There is a subtype of MTF patient who has chronic anxiety, smaller body habitus overall, difficulty with weight maintenance, and "masculinization" despite androgen labs appearing normal, overall poor feminization, chronic pain and brain fog. I think I know what this is and how to treat it.

by u/Drwillpowers · 267 points · 212 comments · source

I've seen this phenotype rather often.

Thin, typically low BMI. Very high anxiety. Sometimes chronic pain/autoimmune issues, hashimotos (not always but often). Brain fog, poor stress tolerance, POTS (or simply high resting heart rate, lightheaded when standing up), high salt thirst (they put salt on everything to compensate for their renal losses of it), poor feminization (despite adequate HRT and separate from low BMI). They sometimes report masculinizing effects despite normal T/DHT testing. They often have a history of PTSD / C-PTSD or other diagnosed mental disorders such as "bipolar" which may simply be the next result of neuronal rewiring after many years of trauma with an insufficient biochemical response to these stressors. Bizarrely, some people tend to love "thrills" in this group, as they feel best when anxious and stressed (due to cortisol being released during those times), and some the complete opposite. They avoid scary things/anxiety provoking things/horror movies etc like the plague. Strangely, despite the decreased cortisol output and "addisonian-ish" picture they present with, they are often very pale rather than tanned.

I've also had a few cases of young "FTM" with this, and one in particular that ended up seeing resolution of their gender dysphoria with treatment. Those cases are always VERY underweight, and that patient had a starting BMI of 13 pre-treatment and now at BMI 18 feels vastly better.

I'm still sorting this out, so consider this a "pre-print" idea, but I've had enough success cases that I think it worth mentioning in case it can help someone else.

Basically, these MTF girls look on paper like someone who should be sort of an Addison's disease picture. However, they do not have hyperpigmentation, and if anything, the opposite, are often quite pale. I'm still trying to mechanistically suss out why this is in terms of the ACTH, CRH pathways.

Regardless, when I test morning and PM cortisol on these patients, its almost never "low". But it is almost always at the bottom range of the normal band. Same goes for the sodium value. Tends to be 135-137.

However, I've taken some of these patients, drawn a cortisol, then had the patient do some vigorous exercise/stress, and drawn another one, only to see the cortisol level fall or remain the same. Or, drawn their cortisol during an immensely stressful time in their life for it to be at the cusp of low, or even "faintly low" but never in the standard "Addisonian" sort of range. Aldosterone/renin are normal.

This had me suspicious they had some sort of subclinical Addisonian-ish situation, to which they can make enough cortisol to survive, but when subjected to any degree of stress, they flat out cannot cope, and crumble.

I think this may be related to my overall MPS theory with Kate, but these specific patients I'm postulating only have only one sort of functional copy of 21 hydroxylase.

Healthy humans have two functional copies of CYP21A2, and then two copies of the CYP21A2P pseudogene which is not supposed to be transcribed.

I think some humans may have less functional copies than two, aka one normal and one weak, or two weak, or even one weak, or perhaps more copies, two normal and two transcribed normal CYP21A2P genes for example, resulting in double the expected cortisol output.

This may partially explain the "Elves and Dwarves" body habitus groups that trans people fall into.

Regardless, enough patients have told me that during periods of high stress, they feel like they are "remasculinizing".

If someone has poor 21a2 function, the act of stressing them will result in high demand for cortisol, but as a side product, a bunch of androgen intermediaries are synthed which do not show up on standard T/DHT testing. Basically, because their cortisol production sucks and makes a lot of androgen byproduct, high stress results in an increase in these levels.

I had no way of measuring this, until one of my very smart patients pointed out that Labcorp has a 11-oxo-androgens panel.

So I've been pulling this on my "I am stressed and feel androgenic" patients and been surprised to see elevated levels in otherwise hormonally "perfect" patients.

Treatment of these patients with a very low dose of hydrocortisone (5-20 mg daily starting at the lowest level and gradually escalating) has resulted in some patients an absolutely astounding result. We're talking massive reductions in anxiety levels, massive improvements in energy levels, decreased pain, improved brain fog, just overall major improvements in function. I am being extremely cautious with this, as these are not "defined" Addisonian patients, but I can't deny the massive improvement in their well being. They are all carefully being monitored with lab testing to ensure no adverse effects from the hydrocortisone.

That being said, I do think there is perhaps a large unrecognized group of people in the trans community who have lived in a state of constant stress/anxiety/trauma and whose adrenal glands are just not up to snuff.

Treatment results in elimination of the elevated 11-oxo-androgens, increased BMI, improved sleep, improved mental health and improved feminization.

Now, I have been considering putting this here for a long time, but I've held off on it as anytime I put anything down that has "improved feminization", people recklessly want to jump on that at the cost of quite literally anything. This is 100% not a thing that should be done without a doctor who is 100% on board, and willing to do the relatively intense monitoring and testing to ensure that this is a net benefit for the patient. It is not something that should be done DIY (nor should HRT be done DIY ever).

After having a few more successes with this these past few weeks, this tipped the "ethics" point where I felt it unethical not to mention, as there are likely people who will read this, and recognize "that sounds like me" and be able to talk to their doctor about it and see how the testing plays out.

Again, I do not advise anyone do this without full clinician supervision. You can quite literally give yourself diabetes. If you take the medicine for awhile, and then suddenly run out and stop, you can quite literally die of an Addisonian crisis. It is not something to trifle with, and should be reserved only for people who fit this very specific niche situation. I only have a handful of these total in the practice, and I've got 3000 trans patients, so by no means, is this "common". But it made such an overwhelming difference in those that I've treated for it, that I finally felt like I should put pen to paper on it, as I feel doing so may help more people than are hurt by it.

Over the years, I've seen my words twisted, run with, or employed recklessly. My goal is the same as it has always been, the improvement of the health and wellness of transgender people as a whole. I just am trying to be a better steward of the platform I have, and recognize how far my words tend to disseminate after I publish them here. So please, hear me out. If this sounds like you, talk to your doctor about it. Do not do this on your own.

Hopefully there are some out there though that this can help.

I also welcome the input of anyone who might explain why the patients tend to be pale, quite literally the opposite of Addisonian patients, as the biochemistry of that is paradoxical to me, and I can't seem to solve the "why". Odds are though, Kate will materialize here with an explanation though shortly.

• Dr Powers

EDIT:

There is more than one way to arrive at this phenotype. I saw a patient the other day who seemed to match it perfectly, and she took a look at her nebula and found this:

CYP11A1 frameshift variantDEL chr15:74343131 T A->T Heterozygous rs757299093 allele frequency 1 in 15,000 Pathogenic in ClinVar: CYP11A1-related condition, Congenital adrenal insuffiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency, not provided

Which is a non 21hydroxylase way to produce a similar output. So keep that in mind. Anything that disrupts adrenal functioning / cortisol synthesis can do similar things.

Edit 2: When I say there are a lot of pathways, I mean a lot. Things like problems with ACTH/CRF which aren't the standard addisonian's presentation, anti adrenal antibodies, problems with corticosteroid binding globulin, etc.

Comments

u/2d4d_data · 1 points

For everyone finding this post in the future, the NCAH - Wiki page is kept up to date with a lot more information about this condition along with links to articles and papers where you can learn even more.

u/[deleted] · 37 points

Some friends and I independently discovered much this in literature review while looking at how the HPA axis might affect hormonal transition. Our angle is investigating solutions for modestly tamping down the HPA axis to attenuate the production of adrenal androgens like the 11-oxos and DHEA/S and A4 (to limit intracrine synthesis of potent androgens). That and/or selectively inhibiting 17,20 lyase activity to preserve glucocorticoid production so the HPA axis doesn’t freak out. Hydrocortisone for patients with an impaired cortisol response is a nice fix.

Looking forward to hearing about anything more that you find out!

u/Drwillpowers · 40 points

Thanks for posting! It's encouraging to see that other people have come to the same conclusion that I have in regards to the molecular biochemistry.

I have terrible imposter syndrome, and sometimes, not being an endocrinologist, I say to myself, are you sure? Do you really know this as well as you think you do?

I know it may sound silly, but I would absolutely be crushed if I ever did something that hurt one of my patients. So safety is pretty much always paramount, but that autism and sense of justice really clashes when I see someone suffering and I think I can solve it. With new things of this nature, I tend to tread carefully.

So thank you for sharing that, because it feels good to know that someone independently came to the same conclusion.

u/[deleted] · 14 points

The next step I’m interested in personally is whether MtF individuals with impairments in the HPA axis or suffering from chronic stress (any of the above, so long as it leads to chronically elevated ACTH) are more likely to have developed testicular adrenal rest tumors (TARTs) (noticeable on palpation or otherwise, even microscopic ones), which are A Thing I’m newly aware of. In XY individuals specifically, during development some portion of adrenal cells migrate with leydig cells to the testes, and then they hang out there forever. Histologically they look like leydig cells, but they’re responsive to ACTH (leading to quite large TARTs in extreme cases) and express adrenal-specific enzymes. So in theory they can be contributing to circulating levels of 11-oxo-androgens and other adrenal androgen precursors, and perhaps significantly so in some portion of the population. My speculation is that perhaps this accounts for some fraction of reported anecdotes of improved feminization after orchiectomy / bottom surgery. It’s going to take a lot of evidence to prove this one out if it’s true, but I have my suspicions right now.

u/EisJess · 2 points

This account was deleted, but the comment is very relevant to me:

About me:

- Doctor Powers’ patient, Trans intersex with suspected Estradiol resistance. I’m on pellets, GNRH agonists, and other medications prescribed by Dr. Powers.

- Little feminization, but we’re hacking it.

Also:

- Had a Testicular Adrenal Rest tumor (TART) since childhood. Concerned for my parents, I saw an endocrinologist at 12. The tumor is near half my testicles, attached to one. The endocrinologist said removal wasn’t necessary unless it caused pain or grew.

In my 30s(now), I suspect TART might be part of the puzzle. Despite a world-class HRT protocol, I have little feminization, except for some genius hacks by Dr. Powers.

