Hypogonadism male

Question 1

definition of hypogonadism - M

Answer 1

syndrome of low testosterone production, sperm production or both

Question 2

aetiology of primary hypogonadism (hypergonadotrophic) - M

Answer 2

testicular failure:

gonadal dysgenesis - kilnefelter’s syndrome (XXY), undescended testes (cryptorchidism)

gonadal damage - post-orchitis/infection (eg mumps, HIV, brucellosis, leprosy), torsion, trauma, autoimmune, iatrogenic (chemo, surgery, radiation)

rare causes - defects in enzymes involved in testosterone synthesis, myotonic dystrophy, anorchia

renal failure, cirrhosis or alcohol excess (toxic to Leydig cells)

Question 3

aetiology of secondary (hypogonadotrophic) hypogonadism - M

Answer 3

pit/hypothalamic lesions

GnRH deficiency - Kallmann’s syndrome (associated with anosmia and colour blindness), idiopathic

hyperprolactinaemia/prolactinoma

systemic/chronic diseases - COPD, HIV, DM

rare - genetic mutations

prader-willi syndrome - loss of critical region on chr 15 = obesity and short stature, small hands, almond shaped eyes, learning difficulty/postnatal hypotonia

laurence-moon-beidl syndrome - obesity, retinitis pigmentosa, learning difficulty

age

Question 4

genetic mutations that cause secondary hypogonadism - M

Answer 4

gene encoding GPR54 (the kisspeptic receptor), GnRH receptor LH, FH. leptin, leptin receptor, DAX1 (associated with congenital adrenal hypoplasia), LHX3, LHX4, HESX1, PROP-1 (transcription factors necessary for early differentiation of the pituitary)

Question 5

epidemiology of hypogonadism - M

Answer 5

primary = 30-40% of male infertility

secondary 1-2%

10-20% cases of male infertility due to disorders of sperm transport and 40-50% are non-classifiable

most common cause of primary = klinefelter’s (one in 500-1000 live births)

Question 6

symptoms of hypogonadism - M

Answer 6

pre-puberty:

• delayed puberty
• incomplete puberty
• reduced virilisation
• eunuchoid body
• reduced secondary sex characteristics

small testes

low libido, impotence, infertility

loss of pubic hair

reduced muscle bulk

increased fat

reduced mood

gynaecomastia

symptoms of the underlying cause eg klinefelters - interlectual dysfunction and behavioural abnormalities which cause difficulty in social interactions

Question 7

signs of hypogonadism

Answer 7

measure testicular volume with prader’s orchidometer (ellipsoids of different sizes) - normal adult testicular vol = 15-25ml

Question 8

signs of prepubertal hypogonadism - M

Answer 8

delayed puberty = high pitched voice, low pubic/axillary/facial hair, small/undescended testes, small phallus

gynaecomastia

eunuchoid proportions - arm span >height, lower segment>upper segment - due to delayed fusion opf epiphyses and continued growth of long bones

features of underlying cause - cryptorchidism, anosmia in Kallmann’s

Question 9

signs of postpubertal hypogonadism

Answer 9

low pubic/axillary/facial hair

soft and small testes

gynaecomastia

fine perioral wrinkles

features of underlying cause eg visual field defects due to a pit tumour, signs of systemic/chronic illness

Question 10

investigations for hypogonadism - M

Answer 10

serum testosterone, SHBG, and albumin - calculate serum free testosterone

LH FSH

primary - low testosterone, high LH FSH

secondary - low testosterone, low or inappropriately normal LH FSH

determine the level of defect:

• primary
  
  • karyotype - exclude klinefelter’s
• secondary
  
  • pit func test s- 9am cortsol, TFTs, prolactin,
  • MRI of the hypothalamus
  • visual filed testing
  • smell tests for anosmia
  • iron studies - ferritin and transferrin saturation of haemochromatocytosis is suspected
  • bone age - in boys with delayed puberty, setermine dby comparison of the radiography of pts bone in L jand and wrist with bone of standard atlas - allow assessment of skeletal maturation and potential future skeletal growth

Question 11

mx of hypogonadism

Answer 11

treatment of underling cause
primary - testosterone either topical / IM

secondary
* prolactinoma - dopamine antagonist (cabergoline)
* hypogonadotrophic hypogonadism - testosterone

Assisted reproductive tech (ART) if wanting fertility (IVF / ICSI)
if secondary - gonadotrophin therapu/selective oestorgen receptor modulator / aromatase inhibitor

Question 12

complications of hypogonadism - M

Answer 12

skin irritation from testosterone patch / gel
erythrocytosis (high haematocrit) - from IM testosterone
increase in PSA
testicular shrinkage
subfertility
pulmonary oil microembolism with long acting IM testosterone - cough, dyspnoea, throat tightening, chest pain, dizziness, and syncope

Question 13

features of klinefelters

Answer 13

often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels