Talk:Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency

note

What does this realy mean ? I've heard of it but dont realy understand the stituation which a sufferer is faced with. What restrictions does it bring and what is diffrent physicaly?

The article actually contains the answers to your questions, but is built on the foundation of the basic congenital adrenal hyperplasia article. This particular type (17OH) is a very rare form that is hardly ever referred to in the popular media. In the congenital adrenal hyperplasia article are links to simpler internet explanations of CAH, like the patient education material from Johns Hopkins Hospital. alteripse 22:39, 6 May 2006 (UTC)

I suffer from the condition and could give you first hand experience of what it meant to me. However, a lot of it was not known until much later in life.

Example:

1. Whether related or not, I knew I was different starting @ the age of 4. I felt female but was declared male at birth. Nothing presented at birth to not make that conclusion, but I suspect I may have been a little under developed.

2. I started having issues around puberty. Lots of downstream issue being caused by the deficiencies by those effected steroids. Delayed puberty was noted, but experiencing a lot of heart palpitations, pulmonary and other issues which the doctors were more concerned with at the time. Most of these were masked when a male puberty eventually kicked in.

3. As time went on, I continued experiencing issues...but each were considered isolated incidences. Blood Pressure was always out of wack...so put on a blood pressure med. Thyroid issues were next (failure). Would have random weird issues that no one could quite explain (salt sheading instances), but were momentary and after an intervention would disappear.

4. When I had my hormones tested to start HRT, some anomalies in their values (Estrogen higher than normal, and Testosterone very low). The start of HRT and Testosterone suppression brought back all of those earlier issues that I experienced at puberty. Over the years of going through those issues, is when we started to realize why and what had been being missed.

The way my adrenal system was working seem to be thinking I always had too much of an androgen. When on T, my DHT levels were likely out of bounds (leading to things like early hair loss), but it was never looked till much later. The flip over to Estrogen resulted in massive amounts of Estrone; which caused issues in feminization effects due to not being able to get the levels high enough.

Lack of Progesterone was found to be the main culprit effecting the Heart palpitations and impacts the pulmonary issues as well.

Today we supplement Pregnenolone, DHEA, Estrogen (vis muscular injection), and hydrocortisone to get around these issues. I am also on Synthroid for the thyroid issues, Valsartan with Hydrochloride to help the resulting blood pressure issues, low dose aspirin to mitigate of increased risk of clotting, and collagen supplements to deal with impacts to ligaments. And to round it out, Rosuvastatin to fix any potential cholesterol issues.

Skeletal shape anomalies were discovered when I broke my pelvis. It was obviously influenced by estrogen and looks very feminine in areas (pubic arch, ischium, distorted opening shape, pelvic tilt, etc.) Other things can be debated. Puberty delays result in not shutting down growth plates till later..so I am very tall, but with short feet, hands and other things that are not typical of a male my size. (Human variation or due to the condition? My sizing is very typical of a female my size.) Like my pelvis, its a mix...

I later transitioned to get everything in alignment. So, while declared male at birth, I live my life as a woman after a long path of physical problems, mental struggles, and family issues. Including having GCS and going through a typical transition process.

It's been a lot of fun to deal with this over the course of my life..to say mildly!

Part of my struggles was with that the case is so rare and no one is familiar with it. And because of that, I am very happy that this page even exists. I have sent links to it to my doctors many times over the years. ChristinePenn (talk) 18:51, 4 May 2025 (UTC)

As with any explanation, it is hard to cover all basis of the effects of something in a simple writing when it really takes a conversation to flush out all the details. So, I will add some additional details I left out above that gets a little more into the specifics.

Only genetic testing can ultimately verify this condition (which I have not had done, mostly due to justification/cost/insurance reasons), but I did have some extensive testing on the operation of every function in my adrenal gland. The results of that indicated genetic enzyme deficiencies in either 17alpha hydroxylase, 3-beta hydroxysteroid dehydrogenase, or P450 SCC (cholesterol side cleavage enzyme). Even though I was likely born with only a partial 17a OHase deficiency, it was not a surprise to have 17a OHase show up in that list, because the progression it has taken over the course of my life. I believe it is the only one that sort of aligns/makes sense to the issues I have over a lifetime. As stated it would take specific genetic testing to verify which specifically of the three it is....but we sort of know from the other testing which one it sort of is already and the result wouldn't really change anything to current treatments. Because, today, it is no longer a partial deficiency but instead has progressed to more an overall failure (complete?). Which was the point of testing levels of every steroid and hormone in the pathways. (Working around insurance limitations.)

So today, we supplement all of the deficient steroids and hormones accordingly. (It changed slowly and drastically at times over the course of my life.) Medication changes to address the on going issues have changed over time and seem to need constant adjustments as it has progressed as more and more problems arose or changed. (Ok for a while, then more problems over time was a never ending repeating pattern and somewhat continues to this day.)

The partial state limited it effects early on, so no ambiguous genitalia, It reared it's ugly head during puberty, but wasn't known at the time and delayed puberty/onset of secondary sex characteristics. Testosterone rose later and started masking other issues and was enough to be able to father children in my late 20's (Up to around 30). After that, the problems stared getting worse and later focusing on the hormones, my testosterone was found to be very low which would have likely blocked the ability to have any further children without supplementing it. (Never went on or attempted.)

