Les testicules Flashcards
What is the normal size of an adult testicle?
Volume –> 18.6 ± 4.8 mL
Length –> 4.6 cm (3.6-5.5)
Width –> 2.6 cm (2.1-3.2)
What are the 3 layers surrounding the testicles?
- Vaginal
- Albuginea
- Vascular
Anatomical location of testes:
Start –> near kidneys
Start descending around 12th week
Mid gestation –> inguinal canal
End –> scrotum (in 12 last weeks)
2 major histological components of the testicles:
- Leydig/C cells (interstitial)
- Seminiferous tubules
- Germinal cells
- Sertoli cells
Hormones in Leydig cells:
- 95% testosterone
- DHT
- Estradiol
Small amounts of: dehydroepiandrosterone, androstenedione
What do Sertoli cells secrete?
Anti-Mullerian hormone (HAM)
Androgen binding protein
Inhibine
Function of seminiferous tubules:
Production of spermatozoids –> NO HORMONE PRODUCTION
Where else can androgens come from?
Andrenal glands:
- DHEA
- DHEAS
- Androstenedione –> testosterone (peripheral)
Precursor conversion:
- Estradiol, estrone
- DHT
- Testosterone
How is testosterone transported throughout the body?
Bound to proteins:
- SHBG (44%)
- Albumin (52%)
Free (2%) –> active testosterone
Mechanism of action of androgens:
Testicles –> testosterone
Partially converted into DHT by 5-alpha-reductase
DHT and testosterone have the same receptor BUT different function
What are the roles of testosterone?
- Regulation of FSH and LH
- Initiation and maintenance of spermatogenesis
- Formation of “male phenotype” –> voice, muscles, virilization
- Sexual maturation during puberty
- Control of libido
What are the roles of testosterone during embryogenesis?
Direct role: differentiation of male internal genital organs
Indirect role: differentiation of male OGE
What are the roles of testosterone during puberty and in adults?
Puberty: secondary sexual characteristics
Adult: libido/potency
Axe hypothalamo-hypophyso gonadique
Three sequential processes of sexual differenciation:
- Chromosomes: XX vs XY
- Gonadal sex: undifferentiated –> ovary vs testicle
- Somatic sex: development of external genitalia
Steps of somatic sex determination:
- 8-10 weeks: regression of muller canals (HAM secretion by Sertoli)
- 9 weeks: differentiation of Wolff canals (testosterone by Leydig)
- 10 weeks: OGE
- Testicular descent:
- 12 weeks: abdomen –> inguinal canal
- 7 months: inguinal canal –> scrotum
Testicular differentiation:
- Sertoli cells –> HAM
- Regression of Muller canals
- C Leydig cells
- Start synthesis of testosterone:
- Differentiation of Wolff canals
- Spermatogenesis
- External virilisation (DHT (5 alpha-reductase))
- Start synthesis of testosterone:
Embryological biosynthesis and regulation of testosterone:
First and second trimesters:
- HCG (placenta) –> stimulus that maintain testicular steroidogenesis
- FSH and LH have NO ROLE
Third trimester:
- Axe hypothalamo-hypophysaire gonadique starts working
- FSH –> stimulates the growth of seminiferous tubules
- LH –> stimulates the production of testosterone in Leydig cells
What is dihydrotestosterone (DHT)?
Shares the same receptor as testosterone
Stronger than testosterone (higher affinity and stability)
Masculinisation of OGE (penis, scrotum, and prostate)
Action of testosterone in utero:
Masculinisation of fetus (XY presentation)
Differentiation of Wolff canals –> epididymis, vas deferens, seminal vesicles, ejaculatory canal
NO DIRECT ACTION OF DIFFERENTIATION OF UROGENITAL SINUS
What is 5 alpha-reductase?
The enzyme necessary for the conversion of testosterone –> DHT
Present in:
- Prostate
- Urogenital sinus
- OGE
Not really present in:
- Wolff canals
How does testosterone vary with age?
Birth: mini puberty around 6 weeks
Puberty: progressive increase of testosterone secretion
Adult: stable max levels
Elderly: gradual decrease of testosterone secretion
Frequent causes of sexual differentiation problems
- Congenital adrenal hyperplasia
- Anomalies with testosterone synthesis/action
- Androgen insensibility
- Deficit in 5 alpha-reductase
- Anomalies of cholesterol synthesis
What is puberty?
