Thank you for the info... I'll definitely read.

***WHAT'S REALLY SCARY is that even if you don't have polymorphisms, these medications can mess you up because they still inhibit/induce (mainly inhibit) the enzymes from working properly.*** These are drugs like Nexium, Zantac, Cymbalta, Prozac, etc.

From the nine (9) tests, my results yielded six (6) polymorphisms. I'm CYP2D6 Poor, CYP2C9 Intermediate (possibly Poor due to currently-undetectable polymorphism), and CYP2C19 intermediate. I'm CYP1A2 Extensive/Normal unless induced, and then I'm UltraRapid. Plus, I have sensitivities to Warfarin and Allopurinol. They even figured out that Tamoxifen, a cancer-fighting drug, will actually give me cancer if I am given it after menopause.

I can't share my Mayo Genome Report due to HIPAA, but let's just say that it was VERY colorful compared to the sample on the CIM web site.

I'm glad that you called it "detoxification" above. That's what I call it because I had no other term to call it. Coming off of them slowly, I stopped taking my last P450 drug on March 11, 2016, and between January and July, I lost 50 pounds and pretty much every single symptom in the list below*** has completely disappeared.

During all of this (2004 - 2016), based on the symptoms below, I was misdiagnosed with a rare endocrine condition called acromegaly despite lacking the clinical physical symptoms of the condition. This resulted in a slew of unnecessary medical treatments, including a brain surgery which caused brain damage.

***My symptom list...

- Constant weight gain that I couldn't lose and that kept slowly-climbing. (When I saw my PDP in January 2016, I was considered obese at just under 200 pounds. When I saw him in April 2016, I was then considered overweight and about 172 pounds. When I saw him on August 1, 2016, his jaw dropped when he first looked at me; I weighed 150 pounds and had a BMI of 23 (normal weight). The only thing I changed during this time was that I stopped taking P450 drugs.

- Body-wide edema. I felt like I was engorged, and I remember telling several doctors that I felt like I was “full of medication.”
o My face was so swollen that the bows of my glasses left indentations on the sides of my face for years, and I could feel my face jiggle when driving.
o Fat pads developed at my belly, upper back (buffalo hump), on my sides above my hips, and above my collarbones.
o Pitting edema in my legs.
o My feet were a half-size bigger.
o My breasts became a full size bigger and always extremely very firm. I also experienced leakage that could not be explained via prolactin lab tests.
o Swollen right hand, then right forearm, then left hand, then left forearm. I couldn’t see my knuckles for years.
o The back of my tongue was swollen for years. I couldn't even sing.
o When I bent forward, my abdomen felt tight like it was about to pop.

- Lymphadenopathy
o Swollen lymph node under my chin
(sub mental gland) that I could feel with my hand and was painful.
o Borderline swollen lymph nodes found on my pancreas.

- Visceral hypersensitivity and pain: I can feel both liver lobes, the head of my pancreas, parts of my small intestine, and my right ovary separately.

- Sicca Syndrome:
o Chronic dry mouth
o Chronic dry eyes - no longer able to wear contact lenses

- Pain:
o Constant body wide aches.
o Sometimes, my legs between hips and knees would hurt. Sometimes shoulders.
o Liver enlargement and pain (both lobes; first off-and-on and then constant) (this was the worst symptom; the right lobe hurt more than the left; my doctors in Rochester, NY kept telling me that you can’t feel with your internal organs, but they are incorrect. Mayo called this visceral pain.
o Kidney pain.
o Small intestine swelling and pain (first off-and-on and then constant)
o Minor bouts of pain in the head of my pancreas
o Intermittent kidney pain
o Pointed pain in right side of neck and in front of neck
o Headache (different from my normal headaches)

- Nasal sores inside of my nose that leaked clear fluid

- Dermatological:
o Bumps on the back of my upper arms
o Cysts that would open on my face and in my hair that would leak clear fluid

- Excessive, exhaustive fatigue

- Whenever I caught a cold/virus, I would always be sicker and longer than every other person in my family. Even my elementary school-aged kids noticed this.

- Odd smell coming from my body
o Skin, armpits, and vagina
o Originally like campfire smoke or combustion engine exhaust; once I ceased P450 meds and started detoxing, it changed to smell more like chemicals or burnt plastic

- Facial flushing despite no physical activity

- Hyperhidrosis (profuse sweating)
o Profuse sweating invoked by minimal activity and feeling extremely hot inside. Once this sweating started, it wouldn’t stop if I stopped moving around.
o Profuse sweating invoked by covering up the back of my neck, wrists, ankles, and torso. I wore my hair up for years.
o I didn’t need to wear a winter coat for a decade, and I live in Western New York.
o Night sweats while sleeping; I would have to woke up in the middle of the night in the winter to change clothes because they were soaked.