I want to see an endocrinologist in Germany, but I want to be prepared with knowledge since not everyone understands.

I’d love to hear more and connect if anyone’s familiar with this topic. I might make a post about it.

u/anaaktri · 37 points

I just love how you actually give a shit about your patients and the lengths you go to help them are incredible. I’ve never seen a dr in my life who shows this level of concern and care about their work or patients. Much love

u/Drwillpowers · 18 points

❤️

u/unexpected_daughter · 35 points

I really hope this can bring about quality of life improvements for some of us. I fit a lot of this myself.

Trauma at the level of CPTSD is associated with many of these same symptoms too, especially “body anxiety”. Rates of diabetes and heart problems are higher in people severely abused as children. I doubt anyone has run large-scale trials of “CPTSD severity versus blood sodium and thyroid” (am I wrong? I’d love to be wrong on this), but which came first, the chicken or the egg? Is this possibly a collection of neurobiological trauma symptoms mediated by gene expression? It’s a depressingly interesting thought that some of us might end up much more traumatized / anxious, all else being equal, because of a gene mutation. And because we inherited these gene mutations from our parents, perhaps we were more likely to grow up in a home with a parent who themselves was frequently dysregulated and thus more likely to traumatize us.

The 2016 paper Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect is relevant here, especially the 9 discussion questions at the end (if you endured abuse as a child I warn you to exercise discretion, as this is a case where a scientific publication can be rather depressing to read): https://www.cell.com/neuron/fulltext/S0896-6273(16)00020-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627316000209%3Fshowall%3Dtrue

Edit: @ u/Drwillpowers, note this specific text from the paper:

“In view of the seminal role of the hypothalamic-pituitary-adrenal (HPA) axis and extra-hypothalamic corticotropin-releasing factor (CRF) circuits in mediating the endocrine, behavioral, immune, and autonomic effects of stress, our early studies focused on the effects of maternal separation on these systems. Brief maternal deprivation, early in life in rats, resulted in increases in basal and stress-induced plasma ACTH concentrations, increases in median eminence CRF concentrations, and downregulation in anterior pituitary CRF-R1 receptor density. Alterations in both extrahypothalamic CRF concentrations and CRF-R1 receptor binding were also observed (Ladd et al., 1996). Subsequent studies revealed long-term consequences of maternal separation in adult male rats including elevated cerebrospinal fluid (CSF) CRF concentrations, as well as increased CRF mRNA expression and CRF concentrations in the paraventricular nucleus (PVN), central nucleus of the amygdala, bed nucleus of the stria terminalis, and locus coeruleus (Plotsky et al., 2005). The maternally deprived rats also exhibited escape from suppression of plasma ACTH and corticosterone by the synthetic glucocorticoid dexamethasone (Ladd et al., 2004). Subsequent studies revealed maternal separation effects on brain-derived neurotropic factor (BDNF) expression and processing in the striatum, hippocampus, and ventral tegmental area (Lippmann et al., 2007). Many of these initial findings have been confirmed and extended by others.”

u/Drwillpowers · 14 points

Not going to lie, that sounds pretty much dead on for what I'm seeing in these humans.

u/unexpected_daughter · 6 points

Do you mean, basically everyone in your patient population with these symptoms exhibits PTSD?

I wonder if there would be any value in using a synthetic long-acting glucocorticoid like dexamethasone, as mentioned in the study’s text up ^ there. You’d think shorter-acting bioidentical hydrocortisone would be preferred, right?

u/Drwillpowers · 21 points

I have been considering the usage of that, or fludricortisone on those patients who have exceptionally positive responses to hydrocortisone, and who have not had a negative biological response. Meaning that they feel better, but the labs stay good.

This is not Addison's disease. This doesn't even have a name. This is a unique situation tailored specifically to transgender people on HRT which is why it's camouflaged. I am treading very carefully with these people, because I do not have a lot of peer-reviewed research to point to in regards to why I'm doing what I'm doing.

So if someone questions it, I'm going to say basically, this patient has an overwhelmingly positive response to this medication, and all the monitoring labs are remaining good. Therefore logically/ethically I should continue it.

But to answer your question, yes, overwhelmingly there's a lot of PTSD in this population.

u/anaaktri · 6 points

I was thinking a lot of this sounds like me, except it all started post tbi and repeated trauma leading to PTSD/cptsd. I also absolutely hate how prednisone makes me feel. Edit - I should add I was somewhat anxious all of my life but mostly post injury. And who knows, if I would have been able to be myself as a child and not be rejected or learn to not trust myself or think natural occurring ideas or desires were wrong, (denied, disapproved of male child who thought they were a girl) I probably wouldn’t have been so anxious.

u/badatbeingtrans · 5 points

Bed nucleus of the stria terminalis jumps out at me, because that's one of the few sexually dimorphic parts of the brain, and iirc studies have shown that it's statistically different in trans people compared to cis people. 

From your summary, it sounds like trauma and dysphoria have some kind of correlation in that they both have measurable changes to this brain structure, but I don't want to try to guess at the causation (does trauma make dysphoria worse? Do prior existing brain structures predispose people to both?)

u/[deleted] · 2 points

I know that there has been a resurgence of interest in treating CTPSD with psilocybin. Can you think of any connection between that and what you just described?

u/unexpected_daughter · 2 points

Psilocybin and other psychedelic compounds can certainly help with trauma healing. You’ll have to be more specific though? If you mean something like, “could psychedelic therapy for people with CPTSD conceivably help with changes in gene expression related to biochemical problems in the HPA axis?” I’m pretty certain the answer currently is “no one has a clue.”

u/sticky3004 · 32 points

Hiiii, I'm one of the patients. For anyone reading this who wonders about the effectiveness of the treatment: I don't know where I rank on Dr Powers's anxious patient ranking, but I assume I'm like top 15 at least. After starting hydrocortisone two weeks ago, I have only taken one or two doses of my buspirone, something which I depended on heavily to maintain composure. If this isn't placebo, it's a game changer for me. I have complete faith in Dr. Powers, he's a good guy who knows what he's doing.

Edit: What the fuck, I checked my sodium value from the day I saw dr powers and he prescribed me hydrocortisone and it is exactly 137. Just thought that was funny, lol.

u/[deleted] · 5 points

[removed]

u/2d4d_data · 12 points

Remember "higher cortisol levels" in this case isn't "high" levels, but more like normal levels.

u/Drwillpowers · 11 points

Also remember this is exogenous cortisol. High stress would produce high cortisol in those who can do so. In these patients high stress produces no cortisol bump. They aren't the normal reaction.

u/Anon_IE_Mouse · 20 points

Do you get a lot of new patient appointments after these posts? You must. I literally know someone who fits this exactly and she just contacted your office.

Thank you for what you do.

u/Drwillpowers · 24 points

I don't really know.

That's probably a question for Laura. I'm more focused on just seeing the humans and fixing the things.

u/uhhhh_yess · 5 points

“Humans“ lol. I like calling my niece and nephews by tiny small or medium humans

u/MandyKagami · 24 points

I read this and really recognized my condition in it. The paleness is more obvious in me because my father is black but I don't even look mixed, my brother is relatively normal, looked very similar to me or at least it is what everyone said, but folks distinguished us based on skin tone. I do deal with a lot of anxiety and stress, ever since I have been dealing with a reckless neighbor I feel I went backwards in the feminization process. I think I even developed facial hair where I didn't have before, been trying to compensate with cyproterone because it is what I have. I was able to gain weight though but only after about 5 years of HRT, before HRT I was at 53kg with a height of 171cm. I don't think it is viable for me to present this to my doctor because they don't really care, and treat doctors with online presence as hacks or nutjobs. Does anyone know if there is anything in diet that could compensate the lack of medication use? I wanna try something to fix things and I have zero hope of a doctor in my country helping me with this.

u/Laura_Sandra · 17 points

> I wanna try something

It may be an option to try Phosphatidylserine. It basically blocks the depletion of Cortisol in those who have low levels anyways. In people who do not have this condition it may block the overproduction so its basically the opposite. Here was also more

You may be much more calm and stress resilient ( coming from a low baseline). It comes in capsules and one 100 -200 mg capsule sublingually in the morning may have noticeable effects.

Additionally using a methylated multivitamin with Methylfolate (methylated B9) and Methylcobalamin (methylated B12) as outlined here: https://www.reddit.com/r/DrWillPowers/wiki/reduced_comt_activity#wiki_diet_.26amp.3B_supplements may have very noticeable effects. One widely available example is here, start slowly with only a part of a pill or capsule a few times a day to avoid ups and downs.

And using a high protein diet like 2 eggs a day and multivitamins may additionally help.

u/Drwillpowers · 8 points

Neat.

This was new to me. Thanks.

u/MandyKagami · 3 points

I guess I was subconsciously treating myself because I felt better eating more eggs and doing vitamin supplementation (but not of all vitamins).
I will check out for Methylated multivitamins.

u/18004206941 · 2 points

> It basically blocks the depletion of Cortisol in those who have low levels anyways.

do you have any source that demonstrates this claim? i can't find anything about it being capable of upregulating cortisol, all i can find is it's ability to lower cortisol levels, especially in response to physical exercise and only in higher dosages (>400mg/day).

it would be really amazing if this really could regulate cortisol to a regular baseline in both ways.

u/OkEmployee5373 · 1 points

hello, may I dm you pls? It's about the paleness.

u/DeannaWilliams222 · 15 points

in before someone reminds dr powers how often i mention the 11-oxo labs on this sub going back over a year

u/Drwillpowers · 12 points

In B4 nameless person in post is outed and credited.

u/AdriTexX · 7 points

I have s question about the 11-oxo androgens. IIRC oxo androgens are elevated in 21-hydroxylase deficiency, right? So if I am not able to do an oxo lab test, can I just get 17OHP and cortisol to know if I have 21-hydroxylase deficiency and in case to be negative also my 11-oxo androgens should be normal?

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819755/

"Recent studies have demonstrated higher than normal circulating levels of 11oxC19 steroids in patients with 21-hydroxylase deficiency and in polycystic ovary syndrome."

