A young girl suddenly grew a beard.
This is what was happening in her ovaries.
KT is a seventeen year old girl
presenting to the emergency room
with nocturnal somnambulation, sleep apnea,
and rapid onset hirsutism.
She tells the admitting nurse that she had gained 50 pounds (22.7 kg)
over the last 3 months
and was in emotional distress as she suddenly grew
thick facial hair overnight.
You see, KT was an adopted American girl.
Her birth mother was uneducated, homeless, and diabetic.
But her adoptive parents offered
a happy childhood full of opportunity.
About 6 years ago when KT was 11,
her parents noticed that she was gaining more weight than the other kids.
"She's just a growing girl," they thought.
The following year at age 12, KT experienced Menarche, or her first period
the event was very normal for a girl that age,
but subsequent menstrual cycles became irregular, erratic.
"Just some growing pains," her parents thought.
Earlier in the year
KT's siblings noticed that she was sleep walking.
Episodes would involve her going into the refrigerator and eating large amounts of food.
At first they thought she was joking but then quickly realized
that she couldn't recall any of the nighttime engorgement.
Visibly, KT was unhealthy.
At physical examination, she presented with
Acanthosis Nigricans
Acantha in ancient Greek referring to spines
or in this case, the Stratum Spinosum layer of the skin.
Osis meaning disease of,
and Nigricans referring to a blackening.
Her skin had velvety gray patches below her neck and axilla.
Indicating insulin resistance and type 2 diabetes.
Similarly, she had elevated serum aminotransferase
Serum referring to the amber colored liquid that separates out when blood coagulates
and aminotransferase being an important liver enzyme.
Elevations of this in a teenager with diagnostic
exclusion of both hepatitis and Wilson's disease,
which is a genetic disorder leading to the accumulation of copper in the body
indicates that KT has nonalcoholic fatty liver disease
All of this was combined with class 3 obesity as she was 5 foot 4 inches (163cm) tall
and weighed 306 pounds (139kg),
as well as a self reported menstruation count of 2 in the past year.
The physical problems of KT are obvious, but the underlying causes are not.
Sleep apnea was first observed at age 13.
The disturbances in sleep that she suffered over the years began to negatively impact her life,
as psychiatric evaluation found her to suffer from mild depression and low motivation
Adolescent sleep derangements are detrimental
as the brain is still developing and growing at this age.
Recent overnight polysomnographs show
worsening intermitent oxygen desaturation
indicating airway obstruction and sleep disruption
consistent with a sudden weight gain of 50 pounds (22.7kg) over 3 months, but something's wrong.
Did she gain 50 pounds (22.7kg) in 3 months because of disturbances in her sleep patterns
or did she develop disturbances in her sleep patterns because she gained 50 pounds (22.7kg) in 3 months?
A blood test reveals that "KT's" serum total testosterone level is 120 nanograms per deciliter.
Two times the upper limit of normal in a woman
and just under half the lower limit of normal for an adult man
We can conclude here that she's suffering from Hyperandrogenemia.
Hyper meaning high
Androgen referring to male hormones mainly testosterone
and emia meaning presence in blood.
High male hormone presence in blood.
But KT is a girl.
If male hormones are made by male parts
but KT is a girl and has female parts
then where are those male hormones coming from?
How is it possible that she has high male hormone presence in blood?
Well, there's a bit of basic human physiology to be known here.
Men and women produce both testosterone and estrogen.
It's the concentration that makes the distinction.
Men have 10 to 20 times more testosterone in their body than women
and women have more estrogen than men
Estrogen refers to a grouping of hormones, the most common being, estradiol.
In humans, testosterone is an obligate intermediate in the biosynthesis of estradiol
meaning that if the body's making estrogen then it has done so in part because it has made testosterone.
In some sense, testosterone is made first and because it promotes the production of estrogen
women must produce testosterone, but men produce estrogen
really only because of testosterone.
These hormones determine physical masculine and feminine characteristics.
