Male Hypogonadism

Question 1

What cell produce testosterone?

Answer 1

Leydig cells

Question 2

Describe testosterone.

Answer 2

Steroid hormone (cholesterol precursor)
Circulates bound to SHBG and albumin
Free testosterone is active
Activated to a more potent form in target tissues

Question 3

How does testosterone effect growth in the pre-pubertal child?

Answer 3

Sex organ growth 
- testicular and penile growth
- erections
- change in the function of the testes
Skeletal muscle
Epiphyseal plates (height)
Larynx growth
Secondary characteristics 
Other effects
- erythropoesis (increases Hb)
- behaviour (more aggresssive)
In the

Question 4

What are the effects testosterone has on the adult male?

Answer 4

Muscle mass maintenance
Mood
Bone mass - lower risk of osteoporosis 
Libido
Body shape

Question 5

How does testosterone affect fertility in the adult male?

Answer 5

Libido
Erectile function
Spermatogenesis

Question 6

Describe the function of the cells involved with spermatogenesis.

Answer 6

Spermatocytes
- mature into spermatozoa
Sertoli cells
- direct contact with the spermatocytes
- forms a blood-testes barrier (for immune protection)
- removes damaged spermatocytes
- secrete androgen protein (holds testosterone in the testes in higher concentrations than the rest of the body)
Leydig cells
- secrete testosterone to promote sperm development

Question 7

Describe the endocrine control of gonadal function.

Answer 7

GnRH release from the hypothalamus
LH and FSH release from the anterior pituitary
LH acts on the Leidig cells to produce testosterone (T then acts on sertoli cells)
FSH acts on sertoli cells to enable spermatogenesis
Testosterone acts as a negative inhibitor on LH and GnRH
Sertoli cells produce inhibin B which inhibits FSH

Question 8

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

Answer 8

Slow growth in teens
No pubertal growth spurt
Small testes and phallus
Lack of secondary sexual development

Question 9

What are the clinical features of hypogonadism in adults?

Answer 9

Depression/low mood
Poor libido
Erectile problems
Poor muscle bulk/power
Poor energy
Sparse body/facial hair
Gynaecomastia 
Gynoid weight gain
Great head hair
Short phallus
Small testes

Question 10

How is hypogondism generally diagnosed?

Answer 10

Height
Weight
History 
- growth
- familial (constitutional delay)
- sexual (do they have kids)
- drugs (OTC and prescribed)
- social (performance, police record)
Examination

Question 11

What tests for hypogonadism are performed?

Answer 11

Testosterone done early morning 
- fT >200
- total >16
- SHBG present
LH and FSH
- pituitary cause?
Fertility
Semen analysis

Question 12

What biochemical signs indicate a pituitary cause?

Answer 12

Low testosterone 
Low FSH and LH
Increased prolactin (can suppress LH and FSH and fertility)
Decreased cortisol 
Decreased IGF-1/GH
Decreased TSH
Increased sodium

Question 13

Name some causes of hypopituitarism.

Answer 13

Genetic syndromes
Pituitary tumour
Pituitary surgery/radiotherapy
Head injury
Kallmann's syndrome
- isolated FSH and LH deficiency 
Cerebellar ataxia

Question 14

What is Kallmann’s syndrome?

Answer 14

Most common form of isolated gonadotrophin deficiency

Failure of cell migration of GnRH cells to the hypothalamus from the olfactory placode

Question 15

What is Kallmann’s syndrome associated with?

Answer 15

Aplasia/hypoplasia of the olfactory lobes
- anosmia or hypoosmia 
Deafness
Renal agenesis
Cleft lip/palate
Micropenis
Cryptorchidism 
Delayed/absent puberty features

Question 16

What are the genetics of Kallmann’s syndrome?

Answer 16

Familial
X-linked absence of KAL gene (KAL1)
Autosomal dominant (KAL2)
Autosomal recessive (KAL3)

Question 17

What biochemical features would you expect to see with primary gonadal disease?

Answer 17

Low testosterone
Normal/high FSH and LH
Normal prolactin

Question 18

Name some causes of primary gonadal disease.

Answer 18

Seminiferous tubule failure
Adult Leidig cell failure
Cryptorchidism 
Complex genetic syndromes
Klinefleter's syndrome (chromosome defects)

Question 19

What is Klinefelter’s syndrome?

Answer 19

Most common genetic cause of male hypogonadism

XXY

Question 20

What is the pathology associated with Klinefelter’s syndrome?

Answer 20

Clinically manifests at puberty
LH and FSH are high, but the seminiferous tubules regress (get scarred and fibrose) and the Leidig cells don’t function normally (no testosterone)

Question 21

What are the clinical signs of Klinefelter’s syndrome?

Answer 21

Wide clinical variation phenotype due to hormonal response to LH surges

• delayed puberty
• suboptimal genital development
• reduced secondary male sexual characteristics
• persistent gynaecomastia
• azospermia
• behavioural issues/learning difficulties

Question 22

What is the treatment for people with Klinefelter’s syndrome?

Answer 22

Androgen replacement
Psychological support
Fertility counselling

Question 23

Why doesn’t androgen therapy make a person fertile?

Answer 23

Provides the systemic testosterone effects, but can’t concentrate it in the testes
Spermatogensis therefore can’t procede

Question 24

What fertility treatment is available?

Answer 24

For hyperstimulation of the testes
- hCG
- Recombinant LH and FSH
GnRH pumps

Question 25

What are the side effects of androgen replacement therapy?

Answer 25

Mood issues
Libido issues
Increased haematocrit 
Possible prostate effects 
Acne, sweating 
Gynaecomastia