My medical mystery continues ...

[nicktheory]

I realize that my situation relates to a smalll number of you out there, but there are a few of you with endo-research interests related to gyne. (And also it puts my situation on thr ecord in cyberspace in case anyone has a similar problem in the future.)

Anyway, to summarize: Have had adolescence-induced gyne for 35 years. Am now 50. Had a complete CBC and the endo found all T's were normal (E2 borderline low, however). My full labs are below. So basically, he said my gyne was ideopathic and my hormones are fine -- go have surgery of you want; it won't grow back. I was suspicious because I have a few other mild symptoms of hypogonadism. But hey the numbers are the numbers, the doc said. I was preplexed by the low estrogen which is really conter-intuitive with gyne. The doc, to humor me, said let's run a bone density scane to check you for osteoporosis. Well guess what: I have it in my left hip and it is starting in my left. The doc is baffled. Says it is very rare. He says he usally only sees this in men my age if they have low testosterone. But my numbers don't show that, in any way shape or form and on several testings. Now he wants to check my thyroid. Could this be a thyroid issue? Both the gyne, the osteoporsis and the low estrogen?

Here are my most recent labs:

1. Total T - 474 with 241-827 ng/dl the reference range.  
2. Free T - 113 with 34-194 pg/ml the range  
3. Free and weakly bound T - 238 with 84-402 ng/dl the range.  
4. SHBG - 29 with 7-50 NMOL/L the range  
 
Hmmmm:  
 
1. T3 reverse - 0.22 with 0.19-0.46 the range  
2. High-sensitivity estradoil - 13 with 10-50 the range  
 
Thoughts?
 
Thanks in advance.  
 

[Hypo-is-here]

But is there a mystery?


You are 50 years old now, you have had the gynecomastia for 35 years making you 15 at the time of its development.

This would be a typical age to develop pubertal gynecomastia, so there is little suspicious in the age at which you developed the tissue.

It didn't go away, now that could mean you have idiopathic gynecomastia with no underlying causation or you might also happen to have an issue that caused the development during puberty.

You have had a free testosterone test that shows a good level of free testosterone and your estradiol level is low meaing that is highly unlikely to have caused a problem independelty of the testosterone level.

Your SHBG is not too high and in combination with the low estradiol has ensured your pretty good free testosterone level.

Your TSH level is also ok and that in 90% of cases rules out a thyroid issue.


So the odds are that your case is idiopathic gynecomastia.


Further investigations are probably only warrented if you are suffering from ill health as well as gynecomastia.

Do you have many symptoms of Ill health?

If so what?

Be as specific as possible here or via a pm including any abnormalities that you have suffered from birth (if of course you want me to help).

If I can see anything that stands out then I could help you get an appointment with the idea of bringing such information to the attention of your consultant.

Certain symptoms may lend themselves to further investigations such as;

Further thyroid checks free T3 free T4, thyroid antibodies, cortisol and DHEAs.

Checking your androgen- dihydrotestosterone level, checking other estrogens- estrone estriol and HCG.

Renal and Hepatic function tests etc etc


I hope that helps.

P.S

If you are well in yourself and have no real symptoms of ill health then I think that idiopathic gynecomastia is the most likely diagnosis that will be made by any consulting doctor.

[nicktheory]

Thanks for the thoughtful and logical post.

The diagnosis of ideopathic gynecomastia made sense to me until I was diagnosed with osteoporsis this week. It seemed to stun my docs, as well. Now, when I think about the issue, I think it just sounds too coincidental to have these two maladies (gyne and osteo) and have neither be connected to each other or either a testosterone/estrogen issue (s). Why? Well, my earlier, pre-osteo, suspicions of the ideopathic gyne diagnosis came about because of a range of minor symptoms that seemed to accompany the onset of gynecomastia, at about age 12 or so. These symptoms ranging from arm span (two inches longer than height) to body shape (slightly euchnoidal) to low muscle mass and endurance (from low normal RBC, I suspect) to high cholesterol to difficult behavior. Many of these symptoms are found in KS sufferers. I did not, however, have with the mini-testes size (low normal here, however), nor the fertility issues (impregnated two women, one when I was 43) nor, and most importantly, according to my doc, the low T-levels. Docs haven't tested me for KS, of course. They shrug off any possibility of KS or even a mosaic because of my labs, fertility, they even say I don't have the shape I think I do, even though clearly I do and others have remarked upon it in my life. Perhaps I should insist, just for the peace of mind.