Thanks.

u/DeannaWilliams222 · 8 points

i don't know if that would give you a definitive answer, as there may be more than one reason why adrenal androgens are being produced in excess, or reasons why 17OHP and cortisol may result abnormally with "normal" 11-oxo results. no clue. but doesn't sound definitive to me.

personally, i don't think there's a "substitute" for direct observation, generally. with labs, the idea is to confirm or rule out hypothesis or suspicions. the human endocrine system is complex. i don't know that shortcuts are the right way to think about this. i know the 11-oxo labs are rare. i can only get them from labcorp and they are a pain to find a location for where i live in michigan. i have to drive about 2 hours to go there.

u/AdriTexX · 4 points

Oh ok, thanks for you reply! I thought you could indirectly know but no luck for me :/

u/Cassady1AndOnly · 13 points

Ah, I'm amongst the really thin type with the 'elvish' features and you just started me on the same treatment recently. I always have had a nightmare of a time gaining weight, I've weighed as low as 110 lbs at 5'7". Highest was 144 lbs when I was a heavy drinker (10-20 standard drinks daily in the years leading up to, and the first 18 months of HRT), when I quit, I rapidly dropped to 110 lbs in about 4 months, stable at 125 now. Puberty was super late for me too, I was 65 lbs and 4'10" when I started highschool (15 y.o.) before rapidly jumping to 110 lbs and 5'8"-ish (17 y.o.). I was still going through changes of male puberty at nearly 30 y.o. when I began to medically transition to female.

I've assumed that I'm as pale as I am due to anemia, however, that can't have always been the case, I've always been pale enough that you can see the blueish veins all over me.

It's interesting to mention what appears to be masculinization when stressed out really bad, that has definitely happened to me several times over the years. I'll pay more attention to this now.

Edit I have gone through periods of time where I suddenly wanted to appear androgynous, or even wear a binder and try to present masculine for the day. Having thought on this overnight, that has ONLY happened when I was at my most stressed out periods of time over the past few years. Hellish work environments were the biggest trigger, once it was during a time of sexual harassment (though I consciously dressed different to get the person trying to make advances to leave me alone), or during other times of major turmoil (relationship problems or financial).

Typically, by the end of the day on such days, I'm hit by major dysphoria and can't wait to get out of such clothes and back to dressing as what I feel is femme for myself.

u/Drwillpowers · 12 points

I do have a legitimate concern that the treatment of some of these people, on HRT, will result in reversed gender dysphoria.

I've seen it reverse in those pre-HRT, but my nightmare is taking somebody who's deep in the transition, fixing their health, and causing this to happen.

u/Cassady1AndOnly · 5 points

Simply an extreme example of cost vs benefit then should that occur. There's simply no easy way to approach such a situation, hopefully more research will shed light on this.

u/baconbits2004 · 3 points

that reverse-dysphoria happened with me on the methylated b vitamins (twice. I did 2 trials of it, to make sure I wasn't just getting in my own head or something the first time).

if the medrol pack I'm on right now functions similarly to hydrocortisone... I think I am going to be filled with euphoria lol.

it's how I have been since I started this last pack 3 or so days ago. idk if it's the swelling going down or what, but my face looks more feminine, and it makes me happy. I haven't noticed any reversed dysphoria-type symptoms any of the times I've taken these packs.

u/Drwillpowers · 6 points

It does. They would share the same glucocorticoid replacement function.

u/baconbits2004 · 5 points

thank you c:

the more I read, the more interested I am in what my test results will show, and learning how all of this stuff comes together.

this current medrol pack I'm on is the first I've taken with Meloxicam, if I'm remembering correctly. it's the best Ive felt in such a long time lol.

I worked out today, for the first time in... quite a while. I guess I got a 'runners high' from it? I've never really felt positive emotion from working out before (in my life!).

normally I just felt anger while lifting weights. same with running / cardio.

u/[deleted] · 2 points

What specific body type would you expect in someone who might have their dysphoria reverse after being treated for this?

u/LaurentheSexDoctor · 13 points

u/Drwillpowers Okay, my mind if officially blown by all this. Other than newborn screening for frank CAH, if you are biologically male, who the heck is checking for oxo-androgens? The mainstream articles just dismiss this outright because elevated androgens in bio males is considered insignificant. And any NCCAH screening I have been taught is strictly 17OHprogesterone in cis females with a presentation similar to PCOS that maybe doesn't add up all the way. I even pulled my 1000 page Yen and Jaffe's Reproductive Endocrinology textbook out to try and understand more about 11-oxoandrogens but THEY AREN'T EVEN LISTED IN THE FREAKING BOOK. Considering that 11-oxoketoT and 11-oxoketoDHT is as potent (or maybe even more potent?) than regular T and DHT, this is insanity that these are not at least offered or taught or even mentioned somewhere in any standards of care for trans women. Wow. Bonkers. I mean, am I missing something here that mainstream medicine is teaching about how to better screen for this that I just totally missed? Most definitely going to be offering this test more often to my patients. Part of me wonders if this should maybe even just be part of the standard lab sets. I mean, if they have undiagnosed NCCAH, why not catch it sooner rather than later?

u/Drwillpowers · 12 points

Welcome to my life.

Every time I stumble into something I'm like.... Why is this not even looked at?

I think the answer honestly is that in the past, the solution to make MTF people go away was to give them their 2mg estradiol and 200mg of Spiro per day and they would leave the doctor happy. Nobody really cared to look any deeper or try and improve on that.

The amount of 21 hydroxylase issues in trans people though is absurdly high.

u/unexpected_daughter · 3 points

I think a big part of it is a disturbingly large number of doctors scraped by on their organic and biochem courses (I went to school surrounded by pre med students, cheating and the use of old test banks through their social circles was rampant), and are lacking in fundamental confidence in their chemistry skills. I’d then ask those pre-meds why they wanted to be a doctor, and a disturbingly large number of them cited reasons other than the actual job of helping people. Money, family pressure, prestige, job security.

I’ve in turn found a shockingly high percentage of doctors I’ve interacted with over the years become immediately defensive whenever chemical names start rolling off my tongue.

When doctors start claiming estradiol can covert to testosterone, when they can’t tell the difference between bioidentical progesterone and medroxyprogesterone acetate, or they think dosing route for estradiol makes no difference… you know the bar is in hell.

u/anaaktri · 1 points

Can you re iterate this in layman’s wording? Reading all of this is like trying to understand Japanese. 😊 I’m chronically ill, i just got on a 5 day methylprednisonolone pack and it’s the best I’ve ever felt. I feel like a normal human. I suspect this is me. Is there a permanent solution to what this may be?

u/GeeAyyy · 11 points

This sounds so much like my wife, I'm going to make a note to bring this up to her, and see if she wants to contact her doctor! Thank you for sharing what you're seeing, to help the community at large. 💜

u/TheSushy · 8 points

Hi Powers and friends

> If you take the medicine for awhile, and then suddenly run out and stop, you can quite literally die of an Addisonian crisis.

Can you explain the healthy process if a stop is needed?

Also, a genome test would be able to tell me if I have the specific gene mutations?

u/2d4d_data · 7 points

Disclaimer: I am not a doctor, but the healthy process to stop (is probably, again see your doc) would be to taper down. Clinician supervision and a full understanding of how to take this is a must for anyone that is on it.

u/2d4d_data · 7 points

>Also, a genome test would be able to tell me if I have the specific gene mutations?

Checkout the CAH wiki pages on this. Some forms of CAH are much harder to detect so you want to use certain services if you want that, but yeah a lot of us are getting tested and I am regularly seeing new dna from the community.

u/TheSushy · 2 points

Thanks for the response!

u/Primary_Opal_6597 · 9 points

I’ve long suspected my adrenal glands have absolutely no idea what is going on most of the time lol

u/Drwillpowers · 9 points

/u/2d4d_data

u/2d4d_data · 15 points

Just going to echo to never consider hydrocortisone without clinician supervision. Incorrectly used Hydrocortisone treatment is associated with death. This is not what the average person with gender dysphoria needs. And even if you consider trying it with your doctor, there are many things to try first!

And to be clear you can have chronic anxiety without this being the appropriate treatment. We have been talking about Hydrocortisone for well over a year and every time I thought it could work I have gone to see if I can find a different solution first.

Edit:

On the pale skin question, a piece could be how Progesterone lightens the skin, estrogen darkens the skin. https://pubmed.ncbi.nlm.nih.gov/27115344/ Here we have a group of folks that estrogen signaling insensitivity (aka low estrogen activity) and also major cortisol production issues so they would have very high progesterone levels. Sure they probably also have Vitamin D deficiency and MC1R genetic variants, but they might only be nudges compared to the progesterone/estrogen or vice vera. Skin tone is complex.

u/nonbinaryatbirth · 8 points

This makes total sense to me especially considering my medical history, 25 weeks gestation birth (June 1982), normal development, have asthma still as well as vocal chord palsy due to intubation for oxygen til age 3.5, (could hydrocortisone possibly jolt vocal chord out of paralysis?),

always felt worn out most of my life until i started hrt in dec 2019 when i had a huge jolt of dopamine but that then subsided over the next 3 years or so...also figured out in the meantime that i have ADHD (inattentive) and started on rubifen a couple of days ago.

I'd love to be able to contribute in some way if i can to this if i can.

u/2d4d_data · 5 points

If you get super depressed on rubifen, ping me, and obviously hang out with someone safe until it wears off.

u/Aural21 · 7 points

Hey. I think this is me. I'm crying at the thought of relief from what my life has been. Because when I take cortisone from -any- source my stress disappears and after a week of prednisone feel like a normal human being but it never lasts.

I'll message Sommer on the portal.

u/[deleted] · 7 points

The most euphoric I have ever felt was on prednisone, which is the total opposite response from most normal people that become very irritable and angry. Maybe this could explain why.

u/Drwillpowers · 6 points

I'll make sure I educate her about this.

u/Aural21 · 5 points

You wonderful man

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u/Drwillpowers · 5 points

I'm sure she would be happy to discuss it with you.

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u/tiramisutra · 8 points

Thank you for posting. This is the best description of my 21 yo mtf daughter I’ve ever seen. She’s seeing multiple specialists for her symptoms which include inability to tolerate stress, high anxiety, chronic pain, CFS/ME, sleep issues/narcolepsy, low energy, paleness etc. She’s quite tall though and very underweight; has a serious Diet Coke(caffeine) and salt addiction . We’ve been wondering how one person can end up with so many different symptoms and possible diagnoses and your theory captures many of them. Probably won’t discuss hydrocortisone treatment as she’s not great at following medical protocols (took herself on antipsychotics and antidepressants cold turkey) but will be following for more results and possible alternatives.

u/Drwillpowers · 11 points

Honestly, she sounds like a textbook version of this.

And really to that, if she did get the treatment, she would likely feel overwhelmingly better quickly. People are generally incentivized to take medications that actually make them feel better instead of ones that don't feel like they're doing anything or make them feel worse.

But I don't really expect that you're going to find some possible alternative to that. Because that's quite literally a genetic defect, and it's fixed with a medicine.

Assuming that I am correct that this is what's wrong, but it sure does sound like she is textbook.

u/Drwillpowers · 3 points

Incidentally, every single thing you describe would fit within my theory. So I don't know which ones you thought weren't part of it. But I could explain to you why each one is related.

u/Laura_Sandra · 2 points

> possible alternatives

Well don´t know if you have seen it ... here were a few things that could be discussed.

Its basically some readily available supplements that may make for improvements if she has this condition ( can confirm ).

This way there may only be few Hydrocortisone necessary in times of elevated stress, like a quarter or half of a pill.

u/tiramisutra · 2 points

Thank you! Just out in an order for some of that. Hoping she’ll try it!

u/HiddenStill · 7 points

How safe is hydrocortisone?

It seems to be a corticosteroid, and I've used another corticosteroid, prednisone, for controlling swelling after electrolysis. I read up on it and and the potential side effects are scary, especially with long term use. I get some people need it, but I'm quite worried about using corticosteroids even when prescribed by a doctor. I try to keep it to a minimum.

I also got a topical corticosteroid prescribed before as well, and then I read that it should never be used on your face as it can damage the skin.

What are the possible side effects of this stuff, and are they reversible (apart from the dying bit)? Do all doctors know how to manage it, or is it more specialist?

u/unexpected_daughter · 11 points

Hydrocortisone is just another name for cortisol, which all humans produce naturally and is essential to life.

Consider that humans need a specific amount of insulin to be secreted per unit of glucose in the blood (ie, in response to rising blood glucose) to maintain glucose homeostasis in our blood (prevent hypoglycemia or hyperglycemia). Failure to do so can mean death. People with diabetes supplement synthetic insulin to make up for what their body doesn’t produce (enough of) naturally. But if you don’t have diabetes, injecting insulin will just crash your blood glucose. A big enough insulin overdose can cause such profound hypoglycemia as to cause death.

A gene mutation causing a human to produce insufficient cortisol at the right times can cause numerous widespread neurobiological health problems. Supplementing the right dose of cortisol would then only be making up for what the body doesn’t produce (enough of) naturally. Goes back to Dr Powers’ point that for people with low cortisol, supplementation might be very helpful, while for everyone else it’ll only produce side effects.

u/DeannaWilliams222 · 7 points

https://www.cancer.gov/publications/dictionaries/cancer-drug/def/spironolactone

i guess you didn't know that spiro is a corticosteroid. commonly used in the united states by doctors for transgender HRT purposes (as well as other uses).

just because one drug is in a group along with another drug, does not mean the two drugs share the same side effects and risks profiles.

u/DeannaWilliams222 · 6 points

> How safe is hydrocortisone?

safe enough that they ran this study: https://pubmed.ncbi.nlm.nih.gov/11089449/

this one may be more of interest to you: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929907/

or this one: https://pubmed.ncbi.nlm.nih.gov/26868122/ > This method of androgen deprivation is largely available, cheap, and nearly devoid of toxicity.

u/learning_the_lyrics · 7 points

Go Dr. P! USING YOUR SUPER POWERS FOR GOOD

u/suomikim · 7 points

I did some oncology work... it was a low risk side effect of the cortisone that is part of the protocol that some of the patients would have temporary diabetes while on the cortisol, or after it was removed. In a smaller subset of cases (usually with children who had family with diabetes) the diabetes would eventually become permanent (there's several rounds of the cortisol treatments during the two year treatment protocol.

so, yeah.. not something to try without doctor's evaluation that this might be the case, and supervision of the protocol.

i am glad that you wrote about this, as I did rarely come across pts where i wondered if something along those lines might be the case.

u/Drwillpowers · 3 points

Thanks for chiming in. It's always good to have other providers involved in the discussion!

u/baconbits2004 · 5 points

I fit this pretty well

except

I am a fatty 😒

sounds like this will turn me into even more of a fatty

u/2d4d_data · 3 points

Yeah it will raise your cortisol and increase weight gain. The fact that you are not underweight suggests that this wouldn't be helpful and could be risky. There are other things that can be tried first about anxiety etc.

u/baconbits2004 · 1 points

we will see what he thinks (risk vs reward). I am on wegovy already. perhaps there is a way to balance it so that I don't gain weight? 🤔

plus, being able to move again regularly without feeling winded/in pain would be incredible. I could maybe even workout again. that could also help? I don't really know how much of a weight gain we're talking about here...

ive been having a myriad of health issues related to an autoimmune condition, and on Methylprednisolone semi regularly already.

I try to push through without it, but it's starting to look like doing that might be affecting my heart lol.

when I was in the ER the first time, one of the ideas the neurologist talked about was potentially being on a steroid fulltime, but he didn't say much more than that. I think he was hoping to get a specific diagnosis before saying 'this is what you need to do'. 🤷🏼‍♀️

u/rawayar · 5 points

elves and dwarfs 😂 it's so true.

so let's say someone fits this to a T and cannot get a doctor's help on this. The goal would be to cut out the stress, right? Not possible for everyone. But in theory, with a good therapist and a good grip on life, minus one source of stress, if a person can cut that source of stress out, this would totally solve the issue? or mostly? or not at all still?

u/Drwillpowers · 6 points

These people can produce some cortisol. Just not enough to deal with high levels of stress.

Things like therapy, antidepressants, stress reduction, overall improvements in health, better diet, better sleep, all of those things would support this problem.

Ultimately though, if it gets bad enough, it's not solvable via other means. A type 2 diabetic can improve their quality of life by changing their behavior. A type 1 can't. They just need insulin. Without insulin, they die. There's no behavioral modification they can do.

u/Laura_Sandra · 2 points

> support this problem

Here are a few things that could be tried out.

This way there may only be few Hydrocortisone necessary in times of elevated stress.

And we had this discussion before ... with this condition the Amygdala may be enlarged and may make for a much higher stress and fear response ( but as upside also for more sensitivity and a better pattern recognition etc.). Its also discussed in the RCCX theory. And many people may also have C-PTSD.

u/ericfischer · 8 points

I've got the anxiety, hypothyroidism, poor stress tolerance, and high heart rate, but my brain fog is now controlled by levothyroxine, and I have high BMI now in middle age. My sodium is normal because I eat a tremendous amount of salt every day. How masculine or feminine I look oscillates with my health. My heat intolerance makes me suspect I have adrenal problems, and I would love to know whether this hydrocortisone treatment (or anything else) would help with it.

u/pilot-lady · 4 points

According to wikipedia, the half life of hydrocortisone is 1-2 hours but the duration of action is 8-12 hours. What's the mechanism by which the duration of action is so long compared to the half life?

And also, even with a duration of 8-12 hours, how does this effect dosing? Are you giving these people once daily oral hydrocortisone? Or more frequent dosing? What happens if a dose is missed? With such a short duration and the possibility of an Addisonian crisis, it seems like a recipe for a "constant spike & crash" type of situation, especially for fast metabolizers, which sounds really unpleasant, and well, dangerous if the crashes can lead to death. Have you noticed anything of the sort in the patients you're treating with this?

u/Drwillpowers · 10 points

So initially, I've been using hydrocortisone as it's easier to deal with, and dosed three times a day.

There are longer acting alternatives such as fludricortisone.

The reason I use hydrocortisone now mostly, is because of the fact that it's short. These people don't always need the drug. Some days they don't need it at all. Stressful days they might need a little more. The goal is to use the minimum possible amount. If somebody is full on addisonian, that's different.

But if I'm correct about this hypothesis, these people have a medical condition which is not very well recognized right now by the institution.

When I do something like this, I get terrible imposter syndrome, because the idea that there's this missing diagnosis out there that tons of people have and that is going untreated and that somehow some family doctor from Detroit figured out seems implausible.

Because I question myself constantly, I do not allow myself to write things that could potentially harm somebody. Therefore I'm always exceptionally cautious with things of this nature.

So as a result I tend to use the weakest, lowest, safest option available until I'm absolutely positively sure that it is a net benefit for the patient. The results with this have been so overwhelmingly positive in the patient's treated that it's hard to not say okay, this is real. But at the same time, you never know. I finally now felt confident enough to make the post. But I've been thinking about making it for a year.

Some of these people I may later move to something else, but for now, I'm erring on the side of caution.

u/Laura_Sandra · 6 points

> But if I'm correct about this hypothesis, these people have a medical condition which is not very well recognized right now by the institution.

Its not recognized at all. But its real. I had numerous med people know that something was wrong with me without being able to put a finger on it. Only with the RCCX theory and the MPS data things started to make sense. And a MTHFR mutation makes things worse.

Its a real thing, and when you know what to look for, you will start to find it.

Untreated it can be a huge hindrance in life.

u/Drwillpowers · 7 points

Dr. Sharon Meglathery's contribution to where we've gotten with this should not be understated.

