male hypogonadism

Question 1

What produces testosterone?

Answer 1

Leydig cells

Question 2

What converts testosterone to its active form?

Answer 2

5 alpha reductase

Question 3

Explain the HPG axis

Answer 3

• hypothalamus releases GnRH
• This causes the anterior pituitary to synthesise and release LH and FSH
• LH acts on the leydig cells to produce testosterone
• FSH acts on the Sertoli cells to stimulate spermatogenesis
• Testosterone and oestrogen (testosterone converted to oestrogen) decreases release of GnRH and LH and FSH by negative feedback mechanism

Question 4

What are the biological effects of testosterone?

Answer 4

Growth: 
•Sex organs
•Skeletal muscles
•Epiphyseal plates 
•Larynx growth 
•Secondary characteristics

Other:
•Erythropoiesis and Hb maintenance
•Behaviour

Question 5

What are the effects of testosterone in adult men?

Answer 5

•Muscle mass and strength 
•Mood 
•Bone mass 
•Libido 
•Body shape 
•Fertility:
 - libido
 - erectile function 
 - spermatogenesis

Question 6

What cells does spermatogenesis involve?

Answer 6

Spermatocytes, leydig and Sertoli cells

Question 7

What is the role of leydig cells?

Answer 7

Secretes testosterone to promote sperm development

Question 8

What is the role of Sertoli cells?

Answer 8

• Blood testis barrier
• Remove damaged spermatocytes
• Secrete androgen binding protein to ensure increased testosterone in the testes

Question 9

What are the clinical features of hypogonadism in children/young adults?

Answer 9

• Slow growth in teens
• No pubertal growth spurt
• Lack of secondary sexual development (small testes/phallus)

Question 10

What are the clinical features of hypogonadism in adults?

Answer 10

• Low mood
• Poor libido
• Erectile dysfunction
• Hot flashes/sweats
• poor muscle bulk/power
• poor energy
• Sparce body/facial hair
• Gynaecomastia
• Gynoid weight gain
• Short phallus/reduced testicualr volumes
• Low trauma fractures

Question 11

Explain clinical assessment of hypogonadism

Answer 11

• Symptoms, growth
• Past medical history- any trauma or head injury
• family history, do they have any children?
• Medications/drugs, over the counter or prescribed
• Social history
• any sign of chronic illness
• Height and weight
• secondary sexual characteristics
• Testicular size

Question 12

Explain the testing for suspected hypogonadism

Answer 12

•Testosterone:

• early morning fasting venous blood sample
• normal: free testosterone>200 or total>10
• SHBG (if low can impact)
• repeat to confirm

•LH and FSH
- determines if pituitary or testicular cause

•Other considerations:

• if concerned about fertility then semen analysis
• ferritin/ACE
• pituitary screen/ MRI of pituitary
• testicular: ultrasound, karyotype
• DEXA

Question 13

Blood test results in secondary hypogonadism

Answer 13

• Hypogonadotrphic hypogonadism
• LH and FSH normal or low
• Low testosterone

Question 14

Blood tests in primary hypogonadism

Answer 14

• Hypergonadotrophic hypogonadism
• LH and FSH high
• Low testosterone

Question 15

What are the causes of hypogonadotrophic hypogonadism?

Answer 15

•Pituitary disease - tumour, pituitary surgery, radiotherapy 
•Head injury 
•isolated LH/FSH deficiency - kallmanns 
•Functional hypothalamic hypogonadism 
 - exercise 
 - weight changes 
 - physical/psychological stress 
 - systemic illness

Question 16

What is Kallmann’s syndrome?

Answer 16

• Isolated gonadotrophin deficiency
• Failure of cell migration of GnRH cells to the hypothalamus
• Associated with aplasia or hypoplasia of the olfactory bulbs - anosmia or hyposmia
• Associated with deafness, renal agenesis, cleft lip/palate

Question 17

Explain the diagnosis of Kallmann’s syndrome

Answer 17

• Anosmia in 75%
• Low testosterone, LH/FSH
• Normal rest of pituitary function
• Normal pituitary MRI but absent olfactory bulb

Question 18

What are the genetics of Kallmann’s?

Answer 18

• Most commonly an isolated gene mutation
• X linked - absence of KAL 1
• Autosomal dominant KAL2
• Autosomal recessive KAL3

Question 19

What are the primary gonadal diseases?

Answer 19

• Chromosome defects e.g. Kleinfelter’s
• Seminiferous tubule or adult leydig cell failure e.g. following trauma, chemo-therapy or part of multi system disorder
• Cryptorchidism

Question 20

What is Klinefelter’s?

Answer 20

• Most common cause of male hypogonadism
• Karyotype: 47XXY or 47XXY mosaicism
• Clincially manifests at puberty
• Elevated LH/FSH but seminiferous tubules regress and leydig cells do not function normally, low testosterone

Question 21

What is the presentation of Klinefelter’s?

Answer 21

Clinical variation in phenotype
•Delayed puberty 
•Reduced testicular volumes 
•Reduced secondary male characteristics
•Persistent gynaecomastia 
•Azospermia
•Behavioural issues/learning difficulties

Question 22

What is the management of Kleinfelters?

Answer 22

•Androgen replacement 
 - IM testosterone or topical
•Psychological support 
•Fertility counselling
 - hCG, recombinant FSH and LH, GnRH pumps

Question 23

What are the side effects of testosterone?

Answer 23

• Mood issues (aggression/behaviour change)
• Libido issues
• Increased haematocrit/polycythaemia
• Possible development of lower urinary tract symptoms
• Acne
• Gynaecomastia due to increased oestrogen