- Shortness-of-breathe feeling in my lungs and coughing

- Malaise (general unwell feeling)

- Emotional/crying for no reason plus unusually irritable

- Mild sore throat off and on

- Low-grade fever off and on

- Bouts of nausea; minor bouts of vomiting

- Borderline low blood sugar off and on

- Ovarian cysts, pain, and spotting (right side only)
o It started a few months after I was prescribed my second P450 drug in 2005 and then stopped before 2006 began.
o It started again in April 2016 after I stopped all P450 drugs, during what I call my detox time.

- Brain fog and worsening memory issues (which cleared-up once I ceased all P450 medications)

- Many friends and nurses told me that my skin was gray-colored.

I started taking my first P450 drug in 2004, and then as time went on more and more were added to my regimen -- sometimes to treat the pain and other symptoms that these very medications were causing. Despite having a liver that always hurt and was enlarged for years, I never became jaundiced, and my liver labs always came back normal.

A symptom overlay like that would be impossible to parse out as a single ideas diagnosis unless it were something aggressively systemic like of course a cancer, or again, lupus or some equally systemic autoimmune disease. To get a handle on it you'd almost have to fall back to a toxicological interpretation and that's essentially what you did. Every major system in your body was simply decompensating and with that many failures, the usual servo systems that would reestablish homeostasis couldn't handle it. So, you were dying basically. The weight gain is what jumps out at me and your wondering how many people are being similarly effected. Been through some of that myself, which I attributed to aging, and still do to some degree, but its worth revisiting. Obesity/metabolic syndrome is what starts the cascade of deterioration for a lot of folks these days through different avenues, heart disease, heart failure, cancer, diabetes, even dementia. There is never a single, simple answer for disease although the mind, by nature, seems to crave simplification. This thing you and Dawn @dawn_giacabazi are onto is very close to being a Rosetta Stone however. Kudos to both of you.

"So, you were dying basically." I totally agree with you! I think I would have been in liver failure this past June and probably dead by the end of this year. For the past four years, I had been to 20 local doctors about this issue, and not a single one had a clue what was wrong with me. I think that half of them thought I was crazy, and the other half believed me but had no clue what was wrong with me.

What stuns me is that every_single_medication_ad_on_TV tells you, "If your liver starts hurting while taking this medication, tell your doctor." After hearing this last April, I stated loudly back to the TV, "AND THEY WILL HAVE NO CLUE WHAT IS WRONG WITH YOU!" (My 14-year-old thought this was hilarious and replied with, "Down, girl." LOL.) When TV ads talk about avoiding grapefruit juice with certain meds, they are talking about P450. Funny how I can google things and find answers to problems, but doctors can't.

"The weight gain is what jumps out at me and your wondering how many people are being similarly effected." Excellent question! After I got my results, I googled "cytochrome P450" and the name of a pharmacy college in my city, and I randomly-emailed the first professor name I found asking her to meet with me. She replied in less than two hours saying yes, and we ended up meeting for four hours. The one major question she had was "Why did you gain so much weight from this?" She also said that in a pharmacist's entire career, they learn a ton about this but never actually meet anyone who has them because no one gets tested. So, she's invited me to speak at her P450 classes. Those will be cool.

Something else that you and @dawn_giacabazi can start thinking about... These same enzymes also metabolize many hormones. Therefore, do I also not properly-metabolize my own hormones? Does this explain my endocrine symptoms? Also...
• Do I have hypersomnia because one of the enzymes that metabolizes melatonin is CYP2C19, and that enzyme in me is Intermediate prior to other drugs making it work even more slowly?
• While pregnant, I was incredibly sick compared to most women -- just as my mother was. Well, progesterone production increases significantly and is one of the hormones that causes the nausea and vomiting, and it is also too-slowly-metabolized by my wonky enzymes. Is this why I was so much sicker than most women while I was pregnant?
• I also wonder if I was misdiagnosed with acromegaly (a disorder where you produce too much growth hormone (GH) and insulin-based growth hormone (IGF1)), because I figured out that these P450 enzymes are modulated by -- ta da -- growth hormone! Maybe if your enzymes aren't working properly, the GH keep trying and trying? And guess what causes too much IGF1? Growth hormone!

I sent these questions to my two Mayo endocrinologists to mull over (no response expected), so I hope that I've catalyzed them to start thinking. I also emailed these questions to a head of Endocrine and Genetics at NIH. He replied with, "Although possible, I am not sure that it is likely." I actually found this to be a positive response. (I also found it interesting that he copied four other NIH doctors on his response to me. Maybe I was able to get some other brains thinking about these things, too.)