A beard is normal for a 30 year old man, but abnormal for a 17 year old girl,
meaning in KT's case, it's a serious sign
of an underlying endocrinopathy: a disease centered on hormones.
Androgens affect ventilatory control and increase visceral fat
so obstructive sleep apnea like in KT's case is typically more common in in boys
after puberty when testosterone levels are high
but it's also common for women who have an ovary syndrome
meaning that KT's weight gain and sleep disturbances
are not caused by one another, but are caused by her hyperandrogenemia.
In normal functioning women
25% of all testosterone produced is from the ovaries.
Another 50% is created through peripheral conversion of androstenedione
the precursor hormone of both estrogen and testosterone
which is produced by the ovaries.
Peripheral, meaning that the conversion happens in the liver, skin, and fat tissue.
The idea of a precursor hormone is important to note
because it indicates that both testosterone and estrogen
are formed from this same common pathway deriving from cholesterol.
Estrogen is produced downstream
meaning that testosterone, for the most part, comes first
and women have to make testosterone.
Disturbing the equilibrium of this state such as adding more testosterone
through anabolic steroid abuse
increases estrogen presence in blood
causing male athlete steroid abusers to have
gynecomastia without the use of anti-aromatase.
Inside the ovaries
excess testosterone will signal a stop to androstenedione production,
so that less testosterone and estrogen are released into the blood.
This negative feedback explains why hormones fluctuate from day to day
and from week to week
but if KT's testosterone levels are high
then why is her body producing more of it?
Negative feedback is supposed to suppress production
when levels are high, right?
Well, let's go back to the source of testosterone production in women.
The ovaries account for only 25%
of all androgen produced in the body
and remember that 50% comes from
the peripheral conversion of androstenedione in the liver, skin, and fat tissue.
Because KT is 17, she's still in puberty so maybe her liver will
get a little bigger, but that's not likely and she also has
nonalcoholic fatty liver disease so its probably not going to
make more testosterone
But how about her skin? Well, she's gaining weight faster
than her skin can expand explaining her
lower abdominal striae, so she's not really growing more skin right now
so that's not a possible source of more testosterone.
But how about the fat tissue?
KT just gained 50 pounds (22.7kg) over the last 3 months
and with confirmation that she's type 2 diabetic
then by definition it means she has hyperinsulinemia
high insulin presence in blood
and insulin is a powerful stimulus
for the fat tissue
to produce more testosterone through
peripheral conversion of androstenedione.
Hyperinsulinemia also increases ovarian steroidogenesis too,
meaning that the weight that she gained perpetuated
her hyperandrogenism, caused her irregular menstruation
leading to anovulation
and provided a condition sufficient for her to grow
coarse facial hair and increase her
chances of infertility and endometrial cancer into adulthood.
Pelvic ultrasound finds that KT has bilateral sclerocystic ovaries.
Slcero meaning hardened.
Cystic referring to cyst
which is an abnormal sac containing fluid
and bilateral meaning on both sides her ovaries are covered
with numerous hardened cysts.
Multiple follicles fail to ovulate, so they accumulate in number
and this morphology confirms that KT
has Polycystic Ovary Syndrome (PCOS).
The abnormal steroidogenesis fed into her obesity,
sleep disturbance, and amenorrhea.
Subsequently, the obesity encouraged her hormone imbalance
by feeding forward into the mechanism of testosterone production
and gave her erratic menstrual cycles, anovulation and hirsutism.
Polycystic Ovary Syndrome is the most common endocrinopathy documented
in women all around the world
and its first report in human history goes back to
Hippocrates who wrote in 400 B.C.
about "women whose menstruation is less than 3 days
with a masculine appearance yet
they are not concerned about bearing children nor do they become pregnant."
The Romans centuries later
in 100 A.D. noted that there was a natural absence of
menstruation in persons whose bodies are of
masculine type and those women
who are rather robust like mannish and sterile women.