Her RCCX theory gets a lot of this right, but I see it from the lens of the gender dysphoria part of the Venn diagram so my patient population has certain specific anomalies more common than in hers.

u/Laura_Sandra · 7 points

I started from your segment and followed your search for the common conditions in trans people and after seeing the RCCX theory, a lot of things started to come together. Many of the things Dr. Sharon Meglathery described are textbook running in my family.

> people have a medical condition which is not very well recognized

This condition as said is not recognized at all. I had med people multiple times state that something is wrong, and just kind of saying its the way some people are. Only few are willing to do tests ( which may then produce nothing substantial if people do not know what to look for), and some old school people may even be adverse. I had a relative who also was a med person tell me I would produce breakdowns on purpose with things I don´t like while in reality I was overwhelmed with stress and could not function at all. The gist from some relatives was to not be a weakling and to try to get my things together. I had up to 30 percent sick leave in school, so much that I said to teachers "I can´t know that, I was not there" if they asked me something, and they were used to that answer.

This condition needs to be treated because it can be a huge hindrance in life. I missed numerous opportunities because at decisive times I was overwhelmed and unable to function. Those opportunities would have been within the mental capacity but due to breakdowns could not be used.

If you look through answers of others, many trans people have this condition. Its real, and imo it comes with a number of connected issues like being prone to C-PTSD, and also being more likely to be neurodivergent ( an enlarged amygdala for example can be considered as acquired neurodivergency ).

I followed threads of others and one trans person recommended Phosphatidylserine. I tried it out and it helped a lot.

https://my.clevelandclinic.org/health/drugs/25129-phosphatidylserine

>The nutritional supplement phosphatidylserine claims to support:

Memory.
Cognitive function.
Attention and ability to focus.
Stress relief.
Sleep.

>The supplement also claims to target symptoms of:

Lipid imbalances associated with ADHD.
Depression and anxiety.
Alzheimer’s disease.

Webmd also says it is safe, its basically a bioidentical substance.

Here was more about it: https://www.braintropic.com/nootropics/phosphatidylserine/

It has a number of effects, a direct effect on the brain, like a relaxing effect, and also a blocking effect on the physiological stress reaction. For people who have this condition, it can be beneficial, for people who do not have this condition, it can over time lower cortisol. Otherwise as said its a bioidentical substance with a number of benefits.

And in general it seems that like with the trans community, and with the things that Dr. Sharon Meglathery discovered, people need to do things themself.

There is also a clear connection with C-PTSD, and this condition only starts to be recognized now. If you are interested, people like Patrick Teahan and Dr. Kim Sage are people who have this condition too and who are passed around in the community as people who try to be helpful, and who try to spread knowledge ( just like you, from their perspective).

And C-PTSD for example was included in the last edition of the ICD-11, which is used internationally, but not in the DSM, which is used nationally. Basically if it would be included, people would have a right of treatment, and there is pushback to not do this. I believe that a number of people know about the condition and that it is widespread, but due to financial implications it gets treated like a hot potato, which leads to people needing to do the work for themselves ( which imo is unacceptable).

But to recapture, its a real condition, and people need treatment.

If you still have contact with Dr. Sharon Meglathery, pointing her to Phosphatidylserine may help her with her segment too.

u/Lsomethingsomething · 3 points

>I followed threads of others and one trans person recommended Phosphatidylserine. I tried it out and it helped a lot.

May I ask what dose of Phosphatidylserine you took and what time of day? I'm interested in trying it myself. :)

u/Laura_Sandra · 2 points

I use capsules of 150 mg, 1 capsule per day sublingually in the morning.

I´d say try out how it works for you ... some capsules may taste a bit bitter so it may be an idea to try another brand in case. And some people use more, like two capsules of 100-200 mg per day, and some use even more.

In general it may be recommendable to try to titrate up slowly, like starting with one capsule for a few days in case you want to try more than one capsule.

And for some the effects are immediate, some say it takes 2-3 weeks until a full effect sets in.

u/Lsomethingsomething · 2 points

Thanks, I'll try that! :) May I ask what effects you noticed as a result?

u/Laura_Sandra · 2 points

For me results are immediate, its a feeling of calmness and being relaxed.

As said I know of some others who said it took a few weeks for a full effect to set in.

In general you may be more calm and more stress resilient, and you may also feel better.

u/Lsomethingsomething · 2 points

That sounds great! Is there a big difference between oral and sublingual administration, in your experience?

u/2d4d_data · 2 points

The problem with the RCCX theory is that it is saying that the 2-3 genes in that one segment of RCCX does everything when that is silly. That is like saying that your blood type determines your eye color and hair color. There are separate gene variants doing separate things.

Folate variants such as MTHFR and others that result in low b12 means lower dopamine. And fast COMT means lower dopamine. RCCX didn't cause my ADHD, these two combined together contributed a whole lot. Nearly every single trans woman has lower to deficient zinc. The zinc genetics are not in RCCX.

While I pay attention to the discussions on Dr. Sharon Meglathery's facebook group, it is passive because they appear stuck on the incorrect idea that everything must result from RCCX. Even in the initial discussion around 21-OHD + MTHFR we had already moved beyond that one segment idea and these days it is about identifying the larger set.

u/Laura_Sandra · 5 points

> these two combined together contributed a whole lot

Yeah ... a lot is in combinations ... if it would only be one factor, many things would have been found already.

And it is necessary to look for underlying mechanisms, and interdependencies.

But her conclusion that there is a whole array of symptoms that are interconnected imo was a huge step, and her listing of conditions that can run in families also made many underlying symptoms visible.

> pointing her to Phosphatidylserine may help her with her segment too

I was more thinking of her main area of expertise being a psychologist or therapist, and it may help in those regards ... many of the symptoms she described in her listings may be helped by it.

u/baconbits2004 · 2 points

>This condition needs to be treated because it can be a huge hindrance in life. I missed numerous opportunities because at decisive times I was overwhelmed and unable to function. Those opportunities would have been within the mental capacity but due to breakdowns could not be used.

>I would produce breakdowns on purpose with things I don´t like while in reality I was overwhelmed with stress and could not function at all. The gist from some relatives was to not be a weakling and to try to get my things together

I haven't had testing done for this yet, but holy cow we could be sisters... this sounds so much like my life lol. I'm sorry to hear someone else go through similar experiences. It's not fun. =[

Curious, do you have problems keeping your hands steady?

i get shaky pretty easily, when the anxiety comes.

But oddly, whenever my wife is scared about something, everything inside me calms down immensely.

ex: she's terribly afraid of storms. The other day I was driving us back from Michigan, and the weather was so bad I could barely see the road in front of me. There was what could have been the start of a funnel cloud in the distance... I could have performed brain surgery while driving that night.

If it were just me in the car, it would have been a completely different story lmao.

u/Laura_Sandra · 3 points

> someone else go through similar experiences

We really are not alone, many trans people have similar issues. It kind of comes with the territory ... if you have certain mutations, and additionally surroundings where you grew up with a family that also has issues like C-PTSD ( in the RCCX theory is a list with a number of things that can run in families ), this kind of development is not unusual.

I don´t shake much tbh, I have learned to kind of flatline when really in shutdown mode, and to not show signs ( to be less vulnerable). And at a certain moment it is possible I switch to a defense mode. I don´t know if you have seen this. Many people with C-PTSD have cluster like parts that hold reactions from trauma ... there are 4 basic possible reactions : fight, flight, freeze and fawn ( you may want to read Pete Walkers book where it is explained).

Due to dissociation there can be certain issues ... the feeling to lose oneself at times, the feeling to need to adapt to others, to be like a chameleon etc. Over time and with knowing it is possible to work more and more towards a more integrated personality ( and have less of a feeling of being stranded in one of the dissociated parts).

> whenever my wife is scared about something, everything inside me calms down immensely

I can relate ... its a fawn response. You basically are trained to be a calming influence, and to calm others.

I have read a comment of someone who had some degree of chaos at work and he said he was the only one staying calm because he was so used to it.

> If it were just me in the car, it would have been a completely different story

It is possible you would be in scanning mode then, not knowing what to look for ( and people with C-PTSD often do not deal well with uncertainty). It may help to concentrate on positive things, and to envision a good outcome. Like using dissociation for good this time, and seeing yourself arriving safe at home for example :)

I would really suggest to try out Phosphatidylserine, it may make a big difference. It helped me feel less overwhelmed and spaced out etc. And the methylated multivitamins may also help ... it may just be necessary to start them slowly, like with a fraction of a pill or the content of a capsule. And with sublingual use no huge amounts may be necessary.

u/baconbits2004 · 2 points

that... makes a lot of sense. when things were rough at home, I was always trying to deescalate things.

I do freeze and dissociate if the spotlight is put on me. if a 'tough' conversation starts, it's like I become a shell of a person, and don't remember what the conversation was about at the end of it.

I used to do this a lot more, but the big problem with it is I lose details and don't remember. hard to (for example) complete a task at work if I can't recall which step I was on.

if the argument at work is between someone else, I can calmly guide the affected person to a resolution.

I'll ask my doctor about phosphatidylserine at my next appointment. we are already working on blood work, plus I'm seeing another doctor (specialist) soon... I don't wanna throw too many ideas at him lol. he's helped me plenty so far. <3

I do have some rare gene variations that make me think I should stick with the methylated vitamins... but I didn't like the personality changes I felt when I was on them. or getting the most intense reverse-dysphoria from seeing myself with feminine features. happened with two separate trials of it. 🤷🏼‍♀️

I had hoped to see if the muscle weakness, brain fog, etc. type stuff would go away before the dysphoria kicked in, but it didn't. I just felt bad + extra dysphoric :/

u/Ok_Progress5565 · 2 points

There is a lot of research on inflammation and mental health disorders. Inflammation is higher in bipolar disorders, psychosis, schizophrenia, obsessive-compulsive disorder. They are testing anti-inflammatory drugs for these conditions. Gender Identity Disorder has similarities to psychosis, OCD, multiple personality disorders.

u/DakryaEleftherias · 3 points

This is interesting. Not sure if I'm within this case, since most of my feminization is result of surgeries and/or weight loss, and I'm smol.

u/spiramirabilis8888 · 4 points

May as well try and get the conversation started here: Is progesterone kind of a corticosteroid? It helps with just about all of these symptoms for me but I'm scared I'm giving myself steroid diabetes (etc) by taking it. Are the patients you see doing well on hydrocortisone ones who were unresponsive to prog? How does this interact with prog -> DHT converters?

u/Laura_Sandra · 2 points

Concerning bioidentical progesterone it may help to look up the metabolisation pathways, here was more: https://www.reddit.com/r/DrWillPowers/wiki/steroidogenic_enzymes_cah_eds#wiki_steroidogenesis_diagrams

And its not directly involved with cortisol.

