Endocrinology block2

obesity is defined as a BMI
>30 kg/m2
true BMI equation
weight/height2 = kg/m2
approximate BMI equation
pounds/inches2 X 704
BMI 18.5 - 24.9
normal weight
BMI 25 - 29.9
BMI 30 - 34.9
Class I obesity
BMI 35 - 39.9
Class II obesity
BMI >40
Class III obesity
for females to have regular menses they must have a minimum body fat of
13 - 17%
If a male has <3% body fat
may suffer from chronic fatigue and increased susceptibility to illness
Etiologies for obesity
High fat/high caloric intake
Increased amount of food eaten Decreased physical activity
genetic risk
- Prader-Willi syndrome
obesity is a major risk factor for what conditions
Coronary heart disease
Diabetes (type2)
obesity is a major risk factor for what other conditions
Osteoarthritis/gout, Sudden death, Congestive heart failure
All-cause mortality, Thromboembolic disease (stroke, DVT), Low HDL cholesterol, Gallstones, Sleep apnea, Restrictive lung disease, Colo-rectal cancer, Endometrial/breast cancer
a good family history for an obese patient includes
Age of onset of obesity, occupational history, previous weight loss attempts and methods, etc
what may you like to include when developing a wise food plan for your obese patient
Have the pt keep a food diary as part of the assessment of present dietary behaviors.
Refer the patient to a dietician
Exercise is a must!
your pt has: rapid weight gain without change in diet or exercise
Signs: upper body obesity, striae, easy bruising, thin skin, HTN, glucose intolerance
you suspect
Adrenal overactivity (Cushing's syndrome)
behavior modification for the obese pt
goal-directed behavior therapy. Small group therapy (Weight Watchers, individual psychotherapy) may be helpful for some patients
Consider this adjunct if there has been little or no progress after AGGRESSIVE attempts to lose excess weight AND the patient has a BMI that justifies use of
weight loss off ____lbs per week is recommended
Weight loss should be in 10 pound increments
to lose 1 lb per week
(current weight x 13) - 500 calories/day = 1 pound/week weight loss
when are low calorie diets utilized
if the BMI > 25 with co-morbidities 800-1000 calories/day (0.8 g protein per kg daily)
BMI > 35 with or without co-morbidities (patients who are at least 30% overweight)
may need a ________diet
very low calorie
High protein, no fat
Safe if monitored
600-800 calories/day
an obese pt that exercises
shows commitment
Reduces risk of developing cardiovascular disease and/or type 2 diabetes
improves their immunity
behavioral changes can help an obese pt by
influence stimulus control, provide positive reinforcement (increases self-esteem), enhance stress management, and are an integral part of the permanent cognitive restructuring that is essential if weight loss is to be permanent
many obese females may have a present or past history of physical, emotional, or sexual abuse and/or depression
SSRI therapy for these patients (Zoloft, Prozac)
androgens act on
sex-hormone responsive hair follicles
Chin, upper lip, chest, axillae, abdomen, pubic region
excessive growth of terminal hairs in androgen-dependent regions of the body in an adult female
Elevated levels of circulating androgens OR
Increased sensitivity of hair follicles to normal levels of androgens
testosterone sources in females
Ovary (60%)
Peripheral conversion of androstenedione (40%)
what is the most potent androgen
how much testosterone circulates freely
testosterone circulates in the blood for _____
30-60 minutes then becomes "fixed" to tissues or degraded and excreted
"Fixed" testosterone is converted to DHT (the active form) by
by 5-alpha-reductase in the skin
Fixed testosterone stimulates androgen-dependent hair follicles
DHT targets
external genitalia, male pattern body hair, temporal baldness, and prostate
testosterone to aromatase in fat --->
testosterone targets
wolfian duct, brain, muscle, body hair, spermatogenesis, and libido
2 main etiologies of hirsutism
adrenal or ovarian neoplasms
other causes of hirsutism
Use of non-prescription DHEA or abuse of androgenic substances
Normal androgen levels
More common in Mediterranean, Middle Eastern ethnic groups
Onset is usually in the peri-pubertal period
There is a slow progression of hair growth
Dilantin (phenytoin)
Anabolic steroids
Certain progestins in oral contraceptives
pharmacologic etiologies of hirsutism
Irregular menses since menarche
Gradual onset of hirsutism
Congenital adrenal hyperplasia (21-hydroxylase deficiency)
Cushing's syndrome
Polycystic ovary syndrome (PCOS)
Unlikely Neoplastic Etiology of hirsutism
Accounts for approximately 50% of cases of hirsutism
Polycystic Ovary Syndrome
A common functional disorder of the ovaries
Excess LH acts on thecal cells of ovaries causing excess androgen production
polycystic ovary syndrome
Signs/Symptoms: hirsutism, amenorrhea, oligomenorrhea, infertility, obesity, insulin resistance
most common cause of hyperandrogenic anovulatory infertility.