Modern understanding of PCOS dates back to
just 1935 where 7 women presented with
amenorrhea, hirsutism, obesity, and
polycystic ovaries
by 1970, reasoning determined
that excess testosterone through an inappropriate secretion of
gonadotropin hormones was the main culprit
and in 1986
a cohort of 19 people who transitioned from
female to male in this lifetime
were treated with exogenous testosterone and 17 of them
developed enlarged polycystic ovaries.
By 1990 the diagnostic criteria
was developed which enabled women with the syndrome
of anovulation, hyperandrogenism, and
polycystic ovaries to be recognized and treated through
classification and diagnosis.
PCOS is a syndrome meaning that it's a group of
symptoms that generally occur together.
The keyword being generally.
Polycystic ovaries can be found in women who aren't obese, but
still have hyperandrogenemia.
Some others may be obese, have anovulation and are hirsute
but don't have actual polycystic ovaries
and diagnostic criteria would still qualify
but not confirm them with PCOS.
This means that diagnosis in adolescents
like KT should be taken with care.
Teenage girls can typically have times of anovulation.
This is a time when menstruation is irregular and erratic,
which means increased testosterone levels leading to temporary development
of acne, hirsutism, and weight gain.
But because this is transient in occurrence
and can be common, a diagnosis of PCOS
cannot be made solely on those grounds.
Confirmation of a diagnosis of PCOS
in an adolescent girl
cannot be had without further evaluation
because it's typically a diagnosis of exclusion,
meaning many other hyperandrogenic disorders need to be ruled out first.
The adrenal glands, which make adrenaline and
sit on top of the kidneys, makes the remaining
25% of testosterone in women so the
adolescent female patient may have
congenital adrenal hyperplasia, a genetically linked
overgrowth of the adrenal glands which can overproduce androgens.
Ovarian tumors can grow at
adolescence and they too can secrete inappropriate
amounts of testosterone.
Thyroid disorders, insulin resistance, Cushing's disease, and
even acromegaly, which is an excess of growth hormone
caused by pituitary tumor
that can take 10 to 15 years to diagnose
all have symptoms that can mimic polycystic ovary syndrome
and they should be ruled out
before diagnosis can be confirmed.
For KT, metformin is
initiated for her diabetes with a regimen of exercise
beginning at 30 minutes for 3 days a week with a personal trainer.
Her sleep apnea is treated with a mask and
positive pressure, but as up to 20% of patients
are typically noncompliant with the treatment
it was used with limited success.
If she has excess testosterone in her blood
the preferred treatment modality for her PCOS is
estrogen combined with progestin.
Combination oral contraceptives will promote menstrual regularity and
by equilibrium reduce ovarian testosterone production
thus reducing hirsutism and acne.
Metformin will suppress liver glucose production
reducing its presence in blood thereby
reducing insulin presence and mitigate
ovarian steroidogenesis, while modestly slowing
peripheral conversion of androstenedione to testosterone.
Physician follow-up is needed with combination oral contraceptives
as they are associated with a four-fold increase
in incidence of venous thromboembolism
which are large blood clots that can develop silently
and once large enough
can break off dislodge into the lungs and cause a pulmonary embolism
and sudden death.
Ethinyl estradiol dosages can increase the risk of stroke and heart attack
by up to two-fold without proper monitoring.
The benefits of this treatment though outweigh its risks.
We are trading a decrease in chance of infertility,
decreasing risk of endometrial cancer,
and alleviation of hirsutism and androgenic presentation
with increased risk of cardiovascular adverse events.
KT is a patient that my colleague saw in the
Illinois Medical District in March of 2009
Most of these case reports in video are patients that I or my colleagues
have seen and while it's impossible for me to know
the entire backstory for each patient
the videos are written, recorded and edited solely by me
and fact checked by my colleagues all across the United States
who practice and research in the topic of each case.
Videomaking or cinematography and storywriting are
things that I've learned on my own and Skillshare
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With adherence to treatment, strong family support, and a caring medical team
KT was able to make a recovery.
Was she able to have children later in life?
Well, thats a part of the story she's still writing.
Thank you so much for watching, take care of yourself
and be well.