Organic acids, Amino acids, and Cortisol results

[Gavman]

Coming off effexor, ive been on b6, zinc and sam-e and thats working well. About to drop it completely as i've halved it the past two months.

From what i can assess, effexor is a noradrenaline inhibitor and ssri, so you'd find people respond to it well. The more anxiety you'd experience, the more adrenaline would pump through. I'd also be looking at pyroluria like hixxy.

 

[cureminded]

I got the rest of my results today, for the neurotransmitters:



No idea what this mean in the context of the other results. It does show a cause of my OI though.

Hi Valentijn,

I called the ELN yesterday, but they said they couldn't tell me a name of a doctor who will order these tests for me. Could you please advise which doctor did this for you? I found one in Zoetermeer who works with the ELN, but she seems to be very expensive. Did you get any of these tests reimbursed?

Thanks

 

[Valentijn]

I asked my naturopath back in Seattle to do it. No reimbursements are possible, since I was going outside of the normal health care. Theoretically any doctor can order it, but I have no idea how that is impacted by insurance regulations in the Netherlands.

 

[Valentijn]

Here's more results, fresh from the lab: cortisol curve, ANA, thyroid, adrenal, urine amino acids, and IgG and IgE food allergies.

I was on a full regimen of vitamins and supplements at the time, which definitely affected the urine amino acid results. I was taking: NAC, Theanine, GABA, Carnitine, Tyrosine, ALA, Q10, Magnesium, Rhodiola, Selenium, Fish oil, Multivitamin, extra C, extra B complex, extra D3, and extra B12.

They messed up and ran the basic blood stuff and blood elements instead of blood platelet neurotransmitters But interesting results anyhow. The new results are in the left two columns, on the stuff in the right columns is from 5 months ago. Still waiting for reverse T3, vasopressin, and angiotensin II.

Any thoughts?

 

[Valentijn]

Well, after a ton of googling I think I have a few ideas.

First of all, the unbalanced elements in the blood. My values are generally low in blood cells and high in blood serum. In the case of copper, at least, this can be explained by inflammation, which I have a ton of. Solution: get less inflamed.

Cortisol has gone from borderline to pretty bad in the past 5 months. I still sleep pretty normally, aside from sometimes napping in midday. I have no idea what controls cortisol. DHEA-S is also at the low end of normal. Again, no idea what that is or what causes it.

Some of my amino acids are high from supplementing 1800mg of NAC per day. That supplementation is probably directly affecting cysteine, homocysteine, methionine, and taurine.

A lot of amino acids that could/should be feeding into the Krebs Cycle after turning into other substances are high: valine, glutamate, isoleucine, and beta-aminoisobutyrate . Maybe high due to my Krebs Cycle being unable function well enough to do anything with them? Also, some of these elevated amino acids are formed from glutamate in various ways: proline, hydroxyproline, aspartate, and beta-alanine. My only low amino acid is GABA, which can turn into glutamate.

I think the high phosphoserine, phosphoethanolamine, leucine, and ethanolamine could be related to cell break down.

Elevated 1-Methylhistidine and 3-Methylhistidine are both related to protein break down. 3-methylhistidine is elevated from breaking down my own muscles, and 1-Methylhistidine probably is as well, since I was eating a normal amount of protein.

I'm hoping I can figure out why so many things relating to glutamate are so off. The NAC I take should be reducing glutamate (and it's lower than it was last year), but it's still way too high. One possibility is that I have issues with alpha-ketoglutarate, which might prevent glutamate and isoleucine turning into useful things. Also, alpha-ketoglutarate reduces ammonia toxicity, reduces nitrogen levels, and helps form antibiotics - so maybe one of those functions is draining my supply of alpha-ketoglutarate.

An ANA level of 194 (presumably 1:194 titer value), means I may have an autoimmune disease. More testing is needed to determine which one, and treating that might help with other issues. I should probably try to see a rheumatologist for that.

 

[Ema]

You've got some great testing here!

