortisolism, but resolution of the underlying primary condition results in the disappearance of the Cushing’s-like state. Such findings may appear particularly in patients with depression and alcohol-induced pseudo-Cushing’s syndrome... In both Cushing’s syndrome and pseudo-Cushing’s states there is prevailing hypercortisolemia, and hence there may be almost complete overlap between groups on basal 24-h UFC collections (58). When the results seen during investigation of individuals with Cushing’s syndrome and pseudo-Cushing’s states are compared directly, a value of UFC above 100 nmol/liter on the second day of a 48-h 2 mg/day LDDST gave a specificity of 100% and a sensitivity of 56% for the diagnosis of Cushing’s syndrome, while a 48-h plasma cortisol of 38 nmol/liter or more gave a specificity of 100% and a sensitivity of 90%. In contrast, although patients with depression usually demonstrate a blunted response to the administration of CRH, there is a large overlap with the responses seen in patients with Cushing’s disease, and thus testing with this peptide does not provide good discrimination END QUOTE
A much better test is the combined Dex/CRH Test. During that test you take the dexamethasone every six hours for two days (with it scheduled so that your last dose is at midnite on day 2). Then early on the next morning you go in and have the CRH test performed. Has something like a 95% reliability rating and is better at providing indicators of pituitary versus adrenal. My doctor also had me do a 24-hour UFC (Urinary Free Cortisol) test on day 2 of the dexamethasone phase.
QUOTE: In an effort to further improve diagnostic accuracy, it has recently been suggested that improved discrimination between Cushing’s syndrome and pseudo-Cushing’s states may be achieved by using a combined test with the administration of CRH after the 48-h, 2 mg/day LDDST, with a response to CRH being seen in individuals with Cushing’s syndrome but not in those with pseudo-Cushing’s states and a mild degree of hypercortisolism (58). In this retrospective study there was complete discrimination between patients with Cushing’s syndrome and pseudo-Cushing’s states, and it has thus been recommended for this purpose (274). Although the basal UFCs showed almost total overlap between Cushing’s syndrome and pseudo-Cushing’s groups (see above), emphasizing the similar biochemical pictures seen in these groups, with postinjection of CRH 100 µg iv, a plasma cortisol value at 15 min of greater than 38 nmol/liter (1.4 µg/dl) was seen in all patients with Cushing’s syndrome, but in none with a pseudo-Cushing’s state, giving it a sensitivity and specificity of 100%. END QUOTE
The BEST test however for determining if it is actual Cushings or "Pseudo Cushings" however is actually a very simple saliva test. It is called the Late Night Salivary Cortisol Test and consists of spitting a certain amount of saliva into provided test tube between 11 PM and Midnite. Cortisol is not secreted at the same rate throughout the day. It begins declining at night (that's what makes you sleepy) and is at a lowest point around 11 PM to Midnite (and somewhat later) and then begins rising again in the morning (that's what wakes you up). That cycle is called the circadian rhythm. People with "regular" Cushings no longer have that circadian rhythm as the offending tumor is "forcing" the excess production of the cortisol at all times. If your levels are definitely within the normal range (not "borderline" or especially not elevated) then there is an excellent chance that you are NOT a regular Cushings.
Here's a link with some better explanation (would print it out and take it to your doctor... btw, Dr. Friedman is considered THE guru of Cushings specialists).
http://www.goodhormonehealth.com/symptoms/pseudocush.pdf
I would NOT take any anti cortisol supps (OTC or otherwise) at any time during the time period of any of this type of testing. If you have real Cushings, the positive effect of OTC anti cortisol products would be very minimal (as they cannot overcome the power of the offending tumor)... BUT, if you are borderline, well, one would not want to do anything that would cause a positive result to end up "borderline".
Cushings is a very serious disorder and one needs to find out absolutely for sure whether or not one in fact has it or not (many doctors unfortunately will try to diagnose it simply by "visual symptoms"... so if you have highly elevated cortisol and a borderline dex suppression test, but don't have the major "usual" visual symptoms, then they declare that you're not Cushings and let it go at that... where in fact Cushings has numerous symptoms and many people do not have the "usual" visual symptoms but in fact ARE Cushings!).
That said, both depression (especially the type more often refered to as "psychotic depression") and anxiety very definitely cause elevated cortisol levels... and elevated cortisol causes increased anxiety and / or depression. Vicious cycle. Also, is very obvious in people who have become treatment resistant.
BTW, there is some clinical information out there that Prozac (and other SSRI meds) actually INCREASES cortisol levels (thereby worsening the situation*). I know that most people go nuts at the idea of benzos, but my psychiatrist put me on Ativan last October (my current problem actually only started last June!), and when that wasn't sufficient she replaced it with Xanax XR (the extended release version), at a low level (1mg twice a day) probably around early December. In addition, she put me on first Ambien and then Restoril as a sleep aid. Usually I would use the Ambien put if I had an especially tough evening, then I would opt to take the Restoril (Actually, now I often can even go without either one and just use Melatonin and Valerain). My main sleep problem currently is that I get up (without fail) between 3:30 and 4:30 AM and frequently have a problem getting back to sleep then... guess what, that's when the cortisol levels are starting to climb up again). In my case, I definitely have the correct circadian rhythm, but when my levels start climbing, they obviously quickly start shooting up above normal which results in that inability to get back to sleep. Anyway, my point is that you might want to talk to your doc - either a psych doc on endo -about getting you on something specifically for the anxiety. I truly believe that the Xanax XR "saved my life" in that the anxiety levels had climbed that tremendously!
