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I got a copy of the latest ACTH / Cortisol results (Test #3) myself and haven't been in for a follow-up with my Endo, but does this look like Primary Adrenal Insufficiency or am I just jumping to conclusions?

Test #1 - ACTH Stim Test (Done @ 2:00pm):
Baseline Cortisol - 3.2
Baseline DHEA(S) - 461 (110-370) - (135% of range)
Baseline Pregnenolone - 11 (13-208) - (-1% of range)
30 Min Cortisol - 12.7 (Ref >20) - More than doubled, but Low
60 Min Cortisol - 15.2 (Ref >20) - More then doubled, but Low

Test #2 - Saliva Cortisol Panel:
Morning - 7 (13-24) - "Depressed"
Noon - 6 (5-10)
Evening - 4 (3-8)
Midnight - 8 (1-4) - "Elevated"
Cortisol Burden - 25 (23-42)
DHEA - 9 (3-10)

Test #3 - Various Blood Tests:
ACTH - 69 (7-50) - (144% of range)
Cortisol @ 11:00a - 8.8 (4-22 @ 9:00am) - (26% of range)

It also bugs me that my DHEA(S) is High, but my Pregnenolone is Low. I thought Pregnenolone was a precursor to DHEA - does this mean I'm not making enough Pregnenolone from Cholesterol, or am I using it up too quickly to make DHEA/Progesterone/Aldosterone and all their products?

Any insight from anyone?
MG -

What tests should I suggest to my Endo to check for Adrenal autoimmune problems?

I'm not taking any supplements or medications at all, so what you see in the numbers is all me. I did accidently eat a little chocolate about 3 hours before my midnight reading, but I called a Doc associated with the Lab that did my saliva testing, and he said that it might have only affected it by 1%.

I just chalked it up to being a "flattened" rhythm, and found a few forums elsewhere (STTM) that say it also points to Adrenal Exhaustion. Even though the Midnight read takes a spike up, I'm still only moving 4 between the lowest and highest points during the day. What I'd really like to see is how ACTH vs Cortisol looks at 11:00p-Midnight, but that will probably not happen since my Endo already dismissed the Saliva Cortisol test by saying they were unreliable.

I'm somewhat hoping that root cause has to do with some other Hormonal issues I'm looking into, and with HC support and restoring other imbalances that the Adrenals will be able to start working again.

The Doc still hasn't called me back to make an appointment. I actually tried to make an appoitment when I went to pick up the lab results because the office has a particularly booked schedule, but they just told me the Dr would call when he wanted to see me.

As they say, "Waiting is the hardest part", (especially when it takes the willpower and faith of Job from the Bible just to roll out of bed each morning when I feel twice as bad as I did when I went to bed...).
Alright, Hormoneman, you asked for it! (and MG, watch it with the Thread Hijacking! ;))

It all started with Thyroid checks:

Thyroid #1 (Late Jan):
TSH - 1.26 (18.8% of range)
FT4 - 1.15 (25% of range, +6% from TSH)
FT3 - 367 (72% of range, +47% from FT4)

Thyroid #2 (Early Feb):
TSH - 0.825 (8.6% of range)
FT4 - 1.07 (19.2% of range, +10% from TSH)
FT3 - 362 (69.4% of range, +50% from FT3)
Reverse T3 - 24 (Ref: 11-32)
Anti-TPO (for Hashi's) - <10 (Ref: <35)
TSI (for Grave's) - 106 (Ref: <=125)

Saliva Sex Hormones (as part of "Test #2" mentioned in first post):
Free Testosterone - 39 (50-80 pg/mL) - (-35% of range)
Progesterone - 39 (5-95 pg/mL) - (38% of range)
Estradiol - 10 (1-3 pg/mL) - (450% of range)