First, you need to know whether any particular mineral should be higher in the serum or in the cell. For example, sodium should be higher in the serum and low in the cell normally and potassium vice versa due to the way the sodium potassium ATP pump works.

I can't help much with the AA portion unfortunately but a few things did jump out at me wrt your hormone profiles.

You are still getting a strong burst of cortisol in the morning which is good but are dropping too low now through the rest of the day and the evening. This looks more to me like HPA axis dysregulation as opposed to autoimmune adrenal destruction. But an easy way to rule this in/out given your high ANA would be to test for adrenal antibodies (21-hydroxylase) at any Labcorp.

Cortisol is ultimately controlled by the hypothalamus in the brain. DHEA is also an adrenal hormone that is considered a "mother" hormone because it can convert to many other hormones, particularly the sex hormones. DHEA may also have effects on the immune system and in the brain may be neuroprotective. I think it is a good idea to replace DHEA when it is low and that may also help modulate your cortisol levels.

I don't think the rhodiola is doing enough for your adrenals at this point. I would talk to your doctor about possibly adding licorice or grapefruit to keep the cortisol from breaking down so fast at noon and into the evening. It's also possible that adding something like Isocort (adrenal CORTEX only; not whole glandular) at noon and midday could help with your energy levels.

Have you tested cholesterol to make sure that you have enough raw materials to make all these hormones in the first place? Most people are focused on levels being too high but they can also be too low. Generally under 150 total cholesterol is considered too low.

I would consider your thyroid levels low. FT3 is generally best in the top third of the range and FT4 at about 50% of the range. Even the very conservative AACE considers a TSH of 2.5 to be a better top of the range limit and you are nearly there. Most functional med doctors like to see TSH between 1-2 and then realize that it is not useful at all for measuring treatment status after replacement has started.

Here is a good website on subclinical hypothyroidism:

http://nahypothyroidism.org/

I would also consider your aldosterone level low though I'm not sure when the blood was drawn to say for sure. Aldosterone levels drawn at 8AM fasting should be about mid-range or higher. Levels lower than that almost always need to be treated for OI symptoms. Licorice or Florinef are options though I seem to recall you saying that you had tried Florinef in the past with less than optimal results.

The higher serum potassium and lower cellular potassium also point to a deficiency in aldosterone. Cellular potassium is generally best at about 70-90% of the range.

Magnesium also still looks low. I might think about changing or adding forms (like taking Epsom salt baths or using the transdermal spray) along with oral supplementation.

Additional zinc may help to improve you zinc/copper ratio and lower the copper level.

Do you have blood sugar regulation problems/insulin resistance?

You might also look at specific herbs like turmeric or incorporating krill oil (astaxanthin) or other anti-inflammatory products in addition to the general vitamins and minerals. Inflammatory cytokines can affect the hypothalamus and cause dysregulation in the endocrine system.

 

[Valentijn]

You've got some great testing here!

First, you need to know whether any particular mineral should be higher in the serum or in the cell. For example, sodium should be higher in the serum and low in the cell normally and potassium vice versa due to the way the sodium potassium ATP pump works

Good suggestion ... I still need to look into that one

You are still getting a strong burst of cortisol in the morning which is good but are dropping too low now through the rest of the day and the evening. This looks more to me like HPA axis dysregulation as opposed to autoimmune adrenal destruction. But an easy way to rule this in/out given your high ANA would be to test for adrenal antibodies (21-hydroxylase) at any Labcorp.

Yeah, I'm planning to get plenty of autoimmune testing, one way or another!

Cortisol is ultimately controlled by the hypothalamus in the brain. DHEA is also an adrenal hormone that is considered a "mother" hormone because it can convert to many other hormones, particularly the sex hormones. DHEA may also have effects on the immune system and in the brain may be neuroprotective. I think it is a good idea to replace DHEA when it is low and that may also help modulate your cortisol levels.

Ah, so that's what DHEA does Also, my DHEA was tested when fasting in the morning, if that makes any difference.