Hypofunction of FSH causes chronic anovulation
Onset of hirsutism is outside the peri-menarchal period
There is rapid progression of hair growth
The hirsutism is SEVERE
There is a recent onset of menstrual irregularity
possibility of adrenal or ovarian neoplasm
Other signs of virilization are typically present:
Temporal hair recession and crown balding
Deeping of the voice
Loss of female body contour or breast tissue
Increased muscle mass, especially upper shoulder girdle
possibility of adrenal or ovarian neoplasm
when evaluating for hirsutism what must be done first
Perform laboratory tests before proceeding to imaging studies
what labs should you order when evaluating for hirsutism
Free and total testosterone
Hcg, urinary free cortisol
Total testosterone > 200 ng/dl or free testosterone > 40 ng/dl necessitates
a pelvic exam and pelvic ultrasound
If the pelvic examination and ultrasound are negative for the presence of polycystic ovaries, what next
perform a bilateral adrenal CT scan
serum androsternedione >1000 ng/dl
indicates an ovarian or adrenal neoplasm
Serum DHEAS > 600 mcg/dl indicates
an adrenal source of androgen
Adrenal hyperplasia or adrenal carcinoma
Perform a bilateral adrenal CT scan
Elevated UFC, cortisol and a suppressed ACTH level indicate
an adrenal etiology.
Whenever the testosterone level is > 200 or the DHEAS level is > 700, suspect a
treatment for neoplastic hirsutism
Surgical/medical treatment of lesion
treatment for idiopathic hirsutism, PCOS, CAH
Oral contraceptive agents with low-androgenic progestins
Suppresses LH/FSH production
Gonadotropin-releasing hormone analogs + estrogen/progesterone
Decreases LH/FSH production - example: leuprolide (Lupron)
Weight loss
treatment of CAH hirsutism
Glucorticoids (but consider long-term side effects)
Inhibits ACTH production
Laparoscopic bilateral adrenalectomy
Glucocorticoids inhibit ACTH production
There is an increased level of ACTH in CAH that is converted to androgens because of the 21-hydroxylase deficiency
Spironolactone (Aldactone)
commonly Rx-ed w/OCPs
Presence of palpable breast tissue in the male
Glandular tissue > 4cm
Often caused by an imbalance of the estrogen-androgen ratio
Endocrine diseases
Systemic diseases
causes of gynecomastia
Idiopathic or Familial Gynecomastia
Breast tissue is extremely sensitive to estrogens OR there is excess conversion of estrogen precursors to estrogen
neonnatal gynecomastia
Reflects high level of estrogens in the maternal-fetal unit
pubertal gynecomastia affects up to
60% of normal teens
Reflects imbalance between estrogen and androgen action on the breasts
Caused by increased sex steroid production
pubertal gynecomastia
usually subsides within a year
may be unilateral or bilateral
Testosterone levels decrease + level of sex hormone binding globulin (SHBG) increase with age and this further reduces free testosterone levels
aging gynecomastia
1/3 of males 50-80
obesity related gynecomastia
Increased fat causes increased aromatase activity
More testosterone is converted to estradiol
Androgen resistance syndromes (testicular feminization)
Aromatase excess syndrome
Klinefelter's syndrome
endocrine causes of gynecomastia
prolactin diminishes the peripheral action of testosterone and suppresses LH/FSH secretion
elevated LH and FSH causes increased secretion of estradiol from Leydig and Sertoli cells in the testes
chronic liver/renal disease is an example of what type of cause of gynecomastia
Steroid-producing neoplasms (estrogen-producing neoplasms of the adrenal glands or testes)
hCG-producing neoplasms of the testes or lung