And here might be a few things that could be discussed.

Its some readily available supplements that may make for improvements.

This way there may only be few Hydrocortisone necessary in times of elevated stress, like a quarter or half of a pill. And this cortisol basically would only make up for a deficit.

u/Girl-UnSure · 4 points

This partially sounds like me, except the super skinny part. But im not one of those smarter patients, so i just hope for the best Dr P.

u/LeapoX · 4 points

Hmmm, I fit this description incredibly well.

Question for your patients being treated with hydrocortisone: Did they experience cravings for sugar when estradiol levels were nearing trough, and did those cravings resolve with the administration of hydrocortisone?

u/Drwillpowers · 4 points

I have not heard of relationship between those things before.

That being said, when people feel shitty, for whatever reason, they seek dopamine to feel better. Often that's in candy or food or whatever.

Some people, they get lucky, and their addiction is to go to the gym. Other times, the addiction is food. Sometimes it's drugs. Humans are basically dopamine seeking machines. We are constantly trying to increase our general level of pleasure. Nearly every decision we make is to do this. Even ones where we deny ourselves pleasure, it's generally so we can give ourselves more later.

u/2d4d_data · 2 points

> Did they experience cravings for sugar when estradiol levels were nearing trough

I wonder if this is because they have low serotonin at that point and sugar is being used to raise serotonin via raising insulin. Trying to raise serotonin via walking, the gym or 5-HTP in those situations would be an interesting experiment.

u/[deleted] · 3 points

Why we have poor reports about spiro then? Since spiro rises cortisol shouldn't it help those girls?

u/2d4d_data · 12 points

Spiro raises your cortisol when you don't need it because spiro is an Aldosterone antagonist (different, but next door path), but also results in higher ACTH). For someone with any form of CAH this is not what you want to be on and just another reason why bica works much better.

u/Drwillpowers · 7 points

I love when you do my job for me. You might be better at it than I am at this point!

u/nonbinaryatbirth · 1 points

out of interest regards spiro (was given it as a baby to age 3.5 at doses of 50mg from birth and increasing every year by 25mg so was on 125mg a day age 3-3.5) and extreme prem birth (born at 25 weeks gestation in june 1982 and in the NICU for 11 months) as well as elevated cortisol (took blood sample pre coffee, vape, anything at 7:56am one morning and it showed 700nmol), have general anxiety, fatigue, don't really like surprises, can't concentrate properly even with adhd meds and more issues too, will be asking my doc more about cortisol, HPA axis which extreme prem birth seems to have had a hand in messing up and all going forward. any suggestions aside from that or what i should ask them about please?

u/NightFox747 · 3 points

Hello! I (like many it seems) fit most of the description mentioned in this post, and have been on E for about 1.5 years now. I thought everything was going well, but I had my first seizure last summer and then another this spring. Also for the past two years my stress level has been very high for other reasons, in addition to transitioning. All this said to keep it brief, I am trying to sort out this whole seizure business, and with the link to cortisol, do you think it could all be connected?? Sorry if this wasn't clear, let me know if there is anything I can clarify

u/Drwillpowers · 2 points

Do you take bicalutamide?

u/NightFox747 · 2 points

No, my only medications are E 6mg daily sublingual, and Prog. 100mg daily oral

u/Drwillpowers · 3 points

Seizure is apparently a very rare side effect of that drug which is why I ask.

u/NightFox747 · 2 points

My thought process was that possibly if something like this was going on, that with the high stress and limited cortisol that a previously non-manifested seizure disorder might be showing up. I've already scheduled with a nero, but I'm just terrified that they'll try to link it to the E and take it away, so I want to investigate what could be influencing, and I fit the bill for what you described, so it got me thinking.

u/Drwillpowers · 2 points

Well, certainly paying attention to your sodium and potassium and also renin/angiotensin system would be reasonable. Because electrolytes being thrown off can also trigger a seizure. And they can be linked to this.

u/[deleted] · 3 points

[deleted]

u/Laura_Sandra · 1 points

Ibuprofen may lower inflammation as discussed here: https://old.reddit.com/r/DrWillPowers/wiki/inflammation

And Cimetidine may make for some HRT like effects and a connected feeling, and it may make for less Cortisol being flushed out:

https://pubmed.ncbi.nlm.nih.gov/7307288/

>Effects of cimetidine on pituitary function: Alterations in hormone secretion profiles

>urinary free cortisol excretion fell 31%

u/FLO_THE_FLOWER_CHILD · 3 points

This is so depressing.

I’m 20, MTF, been on HRT for a bit more than 1.5 years with very good levels.

I’m underweight, 112 lbs for 5”8 and a bmi of 17. I’ve always been very skinny, pale and sick-looking, even pre-transition people have always accused me of having an ED (particularly my teachers at school). But that is NOT THE CASE AT ALL : I am constantly eating copious amount of food, because if I don’t, I loose weight.

I’m always extremely anxious. I have to drink tea, do breathing exercises, and mindfulness meditation x2 a day or I simply cannot function like a normal human being.

I have chronic fatigue, brain fog, dizziness, headaches and sleep problems and have seen so many doctors because of it…A sleep specialist, a neurologist, ent specialist and so on (I’ve never had my cortisol levels tested though). They always tell me that everything seems fine, I might just be too anxious and need to have a healthier lifestyle.

But I used to have a very healthy lifestyle though, and I was still SICK. I used to wake up early, meditate, eat a lot of fruits and vegetables, go for a walk, journal, see a therapist etc, I did everything I could and it didn’t work. I felt better overall, but my health problems were still there. But my doctors refuse to listen to me…

I overall had very limited breast growth from HRT. Other changes like softer skin, less body hairs etc seems to come and go periodically. In fact, my brother has pointed out to me how my face seems to weirdly morph from looking more fem to looking more masc sometimes.

I don’t like to self-diagnosed, but I recognize myself in everything that you just described. It’s exactly me. I live in a non-english speaking country in the middle of nowhere, and I honestly don’t really know what to do.

u/Drwillpowers · 4 points

Well, it does sound like this might be you.

So to that, I would find a doctor. That's going to be your first step.

u/FLO_THE_FLOWER_CHILD · 4 points

It’s gonna be really hard to find a doctor that is willing to listen, but I will try until I find one.

Nonetheless, thank you for being such an amazing and caring doctor !

u/Laura_Sandra · 2 points

> I honestly don’t really know what to do.

It may be an option to try a few things from here.

Here was more about Phosphatidylserine: https://www.braintropic.com/nootropics/phosphatidylserine/

Basically the things in the link may be helpful with a number of issues.

This way there may only be few additional Hydrocortisone pills necessary in times of elevated stress, like a quarter or half of a pill.

And here was a graph that could be discussed with a med person in case. A cortisol deficit was shown there.

And concerning possible tests here and here was more ( there may be some additional conditions though making for a cortisol deficit ... maybe it would be possible to discuss starting a low dose of Hydrocortisone and then seeing if it would make for improvements ).

u/FLO_THE_FLOWER_CHILD · 2 points

Thank you so much !

u/[deleted] · 3 points

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u/Drwillpowers · 3 points

Seems like a good idea to me. Not like she has much to lose. Worst case they just say no.

u/[deleted] · 2 points

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u/2d4d_data · 3 points

You could think of 'anxiety' as just the description someone might use (along with underweight etc) that causes you to go look into the cortisol production ability. This is about dealing with really bad cases of inability to create cortisol. It might be what Dr. Powers already mentioned, but there are lots of options such as someone having both 21-OHD and 11BD.

u/[deleted] · 2 points

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u/Drwillpowers · 8 points

I can't say for sure, because all I can use is what the patient tells me. But so far, initial reports have been overwhelmingly positive for those that fit the exact phenotype and respond this way to the medication.

If someone doesn't have an overwhelmingly positive response to it, I generally terminate it within two weeks.

u/BunnyThrash · 2 points

There’s feedback loops and down-stream effects. Like for stress and anxiety generally, a depressant is a good short term med; but a lot of anti-anxiety meds like tricyclics (decrease Reuptake of norepinephrine) or Clonidine (is an agonist of α2 adrenaline receptors). There’s so many ways that adding cortisol could be working: the most intuitive to me is that it reduces the stress burden on cortisol creating organs including the cortisol releasing hormones and the cortisol precursors; and that it normalizes the Cortisol-Awakening-Response which allows a disregulated HPA-Axis to renormalize.

u/BunnyThrash · 2 points

“””In secondary and tertiary forms of adrenal insufficiency, skin darkening does not occur, as ACTH is not overproduced. … Darkening (hyperpigmentation) of the skin, including areas not exposed to the sun – characteristic sites of darkening are skin creases (e.g., of the hands), nipple, and the inside of the cheek (buccal mucosa); also, old scars may darken. This occurs because melanocyte-stimulating hormone (MSH) and ACTH share the same precursor molecule, pro-opiomelanocortin (POMC). After production in the anterior pituitary gland, POMC gets cleaved into gamma-MSH, ACTH, and beta-lipotropin. The subunit ACTH undergoes further cleavage to produce alpha-MSH, the most important MSH for skin pigmentation”””

.

“”Impaired Steroidogenesis: Some medications interfere with steroid synthesis enzymes … To form cortisol, the adrenal gland requires cholesterol””

.

https://en.m.wikipedia.org/wiki/Addison's_disease

u/Appropriate-River-34 · 2 points

I have high levels of DHEAS ~1000 ug/ml and my doctor adviced me to try prednisolone 0.5 mg. However once I took it I got some reaction on my face in form of red pickles so I discontinued it. I also noticed that whenever I try any cream that contain hydrocortisone, which I used after laser treatment, I feel strangely weak.