Anyway, the new focus appears to be on the thyroid, the borderline-low reverse T3s, I guess. Hypothyroidism? Cause of one or both malady?

The mystery continues (and the medical bills pile up.)

[Hypo-is-here]

There are many causes of Osteoporosis so I wouldn't jump the gun and start assuming too much just yet, despite the fact there can be a connection as I see you are aware.

Liver disorders can also cause both gynecomastia (8% of all gynecomastia sufferers have a liver disorder) and osteoporosis, so that maybe something worth looking into further.

Renal disorders cause gynecomastia (2% of all gynecomastia sufferers have renal problems) and renal problems can also cause osteoporosis.

The parathyroid gland regulates bone metabolism along with calcium and to a less extent magnesium so they should be checked as a matter of course.

In fact you should be on calcium and vitamin D supplementation for the osteoporosis or bisphosphonates if your bone density test warrants it.  Certainly it should be treated one way or the other.

It maybe a good idea having your Growth Hormone levels tested as Growth Hormone also has an impact on bone metabolism and a lack of it can result in some hypogonadal like symptoms.  HGH is tested for by the lab indicator IGF-1.

If your osteoproosis is very bad in terms of your bone density score then a forward thinking doctor could consider testosterone or HGH treatment as these are the only two substances that can actually stop and to some extent reverse bone loss.

They are able to do this because they are osteoblastic stimulators.  They basically boost bone reconstruction.

Ok so what if you don't have a liver or renal problem, your PTH (parathyroid hormone) and calcium levels are ok, your HGH (Human Growth Hormone) levels are ok as well?

Well you need to rule out hyperthyroidism something that can also cause gynecomastia and osteoporosis.  So far you have only really had a TSH test (this rules out a problem in 90% of cases but not all)  Reverse T3 can be a pointer to hypothyroidism but on its own means little.

To rule out thyroid problems completely you would need to have free T3, Free T4, thyroid antibodies and cortisol tested.

If that results in nothing you are down to malabsoption syndromes which can be checked and if still no luck and you still have money ……

You may benefit from seeing a geneticist that they can consider relevant syndromes.

There can be defects that relate to the androgen receptor- CAG repeats or PAIS (Partial Androgen Insensitivity Syndrome) which could allow for a normal testosterone level, but a situation that would result in a lack of androgenic action and gynecomastia and osteoporosis.

If nothing is found in the way an androgen receptor defect, a defect maybe found in another area that accounts for the osteoporosis alone.

A geneticist could also rule out other conditions if symptoms presented such as Hemochromatosis and other chromosomal abnormalities.

Be warned there can be far more questions than answers and when symptoms are lacking testing for given health problems usually results in innocuous findings.  Also you will probably find a lot of red herrings as testing anyone to this extent usually reveals some odd finding that are again fairly innocuous but which in the context of your investigations you could think are more significant than they actually are.

All this is very expensive, time consuming and will exhaust you mentally and you may still never find an answer.

But there are the options.

I don’t think I missed anything but ?

If you want to even consider testing further get a good endocrinologist who specializes in reproductive endocrinology.

Out of interest what are your symptoms other than the osteoporosis and gynecomastia?

P.S

I also have osteoporosis, and am currently seeing a geneticist.

[nicktheory]

There are many causes of Osteoporosis so I wouldn't jump the gun and start assuming too much just yet, despite the fact there can be a connection as I see you are aware.

(Absolutely agreed. Docs says lets get some more thyroid word done. Next week it happens.)

Liver disorders can also cause both gynecomastia (8% of all gynecomastia sufferers have a liver disorder) and osteoporosis, so that maybe something worth looking into further.

(I'm hoping not, as I may be going on statins soon and hope my liver is in top shape.)

Renal disorders cause gynecomastia (2% of all gynecomastia sufferers have renal problems) and renal problems can also cause osteoporosis.

(Never know, but haven't had any kidnet complaints.)

The parathyroid gland regulates bone metabolism along with calcium and to a less extent magnesium so they should be checked as a matter of course.

(Both calcium and magnesium levels are average. Can provide numbers if you like.)

In fact you should be on calcium and vitamin D supplementation for the osteoporosis or bisphosphonates if your bone density test warrants it.  Certainly it should be treated one way or the other.

(In the interim, before any new tests results, I am on 800 Vitamin D and 1200 calcium.)

