Let's have a look at a patient who has Klinefelter
syndrome. The most common chromosomal abnormality
that you will encounter will be the 47 XXY type.
Take a look at the patient. Tall, lanky.
Take a look at the arm span. Might be as long as the
leg span. So obviously you have a tall individual.
And as a differential perhaps Marfan. But with
Marfan, quite simple. Looking for issues in which
the fibrillin gene, the elastic tissue and such has
been compromised. And arachnodactyly so on and so forth.
In Klinefelter, you'll notice that we have arm span
that's quite long and then also take a look at the
eunuchoid features. Eunuchoid referring to features
of both a man and a lady. You'll notice that the
breast here are gynecomastic. And at the same time
though the facial features might be that of a male.
A patient with Klinefelter may present with infertility.
And this is due to the fact that, that there is loss
of the sertoli cells or maybe even perhaps fibrosis
taking place of the seminiferous tubules.
Please picture in the testis the sertoli cells which
are then responsible for proper maturation of sperm.
Correct? Of course sertoli cells require the help of
testosterone. And if the sertoli cells are either not there,
then what may happen is that the sperm may not be
properly formed and so therefore may result in infertility.
Laboratory wise you're looking for increased levels
of FSH. And the concept is exactly what you would
expect with menopause as well. In which the inner
layers, in this case we have the sertoli cells,
has a hormone called inhibin. And so therefore when
the sertoli cells are not present, inhibin is not present.
Inhibin more profoundly inhibits FSH. So therefore,
if inhibin is not present in your Klinefelter patient,
then FSH levels will be high. This patient with
Klinefelter, how would they behave? Well up until
puberty really there is no issue. So, difficult to
actually diagnose prior to puberty. It's during puberty
in which now the patient may not properly function
in society. So suboptimal type of functioning is important.
Now the increase in FSH will then drive, well the
estrogen. And here you will notice once again
the gynecomastia that's taking place. So
there are certain features that are ladily.
Estrogen will bring about female secondary sexual
characteristics as we, as I'd just mentioned.
And keep in mind that the female secondary characteristic
including the gynecomastia and the female distribution.
Legs are disproportionately long as well as the arms
as well. And because of gynecomastia there is an
increased risk of going on to breast cancer.
Here we have androgen insensitivity syndrome.
So here is a child that's been born and you notice
that for all intended purpose, phenotypically
the child and the patient looks like a female.
Take a look at the patient here over to the right.
Phenotypically, looks like a female. However,
genotypically notice that now we have chromosomes
that are of the male type. X and Y. Loss of testosterone
receptors. So therefore, anytime that there is
there is loss of receptor activity, that hormone
that should be working on it is always going to be
elevated isn't it. For example, you've heard of
pseudohyperparathyroidism or here in this case
the receptors for testosterone aren't working. So
testosterone levels are going to be quite high.
Next, the problem is testosterone gives rise
to the, well, the internal male structures.
And those then would include in a male, vas
deferens, your epididymis, the seminal vesicle.
So that would be then your internal male
structures but the testosterone and the receptors
are not accepting it. So therefore that doesn't
develop in this patient. Next, remember
testosterone is converted into a hormone. A testosterone
derivative with the help of finasteride. Excuse me,
well finasteride will be the drug that targets the
enzyme that we call 5 alpha reductase, correct?
So 5 alpha reductase converts your testosterone into
dihydrotestosterone. Well the problem is that is not
happening either. Do you notice a penis in this patient?
No. What about scrotum and such? No. The external
male structures and the prostate is not present in
my patient either. So absolutely no male structures
in my patient here. Except for the obviously testis.
A decresed estrogen and inhibin resulting in
feedback simulation. You might find LH and FSH.
No conversion of your testosterone into DHT.
And so therefore your patient doesn't have any
external male structures, including the penis and
the prostate. We do have the Y chromosome. And then
with the sertoli cells, gives rise to your hormone
that we call mullerian inhibiting factor. And because
of the mullerian inhibiting factor being present
in our patient here, we don't have the internal female
structures which then include our fallopian tube,
the uterus, the cervix, and the proximal 1/3rd of
the vagina. We have a blind pouch. Let's have a
look at a patient who has premature ovarian failure.
