Which are the common medical tests to diagnose PAIS (grade ! & 2)

[Solange]

Hi there;

I'm new to this forum, and I would like to ask for your help. I would like to know which medical tests a person should have to be diagnosed with PAIS, the lowest grade types 1 & 2.

I understand that in grade 2 PAIS, hypospadias are present, so this is an indication that a person has PAIS? But with grade 1 PAIS where the genitals of the person are unequivocally male without hypospadias and the chromosome make up is XY, how can you tell?

Thank you for your help and please forgive my ignorance on the subject.

[Peggy]

Hi all,

Solange wrote,

I would like to know which medical tests a person should have to be diagnosed with PAIS, the lowest grade types 1 & 2.

Disclaimer - I am not a physician. For a reliable diagnosis, you should see a physician. (You are welcome tho share this post with your physician).

In a person who grew up male, has (as is usual in PAIS) functioning testes, and did not have a lot of hormonal treatment since puberty, it is very simple. The test is called a "testosterone challenge".

With no hormone medication for several weeks beforehand, the levels of pituitary hormones, (Lutinizing hormone = LH and Follicle stimulating hormone = FSH), estrogen, and most important, testosterone should be measured.

In PAIS, testosterone should be be high-normal to several times the normal values for males.

Estrogen should be normal to high relative to male norms - possibly within normal female range. (There is an area of overlap.)

LH and FSH should be normal to moderately high (relative to male norms).

If the hormone levels look like the above, if you have not taken any exogenous hormones since puberty, if your virilization since puberty has been much less than typical, and, especially, if you have had spontaneous breast development since the normal age of puberty, then is is very likely you have PAIS.

Basically, PAIS is caused by a weakened response to testosterone, but the testes are still able to make normal amounts of testosterone, and will even try to compensate by making extra to make up for what appears to be missing. (In almost any other condition where virlization is weak, testosterone is low, not high.)

A more common condition that can also cause weak virilization and, sometimes, breast development (but almost always with normally formed genitalia) is Kllinefelter syndrome (KS), characterized by a 47XXY karyotype, so a karyotype should also be done to rule out KS. In PAIS, the karyotype would be normal male = 46XY.

Sequencing the androgen receptor gene is more expensive and is often inconclusive in PAIS.

Question - why are you asking?

Friendly greetings to all,

Peggy

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"When art critics get together they talk about Form and Structure and Meaning.
When artists get together they talk about where you can buy cheap turpentine." - Pablo Picasso

[Schala]

My endocrinologist and also my family doctor were unwilling or (in the latter case) ignorant of how to do this.

Baseline pre-hrt: mid-range total testosterone, medium-high (for a male) estrogen (something like high-end but within 'normal' values).

LH and FSH within normal values.

Virilization was definitely much less than is typical. I started HRT (estrogen) at 23, slightly short of 24. I'm short, petite, lack much facial hair, no armpit hair at all, and no androgenized hair save pubic which is Tanner 4 for a male (or Tanner 5 for a female) ie: no hair above the pubic area going up. Voice is not clearly male or female, people are ambivalent to judge my voice if its the only cue they have to go by (phone). I have never trained it, and I smoke since I was 12 (scrapping it some since I'm 27).

I mentioned thinking of screening for AIS at the time, to my doctor who prescribed hormones (who is neither my family doctor or my current endo). He said my testes were normal, and so I couldn't be intersex (yes he touched them and declared me 'normal').

I mentioned it again to a psychologist and two psychiatrists, all of them mentioned it was very unlikely, without going for any tests.

I mentioned it to my family doctor. He ordered a karyotype, because he thought I might have XXY syndrome. Turned out I have at least some 46,XY chromosomes, so its unlikely (I'm also not tall or hypogonadal, which are hallmarks of the condition.) He didn't pursue the matter any further despite my insistance.

I mentioned it to my endocrinologist. He said something about having to drop HRT to test it and pay something like 1000 or 2000$ out of my pocket. He knew of no other way or alternatives to test it, I also don't have that kind of money. He disbelieved me as well about the possibility.

In other words: I got laughed at or was disbelieved for mentioning the possibility that my lack of virilization had a biological origin.

I don't really care wether I'm intersex and trans, or just trans. I'd still like to know, I'm the curious type. I mention to potential mates that I'm trans, otherwise they run the risk of not knowing til it comes down to sex.