I don’t have any other out-standings in laboratory, beside maybe highish DHT ~ 200 pg/ml. However my progress seem not to be the best even after 2 years on injections - which could possibly be due to high adrenal precursor androgens… I don’t know if I fit in this group since my BMI is not that low. But I do seem to have positive antibodies for Hashimoto ( which is still under control) and very low folate.

u/Drwillpowers · 6 points

I'm sorry but if you have a DHEAS over a thousand, and your DHT is 20ng/dl, your androgens just aren't controlled. Those aren't adrenal androgens. Those are just regular old androgens.

u/Appropriate-River-34 · 5 points

I currently do 5mg EV each 4 ½ days and my T is around 0.5 ng/ml both LH, FSH <1. So mono-therapy seem to work I guess in terms of suppressing LH/FSH and total T. I was taking low dose cyproterone for the first year of transition but then I stopped it.

DHEAS was elevated even prior to HRT, however it was back than ~700. Not sure if there is need to add something more to my therapy or I can just continue EV monotherapy since my doctors keep telling me everything is perfect … and I m kinda obligated to do DIY

u/FrostCat777 · 2 points

>I've also had a few cases of young "FTM" with this

Did the same treatment work for them as well?

u/Drwillpowers · 4 points

Yes, but strangely, it seems to reverse gender dysphoria more often in them.

I have not seen the elimination of gender dysphoria as much with treating this in a pre-HRT MTF.

Or even a post HRT one.

That being said it seems easier to eliminate gender dysphoria chemically without utilizing HRT in FTM patients far more than in MTF anyway. So it's not exactly a fair comparison.

u/FrostCat777 · 1 points

Thank you for the reply!

Huh... But what about those who still remained dysphoric? Did they have any issues with HRT or was it the other way around (easier masculinisation)?

Oh... So, proportionally, it's about the same as in those who don't have this issue?

By the way, that makes me curious, have you ever had patients with mixed sexual characteristics and/or severe hypogonadism - whether ItM or ItF - who fit this profile or had similar issues?

u/[deleted] · 2 points

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u/Drwillpowers · 5 points

I don't know the answer to that yet.

I don't have enough 11 oxo androgen panels at the same time as three alphas to be able to tell you.

If you're my patient, I will be more than happy to receive a portal message requesting that I place the lab order with LabCorp while simultaneously placing one with quest for the three alpha. I'm basically relying on my Medicaid patients right now who volunteer as tribute to advance the lab testing aspects of this, because they don't pay for anything. I don't like ordering lab tests of which I'm not sure are going to be clinically significant on somebody that has to foot the bill for them. I order a LOT of labs. But I try to only order what is actually going to change what I'm going to do for the patient based on the results.

u/Slg407 · 2 points

oh wow, i fit into this perfectly, might have to look into it with my doc

(also heyy again, Lia here with another weird idea, for patients that don't respond to anything in regards to breast growth, dinoprostone or bimatoprost intraductal injections! the idea here is that by injecting a small amount of a PGE2 receptor agonist directly into the mammary ducts, in a similar way to a galactography dye injection, you would stimulate the release of amphiregulin, the PGE2 agonist would then cause a cascade of positive growth induction by inducing COX-2 by activating the PGE2 receptor which would make more PGE2 and more amphiregulin and COX-2 resulting in a self perpetuating cycle of growth amplification)

u/Brilliant_Bet_2075 · 2 points

Dr, I have similar symptoms and don’t know if I have this and how can I find out if I do and how to treat it. I made a post stating more things that happened to me, if you have the time could you read it? Thank you! I feel like I’m going crazy and don’t know what to do…

u/VexhiaRose · 2 points

This description fits me exactly, except I am shorter. I have crushing chronic fatigue and brain fog, which causes me to have trouble concentrating, speaking, and with fine motor functions. I have a constantly high level of stress and physical tension, which further leads to exhaustion. How can I bring this up with my doctor to ask for treatment?

u/Laura_Sandra · 2 points

> How can I bring this up with my doctor to ask for treatment?

Here was more concerning one possible test, and also here.

And here was more in general: https://old.reddit.com/r/DrWillPowers/wiki/meyer-powers_syndrome_faq

u/[deleted] · 2 points

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u/Drwillpowers · 3 points

No worries. And cheers on finding a doctor who has an open mind!

u/Muted_Will_2131 · 2 points

For Dr. Powers, I found an interesting study that you may already be familiar with. https://www.researchgate.net/publication/6882269_Relationship_between_salivary_cortisol_and_progesterone_levels_in_humans Getting back to the topic of masculinization during stress, this study also confirms the release of progesterone by the adrenal glands in genetic males during stress. Given the backdoor conversion of progesterone, this may also be the answer to the cause of masculinization in MTFs. Many of the transgender people are under constant stress, which can provide constant production of androgens through the backdoor.

u/Drwillpowers · 1 points

I have not seen it!

There's just so many. We have set up a little algorithm that shows us potentially interesting studies, but it doesn't catch everything.

Thank you for sharing this. It is particularly interesting because this would give a secondary pathway for masculinization under stress in those that do not have NCCAH

u/OkEmployee5373 · 2 points

This is me but my body fluctuates between tanned bronze like skin to pale all in one day. Is there a way I could share my case with you?

u/Drwillpowers · 2 points

Actually yes, believe it or not, become my patient.

u/spiramirabilis8888 · 1 points

How does this work with autoimmune issues? I'm considering biologics or MTX for psoriasis+suspected psoriatic arthritis right now, have you seen any patients with untreated or poorly controlled autoimmune issues go into remission when you started them on hydrocortisone?

u/2d4d_data · 2 points

On the psoriasis, have you resolved any vitamin D deficiency (the first thing to check)?

u/[deleted] · 1 points

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u/Laura_Sandra · 4 points

> when I test morning and PM cortisol on these patients, its almost never "low". But it is almost always at the bottom range of the normal band.

Those would be people who have lower cortisol functioning, for whatever reason ( most common is 21-Hydroxylase deficit or non classic CAH etc.).

They should fall in the Elves- category.

The dwarf like people should be those with a higher cortisol functioning.

u/Drwillpowers · 6 points

Correct

u/FutureCookies · 1 points

huh, i fit this type to some degree with a few weird caveats that ive not seen in anyone else: my tests always come back with high cortisol levels but i don't really experience stress or anxiety. my resting heart rate is very very low too, i'm actually in very good health.

puberty did very little to me, i didn't even get body hair. i can't count the number of people who have said it's uncanny how puberty really missed me. i used to suspect low T but my first ever pre-hrt labs showed them as being normal, i sometimes wonder if i have an intersex condition but i was dna tested at a young age and nothing was ever mentioned about it.

i've never experienced a libido or morning wood or anything like that in my life. i consider myself completely asexual and i feel like i was born like this.

despite all this, im 3 years on HRT (injections and bica) with perfect levels but never seem to feminize. i pass on the virtue of just looking feminine and having feminine features. very poor breast growth, no fat redistribution, no skin changes, nothing.

in reference to the above i went through some pretty dramatic, traumatic experiences throughout my childhood that are probably beyond what would be considered typical even in trans circles but i've come out mostly unscathed considering.

i've never met anyone in my situation honestly, i would have said i must be resistant to estrogen but given that testosterone doesn't seem to have done anything to me either i wonder if i just have a really weird endocrine system. the only option i have left is to get an orchi and see if that does something, otherwise i'm completely out of ideas.

u/Silly-Witch · 1 points

i fit exactly this, like... cant stop shivering levels of fitting. i would love to perform riggorous testing and monitoring regarding this topic on myself. (and to share and provide as much data in case it can help with research)

where and how can i do this? either under Dr Powers or with my own team of doctors.

u/Laura_Sandra · 1 points

> where and how can i do this?

Here was a graph that could be discussed, and it may be possible to discuss and try out a number of the other things there.

hugs

u/PeriKardium · 1 points

What's the "long-term" plan with the steroid?

Hydrocort is definitely less potent than, say, Prednisone - which we do see occasional long-term use followed by long-tapers in Rheum (ie polymyalgia rheumatica); though still a persistent long-term exposure has it's risks (as you pointed out).

How are you approaching that aspect?

u/Drwillpowers · 4 points

Assuming somebody is doing incredibly well on it, eventually I would switch them to a low dose but longer acting form of something like fludricortisone. Then, monitor them for any sort of complication. The goal here is to use the absolute bare minimum possible to do the job.

Remember, if they are under producing, giving them what they would physiologically produce would make them no different than any other human.

Basically, if you're giving somebody the amount that would naturally be produced by an average persons adrenal glands, there should be no significant physiologic difference from them to anybody else who is healthy.

u/punk_cherry · 1 points

literally me except for the being afraid of horror movies part- thanks for the advice dr p B)

u/Transgoddess · 1 points

hmm, i fit all of this, but I'm not a small skinny elvish person 😗

u/Laura_Sandra · 1 points

Well I def. fit into the category and using a small dose of Hydrocortisone ( like 2.5 mg ) helps A LOT with stress symptoms, like feeling mentally and physically much better ( I get the Hydrocortisone at times for asthma ).

But my values of cortisol are not low but slightly raised with 190 ( range 60-184 ) ( no hydrocortisone was used a few days before the test).

I´m in a stressful time atm. So what is going on ? Should the levels even be higher due to stress ? Or something like this?