The way that you want to approach this rather
quickly, so you're able to identify your patient and
move on, is the fact that this is a young lady.
In young I mean less than 40. And she's presenting
with exactly the same symptoms or nearly that of menopause.
It's unfortunate. Now in menopause obviously there's
no bleeding taking place in menopause. Remind me
which hormone that you're looking for to be elevated?
And that would be your FSH. That's because inhibin
level will be; significantly will be FSH. That's
because inhibin level will be lost due to the fact that
you have your granulosa cells normally responsible
for producing inhibin not being there.
So FSH levels will be elevated. So if you have
like young lady presenting with amenorrhea,
there is no bleeding. Premature ovarian failure.
Loss of the entire ovarian function. So therefore
as I told you, the granulosa cells of the follicle
are not producing inhibin. There is decreased estrogen
and then inhibin causing a decrease. However,
will then cause significantly a rise in FSH.
And if you were to mimic menses. For example, at this
point understand the concept please. This test
known as a progesterone challenge test or the withdrawal
test refers to the fact that you are mimicking
the last stages of the menstrual cycle.
So let's say that a young lady is on a 28 day cycle.
And then on the 28th day all hormones have been
withdrawn. So therefore there is now apoptosis
taking place of the endometrium resulting in
sloughing off and then bleeding taking place.
That's in normal patient. Our patient with premature
ovarian failure, the ovaries are not present or
excuse me, the ovaries are not functioning. And if
they are not functioning, you are not going to have bleeding,
negative of bleeding taking place in your patient.
Here we have a patient with polycystic ovarian syndrome.
So female, presents with amenorrhea and hirsutism.
There is increased production of LH with an intact ovary.
I emphasize intact ovary because in premature ovarian
failure, we had an ovary that was completely not intact.
So now, this patient please know you're going to
begin here. What you have to accept is that a patient
has increased LH. Next, LH is going to work upon the
follicle. Intact ovary. Important that you understand that.
LH then works upon the? Theca cells, correct? The
LH receptor working and being triggered by LH.
That increase in LH will cause an increase in
production of testosterone. This testosterone
will then give you the male hair like distribution
which we then call hirsutism. Next, that testosterone
will then be aromatized into estrogen.
And then what happens now is the following.
So now with this FSH being low in this patient with
polycystic ovarian syndrome, that perhaps, perhaps
the follicle is not going to be chosen. In other
words, lack of development of a follicle in the ovary.
If that follicle in the ovary does not develop and
it sits there dormant, it is increasing its
physiologic osmotic pressure isn't it? Now, this
osmotic pressure is pulling in fluid into the follicle
and then now we call this technically a cyst. So
that statement there gives you the pathogenesis
of the cyst like formation of polycystic ovarian
syndrome. I remind you once again you don't have to find
a cyst. So what's the criteria? Number 1, there
will be oligoovulation. What does that mean?
Well, there could possibly be ovulation. However,
if a normal 28 days in average and on the 14th day
approximately, you have LH surge and ovulation.
If it's oligoovulation, instead of that occuring,
well maybe it's a delayed or perhaps even it's
absent. Number 1 criteria, oligoovulation.
Number 2, clinically or laboratory. Clinically
meaning observation by you the doctor, or number 2,
interpretation of the lab. There are findings in this
patient of, well, masculinization. In other words,
you're going to find increase in testosterone
obviously. And in clinically upon obeservation
of your patient, you're going to find male hair
like distribution aren't you. Those are all signs of
masculinization. So that's two. If you find just
those two androgen type of issues. And number 2,
oligoovulation, that's good enough to diagnose
polycystic ovarian syndrome. Now, just to be complete,
guess what that third criteria is, the polycyst or
multiple cyst in the ovary. But you only need 2
of the 3 criteria to diagnose polycystic ovarian.
Be careful. Here we have estrogen and because you do
have estrogen, if you're able to mimic the menses
or the menstrual cycle, here in this case with
polycystic or progesterone challenge test, you
would indeed find positive for bleeding.