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MD1 endocrinologie > Les testicules > Flashcards

Les testicules Flashcards

1
Q

What is the normal size of an adult testicle?

A

Volume –> 18.6 ± 4.8 mL

Length –> 4.6 cm (3.6-5.5)

Width –> 2.6 cm (2.1-3.2)

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2
Q

What are the 3 layers surrounding the testicles?

A
  1. Vaginal
  2. Albuginea
  3. Vascular
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3
Q

Anatomical location of testes:

A

Start –> near kidneys

Start descending around 12th week

Mid gestation –> inguinal canal

End –> scrotum (in 12 last weeks)

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4
Q

2 major histological components of the testicles:

A
  1. Leydig/C cells (interstitial)
  2. Seminiferous tubules
    1. Germinal cells
    2. Sertoli cells
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5
Q

Hormones in Leydig cells:

A
  1. 95% testosterone
  2. DHT
  3. Estradiol

Small amounts of: dehydroepiandrosterone, androstenedione

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6
Q

What do Sertoli cells secrete?

A

Anti-Mullerian hormone (HAM)

Androgen binding protein

Inhibine

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7
Q

Function of seminiferous tubules:

A

Production of spermatozoids –> NO HORMONE PRODUCTION

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8
Q

Where else can androgens come from?

A

Andrenal glands:

  • DHEA
  • DHEAS
  • Androstenedione –> testosterone (peripheral)

Precursor conversion:

  • Estradiol, estrone
  • DHT
  • Testosterone
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9
Q

How is testosterone transported throughout the body?

A

Bound to proteins:

  • SHBG (44%)
  • Albumin (52%)

Free (2%) –> active testosterone

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10
Q

Mechanism of action of androgens:

A

Testicles –> testosterone

Partially converted into DHT by 5-alpha-reductase

DHT and testosterone have the same receptor BUT different function

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11
Q

What are the roles of testosterone?

A
  1. Regulation of FSH and LH
  2. Initiation and maintenance of spermatogenesis
  3. Formation of “male phenotype” –> voice, muscles, virilization
  4. Sexual maturation during puberty
  5. Control of libido
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12
Q

What are the roles of testosterone during embryogenesis?

A

Direct role: differentiation of male internal genital organs

Indirect role: differentiation of male OGE

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13
Q

What are the roles of testosterone during puberty and in adults?

A

Puberty: secondary sexual characteristics

Adult: libido/potency

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14
Q

Axe hypothalamo-hypophyso gonadique

A
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15
Q

Three sequential processes of sexual differenciation:

A
  1. Chromosomes: XX vs XY
  2. Gonadal sex: undifferentiated –> ovary vs testicle
  3. Somatic sex: development of external genitalia
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16
Q

Steps of somatic sex determination:

A
  1. 8-10 weeks: regression of muller canals (HAM secretion by Sertoli)
  2. 9 weeks: differentiation of Wolff canals (testosterone by Leydig)
  3. 10 weeks: OGE
  4. Testicular descent:
    • 12 weeks: abdomen –> inguinal canal
    • 7 months: inguinal canal –> scrotum
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17
Q

Testicular differentiation:

A
  1. Sertoli cells –> HAM
    • Regression of Muller canals
  2. C Leydig cells
    • Start synthesis of testosterone:
      1. Differentiation of Wolff canals
      2. Spermatogenesis
      3. External virilisation (DHT (5 alpha-reductase))
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18
Q

Embryological biosynthesis and regulation of testosterone:

A

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
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19
Q

What is dihydrotestosterone (DHT)?

A

Shares the same receptor as testosterone

Stronger than testosterone (higher affinity and stability)

Masculinisation of OGE (penis, scrotum, and prostate)

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20
Q

Action of testosterone in utero:

A

Masculinisation of fetus (XY presentation)

Differentiation of Wolff canals –> epididymis, vas deferens, seminal vesicles, ejaculatory canal

NO DIRECT ACTION OF DIFFERENTIATION OF UROGENITAL SINUS

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21
Q

What is 5 alpha-reductase?

A

The enzyme necessary for the conversion of testosterone –> DHT

Present in:

  • Prostate
  • Urogenital sinus
  • OGE

Not really present in:

  • Wolff canals
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22
Q

How does testosterone vary with age?

A

Birth: mini puberty around 6 weeks

Puberty: progressive increase of testosterone secretion

Adult: stable max levels

Elderly: gradual decrease of testosterone secretion

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23
Q

Frequent causes of sexual differentiation problems

A
  1. Congenital adrenal hyperplasia
  2. Anomalies with testosterone synthesis/action
  3. Androgen insensibility
  4. Deficit in 5 alpha-reductase
  5. Anomalies of cholesterol synthesis
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24
Q

What is puberty?