[JOS]

...it's annoying they're just not more curious sometimes isn't it?

To be fair they're probably pretty tied up with other "urgent" issues but you'd think there'd be a certain amount of "I wonder if..."

especially when you do push issues and then it turns out it was all there in your notes if only someone had taken the time to figure it out :dunno:

[Aseras]

I think the two most common "bad" doctors you will find are the ones who ignore you and hope you go away through neglect or whatever and the ones who run every test under the sun, so much to nearly bankrupt you and then still give you nothing but a shrug.

I think you'll find is is very hard to find a doctor who know what they are doing enough to order thr right tests AND know what it means and where to look next.

These days it is hard enough to find a doctor slightly more competent than the burger flippers at a local fast food joint.

[fraulein_Maria]

[QUOTE=Schala;21638]My endocrinologist and also my family doctor were unwilling or (in the latter case) ignorant of how to do this.

>>> although you may (or may not) wish to be a father.... the doctor most likely (as an adult) to have seen PAIS is a reproductive endocrinologist... basically a fertility clinic.

I say this from long expensive experience with endocrinologists.... who seldom (regardless of what they say other-wise) are competent to dx or treat anything other than diabetes. <<<

[Aseras]

I say this from long expensive experience with endocrinologists.... who seldom (regardless of what they say other-wise) are competent to dx or treat anything other than diabetes. <<<

bingo, a regular endo is only good for diabetes and thyroid problems.

The only doctors I have had any luck with for my issues are gynecologists and reproductive endocrinologists.

[Peggy]

Hi Schala,

Hmm... do I know you from somewhere else in cyberspace, someplace where Cafe' Inter-lectuals like to hang out? If that's you, you are not far from where I live (a bus runs practically door-to-door) and perhaps you'd like to join one of the local intersex support meetings we have from time to time.

You wrote,
Baseline pre-hrt: mid-range total testosterone, medium-high (for a male)...

...my endocrinologist...said something about having to drop HRT to test it and pay something like 1000 or 2000$ out of my pocket...

You would need to discontinue HRT for a while only to get baseline hormone values, but you already have those. The 1 or 2 grand would be to sequence the androgen receptor (AR) gene, which is usually where the genetic mutation is that causes PAIS.

However, sequencing the gene would not really tell you anything you don't already know and perhaps (if they didn't find any mutation at all, which happens sometimes) it would tell you absolutely nothing. The gene sequencing is good for identifying others in one's family who could be carriers of PAIS, but it is not especially useful as a diagnostic tool.

In CAIS, sometimes the mutation consists of large amounts of DNA missing or disrupted. so something is obviously wrong (but in CAIS, diagnosis is easy to make from clinical signs once a doctor knows what he is looking for). In PAIS, the mutation has to be small enough so that some AR function is still left, which sometimes means that it is so small or subtle that it can not even be detected.

The AR gene also has "polmorphisms" or variations that have either no effect or only a small effect on function. Even the experts do not know enough about how the gene works to always be sure what effect a given change in the gene might have on AR function - whether it would cause AIS at all, or what grade. One of the leading experts on the genetics of AIS even told me that she is unsure whether there is really a meaningful difference between Grade 1 PAIS and "normal" variations in the AR gene that cause virilization to be weaker than average.

Geneticists are still figuring out the kind of mechanisms that might cause AR function to change from one stage of life to another, but it is plausible that it could change. Given the large number of people like one hears about who appear to have something like grade 1 PAIS , it would be a good thing for some researcher to look into this.

If you are anatomically "Grade 1 PAIS" (typical male), then obviously, you had near-normal function of the androgen receptor before birth. Your hormone levels also showed that if your virilization since puberty was weak, it was not due to insufficient testosterone. Knowing more about the exact mechanism that caused this to happen wouldn't change your situation very much. There is no blood test that will tell you whether you should live as a girl or a boy.

I don't really care wether I'm intersex and trans, or just trans. I'd still like to know, I'm the curious type...

I think it would be good if you could get clear answers to these questions: Could you get more virilization if you used supplemental testosterone? Would you be fertile as a male? I'm not trying to push you on that pathway but the ideal for decision-making is to know what all your choices are.

In other words: I got laughed at or was disbelieved for mentioning the possibility that my lack of virilization had a biological origin.