gynecomastia caused by neoplasms
Unilateral, irregular, painless, firm/hard mass that is fixed to underlying tissues
breast cancer
There is a higher incidence of breast cancer in men with Klinefelter's syndrome`
Type I and II 5-alpha-reductase inhibitors - Proscar (finasteride), Avodart (dutasteride)
Exogenous steroids and androgens
medications that can ncause gynecomastia
Laboratory Investigation of Gynecomastia
initial tests
Prolactin and beta-hCG:
Elevated levels of either indicate a testicular tumor or other malignancy (usually lung or liver) Low levels of beta-hCG indicate primary hypogonadism
LH and testosterone:
Diagnoses primary and secondary hypogonadism
Estradiol - usually normal
Increased in testicular tumors, liver disease, obesity, and with increased beta-hCG
In cases of persistent gynecomastia without an identifiable etiology
Karyotype for Klinefelter's Syndrome
Suspicious unilateral or asymmetric enlargement
needle biopsy
In unclear cases
May reveal bronchogenic or metastatic carcinoma
chest X-ray
Idiopathic or pubertal: observe and reassure
A follow-up visit at 6 months is appropriate to check for resolution
Medication-induced gynecomastia
stop offending drug if possible
Painful gynecomastia treatment
Tamoxifen (antiestrogen)
Danazol (testosterone derivative)
hypogonadism gynecomastia treatment
Not aromatized to estradiol
Persistent or severe gynecomastia
GnRH: released in a
pulsatile manner
LH: binds to specific receptors on
Leydig cells in the testes and stimulates production of testosterone
FSH: binds to receptors on
Sertoli cells of the seminiferous tubules
Necessary for spermatogenesis
Early prenatal testosterone deficiency
Ambiguous genitalia
Either testes or ovaries but not both
inEarly prenatal testosterone deficiency accessory sex organs and/or the external genitalia
are not completely developed or are inappropriate for chromosomal sex
Later prenatal testosterone deficiency
Failure of one or both testes to descend
Testosterone deficiency in puberty (delayed puberty)
Poor muscle development
Decreased strength and endurance
High-pitched voice
Sparse axillary and pubic hair
Absence of facial and body hair
Testosterone deficiency in puberty
Long bones may continue to grow under influence of GH
Eunuchoidal proportions
arm span > height
crown-pubis < pubis-floor
normal proportions
arm span = height
crown-pubis = pubis-floor length
Post-pubertal testosterone deficiency
Decrease in libido
Low energy
Fine wrinkling around eyes and mouth
Diminished facial and body hair
Testes may be small or normal in size
3 Types of Hypogonadism
Defect in androgen action
Primary hypogonadism - defect of the testes
Low testosterone, elevated LH/FSH
Secondary hypogonadism - hypothalamic-pituitary defect
Low testosterone, low LH/FSH
Defect in androgen action:
Elevated testosterone, elevated LH/FSH
when do you want to measure serum free testosterone
nonfasting morning specimen
Free testosterone
1-2% of total testosterone
It is the biologically active portion
Total testosterone
60-75% is bound to SHBG
Elderly men have increased SHBG that decreases level of free testosterone
at what age are testosterone levels the highest
20-30 years
If the LH and FSH are low
further evaluation of pituitary function is warranted
causes of primary hypogonadism
Klinefelter's syndrome
Bilateral anorchia
Acquired gonadal failure
Other etiologies:
Lymphoma, anti-tumor chemotherapy, radiation therapy, testicular trauma
The most common congenital cause of primary hypogonadism
Klinefelter's Syndrome
47 XXY genotype
Klinefelter's Syndrome
male phenotype
Puberty findings of?