A

Ensemble des phénomènes physiques, psychiques, mentaux, affectifs qui caractérisent le passage de l’enfance –> adulte

Takes around 4 years

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25
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
26
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
27
What characterizes puberty in boys?
1. Apparition of secondary sexual characteristics 2. Growth spurt 3. Peak of bone density 4. Increased muscle mass 5. Gynecomastia (50-60%)
28
What is an orchidometer?
medical instrument used to measure the volume of the testicles
29
Tanner stages of male puberty:
30
Chronology of puberty in boys:
1. Increased testicular volume (1st sign of puberty... has to be \> 4 cm) 2. Pubic hair 3. Penis growth 4. Growth spurt 5. Axillary hair growth (12-18 months later) 6. Voice drop (12 months later) 7. Facial hair (Tanner 4/5)
31
What is gynecomastia?
Benign proliferation of glandular tissue IN MEN Presence of firm, concentric mass under areola
32
What is adipomastia?
Accumulation of fat without glandular proliferation
33
Physiopathology of gynecomastia:
34
Physiological causes of gynecomastia:
Newborn, puberty, old age
35
Gynecomastia in newborns:
In 60-90% of newborns Transitory --\> disappears in 2-3 weeks Maternal passage of milk Galactorrhea
36
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
37
What is macromastia?
Severe gynecomastia (\> 4cm) Can persist pas adolescence Often associated with an endocrinopathy
38
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
39
Age linked gynecomastia
In 24-65% of men between the ages of 50-80 years old due to a decrease in testosterone production
40
Pathological causes of gynecomastia:
**Relative excess of estrogen/relative decrease of testosterone:** 1. Klinefelter Syndrome (47 XXY) 2. Congenital anorchia 3. Androgen insensitivity (46 XY but presents as XX) 4. Secondary testicular insufficiency **Increase In estrogen production:** 1. Testicular tumours, hermaphroditism, hCG secreting tumours 2. Increased substrate for aromatase (converts testo --\> estro) 1. Adrenal/hepatic insufficiency, hyperT4 2. Increased extraglandular aromatase
41
Other pathological causes of gynecomastia:
Medication, drugs, idiopathic (no known cause even after tests)
42
Bilan for gynecomastia:
FSH/LH Estradiol and testosterone TSH and T4 Karyotyping (47 XXY?...) Spermogram bHCG, alpha foeto-protein AST, ALT, BUN, Creat.
43
What is hypogonadism?
Decrease in at least 1/2 functions of the testicles: 1. Spermatogenesis 2. Testosterone production **Can be caused by:** 1. Testicular issue --\> primary 2. Hypothalamus/pituitary --\> central
44
Hypogonadism in adolescents:
Absence or stop of puberty Gynecomastia/anosmia Decreased growth speed **except for in Klinefelter** Loss of bone density
45
Hypogonadism in adults:
Infertility and loss of libido Gynecomastia Osteoporosis
46
Complications of hypogonadism:
Infertility Osteoporosis Gynecomastia Psychological repercussions
47
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)
48
Central hypogonadism: congenital
Causes: 1. Kallmann Syndrome 2. SNC malformation 3. Isolated --\> GnRH-R mutations, LH-B or FSH-B butations 4. Syndrome associated: Bradet-Biedl/Prader-Willi 5. Idiopathic
49
Central hypogonadism: acquired
Any damage to hypothalamus/pituitary: * Tumors --\> craniopharyngioma/histyocysosis * Trauma * Infections * Gonadal steroids (Rx) * Chronic illnesses * Anorexia
50
Central hypogonadism: endocrine
1. Cushing 2. HypoT4 3. Hypopituitarism 4. HyperPRL (interferes with FSH/LH secretion)
51
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
52
How to dx central hypogonadism?
Labs: * Dim. testosterone * Dim. LH/FSH * Dim. spermogram Imagery: * Lowered bone density * Bone age * MRI
53
What is primary hypogonadism?
**Testicular problem** Usually more serious impact on spermatogenisis * Low/normal testosterone * Increased +++ FSH/LH
54
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
55
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**
56
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
57
Diagnosis of Klinefelter
Clinical presentation Biologic: dim. testo, increased LH/FSH Karyotyping (47 XXY)
58
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
59
Causes of testicular tumours
Cause is really unknown FDR: * Cryptorchidism * Testicular dysgenesis * Trauma? Bilat. gynecomastia quite rare
60
What are the two kinds of testicular tumours?
1. Germinal cell tumours 2. Leydig tumours
61
Germinal cell tumours
Seminomas --\> 33-50% Tumeurs des C embryonnaires --\> 20-33% Teratomas --\> 10-30% Choriocarcinomas --\> 2% **Tumoural markers:** * **bHCG +++** * **afoeto-protein**
62
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
63
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
64
What is andropause?
Progressive loss of gonadal function with age (usually after 50 years old)
65
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.
66
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
67
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)
68
What are the indications for taking testosterone?
Induce and maintain puberty --\> kids and teens Hypogonadism --\> adults
69
Goals of testosterone replacement therapy
Induce/restore: * Secondary sex characteristics * "Male" behaviour Assure proper somatic development
70
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
71
How is testosterone administered?
IM injections S/C injections Transdermal gel Transdermal patch (scrotal, non scrotal, gel) **ORAL IS NOT YET AVAILABLE**

MD1 endocrinologie (6 decks)

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