Addendum to "Test #3" mentioned in first post:
T, Total - 248 (241-827) - (1% of range)
T, Free - 73 (34-194) - (24% of range)
T, Free & Weakly Bound - 166 (84-402) - (25% of range)
Albumin - 5.0 (3.6-5.1) - (93% of range)
SHBG - 14 (8-48) - (15% of range)
LH - 1.8 (1.5-9.3) - (3.8% of range)
FSH - <0.7 "Undetectable" (1.6-8.0)
Prolactin - 6.1 (2.0-18.0) - (25.6% of range)
IGF-1 - 266 (106-255) - (107% of range)
ACTH - 69 (7-50) - (144% of range)
Cortisol @ 11:00a - 8.8 (4-22 @ 9:00am) - (26% of range)

CBC (last week):
WBC - 4.8 (4.0-11.0)
RBC - 4.77 (4.60-6.10)
HGB - 13.4 (13.5-18.0)
HCT - 39.3 (41.0-53.0)
MCV - 82.3 (80.0-98.0)
MCHC - 34.1 (32.0-36.0)
RDW - 14.4 (11.5-14.5)
PLT - 220 (130-400)

CMP (last week):
Glucose, Fasting - 82 (70-100)
Sodium - 142 (135-145)
Potassium - 4.2 (3.5-5.5)
Chloride - 103 (98-107)
CO2 - 27 (23.0-31.0)
Anion Gap - 12 (7-16)
BUN - 11 (5-25)
Creatinine - 0.9 (0.5-1.4)
Calcium - 9.6 (8.7-10.2)
Bilirubin, Total - 0.5 (0-1.0)
Bilirubin, Direct - 0.0 (0.0-0.4)
Total Protein - 7.4 (6.3-8.2)
Albumin - 4.9 (3.5-5.0)
AST (SGOT) - 32 (14-50)
ALT (SGPT) - 35 (21-72)
Alk Phosphate - 97 (50-136)
GGTP - 23 (8-78)
eGFR - >60 (Ref: >60)

Iron / Anemia Profile (Last Week):
Iron - 66 (60-180)
Iron Binding - 400 (200-400)
Percent Saturation - 16.5% (14-55%)
Ferritin, Serum - 8 (25-335)

Lipid Panel (Last week):
Cholesterol, Total - 150 (Ref: <200)
Triglycerides - 211 (Ref: <150)
HDL - 29 (40-59)
LDL - 79 (Ref: <100)
VLDL - 42 (No Ref given)
LDL/HDL Ratio - 2.7 (Ref: <3.55)
TC/HDL Ratio - 5.2 (Ref: <4.97)

Various Other Labs (Last Week):
Vit B12 - 355 (Ref: >240)
RBC Folate - 1150.1 (Ref: >160)
Phosphorous - 3.5 (2.5-4.5)
Uric Acid - 6.0 (3.5-8.0)
Relative Retic - 1.85% (0.1-2.0%)
Absolute Retic - 88 (5-94)

I've read the ACTH "Inperpretation Guide" on other forums (STTM) before, and I too was leaning towards Secondary, but my ACTH vs Cortisol looks like my Pit knows it's too low and is "raising it's voice" (we don't yell/shout in our household :D) to try to get more Cortisol.

Do you have references (that are legal to post here) that state that low Pregnenolone is a marker for Hypopituitarism? I thought since Preg. was a precursor for DHEA, and since my ACTH is probably high all the time, that it is all used up making DHEA and the other Adrenal products, (but not Cortisol for some reason - maybe an enzyme deficiency that is blocking Cortisol synthesis?). Doesn't the high ACTH in response to chronic lower Cortisol make Hypopituitarism less likely? (FSH/LH are low, but we'll get to that later). Also, since Aldosterone isn't ACTH depentent, wouldn't Pregnenolone need to be indepentend of ACTH as well, (or am I out in left field)?

Hopefully in "Round 2" with my Endo, he'll do the Aldosterone/Renin tests, (along with the Estradiol since it was high on the Saliva stuff). I have the "Hard to handle outside heat" thing, but I live in the Southern States, so that doesn't say much. ;) I haven't noticed any "excessive sweating" or "excessive urination", but if it were congenital, (which I suspect it is), then I wouldn't have a good point of reference to compare "excessive" to. Potassium and Sodium look ok. I did have a slightly low Potassium of 2.9 once back in 1994, but that was a while ago.