I don't think the rhodiola is doing enough for your adrenals at this point. I would talk to your doctor about possibly adding licorice or grapefruit to keep the cortisol from breaking down so fast at noon and into the evening. It's also possible that adding something like Isocort (adrenal CORTEX only; not whole glandular) at noon and midday could help with your energy levels.

I've tried licorice in the past, without any results ... but I wasn't taking Rhodiola at the same time. Could be worth a try.

Have you tested cholesterol to make sure that you have enough raw materials to make all these hormones in the first place? Most people are focused on levels being too high but they can also be too low. Generally under 150 total cholesterol is considered too low.

My cholesterol was right in the middle of normal when I first got diagnosed, and has since got a bit above normal, and then down to barely above normal. A nurse tried to prescribe me a statin for it

I would consider your thyroid levels low. FT3 is generally best in the top third of the range and FT4 at about 50% of the range. Even the very conservative AACE considers a TSH of 2.5 to be a better top of the range limit and you are nearly there. Most functional med doctors like to see TSH between 1-2 and then realize that it is not useful at all for measuring treatment status after replacement has started.

I'll look into that more too. I also have a reverse-T3 result coming back soon, so maybe that'll help shed light on things as well.

I would also consider your aldosterone level low though I'm not sure when the blood was drawn to say for sure. Aldosterone levels drawn at 8AM fasting should be about mid-range or higher. Levels lower than that almost always need to be treated for OI symptoms. Licorice or Florinef are options though I seem to recall you saying that you had tried Florinef in the past with less than optimal results.

It was drawn at 9am and fasting. It's one I asked for to look into the OI problems more, and thought normal meant normal, so it's good to know that a lowish value might be problematic depending on the circumstances. I haven't tried Florinef or anything prescribed ... I'm still fighting to get my OI diagnosed. Fortunately I finally got an appointment at an orthostatic hypotension clinic at the Academic Medical Center in Amsterdam, on December 5th.

The higher serum potassium and lower cellular potassium also point to a deficiency in aldosterone. Cellular potassium is generally best at about 70-90% of the range.

Magnesium also still looks low. I might think about changing or adding forms (like taking Epsom salt baths or using the transdermal spray) along with oral supplementation.

Additional zinc may help to improve you zinc/copper ratio and lower the copper level.

Thanks, I haven't been able to look into those yet. I wasn't sure about the zinc, since it's fairly normal itself, and it's copper that's being super wonky. But if the zinc helps sort the copper that does make sense, especially since zinc is low-normal in the serum where everything else is elevated.

Do you have blood sugar regulation problems/insulin resistance?

Nope, my glucose is always normal, except when I've gone a bit hypoglycemic a couple times when not eating recently enough.

You might also look at specific herbs like turmeric or incorporating krill oil (astaxanthin) or other anti-inflammatory products in addition to the general vitamins and minerals. Inflammatory cytokines can affect the hypothalamus and cause dysregulation in the endocrine system.

I usually do 3 grams of fish oil per day, and am doing 6 the past couple days to hopefully help with all the extra swelling I'm having. I think that's the same effect as krill oil, just from a different source?

Thanks for the suggestions, very helpful

 

[Ema]

Yeah, I'm planning to get plenty of autoimmune testing, one way or another!

I just listened to an interesting podcast on the autoimmune testing now available through Cyrex labs. Some of the panels have to do with celiac but there is an array that tests for antibodies to just about every part of the brain and endocrine system.

http://www.blogtalkradio.com/underg...tecting-autoimmunity-early-w-dr-thomas-obryan

http://www.cyrexlabs.com/

Ah, so that's what DHEA does Also, my DHEA was tested when fasting in the morning, if that makes any difference.

I don't think it makes a difference with DHEA when it is tested but it does peak in the AM. So your low value was probably the max of what you are able to make.

I resisted taking DHEA for a while because I had taken it a long time ago without noticing any results. I read a lot about it though and am glad that I ended up adding it back in. I do think it makes a difference to take the micronized (or lipid matrix) form. I would also start with a low dose and work your way up. I don't think women should take more than 25 mg/day without bloodwork showing that more is really necessary. I shoot for about 150 on a DHEA-S blood test. It takes 20 mg/day for me to get to that level.