> problems with corticosteroid binding globulin

What would be the next step to test ? A cortisol stress test and a test of ACTH ?

u/Alysane · 1 points

Is heterozygous chr6:32041006 C->T (rs6445) a variant I should be concerned about with regard to remasculinization or poor feminization?

u/2d4d_data · 1 points

heterozygous rs6445 is a common (in our community) Nonclassic CAH. It is something to be aware of. Reducing inflammation and any hpa-axis requirements will reduce androgen production from the adrenals. The wiki has a bunch on this.

u/EisJess · 1 points

I suspect I have this when I drink alcohol and when I exercise long periods of time. How do I know? I can literally see the hair growing on my skin and starting to spike in such an extremely short period of time. Still figuring out what to do about this…

u/[deleted] · 1 points

I came to the same conclusion when I was experiencing remasculinsation during high stress periods, although I do present with hyperpigmentation, I prompted my endo to take a look into it for me, hopefully I can finally get some answers 😩

Having pretty much perfect levels, a slightly higher E but remasculinisation has thrown my medical support networks into a confusing mess.

u/Emma_stars30 · 1 points

My mosaic of all the problems seems to be slowly coming together. I have been off full HRT for about 2 months now and in the last weeks my condition has rapidly worsened and chronic stress and anxiety, insomnia, headaches, heartaches and palpitations have been added to the long term problems, plus I have lost maybe a third/half of my hair in that time, all without an external stress cause. I went through the CYP21A2 gene again and in addition to the orange heterozygous and apparently benign rs61338903, rs6474 and rs6472, I also found rs6467 (https://www.snpedia.com/index.php/Rs6467.. I am C/A, so carrier of allele for congenital adrenal hyperplasia?), which would fit in between the already potential health problems and the already discovered mutations above all in HLA-A/B/C, HLA-DQB1, HLA-DRB1, TNXB and COL genes and would also explain only partial feminization (resulting in higher 11-oxos and a general problem with peripheral androgens + without Bica absolutely minimal feminization + I also struggled from my 11 with acne, oily skin, stress, melancholic and depressive episodes, mood swings, OCD, difficulty gaining weight and slim figure).. I thought that my problem is mainly subclinical/secondary hypothyroidism (permanently higher TSH, thyroid ultrasound a few months ago revealed only microcysts, but it is a common disease in the family) and some unexplained autoimmunity in the background (which is also confirmed by WGS, symptoms and long-term positive ANA and increased monocytes) and also some connective tissue disorder, but it seems that it will be a mix of all of these and I simply fit into the category of patients with gender dysphoria who have many other associated abnormalities of autoimmune/endocrine origin and also genetic mutations not only within steroidogenesis.

I'm thinking about some kind of stimulation test or rather a 24-hour urine test for cortisol production, perhaps an MRI of the brain/hypothalmus/pituitary and probably also of the adrenal glands would be appropriate to rule out other possible causes and also checking 11-oxo androgens, but I'm not unsure how to proceed now. Is there any further examination or specific procedure that you would recommend for me now?

So I wish I could finally crack the puzzle that I've been solving basically since I started HRT 3 years ago, but also years before. I wish I could finally find a solution..

u/Drwillpowers · 3 points

I mean this is literally MPS. This is what I see.

Quest has a CAH steroid panel. The most accurate test I've found for this so far is that coupled with a morning cortisol, and ACTH and aMSH, followed by an hour of intense exercise, and then drawing the cortisol again 30 minutes after the end of the exercise.

Anomalies in the system, things like NCCAH show up often on this.

If the person has absolutely no positive testing results at all, I will do a brief trial of hydrocortisone if it seems like they have every other aspect of the thing even if I can't prove it on paper. If they get an overwhelmingly positive response to it, I then will allow them to continue carefully. If they don't, it's not the right answer.

u/Muted_Will_2131 · 1 points

Dr. Powers, I have a complex question for you.

I suspect high 11-0H androgens, but no tests have been done. My clinical picture is similar to what you describe.

By "lucky" coincidence, I have a neck injury after a car accident and my orthopedist prescribed me Prednisolone 20 mg for a month because of neck and head pain (Nurofen 2x600 mg / day for a month did not help me). Is it possible to recalculate the dosage from Hydrocortisone to Prednisolone, in this way to practically check my adrenal glands for hidden production of androgens? Or will the therapeutic effect of Prednisolone for treating the neck be insufficient?

Tomorrow (in 27 hours) I have an appointment with my Endocrinologist, and of course I will get some advice from him, but I very much doubt any action on his part, since previously he ignored my complaints.

u/Drwillpowers · 1 points

Taking that much prednisolone would vastly exceed what would normally be dosed for hydrocortisone.

So it would be more than effective enough to let you know if that made a difference for you.

u/anaaktri · 1 points

I had suspected this may be me & oddly enough I just got put on 5 day methylprednisolone pack and I feel incredible. So much less body pain, fatigue, less anxiety, less brain fog, depression basically gone. I actually feel alive and like I have a personality. What is happening?!

u/Sweaty_Bumblebee8002 · 1 points

Okay, so not trans but I'd say I'm a naturally masculine woman. I have non classical congenital adrenal hyperplasia, and i fit these symptoms. 17OHP 7000 ish. It's really hard when your hormones aren't right. Most doctors i see are nonchalant because there is no treatment besides maybe birth control or spironolactone. Neither have helped me. None of my endocrinologists monitored me regularly. testosterone stays over 100, my lipid panel and a1c are always out of whack on and off. My immune system sucks. Just got steroids for bronchitis and my muscles started hurting and felt that "kidney" pain which is probably just low potassium or angry adrenal glands since I'm messing with them now. So I got 2 days into the dose pack and decided to stop. Not worth it, but surprisingly my lungs felt better the first day like magic so win/lose i guess? I was always curious if estrogen would help, but all my doctors just look at me like I'm an alien with no idea what to do lol.... Just over here embracing my mustache, deep voice and female genitalia! Praying I don't end up with diabetes or heart disease! Any insight or advice is appreciated. Oh and what cured my panic disorder and somatoform disorder was clonazepam (low dose) which ... suppresses the HPA axis!

u/Drwillpowers · 2 points

I mean you literally have NCCAH. 21OHD. You need cortef and bica. Maybe fludrocortisone as well. Not sure why you're having problems getting treatment with labs like that.

u/Golurkcanfly · 1 points

Oddly enough, I've been having similar issues with chronic pain, brain fog, and mental health issues on HRT, but I don't fit the phenotype presented here. I am quite pale with chronic anxiety and brain fog (it worsened on HRT, actually), but am rather stocky and have experienced a solid degree of feminization. In addition, I do seem to remasculinize somewhat under stress, and my DHT levels are notably high (18ng/dL) compared to my Testosterone levels (35ng/dL). I also experience severe crashes in the afternoon, especially when I get home from work.

However, my older sister, who recently passed away from suspected ME/CFS, did follow the phenotype you describe. She was pale, skinny, chronically anxious, had bad brain fog, and experienced very poor feminization on HRT (one of the reasons I delayed my own transition).

How would you best go about testing for this? I am hoping to switch to a proper endocrinologist soon after using FOLX for my HRT because of some unusual issues I have had on HRT.

u/Drwillpowers · 1 points

I'm sorry to ask you something difficult but please clarify how she passed away from ME/CFS.

I mean they suck, but they aren't fatal. They're not a terminal illness.

Quest has a good CAH panel, pair that with a corticosteroid binding globulin and an ACTH.

Most of the people that have this if they don't have an NCCAH case, what I see is a 17 hydroxy progesterone of zero. Not low, zero.

Basically, they cannot make enough precursors because of the HPA suppression from hormones coupled with whatever genetic mutations they have, and effectively are operating a just in time economy for cortisol synthesis. If there's any increase demand on the system, there is no 17 alpha available to use to make the next step in the synthesis. It's just not there. So the cortisol level does not rise on demand.

Another way of seeing it on paper is to draw cortisol level, and then subject the person to a lot of physical exercise for an hour, wait 30 minutes, draw it again, and it goes down or stays the same. There is no increase in cortisol under load.

u/FloatingInHoney · 1 points

I fit this picture reasonably well - my BMI sits at the lower end of normal, rather than low, but I've always been described as slim/skinny/willowy. Very high anxiety. Brain fog, poor stress tolerance, [sometimes] lightheaded when standing up, poor feminization (despite adequate HRT and separate from low BMI). History of PTSD / C-PTSD or other [major depression, social & generalized anxiety disorders] Avoid scary things/anxiety provoking things/horror movies etc like the plague [but feel completely normal/focused during emergency situations]. Very pale rather than tanned.

+ chronic fatigue (with recent ME/CFS disgnosis, but long term history from late childhood following glandular fever) & sleep disruption/insomnia.

I was hoping that this may present a treatment option, but my cortisol just came back high, at 529 nmol/l 😞

u/Drwillpowers · 3 points

Run the corticosteroid binding globulin. And if you get really hardcore you can look at the code for the glucocorticoid receptor. Often those people have high cortisol but don't look like they do. It's because they are either insensitive to it or because it's bound

u/The_Dayne · 1 points

Commenting as I have a cool essay to share with you . Maybe we can collab on some ideas

u/Zealousideal-Ad-8330 · 1 points

Can I ask what is timeline for this treatment? i fit some of those descriptions, however I am cah 21oh carrier, it means I have one impaired gene but two are neccessary for it to be clinically significant. I however have cortisol spikes, have poor stress, caffeine and physical activity tolerance and my androgens are high resultint in pcos like clinical picture except that no typical pcos treatment helps me and I am lean with no insulin resistance homa-ir 0.9 Am I a candidate for such a treatment as well?

u/Drwillpowers · 1 points

Let me stop you right there and tell you that it takes only one for it to be significant.

I have absolutely seen hundreds of people with heterozygous mutations that end up affecting their health. So, yes, homozygous is what's necessary for you to be critically ill as an infant, but people with heterozygous mutations often present with symptoms in teen years or in their 20s

u/Terry93D · 1 points

almost all of this, almost all of what others describe, and almost all of what is described in other posts/comments related to this matches up with me. I have an appointment with Sommer in a couple weeks and will be pitching this to her—it has the potential to be a huge game-changer. my fingers will be crossed.

u/Noodle_nose · 1 points

If you theoretically had this, could it possibly be accompanied by tremors, PGAD like symptoms, could spironolactone exacerbate symptoms?

u/TheGamingEntity · 1 points

wait are you telling me my transition has been permanently ruined?

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