The earlier state and later mix affected various sexual characteristics in development, which compelled me to transition from my assigned sex at birth as well as start on a Hormone Replacement Therapy (Estrogen base). It did not go smoothly and did not match the experience of other transgender women. This started the investigation into why that was which eventually led to where I am now. Supplementing Progesterone, Estradiol, DHEA, Pregnenolone, Hydro corticosteroid, and ones for the other downstream failures they cause. (Blood Pressure, Thyroid, Collagen, and Sports Drinks to help with Salt and Potassium issues.)

End result, it is a massive regimen to just have my body ack in a more "normal" fashion...and needs constant management and adjustments as things change over time. One of the things I find funny, is that today I am on a Testosterone supplement - because due to what I pursued, removed it totally out of my system which over led to other bad effects (your absolutely need some!). (Failed to mention that before...)

Hope that helps clarify some things further....for my particular experience. Any more details likely needs a debate or conversation to get into even more specifics. ChristinePenn (talk) 13:51, 11 May 2025 (UTC)

question

HI; I am interested in this condition.

Is it always autosomal recessive? or would 'carriers' have reduced activity/expression of 17 alpha hydroxylase?

I would like to know if anyone has case experience of an infant mistaken to have PAIS, when the real issue is 17 alpha hydroxylase deficiency? Would anyone care to comment on what could happen to an individual given large doses of testosterone and HcG as an infant over time?

I also wonder that in such a case would natural surges in gonadotrophins over time give the enzyme some activity, both by gonadotrophins increasing the enzymes activity, and once testosterone is present at a reasonable level would it induce extra expression of 17 alpha hydroxylase to compensate for it's lack of activity?

I have read of a large variety of phenotypes for this condition. One thing I am interested in particular is, the example of an XY individual who is give testosterone and growth hormone to treat genital ambiguity... Recent literature has suggest that increased 17 alpha hydroxylase enzyme levels can increase the production of things like TNF alpha dramatically. Couldn't that be dangerous? Would it really be sensible to maintain a course of testosterone throughout life given this? User:nic@sounddesign.co.nz 11:43, 21 April 2007 (NZ time) cheers if anyone could offer any insights, Nic. nic@sounddesign.co.nz

Hi to NZ. Note that all the following answers are speculation, not medical advice.

Always recessive? Short answer: all reported cases of the disease have been autosomal recessive. Long answer: As the gene is on chromosome 10 and codes for an enzyme (so that everyone has two copies), one would predict that both copies of the gene would have to be defective to produce any detectable disease. There are few examples of dominant disease caused by mutations of single genes for enzymes. None of the described cases in which genotyping was performed were due to defects of only a single gene. None of the handful of reported families demonstrated a dominant inheritance pattern. There are no clinically detectable effects in those who carry only a single gene of the more common forms of CAH. However, although there is no disease caused by having a single copy, it is possible that mildly reduced enzyme activity in adrenal or gonadal tissue could be demonstrated, since it is possible to have a mild reduction of an enzyme activity without it causing any problems.

Mistaken for PAIS? As mentioned in the article, severe 17OH CAH occurring in a genetic male could easily be mistaken for PAIS in infancy.

Thank you for your promt response, I really appreciate it.

Testosterone/hCG effects? Administered testosterone effects are difficult to quantify in infants, and androgen receptor testing has only recently become available. If an infant with this condition were given standard infant doses of testosterone and hCG (as is often done in the evaluation or treatment of XY infants with ambiguity), one would predict a normal response because there is no defect of tissue responsiveness or 5α-reduction. No risk is known for this treatment. I am not sure what you mean by "given large doses over time". If testosterone is given for a prolonged period, one would expect to see appearance of pubic hair and acceleration of growth and bone maturation, similar to that seen with untreated non-saltwasting 21OH CAH. Standard therapeutic hCG courses are typically about 5 weeks, and no harm is known to occur to normal testes. If you aren't asking about ten times that much, maybe nothing detectable would happen.

Actually funny you should mention it I was talking about ten times the amount of testosterone administered to an infant. 250 units (I can't remember the particular unit sorry), as opposed to the more standard 25 units give three times.

Would this enhance 17OH activity? Testosterone is not known to induce the enzyme. hCG might induce the enzyme to some degree, but not permanently. Part of the problem in imagining treatment with hCG is that after a baby is born, more testosterone or hCG will not fix ambiguity, just make the penis a little bigger. At puberty, these people have high LH levels. Since LH and hCG are quite similar in their effects and act on the same receptors, it is difficult to think of any reason to keep giving hCG to an adolescent or adult male with this condition. Their sensitivity to testosterone is normal, and that would be the best post-pubertal treatment for this impairment of testosterone synthesis.

Would testosterone treatment be dangerous? Don't confuse replacing a deficient hormone with giving unnaturally high amounts. If the doses are normal replacement doses for a male with impaired ability to make testosterone, there is no known harm compared to normal male disease susceptibility. If a man with a severe form of this condition did not take testosterone for most of his adult life, one would expect osteoporosis, poor muscle maintenance, diminished libido and energy. alteripse 18:34, 21 April 2007 (UTC)

compound heterozygous

I note a recent case in the literature describing a compound heterozygous polymorphism causing 17 hydroylase deficiency

That means that the two CYP17 genes had two different mutations, not an unusual finding in all the forms of CAH, since they are recessive enzyme deficiencies. alteripse 12:10, 19 May 2007 (UTC)

I have only read of one compound heterozygote for CAH. Are you sure it's so common? Thanks for your comments alterpise. I have ascertained (at least in my case) that my LH theory doesn't hold true. Nic Nic 00:07, 12 June 2007 (NZ time)