Sex hormones are another puzzler. As you can see, my T's, SHBG, and my FSH/LH are low, but my IGF-1 and Albumin are high. He didn't check Estradiol (E2), but since it was pretty high on the Saliva testing, I suspect it's pretty high. I read in some Endo training materials that the Hypothalamus can't tell T from E2, so if E2 is high it will lower GnHR and thus drop LH/FSH, and lower T/DHT production. Since low T/DHT means E2 synthesis isn't as repressed, more E2 is produced, the Hypothalamus sees too much sex hormones, and the cycle continues. I don't have Gynecomastia, (male boobies), but I don't think that rules out "Male Estrogen Dominance". It may be something as simple as too much T is being Aromatased into E2, and could I just use something to slow down the conversion, but there isn't a lot of info on this topic that I've found. I've called my Endo and left several messages asking to come in and check E2 and Aromatase rate, but I haven't heard anything back yet.

Thyroid function looks normal, (as far as TSH vs FT4), since it looks like my Thyroid is "following orders" and making as much T4 as the Pit wants. I know the TSH is lowered, but I think that has to do with low Cortisol downregulating Thyroid function instead of Hypopituitarism. The real puzzler is what is causing my FT3 to be +50 percentile higher then my FT4. I thought it was low Cortisol which prevents binding of the T3 at the cell and thus causing an increase in circulating T3, (what I term "Effective Hypothyroidism" since it's there but I can't seem to use it). I also read on a few other boards that E2 and T3 both compete for the same receptors, so high E2 might also explain the extra floating T3, (but I don't have any references other then a few posts on a Body Building forum). I'm still a little unsure as to if the Hypothalamus looks at FT4 or FT3 to regulate the Thyroid, so the relative elevated FT3 could also be a factor in causing the lowered TSH.

Prolactin, WBC, and RBC look good, so I don't suspect a tumor.

Iron, Ferritin, HGB, and HCT are a bit low, but that has to do with giving myself temporary low-iron Anemia, as I stated previously.

(Is it just me, or is this starting to feel like an episode of "House"...) :(
MG -

I found a few similar pages showing the pathways of steroid "cascade", as well as a lot of research about how to find enzyme problems by looking at the "precursor-to-product ratios".

I'm sure this is an over simplification, (and I'm not sure if it really even works this way), but I look at each step in the cascade like the old "flow rate" problems they used to make us do in school. Each steroid chemical is a seperate bucket, and it has inputs (enzymes that produce the chemical) and outputs (enzymes that turn the chemical into a different steroid), each with their own flow rate (level of enzyme conversion). Theoretically speaking, if a bucket is low it doesn't necessarily mean that it isn't filling up fast enough, it could also mean that it's emptying out too fast. I think some enzyme activity is constant, and some is mediated by Pituitary hormones, (ACTH / FSH / LH / etc).

Since Pregnenolone is the "mother hormone" for all the other steroids, and since my Total Cholesterol or LDL's aren't too high, I assume normal generation of Pregnenolone. My Pregnenolone is low, but later things such as DHEA(S) and Estradiol (at least on the saliva tests) are high; I take that also to mean that I'm making enough Preg. since I'm not running low on all the steroids.

The DHEA(S) was high (probably in response to high ACTH), my Testosterone was low, and my saliva Estradiol was high. Since DHEA is a precursor to the Androgens, the increase will probably show up in them somewhere as well, (that extra DHEA has to go somewhere...). Because the Testosterone was low, this once again leads me to believe that when we check my Estradiol via blood, it will also be elevated, (or, it could be low as well, which means one of the DHEA enzymes aren't working).

Progesterone was normal on saliva, and I think we've pretty much established that I've got low Cortisol production. My current hunch is that if we also check Aldosterone (a product of Prog.), we'll see a decrease there as well, and might even be able to trace back to what enzyme is having problems. I'm currently leaning towards "11B-hydroxylase", because if it was "21-hydroxylase" I would think we'd see elevated Progesterone.

Once again, this is all stuff I just made up and I'm sure it has no scientific basis, but at least it gives me something to think about while I'm waiting for the Endo to call me back so I don't go crazy. :dizzy:





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