Ensemble des phénomènes physiques, psychiques, mentaux, affectifs qui caractérisent le passage de l’enfance –> adulte
Takes around 4 years
Physiology of puberty:
Axe hypothalamo-hypophyso-gonadique inactive during prepubescence
GnRH –> reamplification of its pulsatility
Pituitary:
- increased sensitivity to GnRH and LH/FSH (LH>FSH)
- Gonadic maturation –> secondary sexual characteristics
What factors influence the start of puberty?
- Genetics
- Age of puberty in parents
- Bone age
- Integrity of the axe
- Growth hormone
- Facilitates the start of puberty
- Nutrition
- Fatty tissue
What characterizes puberty in boys?
- Apparition of secondary sexual characteristics
- Growth spurt
- Peak of bone density
- Increased muscle mass
- Gynecomastia (50-60%)
What is an orchidometer?
medical instrument used to measure the volume of the testicles
Tanner stages of male puberty:
Chronology of puberty in boys:
- Increased testicular volume (1st sign of puberty… has to be > 4 cm)
- Pubic hair
- Penis growth
- Growth spurt
- Axillary hair growth (12-18 months later)
- Voice drop (12 months later)
- Facial hair (Tanner 4/5)
What is gynecomastia?
Benign proliferation of glandular tissue IN MEN
Presence of firm, concentric mass under areola
What is adipomastia?
Accumulation of fat without glandular proliferation
Physiopathology of gynecomastia:
Physiological causes of gynecomastia:
Newborn, puberty, old age
Gynecomastia in newborns:
In 60-90% of newborns
Transitory –> disappears in 2-3 weeks
Maternal passage of milk
Galactorrhea
Gynecomastia during adolescence:
Transitory increase in mammary tissue in 50-60% of teenage boys
Usually happens around age 14 and disappears after around 18 months
No galactorrhea
Rare to still be present after 17 years old
What is macromastia?
Severe gynecomastia (> 4cm)
Can persist pas adolescence
Often associated with an endocrinopathy
Physiopathology of gynecomastia in adolescents:
Relative increase in estradiol compared to testosterone
Increased estrone compared to other adrenal androgens
Local formation of estradiol in mammary tissue
Age linked gynecomastia
In 24-65% of men between the ages of 50-80 years old due to a decrease in testosterone production
Pathological causes of gynecomastia:
Relative excess of estrogen/relative decrease of testosterone:
- Klinefelter Syndrome (47 XXY)
- Congenital anorchia
- Androgen insensitivity (46 XY but presents as XX)
- Secondary testicular insufficiency
Increase In estrogen production:
- Testicular tumours, hermaphroditism, hCG secreting tumours
- Increased substrate for aromatase (converts testo –> estro)
- Adrenal/hepatic insufficiency, hyperT4
- Increased extraglandular aromatase
Other pathological causes of gynecomastia:
Medication, drugs, idiopathic (no known cause even after tests)
Bilan for gynecomastia:
FSH/LH
Estradiol and testosterone
TSH and T4
Karyotyping (47 XXY?…)
Spermogram
bHCG, alpha foeto-protein
AST, ALT, BUN, Creat.
What is hypogonadism?
Decrease in at least 1/2 functions of the testicles:
- Spermatogenesis
- Testosterone production
Can be caused by:
- Testicular issue –> primary
- Hypothalamus/pituitary –> central
Hypogonadism in adolescents:
Absence or stop of puberty
Gynecomastia/anosmia
Decreased growth speed except for in Klinefelter
Loss of bone density
Hypogonadism in adults:
Infertility and loss of libido
Gynecomastia
Osteoporosis
Complications of hypogonadism:
Infertility
Osteoporosis
Gynecomastia
Psychological repercussions
Central hypogonadism: decrease/loss of secretion of LH and FSH
Associated with:
- Dim. spermatogenesis
- Dim. testosterone
- Possible cryptorchidism depending on when it started
- Small testes
Not typically associated with gynecomastia (FSH and LH not increased therefore less aromatase stimulation)
Central hypogonadism: congenital
Causes:
- Kallmann Syndrome
- SNC malformation
- Isolated –> GnRH-R mutations, LH-B or FSH-B butations
- Syndrome associated: Bradet-Biedl/Prader-Willi
- Idiopathic
Central hypogonadism: acquired
Any damage to hypothalamus/pituitary:
- Tumors –> craniopharyngioma/histyocysosis
- Trauma
- Infections
- Gonadal steroids (Rx)
- Chronic illnesses
- Anorexia
Central hypogonadism: endocrine
- Cushing
- HypoT4
- Hypopituitarism
- HyperPRL (interferes with FSH/LH secretion)
What is Kallmann Syndrome?