I've tried licorice in the past, without any results ... but I wasn't taking Rhodiola at the same time. Could be worth a try.

It could be worth a try. This is the one I took. It also contains ashwagandha and rehmannia which are other adrenal adaptogens.

http://www.metagenics.com/products/a-z-products-list/Licorice-Plus

Here is my favorite article on how licorice works:

http://drholly.typepad.com/licorice/

My cholesterol was right in the middle of normal when I first got diagnosed, and has since got a bit above normal, and then down to barely above normal. A nurse tried to prescribe me a statin for it

I'm so glad you knew better! Oh, that just makes me crazy...if it is low now, you may wish to look into pregnenolone. That is the other "mother" hormone along with DHEA.

I'll look into that more too. I also have a reverse-T3 result coming back soon, so maybe that'll help shed light on things as well.

I'd be so surprised if your RT3 isn't high. Let me know if you need help calculating your ratio. I have an Excel spreadsheet that converts the units automatically!

It was drawn at 9am and fasting. It's one I asked for to look into the OI problems more, and thought normal meant normal, so it's good to know that a lowish value might be problematic depending on the circumstances. I haven't tried Florinef or anything prescribed ... I'm still fighting to get my OI diagnosed. Fortunately I finally got an appointment at an orthostatic hypotension clinic at the Academic Medical Center in Amsterdam, on December 5th.

Salt also suppresses aldosterone so if you had a lot of salt the day before, that could also influence the results. But either way, if you haven't tried Florinef, I hope they will agree to give you a trial. It changed my life. I could hardly get upright before Florinef.

I ended up needing a fairly hefty dose of Florinef and did quite a bit of reading on the topic, especially through the posts of people on a POTS forum. It turns out that most people with HPA dysfunction need much higher doses of Florinef (up to .4 mg a day is not uncommon) whereas most people with Addison's only need about .05-.1 mg. It has to do with aldosterone resistance, they think. So my .2 mg is not actually a crazy dose and may in fact be more typical than those on primarily Addison's forums may think. And renin may not be the best measure of Florinef dosing for those with HPA dysregulation either. It may be best to titrate Florinef based on electrolytes and BP for the most part.

I also learned that renin can be suppressed by high 1,25 Vit D levels. And this can cause low aldosterone. This is a problem because many of us are taking high doses of Vit D based on our 25-OH Vit D levels. But unfortunately, inflammatory illness can cause problems with the Vit D receptor and the active 1,25 levels can spiral out of control. This actually causes an immunosuppressive state even while the storage Vit D level looks "optimal". It seems like a real problem especially given how much doctors are giving out high doses of Vit D supplements these days.

http://arizonaadvancedmedicine.com/articles/immune_system_dysfunction.html

Nope, my glucose is always normal, except when I've gone a bit hypoglycemic a couple times when not eating recently enough.

Normal according to lab tests or optimal meaning between 75-85 fasting, never spiking above 140 and back down to fasting levels by 2 hours post-prandial?

Have you tested fasting insulin or leptin?

I usually do 3 grams of fish oil per day, and am doing 6 the past couple days to hopefully help with all the extra swelling I'm having. I think that's the same effect as krill oil, just from a different source?

Fish oil is good (though Dr Jack Kruse has some different opinions here that are very interesting and worth considering).

http://jackkruse.com/is-fish-oil-good-or-bad/

But the krill oil contains astaxanthin which fish oil does not and that is the anti-inflammatory agent.

From Dr Eades blog:

"The phospholipid structure of the EPA and DHA in krill oil makes them much more absorbable and allows for a much easier entrance into the mitochondria and the cellular nucleus. In addition to EPA and DHA krill oil contains a complex phospholipid profile including phosphatidylcholine, a potent source of reductive-stress-reducing choline, which also acts as a natural emulsifier."

http://www.proteinpower.com/drmike/inflammation/why-krill-oil/

I hope the swelling goes down soon! Is the elimination diet helping at all?

Ema

 

[Ema]

Yeah, I'm planning to get plenty of autoimmune testing, one way or another!