Of course it has a biological origin, it is a biological mechanism. ;^) The question is whether it would make sense to label it as a "condition" like "Grade 1 PAIS" or just as low virilization in an otherwise normal person.

I'm guessing (trying to charitable towards him) that your physician is reluctant to give you the "intersex" label because that would tend to encourage you on the path towards sex reassignment, and he probably views that as a very drastic intervention with many disadvantages. That remains true (from a practical point of view, as well as a moral one) whether you have PAIS or not. Nobody is handing out prizes for being "intersex".

• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
"When art critics get together they talk about Form and Structure and Meaning.
When artists get together they talk about where you can buy cheap turpentine." - Pablo Picasso

[Schala]

[QUOTE=Schala;21638]My endocrinologist and also my family doctor were unwilling or (in the latter case) ignorant of how to do this.

>>> although you may (or may not) wish to be a father.... the doctor most likely (as an adult) to have seen PAIS is a reproductive endocrinologist... basically a fertility clinic.

I say this from long expensive experience with endocrinologists.... who seldom (regardless of what they say other-wise) are competent to dx or treat anything other than diabetes. <<<

My endocrinologist is one of only two who will (and has) treated trans people (officially anyways) in the province of Quebec. So he's obviously more exposed to trans and intersex issues than your average thyroid endo.

[Schala]

Hi Schala,

Hmm... do I know you from somewhere else in cyberspace, someplace where Cafe' Inter-lectuals like to hang out? If that's you, you are not far from where I live (a bus runs practically door-to-door) and perhaps you'd like to join one of the local intersex support meetings we have from time to time.


I'm not sure. I live in sub-urbs north of Montreal. Town of Saint-Jerome, Quebec province. I don't know many local intersex people. I've been in contact with one in person from OII, the one responsible for the Genders in X forum, Andre Lorek.

Besides that, I know a few online, including Kailana.


You wrote,

You would need to discontinue HRT for a while only to get baseline hormone values, but you already have those. The 1 or 2 grand would be to sequence the androgen receptor (AR) gene, which is usually where the genetic mutation is that causes PAIS.

However, sequencing the gene would not really tell you anything you don't already know and perhaps (if they didn't find any mutation at all, which happens sometimes) it would tell you absolutely nothing. The gene sequencing is good for identifying others in one's family who could be carriers of PAIS, but it is not especially useful as a diagnostic tool.

In CAIS, sometimes the mutation consists of large amounts of DNA missing or disrupted. so something is obviously wrong (but in CAIS, diagnosis is easy to make from clinical signs once a doctor knows what he is looking for). In PAIS, the mutation has to be small enough so that some AR function is still left, which sometimes means that it is so small or subtle that it can not even be detected.

The AR gene also has "polmorphisms" or variations that have either no effect or only a small effect on function. Even the experts do not know enough about how the gene works to always be sure what effect a given change in the gene might have on AR function - whether it would cause AIS at all, or what grade. One of the leading experts on the genetics of AIS even told me that she is unsure whether there is really a meaningful difference between Grade 1 PAIS and "normal" variations in the AR gene that cause virilization to be weaker than average.

Geneticists are still figuring out the kind of mechanisms that might cause AR function to change from one stage of life to another, but it is plausible that it could change. Given the large number of people like one hears about who appear to have something like grade 1 PAIS , it would be a good thing for some researcher to look into this.

If you are anatomically "Grade 1 PAIS" (typical male), then obviously, you had near-normal function of the androgen receptor before birth. Your hormone levels also showed that if your virilization since puberty was weak, it was not due to insufficient testosterone. Knowing more about the exact mechanism that caused this to happen wouldn't change your situation very much. There is no blood test that will tell you whether you should live as a girl or a boy.


I transitioned to female (hormonally and socially) 3 years and a half ago, so I'm not looking for medical advice on wether or not to transition, that's an accomplished fact, and regardless of consequences, I'll also have surgery (once I can afford it).


I think it would be good if you could get clear answers to these questions: Could you get more virilization if you used supplemental testosterone? Would you be fertile as a male? I'm not trying to push you on that pathway but the ideal for decision-making is to know what all your choices are.


Since I don't produce sperm, I'm very unlikely to be fertile as male. I never produced sperm. My endo explained that away as ejaculating "inwardly". I totally don't believe that though.

