Transcare “Adventures” Update
(note: much of this was written 3–6 months ago, in the spring and summer of 2019)
Tomorrow I go for a genetics test for cyp21 mutations, 9 months since my previous article. I’m guessing there is about a 1/3 chance it turns something up. It shouldn’t have taken 9 months, but that’s the way our medical system works, apparently.
To review, briefly, I was having some health problems, which I thought, might be partly an abnormal stress response that had shown up in test results from many years ago, and never been properly followed up on. Those results turned up during holiday cleaning:

The image isn’t great, but you should be able to see, in the numbers, that cortisol is depressed while DHEA is very high. You can also see this in the chart on the left. The chart on the right is as blank as it looks. My result would be off the right side if it were extended… still in the bottom right section without a label. You’re *really* not supposed to be here.
This is the pattern of a broken endocrine circuit where you don’t produce enough cortisol to shut the steroid production system down, so sex steroids overshoot. Counterintuitively, according to researchers here this can, “ lead to adrenal over secretion of the weak androgen DHEA in prenatal life, which is aromatized to estrogens in the placenta… resulting in partial demasculinization of the brain.” I point this out because it was this paper that allowed me to connect my earlier test results and my (brief) use of hormones, realizing transness could point towards other, actionable, medical problems. This has given me just enough confidence to pursue this line, and write it all up here, despite the self doubt inducing nature of the medical system as it stands. I can’t imagine how many people there are with only some piece of this puzzle, who haven’t made it this far.
Enough reviewing. Last summer, after the endocrinologist declined to complete the ACTH test, I looked for ways to route around the damage in the medical system. My first stop was Dante Labs, a startup offering whole genome sequencing(WGS). Unfortunately, it wasn’t exactly whole genome sequencing. The cyp21 gene is located in the notoriously complex MHC region on chromosome 6. Dante appears to have approached this problem by simply reporting (almost) no information from this region. For their health report, they appear to hand the data off to a 3rd party who doesn’t seem to know that they shouldn’t trust this (lack of) data. Specifically, an snp associated w/HLA B57 is used as a proxy for abacavir sensitivity. B57 is also associated with psoriatic arthritis, common in my family, which is why I made a mental note of it when it turned up on both my 23andme AND my Ancestry data. But the health report from Dante said that I didn’t show abacavir sensitivity. I reported it to them twice in the course of several emails, but they didn’t seem interested. Spot checks beyond this make me think that most of the other results are reliable.
Looking at Dante’s .vcf file using Integrated Genomics Viewer(IGV), I see a few dozen snp variations over a few million of the most variable base pairs, a sharp dropoff just when you’d expect the number to be increasing. Comparing it to data from the 1000 genomes project, it starts looking pretty implausible that anyone show so little variation. The new short read technology used to make WGS affordable may complicate making sense of this stretch of dna. Nevertheless, recently developed algorithms may help. It’s a long shot, but If I could have gotten ahold of the raw read data, I may have been able to run the .bam file through xHLA, designed for just this type of short read data, and get an association with a nearby HLA gene. Unfortunately, many of the known cyp21 mutations that I’m interested in are not tied exclusively to one HLA type. Everyone carries a non-functional cyp21 “psuedogene” that does nothing, but still gets swept along in the reproductive process, acting as a reservoir of errors that occasionally get copied over to the active gene, reducing it’s functionality. In the process, useful associations with nearby genes are limited. The most useful is the connection between HLA-B47 and a 30kb deletion that takes out 4 genes, including the entirety of cyp21. In practice, I ordered the hard drive from Dante over 3 months ago and have not received it yet. (The size of raw read data makes downloads difficult.) [at the time of medium publication, I have received the drive, 9 months after placing the order.] I wish I could recommend commercial WGS as a medical system hack to find out whether cortisol supplementation might help with fatigue or a number of other problems which a poor cortisol response might make worse. Unfortunately, it seems like it’s not quite there yet for this purpose.
After starting down the Dante road, I realized it was going to be slow going, so I went ahead and contacted the local, well regarded, genetics center where I had been a patient decades ago for Trimethadione exposure. I was surprised to find the doctor/researcher who had my case was still there, and he was eager to meet with me to do a long term followup. I had hoped to pique his curiosity, but when he showed me the writeup of our meeting, for my feedback, he seemed mostly interested in finding a success story, declaring that I was in good health despite me telling him that I had found my way back to him due to ongoing health problems that I was seeking answers to. He noted that I had been “diagnosed with depression” when younger, but failed to note the abnormal endocrine test results which I had in hand and showed him. I pushed back “good” health to “ok”, but didn’t think about suggesting a note about the previous endocrine results.
During our meeting, I think I gave too good a showing of myself for the hour we talked, very alert and engaged. I left drained, still not quite 100% the next day. To be fair, he didn’t have to talk to me at all, though he obviously got something out of the meeting as well. He offered to make a copy of my file for me and to look at the .vcf file I had gotten from Dante, telling me there were questions over the quality of Dante’s data. In the end, when I asked for a gene test, all was willing to do was give me a referral to an endo. I wasn’t willing to roll some very expensive dice, both timewise and moneywise, by going back down that road.
As these 2 paths began to look less promising, I made an appointment on queermed.com. I was getting accustomed to having to stay ahead of the failure curve if I hoped to find out anything in this lifetime. Dr. Lowell was very upfront that she could not do an ACTH test, but she was open to ordering a gene test for me. And… she did!!
So, I will at least get an answer with respect to the most common genetic problem that can lead to my past results. If it’s a miss, I have no idea how I will re-approach the ACTH test for potential imprinting problems. If there’s some researcher out there that wants a mostly finished case study, let me know here or on twitter.
Fast forward several months from the writing of the last paragraph and I actually have the test results before publishing. My indecisiveness becomes your instant gratification. The test didn’t turn up anything. If I recall correctly, this test covered about 92% of the known pathological mutations in this gene (adjusted for weight/frequency). This moves the probably cause for the old test results back in the direction of 3b-hsd imprinting or some failure of the original test.
I’m not a medical professional. Getting this far took an unreasonable amount of time and effort when I simply wanted a test done, a test which I had the money to pay for. The broken medical system makes it so that transpeople must talk publicly about biology as it relates to trans identities, whether it is to get reasonable results from transition related medicine, OR because transness can be point to other actionable medical diagnosis having nothing to do with transitioning. A pleasant side effect of this is to highlight the cartoonishly truncated view of biology transphobes put forward every day.