See: http://www.remedyfind.com/HC-Anxiety.asp
http://www.remedyfind.com/all_remedies.asp?id=85BTW, have you had any similar - or otherwise related - physical symptoms?
* QUOTE: Studies at the University of Colorado and Greenslopes Private Hospital in Brisbane, Australia, showed that Prozac (fluoxetine) increases both cortisol and ACTH levels... Research at the Vanderbilt University School of Medicine in Nashville, Tennessee, also documented the cortisol-boosting effects of Prozac. .. Laudenslager ML, Clarke AS. Antidepressant treatment during social challenge prior to 1 year of age affects immune and endocrine responses in adult macaques. Psychiatry Res. 2000 Jul 24;95(1):25-34... Torpy DJ et al. Diurnal effects of fluoxetine and naloxone on the human hypothalamic-pituitary-adrenal axis. Clin Exp Pharmacol Physiol. 1997 June; 24 (6):421-3
http://members.aol.com/atracyphd/
http://health-essentials.info/science/health-issues/ssri01.htmlI have even read some information that indicates 5HTP (and tryptophan?) might cause increases in cortisol... and hope that someone like Larry Hoover might have some further information on that.... (that would be very unfortunate as tryptophan/5HTP are highly touted natural anti-anxiety supps).
http://www.earthtym.net/ref-serotonin.htm
http://www.rdc.ab.ca/scottpsych/website/student/herbal.htm
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15202683I know that elevated cortisol has a strong effect on the utilization of tryptophan and believe that 5htp - if it in fact does NOT increase cortisol - might be a better choice than tryptophan....
QUOTE: Why should I consider 5-HTP supplementation?
All serotonin used by brain cells must be made within the neurons, since serotonin cannot cross the blood-brain barrier. Therefore, the synthesis of serotonin is heavily dependent upon the availability of L-tryptophan within the CNS. The production and transport of L-Tryptophan from the bloodstream into the CNS can be compromised by several factors including ostress, elevated cortisol levels, vitamin B6 deficiency, and even high dosages (above 2,000 mg) of L-Tryptophan, which all stimulate the conversion of L-Tryptophan to kynurenine, lowering serum tryptophan levels.1-3o END QUOTEhttp://www.millnut.com/L5HTP.shtml
http://www.smart-drugs.net/ias-tryptophan-article.htmWell, getting way off topic here.
I'm going to go out on a limb here - while insisting that proper follow-up testing be conducted - and offer my opinion. I believe that you will test out as non Cushings - or more technically correct as "Pseudo Cushings".
I suggest that as you make the following statement: "... have also begun to have uncontrollable fear or terror in the mornings upon waking. It lasts most of the day and goes away spontaneously at night." That shouldn't be the case with "real" Cushings (though maybe it's an early onset - which is why one should have the testing!).
That SUGGESTS to me that your cortisol levels are following the normal rhythm pattern of declining at night and then rising significantly in the morning (and staying high through the day before once again declining at night).
Sounds very, very familiar to me!
Please keep updated as to testing done and results of same.... in addition to testing for Cushings, it might be of interest to have tests done for a Pheo tumor. While quite rare (a tumor inside an adrenal gland), Pheo tumors are notorious for producing anxiety. Generally those are accompanied (tho not always) by very high blood pressure. You mentioned "Metanephrines were normal although normetanephrine was high normal"... that sounds like it may have come from a test for checking the possibility of a Pheo tumor. Do you know if that was the case? I "believe" that in the case of a Pheo tumor that your Metanephrine would be highly elevated....
ElroyX
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> This is fascinating to me. I also have highly elevated cortisol levels (along with a small pituitary tumor). My dexamethasone suppression test was "borderline." Metanephrines were normal although normetanephrine was high normal.
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> My next test is the corticotropin releasing hormone deal where you get injected with a drug and then blood is drawn periodically afterward. I believe this is supposed to rule out Cushings?
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> The reason this is so important to me is that my formerly treatable depression has become treatment resistant in the last few years. I have also begun to have uncontrollable fear or terror in the mornings upon waking. It lasts most of the day and goes away spontaneously at night.
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> My endoc. doesn't think the tumor is causing the problems but obviously something is going on. I don't know what other tests to ask for - I need to know what tests might conclusively reveal an endocrine problem causing depression/anxiety. I thought of just asking him to test for anything that could possibly be causing this but they tend to take you more seriously if you are well informed when you go in.
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> Any advice would be much appreciated.
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> Marsha
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poster:Elroy
thread:493827
URL: http://www.dr-bob.org/babble/20050516/msgs/500134.html