I also don't want more virilization. I want feminization. It's been pretty effective so far.


Of course it has a biological origin, it is a biological mechanism. ;^) The question is whether it would make sense to label it as a "condition" like "Grade 1 PAIS" or just as low virilization in an otherwise normal person.

I'm guessing (trying to charitable towards him) that your physician is reluctant to give you the "intersex" label because that would tend to encourage you on the path towards sex reassignment, and he probably views that as a very drastic intervention with many disadvantages. That remains true (from a practical point of view, as well as a moral one) whether you have PAIS or not. Nobody is handing out prizes for being "intersex".


I'm already on a path towards sex reassignment surgery, and he probably knows very well I'm not about to change my mind - I would have been screened beforehand, not 3 years after starting estrogen and anti-androgens.

By the way, anti-androgens have had no ill-effects on me. Contrary to popular beliefs that reducing testosterone will reduce libido in a trans woman, it increased mine. I was barely sexual before, I could have qualified as asexual. Now I'm pretty sexual, and my boyfriend can testify to that - though my genitals are less responsive than before, which is normal - takes very little testosterone to affect genitals and give unwanted erections.

I don't want a prize for being intersex. I really just want to know, both for my intellectual curiosity about myself and the world, and personal curiosity about how I ended up looking like a 18 year old girl at 27 years old, when raised as a male, with normal androgen levels until nearly 24 (anecdotally, from what I've seen, trans women who transition past their 20s often need lots of cosmetic (permanent and costly) changes to look female enough to be seen as cissexual).

[fraulein_Maria]

[QUOTE=Schala;21691]

I don't want a prize for being intersex.

>>> most posers do. Please forgive Peggy and the rest of us for any sckepticism that may be unwarrented. <<<

I really just want to know, both for my intellectual curiosity about myself

>>> no prob. though you should have been tested for an IS condition before anything else was done... that's protocol.... and possible why Peggy was suspicious. The test for PAIS is actually quite simple.... its a tissue sensitivity test for androgens.

Another test that can be done is an HCG test though that is more dangerous, and not doable any longer if your testis have been removed.

Good luck

[Peggy]

Hi Schala (& Fraulien Maria),

Nothing I wrote was intended to express skepticism or as an insinuation that you are not being honest.

What I meant about there being no prizes for being intersex is that having a condition with the "intersex" label would not change your situation much from what it would be if you were just a biological male with weak virilization.

Peggy

[Aseras]

Being intersex makes everything MUCH more complicated. It's not an excuse its a curse.

[Kailana]

Being intersex makes everything MUCH more complicated. It's not an excuse its a curse.

Agreed, perhaps life really woudln't be so bad, if the medical community hadn't of chosen to make being intersex an abomination that shouldn't exist. See that attitude we all are living with, ie the consequences all have experienced because of standing treatment protocols it has become much harder to get help becuase we have been labeled as not normal human beings, and our treatment has seldom been up to us to decide instead doctors and parents have chosen what we are to be.


Oh and by the way I do want a Prize.

Specifically I want the entire issue over my genotype validated and clarified because i am quite sure that I would be the 1st Intersex True-hermaphrodite genetic Xx(whatever deletion or translocation error that is present) female to serve in the US Army in a Combat MOS with a Honorable Discharge and successfull carreer in what is considered a our current Army that will allow other intersex people to indeed serve with honor in our Armed Services if they so choose too.

Quick questioin: Has anyone posted links to Xx Males showing banding patterns and the difference in normal women and men to compare what is commonly found and why often an Xx Male is mistakenly misdiagnosed as XY?
Will provide links if anyone is curious.

[spacegirl]

Hi Kailana,
What are banding patterns?

Regarding intersexed in the american military, in times gone past when being drafted was the norm, like in world war 2 where everyone vaguely fit was cannon fodder, there might have many xx males who served with distinction, but I wonder if anyone has tried to find out which veterans were later tested and found xx?

Maybe your mosaicism was the only thing that kept you in the service? I know of one xx male who in the mid-80's was in the service for just until a dna test came back (part way through boot camp) Then he was medical discharged with no officially specified reason.

[fraulein_Maria]

[QUOTE=spacegirl;21792] I know of one xx male who in the mid-80's was in the service for just until a dna test came back (part way through boot camp) Then he was medical discharged with no officially specified reason.