Another thing I also told my Mayo endocrinologists... I feel that once a person is diagnosed with these polymorphisms, Pharmacogenomics should be referring patients to related specialties, such as Endocrine. I also want to know what long-term use of these drugs has done to the other parts of my body, especially my liver.

The problem is, all of this is so new, that science, research, and discovery hasn't gotten there yet. Bummer.

There's a concept called "allostatic load" which describes how you hit a tipping point and the downward cascade accelerates. You were probably near that tipping but and had you been older, or had one more stressor, would have gone over. No doubt many people succumb without ever having had any idea what precipitated their final decline. I lived in Oregon not too long ago and the major 'health' megaplex I went to in Portland had so many seriously sickly looking people going in and out that it looked like the Court of Miracles. The vast majority were seriously overweight. That's a trend that it it can be even slightly reversed much suffering will be averted.
As far as this issue causing endocrine disorders, its easy to start over-generalizing once you get momentum. Quite possible, or a complicating factor, much like how a fatty liver wrecks so many things, but the root cause of most endocrine problems probably unlikely.
We'd all like a unified field theory to explain all misery but its never going to materialize is my guess.
Once I get some more clarification of an issue I'm dealing with I'll look into this, mainly as a way to help weight loss. Shedding 30 lbs would help a lot of things.
This won't explain everything, but its a very good jump on a lot of problems.
https://en.wikipedia.org/wiki/Allostatic_load

Allostatic load -- This perfectly explains what was happening to me! I had my own theory about this, but had no idea that there was a name for it.

I bet this is one factor of, maybe even the main contributing factor to, epigenetic switches being turned on, and perhaps also the cause of conditions such as fibromyalgia.

I truly-and-firmly believe that I was on-the-edge on my final decline. Years and years of feeling more and more ill and battling doctors all while trying to have a normal life (and the stressors of failing at that). It was at this point in August 2015 that I came home from yet another doctor's appointment crying because I was told once again that I my tests had come back normal and nothing was wrong with me. I finally stopped crying and got mad enough at the situation to call Mayo Clinic and ask if I could come. Thankfully, my insurance requires no referrals to see other doctors.

Looking back now, it's as if P450 drugs caused me to have a pseudo-acromegaly (with high but not super-high GH and IGF1 levels, which is usually the case, and lacking all physical symptoms). Another good example is that it caused me to have a buffalo hump, yet I always had normal cortisol levels, so no Cushings. When my PCP examined me on August 1, he lifted my hair and quickly said, "Oh my gosh, it's gone!" The hump was there for years, and was still there when he saw me the previous mid-April.

And I do realize that it could be that I, as an individual, have a super-wonky set of polymorphisms even compared to most people out there. For example, 33% of caucasians like me are CYP2D6 Poor, BUT are they also CYP2C9 Poor/Intermediate and also CYP2C19 Intermediate, etc.? When I came to Mayo a year ago, I was on 12 medications; the more medications you are on, the more likely these issues are likely to occur. BUT, my P450 symptoms actually started in 2005 after adding Celexa to the Nexium that I had started in 2004. (An additional theory I have is that this seems to occur to those of German ancestry more than other caucasians.)

Feeling better is great, but seeing all of my physical symptoms completely disappear from ceasing these drugs seems to have been the most fascinating factor for doctors. Knowing that I have lost 50 pounds in six months solely from ceasing metoprolol, omeprazole, ranitidine, and duloxetine has stunned them.

When you get a chance, please do look into this for yourself. One thing that my Mayo pharmacist said that struck me was, "I feel that every person should have this testing done." I feel that he's spot-on with this. He said that for all of the people he had tested from August 2015 through February 2016, most people had at least one polymorphism.

One other battle that I'm still in is getting doctors and pharmacists to realize that there are non-P450 metabolized medications that also inhibit/induce these enzymes. Currently, they stay inside-the-box and don't consider other meds; they assume that a drug metabolized elsewhere in the body won't affect things, and they also neglect to consider that things like vitamins. I know these things do because I lived it and felt this happen to me -- and the symptoms were exactly the same with these drugs as they were for metoprolol, omeprazole, ranitidine, and duloxetine. I think the problem is that they look things up on sites like clinicalpharmacology.com, which lacks information. Knowing that my clinical symptoms didn't match what my Mayo pharmacist was telling me (i.e., non-P450 drugs don't affect this), I did more research and was able to locate a Canadian database that acknowledges that these other drugs and supplements indeed do inhibit/induce, and this exactly-matches my clinical symptoms regarding taking non-P450 drugs / vitamins and inhibiting/inducing P450 enzymes. (It's called http://www.drugbank.ca, and it was developed by their government and their genome institutes. It's also acknowledged by some P450 doctors and pharmacists in Germany that I correspond with. These people have another database and also a tool that I'm looking into. The tool let's you enter your specific polymorphisms and medications and it will give you severity results.)