Anomaly with the migration/adhesion of GnRH neurons (with smell) –> anosmia
Transmission: autosomal dominant, recessive, X-linked, sporadic, familial
Associated with:
- Anosmia/hyposmia
- Median line anomalies
- Neurosensorial deafness
- Colour blindness
How to dx central hypogonadism?
Labs:
- Dim. testosterone
- Dim. LH/FSH
- Dim. spermogram
Imagery:
- Lowered bone density
- Bone age
- MRI
What is primary hypogonadism?
Testicular problem
Usually more serious impact on spermatogenisis
- Low/normal testosterone
- Increased +++ FSH/LH
Most common causes of primary hypogonadism:
- Chromosomal: Klinefelter
- Chimio/radiotx
- Infectious: orchite/oreillons
- Testicular torsion/trauma
- Congenital anorchia
- FSH-R/LH-R mutations
- Mutations with steroidogenesis enzymes
What is Klinefelter Syndrome?
47 XXY (usually due to egg being XX but can be due to XY sperm in rare cases)
1/500-1/1000 births
More frequent if mother is older
Expression during puberty/adult age… not possible to know at birth without checking for it
Presentation of Klinefelter
Before puberty: NO SIGNS, but can have behaviour/school issues
Puberty:
- Stagnation of puberty
- Small testicles
- Eunoichidism
- Gynecomastia
- Tall, long arm/legs
- Degeneration of seminiferous tubules (fibrosis) –> testicular shrinkage and can lead to azoospermia
- Increased estradiol –> increased SHBG
- Dim. testosterone
Adulthood:
- Small testicles/eunochoidism
- Gynecomastia
- Decreased hair
- Infertility
- Osteoporosis
Diagnosis of Klinefelter
Clinical presentation
Biologic: dim. testo, increased LH/FSH
Karyotyping (47 XXY)
Prevalence of testicular tumours
1-2% of malignant tumours in men
4-10% of genitourinary cancers
2nd most common cause of cancer in men between 20-34 years old
Causes of testicular tumours
Cause is really unknown
FDR:
- Cryptorchidism
- Testicular dysgenesis
- Trauma?
Bilat. gynecomastia quite rare
What are the two kinds of testicular tumours?
- Germinal cell tumours
- Leydig tumours
Germinal cell tumours
Seminomas –> 33-50%
Tumeurs des C embryonnaires –> 20-33%
Teratomas –> 10-30%
Choriocarcinomas –> 2%
Tumoural markers:
- bHCG +++
- afoeto-protein
Clinical presentation of germinal cell tumours
Increased testicular volume (no pain)
“Sensation de plénitude”
80% –> tender mass
25% –> pain/increased sensitivity
6-25% –> history of trauma
5-10% –> Sx of metastasis
Can cause premature puberty
Leydig cell tumours
Children: premature puberty (increased speed of growth, bone density, development of secondary sexual characteristics)
Teens: accelerated growth, testicular masses
Adult: unilateral testicular mass, gynecomastia, if tumour Is active (endocrine)
- Decreased FSH and LH –> decreased testosterone
- Loss of libido
- Azoospermia
What is andropause?
Progressive loss of gonadal function with age (usually after 50 years old)
Physiology of andropause:
A gradual decrease of testosterone secretion with an increase in SHBG
Decreased response in Leydig cells to hCG
Increase in LH (compensation)
Histopathology: degeneration of seminiferous tubules and # and volume of Leydig cells
Also due to microvascular insuff.
Clinical presentation of andropause
Loss of libido
Erectile dysfunction
Emitonal instability
Fatigue/loss of concentration
Loss of muscle mass/force
Vasomotor instability (palpitations, hot flashes, diaphoresis)
Diffuse myalgia
IF SEVERE –> loss of testicular volume/texture
Lab findings in andropause
Low/low normal testosterone
LH in limits of normal or slightly high
Spermogram: oligospermia
Loss of bone density (dim. minérilisation osseuse)
What are the indications for taking testosterone?
Induce and maintain puberty –> kids and teens
Hypogonadism –> adults
Goals of testosterone replacement therapy
Induce/restore:
- Secondary sex characteristics
- “Male” behaviour
Assure proper somatic development
Side effects of taking testosterone:
Intrahepatic cholestasis
Hepatocellular carcinoma
Premature epiphysis closing (in kids)
Hydrosodium retention
Erythrocytosis
Gynecomastia
Priapism, acne, aggressiveness
Oligospermia and testicular atrophy
How is testosterone administered?
IM injections
S/C injections
Transdermal gel
Transdermal patch (scrotal, non scrotal, gel)
ORAL IS NOT YET AVAILABLE
