Hypogonadism Flashcards
What does it mean when hormones are pulsatile & examples
Released at different frequencies & amplitudes
GnRH, LH & testosterone
What is the circadian rhythm of male endocrine system
Increases in early a.m 4:00-8:00
Decrease in late p.m 16:00-20:00
What is the feedback mechanism of endocrine system
Negative feedback
What is the 2 types of testing in endocrine system
- Standard testing
- Dynamic testing
What is the hypothalamo-pituitary-gonodal axis
Hypothalamus release GnRH that stimulate anterior pituitary to release FSH & LH
FSH act on Sertoli cells in testicles allowing for spermatozoa @ seminiferous tubules & release inhibin to inhibit release of FSH from anterior pituitary
LH act on Leydig cells in testicles that produce testosterone from cholesterol that also stimulate Sertoli cells to produce spermatozoa or go to target tissue
Testosterone also provides negative feedback to anterior pituitary & hypothalamus
What is androgens
Sex hormones with cholesterol as precursor
What is the 2 male androgens
Testosterone
Dihydrotestosterone
What is the 3 functions of androgens
- Masculination of genital tract
- Development & maintenance of male secondary sexual characteristics
- Anabolic effect on muscle mass, bone density & decrease fat mass)
What is the pathway of testosterone biosynthesis
- Cholesterol
- Pregnenolone to progesterone & DHEA
- Progesterone to mineralocorticoids & glucocorticoid
- DHEA & progesterone to androstenedione
- Androstenedione to oestrone & testosterone
- Testosterone to oestrodiol via aroma taste at liver/fat cells & DHT via 5-alpha reductase
What 8 factors affect testosterone production
- Sex difference
- Age
- Pulsatility
- Diurnal rhythm
- SHBG concentration
- Health state (stress, illness, diabetes, metabolic syndrome, obesity)
- Hyperprolactinaemia
- Medication
What is the 2 forms of testosterone
- Free that is active & bioavailable
- Bound to proteins
To what proteins do testosterone bind
- Sex hormone binding globulin that has high affinity & low capacity
- Albumin that has low affinity & high capacity & bioavailable
What is SHBG
Glycoprotein produced at the liver
What 3 things does SHBG bind
Testosterone, DHT, estrogen
What is the function of SHBG
Regulate bioavailability of sex hormones to tissue
What is used to provide an estimate of free testosterone
Free androgen index
3 examples of increased SHBG
Hyperthyroidism
Aging
GH deficiency
3 examples of decreased SHBG
Obesity
Hypothyroidism
GH excess
What is testosterone mechanism of action
Testosterone is synthesized & enter the cells (lipophilic molecule) & can be converted to DHT or directly bind to androgen receptor
If converted to DHT it then binds to androgen receptor in cytoplasm
After binding it gets translocated to nucleus, gene regulation, protein synthesis & target tissue effects
What is androgen insensitivity syndrome
Mutation of androgen receptor & dysfunctional receptors
Can be complete or partial
What is the 3 places where DHT conversion occur
Prostate, skin & hair follicles
What is the 3 functions of DHT
- Development of male external genitalia
- Prostate growth & function
- Secondary sexual characteristics
What is the important enzyme that converts testosterone to DHT
5-alpha reductase
What does hypogonadism mean
Decreased function of testes
What 2 things does hypogonadism affect
Sperm production
Testosterone production
What 2 things does hypogonadism leads to
Infertility
Loss of secondary sexual characteristics
Where does primary & secondary hypogonadism occur
Primary: testicular failure
Secondary: hypothalamus or pituitary failure
What is chemical results of primary hypogonadism
High FSH & LH w/ low testosterone
What is chemical results of secondary hypogonadism
Low or inappropriate LH & FSH w/ low testosterone
What is another name for primary hypogonadism
Hypergonadotrophic hypogonadism
What is another name for secondary hypogonadism
Hypogonadotrophic hypogonadism
What is the causes of primary hypogonadism
Congenital: Klinefelter syndrome
Acquired: damage to testes, infection, chemotherapy/radiation
What is causes of secondary hypogonadism
Congenital: Kallmann syndrome
Acquired: tumors, systemic disease, medication, obesity & metabolic syndrome
What dynamic test is done w/ primary hypogonadism
HCG stimulation test
What 2 dynamic test is done w/ secondary hypogonadism
- Clomiphene stimulation test
- GnRH stimulation test
What is 3 clinical features of hypogonadism pre-natal
Affects primary male sex structures
Incomplete virilization
Cryptorchidism
What is 3 clinical features of hypogonadism before puberty
Lack of secondary sex characteristics
Eunuchoid body proportion
Delayed puberty
What is 6 clinical features of hypogonadism post puberty
Osteoporosis
Fatigue & mood change
Increased fat
Gynaecomastia
Decrease muscle
Decrease libido & erectile dysfunction
Testes atrophy & infertility
What is 4 clinical features of hypogonadism elderly
Same as adult
Cognitive changes
Andropause
Insulin resistance, central obesity, increased CVS risk
Define gynaecomastia
Enlargement of male breast tissue
What is 4 causes of gynaecomastia
Idiopathic
Obesity
Hormonal imbalance
Liver disease
How to test for gynaecomastia
Assess hormone levels
Rule out underlying pathologies
How is total testosterone measured
8-10am
To confirm hypogonadism test should be repeated on separate occasion
When to test LH & FSH
When confirmed low testosterone
When is LH & FSH high & low
High: primary
Low/inappropriately normal: secondary
How does HCG test work
Tests Leydig cells function & mimic LH response to stimulate testosterone & normally increases
How does GnRH test work
Test HPG axis function by stimulating GnRH to stimulate LH/FSH release
If hypothalamic disease LH & FSH should increase but if pituitary disease LH & FSH will not increase
How does clomiphene test work
Tests hypothalamic-pituitary response by inhibiting estrogen feedback & GnRH should increase in secondary but not in primary