I also meant to ask if you had had thyroid antibodies tested? Specifically TgAB and TPO-AB?

Hashimoto's thyroiditis can also cause a high ANA.

http://www.stopthethyroidmadness.com/hashimotos/

 

[Valentijn]

I also meant to ask if you had had thyroid antibodies tested? Specifically TgAB and TPO-AB?

Hashimoto's thyroiditis can also cause a high ANA.

Nope, not yet. When I got diagnosed, very very little was tested. It's pretty shocking actually, how little was ruled out. My US Naturopathic Doctor wanted some things tested, and I asked to throw in the ANA and a couple other things, which he thought was a good idea.

I'll probably just get it done in the US, where I have a fully cooperative doctor, thought I might wait til I'm back in the Netherlands to see if I can get a specialist there to take me seriously - not something I've had much luck with thus far. But one way or the other, I am going to insist on getting tested for every potentially relevant autoimmune disease

Salt also suppresses aldosterone so if you had a lot of salt the day before, that could also influence the results. But either way, if you haven't tried Florinef, I hope they will agree to give you a trial. It changed my life. I could hardly get upright before Florinef.

I generally avoid salt leading up to any testing, since I want results at my worst

Normal according to lab tests or optimal meaning between 75-85 fasting, never spiking above 140 and back down to fasting levels by 2 hours post-prandial?

Have you tested fasting insulin or leptin?

A few random glucose tests, and a couple fasting. I also check it with my fiance's spare glucose meter at various times, and it's never been high. Insulin and Leptin haven't been tested - I'm assuming those would indicate problems with carbohydrate and fat metabolism?

I hope the swelling goes down soon! Is the elimination diet helping at all?

It's helping a little bit. Still more swollen than usual though. One thing I'm noticing is that it goes down overnight, then increases during the day. Either reacting to food still, or maybe there's an orthostatic component to the swelling. Maybe I'll try laying down most of the day tomorrow to see what happens.

 

[Valentijn]

As a brief update, I saw my naturopathic doctor yesterday in person, though some of my results STILL aren't in from ELN (after 5 weeks!). He gave me a B12 and folate shot, since he thinks my serotonin precursor issues may be gut related, and I'm not absorbing things well. Also he had me get blood drawn for retesting ANA (with pattern), and ESR, and added the tests for the Q-fever and Lyme bacterias (western blot I think).

No supplements added to my regular bunch (multi, b-complex, b12, magnesium, fish oil, NAC), since the full regimen he had me try didn't result in any improvements on my amino acids, cortisol, etc tests. I am going to be doing a proper elimination diet again though, but my foods are already so restricted that I don't think I'll notice a difference He checked my BP a bit, lying, sitting, and standing, and my Pulse Pressure did get a bit narrow (under 30), though he only tested 4-5 times in 5 minutes or so.

I also spoke to him about Strattera, which some people here have had great results with for their OI. He suggested Effexor, but said Strattera would be fine if that's what I want (he knew I'd researched it thoroughly). I told him I thought Effexor would be a problem for some reason, but couldn't remember what it was - getting home I realized it's an SNRI, not an NRI, and I had a bad reaction to an SSRI in the past, and to any supplements affecting serotonin. So he prescribed the Effexor for my "anxiety symptoms" for a two week trial.

I go back in two weeks for another B12/folate shot, and to see how the Strattera is affecting me and getting a refill if it's working out. By then I should have the rest of my ELN lab results, and maybe from the new blood tests as well.

 

[Crux]

Hi Valentijn;

I noticed that your MCV is low...
I've read that it may occur with low iron. Have you had ferritin measured ? Apparently, there can be low iron stores even when hemoglobin is in normal range.

The OI symptom may be related to low iron, even though the terms, dizziness and lightheadedness, are used more often.

 

[Valentijn]

Hi Valentijn;

I noticed that your MCV is low...
I've read that it may occur with low iron. Have you had ferritin measured ? Apparently, there can be low iron stores even when hemoglobin is in normal range.

