Male Hypogonadism Flashcards
Male H-P-G axis in a nutshell (4)
Hypothalamus is stimulated by kisspeptin to release pulses of gonadotropin-releasing hormone (GnRH)
Anterior pituitary is stimulated by GnRH to release luteinising hormone (LH) and follicle stimulating hormone (FSH)
Gonads (testes) are stimulated by LH/FSH to produce testosterone
Testosterone provides NEGATIVE FEEDBACK to hypothalamus and pituitary
Testosterone production (3)
-Testosterone is produced by Leydig cells under the control of LH
-Majority is bound to SHBG and albumin, only 0.5-2% is ‘free’
-Converted to dihydrotestosterone (highly active form) and oestradiol
What is male hypogonadism? (4)
-hypo= low/reduced
-gonadism= gonadal (testicular) function
A clinical syndrome comprising of signs, symptoms and biochemical evidence of testosterone deficiency
More common with age – incidence 2-5% in men aged 40-79 years
Primary hypogonadism (5)
Testes primarily affected
Decreased testosterone = decreased -ve feedback
Anterior pituitary secretes higher amounts of LH/FSH
“hypergonadotrophic hypogonadism”
Spermatogenesis is affected more than testosterone production
Primary hypogonadism- causes = congenital (3)
Klinefelter’s syndrome
Cryptorchidism
Y-chromosome microdeletions
Primary hypogonadism- causes = acquired (6)
Testicular trauma/torsion
Chemotherapy/radiation
Varicocele
Orchitis (mumps infection)
Infiltrative diseases (e.g. haemochromatosis)
Medications (glucocorticoids, ketoconazole)
Klinefelter’s syndrome (4)
Most common genetic cause of hypogonadism (1/500-600 live births)
Not inherited, caused by nondisjunction
Usually 47, XXY but can have 46, XY/47, XXY mosaicism
Presentation variable and therefore diagnosis can be late or missed
Klinefelter’s syndrome- symps/ risks (8)
Affected men are typically infertile (due to tubular damage) and have small, firm testes
Increased incidence of cryptorchidism, learning disability and psychosocial issues
Increased risk of breast cancer and non-Hodgkin lymphoma
Secondary hypogonadism
Hypothalamus/pituitary affected, testes capable of normal function
LH/FSH low (or inappropriately normal) despite low
testosterone
“hypogonadotrophic hypogonadism”
Spermatogenesis and testosterone production are affected equally
Secondary hypogonadism- causes= congenital (3)
Kallmann’s syndrome
(“isolated hypogonadotrophic hypogonadism”)
Prader-Willi syndrome
Secondary hypogonadism- causes= acquired (11)
Pituitary damage
-Tumours
-Infiltrative disease
-Infection (TB)
-Apoplexy
-Head trauma
-Hyperprolactinaemia
-Obesity, diabetes
-Medications (steroids, opioids)
-Acute systemic illness
-Eating disorders, excessive exercise
Kallmann’s syndrome (4)
Genetic disorder characterised by isolated GnRH deficiency and hyposmia or anosmia
Isolated GnRH deficiency is also associated with other abnormalities: unilateral renal agenesis, red-green colour blindness, cleft lip/palate and bimanual synkinesis
Prevalence 1/30,000 males (also affects females, but less commonly)
> 20 gene mutations have been reported (only account for 30% cases)
Inheritance pattern depends on mutation
Symptoms & signs of hypogonadism- pre pubertal (6)
Small male sexual organs e.g. small testes (volume <5 mL), penis and prostate
Decreased body hair, high-pitched voice, low libido
Gynaecomastia
‘Eunuchoidal’ habitus (tall, slim, long arms and legs)
Decreased bone and muscle mass
+/- symptoms due to cause (e.g. anosmia with Kallmann’s syndrome)
Symptoms & signs of hypogonadism- post pubertal (8)
Normal skeletal proportions, penis/prostate size and voice
Decreased libido, decreased spontaneous erections
Decreased pubic/axillary hair, reduced shaving frequency
Decreased testicular volume
Gynaecomastia
Decreased muscle and bone mass
Decreased energy and motivation
+/- symptoms due to cause (e.g. pituitary lesion causing visual field defect)
Diagnosis (6)
IF AM testosterone + repeated abnormal=
LH/FSH elevated= primary hypogonadism
LH/FSH low= secondary hypogonadism