low testosterone: Small, firm testes measuring < 2 cm (normal > 3.5), Testes were of a normal size during childhood
Body hair and external genitalia mature to varying degrees
Gynecomastia, impotence, infertility
Eunuchoidal proportions - tall stature
Klinefelter's Syndrome
Female habitus, poorly virilized, gynecomastia, eunuchoidism, small phallus, small testes, and sparse body hair
Klinefelter's Syndrome
Eunuchoid, normal phallus, small testes & gynecomastia
Klinefelter's Syndrome
Undescended testes
Occurs in 3% of full-term male infants
By 1 year of age 0.75% of those infants are still affected
Undescended testes may become
cancerous after several years
Bilateral Anorchia
Vanishing testicle syndrome
Testes are present during the 1st 14-16 weeks of gestation
The scrotum is empty at birth
Growth and development are normal until secondary sexual development fails to occur at puberty
no increase in testosterone after injection of hCG
bilateral anorchia
hCG stimulation is used to differentiate
between bilateral anorchia and cryptorchidism
acquired gonadal failure at the level of the seminiferous tubules
Mumps, gonorrhea, leprosy
Vascular injury
Alcohol ingestion
FSH level is usually elevated, but may be normal
acquired gonadal failure at the level of the Leydig cell level
The LH level is usually elevated
when treating for primary hypogonadism how often and how to you give testosterone
IM every 2-3 weeks
May also use the following formulations:
Transdermal patches (Testoderm, Androderm)
Used on scrotal and non-scrotal areas
Gel - 1% testosterone (Androgel)
Same areas as patch
Oral (methyltestosterone, fluoxymesterone)
Not as effective as IM therapy
what must be done before testosterone therapy is begun
Prostate cancer screening prior to testosterone therapy is appropriate for older men (DRE and PSA)
contraindications of testosterone use
Prostate hyperplasia
Prostate cancer
Should not be used in boys < 13 years old to avoid premature epiphyseal closure and short stature
side effects of testosterone
Side effects: acne, decreased HDL levels, gynecomastia
testosterone administration follow up
Check testosterone at 1 month, then every 6 months
At 3 months, lipid levels and hemoglobin/hematocrit
DRE every 6 months, PSA
Other etiologies
secondary hypogonadism
The most common form of secondary hypogonadism
Kallmann's Syndrome
Associated with the inability to discriminate odors (anosmia)
Kallmann's Syndrome
Kallmann's Syndrome
defective development of hypothalamic cells that secrete GnRH (these cells are near the olfactory bulbs
The individual will have prepubertal testes, eunuchoidal proportions, and gynecomastia
Congenital disorders
Infarction from vascular insufficiency
Autoimmune diseases
secondary hypogonadism
pituitary adenoma
Inhibits normal GnRH release
Inhibits the action of testosterone
Decreases the effectiveness of LH
secondary hypogonadism
ETOH abuse
Chronic illnesses (renal failure, CHF, others)
Obesity (BMI > 40 kg/m2)
Marijuana use
Cushing's syndrome
Cancer, AIDS
etiologies of secondary hypogonadism
Testicular feminization
complete androgen insensitivity
Testes function normally but are located intra-abdominally
Abnormal receptors in the pituitary gland do not recognize testosterone so development proceeds as if there is a lack of testosterone
Incomplete testicular feminization
incomplete androgen insensitivity
There is a mixed pattern of virilization and feminization
5-alpha-reductase deficiency
(variable degrees of gynecomastia, hypospadias, cryptorchidism) (hypospadias)
There are elevated levels of FSH/LH and testosterone
External female genitalia is observed
There is no uterus or fallopian tubes
There are no male accessory sex organs
The testes are cryptorchid
Child has appearance of a normal prepubertal girl
Testicular Feminization - Genetic Male
At puberty, the testes secrete large amounts of testosterone:
Converted by adipose tissue into estrogens
Result is a phenotypic female with well-developed breasts that never menstruates
Testicular Feminization - Genetic Male
Testicular Feminization - genetic male
Testosterone is not recognized so it is converted to estradiol by aromatase in adipose tissu
There is an abundant amount of testosterone produced by the testes. Some is converted to DHT but the vast majority is converted into estradiol.
The estradiol causes female sex characteristics to develop.
what treatment restores androgen receptors
There are no treatments that can restore androgen receptors
Phenotype and gender assignment are female
Estrogen treatment is provided to develop secondary female sexual characteristics
Intra-abdominal testes must be removed to avoid
LH, FSH, and testosterone levels are normal
Internal sex organs develop normally
There are cryptorchid (intra-abdominal) testes
5-Alpha-Reductase Deficiency (DHT Deficiency)
Dihydrotestosterone-dependent structures fail to develop
The prostate and external genitalia are poorly developed
The individual appears female or has ambiguous external genitalia at birth
At puberty, testosterone levels rise dramatically to overcome the defect:
Secondary sexual characteristics develop
The external genitalia becomes masculinized
A penis develops at this time
5-Alpha-Reductase Deficiency (DHT Deficiency)
("guevedoce" = penis at 12)
hCG increases
A rise in testosterone after hCG administration indicates
the presence of functional testicular tissue (cryptorchidism).
If there is NO rise in testosterone after hCG administration indicates
then bilateral anorchia is present