The OI symptom may be related to low iron, even though the terms, dizziness and lightheadedness, are used more often.

Iron has been measured and was "great". This blood sample was taken right after my period, which can influence that result. Ferritin hasn't been measured.

 

[aquariusgirl]

i think christine was right about copper.. it's being stockpiled somewhere cos of lack of carrier proteins....

 

[Valentijn]

I got the rest of my results, minus the blood platelet catecholamines because the lab messed up

Reversed T3 83 pmol/24h (46 - 130) - 1800mL 24 hour volume = 46.1 pmol/L?
Free T3 4.67 pmol/l (4.00 - 7.85)
Free T4 15.4 pmol/l (10.3 - 24.5)
TSH 2.250 mIU/l (0.400 - 4.000)
 
Vassopressin 3.7 pg/ml (0.0 - 4.5)
Angiotensin II 41.2 pg/ml (15.0 - 67.0)
Aldosterone 382 pmol/l (110 - 860)
DHEA-S 3 μg/l (3 - 10)
Morning cortisol 25 nmol/l (13 - 24)
Noon cortisol 2 nmol/l (5 - 10)
Afternoon cortisol 2 nmol/l (3 - 8)
Midnight cortisol 1 nmol/l (1 - 4)
Cortisol Burden 30 - (23 - 42)

So none of the new values (vasopressin, angiotensin II, reverse T3) are out of range. Though it looks like my free T3 to reverse T3 ratio might be low.

 

[Ema]

Reversed T3 83 pmol/24h (46 - 130) - 1800mL 24 hour volume = 46.1 pmol/L?
Free T3 4.67 pmol/l (4.00 - 7.85)
Free T4 15.4 pmol/l (10.3 - 24.5)
TSH 2.250 mIU/l (0.400 - 4.000)
 
Vassopressin 3.7 pg/ml (0.0 - 4.5)
Angiotensin II 41.2 pg/ml (15.0 - 67.0)
Aldosterone 382 pmol/l (110 - 860)
DHEA-S 3 μg/l (3 - 10)
Morning cortisol 25 nmol/l (13 - 24)
Noon cortisol 2 nmol/l (5 - 10)
Afternoon cortisol 2 nmol/l (3 - 8)
Midnight cortisol 1 nmol/l (1 - 4)
Cortisol Burden 30 - (23 - 42)

So none of the new values (vasopressin, angiotensin II, reverse T3) are out of range. Though it looks like my free T3 to reverse T3 ratio might be low.

How are you calculating pmol/L for RT3? If 46.1 pmol/L is correct, then your FT3/RT3 ratio would be about 100. This seems unlikely given how low the rest of your thyroid values are. Ft3 should be in the top third of the range and FT4 at about 60% give or take.

Those are the old aldosterone/cortisol/DHEA-s results, right?

 

[heapsreal]

Cortisol is definately dropping off, look into pregnenolone cream which can help both cortisol and dhea, many still add dhea even if they use pregenolone but need testing to confirm it. ASnother thing that can help the ladies with low cortisol is progesterone cream, not only can it help with sleep and anxiety but body can use it to make cortisol??
U would want dhea to be higher if u can.

 

[Valentijn]

How are you calculating pmol/L for RT3? If 46.1 pmol/L is correct, then your FT3/RT3 ratio would be about 100. This seems unlikely given how low the rest of your thyroid values are. Ft3 should be in the top third of the range and FT4 at about 60% give or take.

Those are the old aldosterone/cortisol/DHEA-s results, right?

The results say the amount is for 24 hours, not per liter, and there was 1.8 liters in the 24 hour urine. So I divided the amount by 1.8 to get pmol/L. The calculators I looked at online said the ratio was about 10, which is a little weird because it doesn't match up with the formulas they say they're using.

Yeah, those are the aldosterone/cortisol/DHEA from a few weeks ago. I just relisted them to put the new results in context.

 

[Ema]

Were all the thyroid labs done in urine or just RT3?

 

[Valentijn]

Were all the thyroid labs done in urine or just RT3?

They were blood, except the RT3.