>>> the military was embarrassed. they are supposed to perform a pelvic exam on EVERYONE before entry and declare 4-F anyone with with missing or damaged gonads.<<<

[Kailana]

they only will declare someone 4-f if they require any kind of medical treatmetn that may limit their duty or ability to perform while in the service. which these days is a load of crap as tons of meds are being used for many reasons for mental conditions and soldiers are still serving.

REally the only time you arent allowed to serve is if there are any medical isses that would limit your ability to do your duties.

I had none that they were aware of, and even as a true-hermaphrodite as an assigned male there are no limitations on not serving as there is for a female assigned true-hermaphrodite.

And most conditions if they are fixable and enough recovery time has passed to show that your ok, and whatever issue might of been a problem us taken care of then you can serve, basically can get the 4-F waived as long as there arent any other problems.

Very few people seem to actualy read medical restrictins by the way.

oh and the banding patterns in lamens term is the reference range for the size of the Chromosomes, an X Chromosome is much larger then the Y normal rang is 550-650, where the little Y is typically 275-350, there is often some variation to do micro-deletions, now the real issue is that if you dont fit the 550-650 range often with the simple blood karyotyping a false Y ends up being found, sort of like a
If the banding pattern is within 550-650 then its a X, Else its a Y.

and generally that is how mistakes are made, typically a Xx(var) male will infact run anywhere below the 550 down to 450 usually, my issue is actually that I only have my newest report that unfortunatlely states Banding resulution at 400, so there is a little confusion for me if that is the same thing as the banding pattern, sorry I am not that smart, and I do know I have a Translocation error but its on the 20th Chromosome, I however didn't get an explanation of where the extra material was coming from so again yeah I do have lots of records, fairly new, but doesnt do much good when noone acknowledges that there is a known error present that is documented but they have chosen not to explain what it means. Although my last endo did say it was not a translocation from the Y chromosome, and I am questioning whether or not I actually have a Y. sort of like it looks like a Y but its kind of bigger and the error they show on the 20th Chromosome is obvious cause its really large and circular. which it should not be. and as I dont really feel like trying to figure out how to post a pict, large Jpeg if you know how to get picts to post, large ones then i can email what i am trying to explain if your really curious.



I have te other karyotype from 2005 that does state the banding pattern is between 550-650, but all the other data conflicts with the normal male 46XY karyotype, and all the complete and partial chromosomes that are not explained what the complete or partials mean and I do understand why none are willing to do so.

[Kailana]

[QUOTE=spacegirl;21792] I know of one xx male who in the mid-80's was in the service for just until a dna test came back (part way through boot camp) Then he was medical discharged with no officially specified reason.

>>> the military was embarrassed. they are supposed to perform a pelvic exam on EVERYONE before entry and declare 4-F anyone with with missing or damaged gonads.<<<

There are both SRY Pos and SRY Negative Xx Males that have testes. and they are easily passable as men and could infact serve especially if thier medical records have been sealed then they may get in if those records arent available when they inprocess.


oh anyways think I am going to make a video and once done will provide a link so you all can see and perhaps learn something and yeah here me complain and bitch once more.

[Kailana]

hmm, ok I have been having a real hard time relocating a good link. it appears that the document I was using before to show the different banding patterns, for the many variations in chromosomes, ie X, Y, and partial X's and even partial y's.
I really need to explain the difference in the use of resolution as well, that is just what was used when the test were performed, sort of like the quality of the banding resolution, ie like looking in a microscope and using a 10X verses a 40X, the 40X would allow for better larger close up images.


but I had requested the actual banding pattern of my Y's if they are indeed Y's. because with an exact banding pattern I could of referenced if they are indeed normal Y's versus a Y with a deletion or microdeletion and or if they are partial x's, and because I had asked for the banding pattern both times with the band level reported in 2005, that only adds confusion with a 550-650 range, and makes it unclear if that is the resolution used to see if its a y, or if that is the actual band pattern. ie size of the Y, if its the size then its clearly not an Y they found yet reported a Y. if its just the resolution used and they found a Y, then it would say that yes its a Y, ie better detail basically. so it is hard to understand what is meant when there is no clarification.

is no longer available and havent found a good one yet that will work.