It maybe a good idea having your Growth Hormone levels tested as Growth Hormone also has an impact on bone metabolism and a lack of it can result in some hypogonadal like symptoms.  HGH is tested for by the lab indicator IGF-1.

(Believe it or not, my endo tested for IGF-1 and it is fine.)



If your osteoproosis is very bad in terms of your bone density score then a forward thinking doctor could consider testosterone or HGH treatment as these are the only two substances that can actually stop and to some extent reverse bone loss.

(My z-scores for osteo are "of concern" and "very rare", according to my endo. Not like I am breaking bones. But I am on my way there a good 10 years ahead of schedule. We haven't discussed treatment yet. Waiting foir additional tests. We haven't discussed to "coincidence" of having gyne and osteo - but no labs to back up a low testosterone finding. I definitely intend to pursue this.)

They are able to do this because they are osteoblastic stimulators.  They basically boost bone reconstruction.

(Understood.)

Ok so what if you don't have a liver or renal problem, your PTH (parathyroid hormone) and calcium levels are ok, your HGH (Human Growth Hormone) levels are ok as well?

Well you need to rule out hyperthyroidism something that can also cause gynecomastia and osteoporosis.  So far you have only really had a TSH test (this rules out a problem in 90% of cases but not all)  Reverse T3 can be a pointer to hypothyroidism but on its own means little.

(I think hyper and hypothyroidsism are the next two thing sthe doc will chcck for.)

To rule out thyroid problems completely you would need to have free T3, Free T4, thyroid antibodies and cortisol tested.

(Guess what? The doc tested them: free T3, T4 and cortisol are all normal. Nada on the test about the antibodies.)

If that results in nothing you are down to malabsoption syndromes which can be checked and if still no luck and you still have money ……

(Will mention malabsorbtion.)

You may benefit from seeing a geneticist that they can consider relevant syndromes.

(I am considering it, but finding that they are harder to find than endos in south Florida.)

There can be defects that relate to the androgen receptor- CAG repeats or PAIS (Partial Androgen Insensitivity Syndrome) which could allow for a normal testosterone level, but a situation that would result in a lack of androgenic action and gynecomastia and osteoporosis.

(I checked into these and MAIS comes the closet to a possibility but even that really doesn't. I just don't have the physical chaacteritics often found in these syndromes)


If nothing is found in the way an androgen receptor defect, a defect maybe found in another area that accounts for the osteoporosis alone.

(Will keep that long shot in mind.)

A geneticist could also rule out other conditions if symptoms presented such as Hemochromatosis and other chromosomal abnormalities. (KS mosaic is my long-shot bet if the gyne and the osteo remain ideopathic.)


Be warned there can be far more questions than answers and when symptoms are lacking testing for given health problems usually results in innocuous findings.  Also you will probably find a lot of red herrings as testing anyone to this extent usually reveals some odd finding that are again fairly innocuous but which in the context of your investigations you could think are more significant than they actually are.

(Am very aware of how much guesswork there is in medicine and often defginitive answers are impossible to ascertain.)

All this is very expensive, time consuming and will exhaust you mentally and you may still never find an answer.

Agaian, I am very aware of this. But fortunately have some time and dough.)

But there are the options.

(Thanks. And much thanks for all your insights.)

I don’t think I missed anything but ?

If you want to even consider testing further get a good endocrinologist who specializes in reproductive endocrinology.

(Contemplating second opinions as I write this.)


Out of interest what are your symptoms other than the osteoporosis and gynecomastia?

(Well if you look at the KS list of symptons, I have about two-thrids of them -- nut not infertility, low T scores, tiny testes or diminished intellect. I do have the others: arm span, behavior problems, light beard growth, some impotence or lack of interest in sex. wide hips/narrow shoulders, mild dyslexia, etc. Add gyne and osteo plus high cholesterol and it makes me wonder about KS mosaicism, It's a long shot. But so, too is having unrelated cases of gynecomastia and osteoporsis in a man at age 50.

The only other things that stand out is a sister who, tragically, had Usher's syndrome -- deafness at birth and a slow loss of sight; she died of breast cancer at 48. Another cause for KS concern would be the KS link with male breast cancer.

I also, oddly for my age, but not astonishigly so, had shingles three months ago. Stress or over working out was the likely cause, however.)

P.S

I also have osteoporosis, and am currently seeing a geneticist.