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
Hypertension
Coronary heart disease
Diabetes (type2)
hyperlipidemia
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
medications
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
Consider
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
hirsutism
hirsutism
Elevated levels of circulating androgens OR
Increased sensitivity of hair follicles to normal levels of androgens
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
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
IDIOPATHIC OR FAMILIAL HIRSUTISM
Minoxidil
Cyclosporine
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
PCOS
most common cause of hyperandrogenic anovulatory infertility.
Hypofunction of FSH causes chronic anovulation
PCOS
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
Clitorimegaly
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
Serum DHEAS
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 DHEAS > 600 mcg/dl indicates
an adrenal source of androgen
Adrenal hyperplasia or adrenal carcinoma
Perform a bilateral adrenal CT scan
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
Idiopathic
Physiologic
Endocrine diseases
Systemic diseases
Neoplasms
Medications
causes of gynecomastia
Idiopathic or Familial Gynecomastia
Breast tissue is extremely sensitive to estrogens OR there is excess conversion of estrogen precursors to estrogen
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
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
Hyperprolactinemia
Klinefelter's syndrome
Hypogonadism
endocrine causes of gynecomastia
hyperprolactinemia
prolactin diminishes the peripheral action of testosterone and suppresses LH/FSH secretion
hypogonadism
elevated LH and FSH causes increased secretion of estradiol from Leydig and Sertoli cells in the testes
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`
marijuana
amphetamines
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
Idiopathic or pubertal: observe and reassure
A follow-up visit at 6 months is appropriate to check for resolution
LH: binds to specific receptors on
Leydig cells in the testes and stimulates production of testosterone
Early prenatal testosterone deficiency
Ambiguous genitalia
Pseudohermaphroditism
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
Micropenis
Cryptorchidism
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
Post-pubertal testosterone deficiency
Decrease in libido
Impotence
Low energy
Fine wrinkling around eyes and mouth
Diminished facial and body hair
Testes may be small or normal in size
Total testosterone
60-75% is bound to SHBG
Elderly men have increased SHBG that decreases level of free testosterone
causes of primary hypogonadism
Klinefelter's syndrome
Cryptorchidism
Bilateral anorchia
Acquired gonadal failure
Other etiologies:
Lymphoma, anti-tumor chemotherapy, radiation therapy, testicular trauma
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
Cryptorchidism
Undescended testes
Occurs in 3% of full-term male infants
By 1 year of age 0.75% of those infants are still affected
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
acquired gonadal failure at the level of the seminiferous tubules
Mumps, gonorrhea, leprosy
Irradiation
Vascular injury
Trauma
Alcohol ingestion
Chemotherapy
FSH level is usually elevated, but may be normal
acquired gonadal failure at the level of the Leydig cell level
Aging
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
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
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
Tumors
Infarction from vascular insufficiency
Autoimmune diseases
Trauma
Infections
Panhypopituitarism
secondary hypogonadism
pituitary adenoma
Inhibits normal GnRH release
Inhibits the action of testosterone
Decreases the effectiveness of LH
hyperprolactinemia
secondary hypogonadism
ETOH abuse
Chronic illnesses (renal failure, CHF, others)
Obesity (BMI > 40 kg/m2)
Marijuana use
Idiopathic
Cushing's syndrome
Hypothyroidism
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
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)
A rise in testosterone after hCG administration indicates
the presence of functional testicular tissue (cryptorchidism).