Male Hypogonadism & Gynaecomastia Flashcards
Describe the male HPG axis
Kisspeptin stimulates the hypothalamus
The hypothalamus releases GnRH
The anterior pituitary releases FSH & LH
The testes release testosterone
Testosterone negatively feedbacks to the hypothalamus & pituitary gland
Where is testosterone produced and which hormone controls this?
Testosterone is produced by Leydig cells under the control of LH.
The synthesis of LH is controlled by negative feedback mechanisms of testosterone
Which hormone acts on Sertoli cells?
What protein is produced by Sertoli cells?
What is the role of these cells in the negative feedback of the male HPG axis?
FSH acts on Sertoli cells
Sertoli cells produce androgen binding protein.
They also produce inhibin which negatively feedbacks on the hypothalamus/pituitary gland
What is the other name for a) primary hypogonadism b) secondary hypogonadism
A) primary hypogonadism aka hypergonadotrophic hypogonadism - testicular failure
B) secondary hypogonadism aka hypogonadotrophic hypogonadism - hypothalamic/ pituitary cause
State the effect of hypergonadotrophic hypogonadism and hypogonadotrophic hypogonadism on a) spermatogenesis b) testosterone production.
Hypergonadotrophic hypogonadism
- Spermatogenesis affected > testosterone production
Hypogonadotrophic hypogonadism
- Spermatogenesis affected = testosterone production
hypergonadotrophic hypogonadism aetiology
- Vascular e.g. varicocele
- Infections (orchitis) e.g. mumps
- Drugs e.g. corticosteroids, ketoconazole
- Iatrogenic e.g. Chemotherapy/radiation
- Congenital e.g. Klinefelter’s syndrome
- Trauma e.g. Testicular torsion
- Metabolic/Infiltrative e.g. haemochromatosis
Describe the genetics of Klinefelter’s syndrome
NOT inherited
Caused by non-disjunction
Usually 47 XXY
Klinefelter’s syndrome presentation
- Infertility (tubular damage)
- cryptorchidism, small testicular size
- learning disability, psychological effects
- Increased risk of breast & non-Hodgkin lymphoma
Klinefelter’s syndrome investigations
Diagnosed by karyotyping
Hypogonadotrophic hypogonadism
- Infection e.g. TB
- Neoplasm e.g. pituitary tumour
- Drugs e.g. Corticosteroids, opioids
- Congenital e.g. kallmann’s syndrome
- Trauma e.g. head trauma, pituitary damage
- Endocrine e.g. hyperprolactinaemia
- Other conditions - Eating disorders, excessive exercise, obesity, diabetes
Describe Kallmann’s syndrome
Genetic disorder (mutation) that causes hypogonadotropic hypogonadism and an impaired sense of smell (asomnia).
Diagnosed by hormone, olfactory function & genetic testing. Treated with HRT
Hypogonadism presentation (pre-pubertal)
DIFFERENT
- Small male sexual organs (testes, penis, prostate)
- high-pitched voice
- ‘Eunuchoidal’ habitus (tall, slim, long arms and legs)
SAME
- Decreased body hair, low libido
- Gynaecomastia
- Decreased bone and muscle mass
- +/- symptoms due to cause (e.g. asomnia with Kallmann’s syndrome)
Hypogonadism presentation (post-pubertal)
- Normal skeletal proportions, penis/prostate size and voice
- Decreased energy and motivation
- Decreased testicular volume
- Decreased libido, decreased spontaneous erections
- Decreased pubic/axillary hair, reduced shaving frequency
- Gynaecomastia
- Decreased muscle and bone mass
- +/- symptoms due to cause (e.g. pituitary lesion causing visual field defect)
Hypogonadism investigations
- 9am testosterone (repeat x2, 2 weeks apart)
- hypogonadism diagnosis
- LH/FSH test
- hyper vs hypo gonadotrophic differentiate
- Aetiology specific tests
- e.g. MRI, karyotyping, iron studies, prolactin levels…
Why is both SHBG & total testosterone measured & ‘free testosterone’ calculated when measuring testosterone levels?
- A portion of testosterone is bound to SHBG,
- making it not ‘free’ or active.
- SHBG levels vary between individuals
- Total testosterone includes the SHBG-bound testosterone
- Therefore SHBG must also be measured
- To calculate an accurate ‘free testosterone’ level
Hypogonadism treatment
If fertility is important
- GnRH or LH/FSH therapy OR
- Sperm donor
If not
- Testosterone replacement therapy (gel/capsule/IM)
Testosterone replacement therapy contraindications
- Hormone responsive cancer e.g. prostate/ breast (history/current/possible diagnosis)
- Haematocrit > 50%
- Severe OSA or HF
Testosterone replacement therapy monitoring
- Testosterone levels
- Prostate cancer screening
- Haematocrit levels
- OSA symptom monitoring
State the two fates of testosterone and state the effects of these two molecules
1) Dihydrotestosterone (highly active form)
- Sebum production
- Prostate growth & enlargement
- Effects on skin, hair follicles & external genitalia
2) Oestrogen
- Epiphyseal fusion
- Bone mass
- Certain sexual behaviours
- Verbal memory
- Plasma lipids
Where are Leydig & Sertoli cells located?
Leydig - Interstitial tissue between seminiferous tubules
Sertoli - Seminiferous tubules
Gynaecomastia definition
Condition by whichmales develop breast tissuedue to animbalanced ratioof oestrogen and androgen activity
Gynaecomastia aetiology
Physiological
- adolescence, delayed testosterone surge relative to oestrogen at puberty
- older population, decreasing testosterone with age
Pathological
- lack of testosterone (Klinefelter’s syndrome, androgen insensitivity, testicular atrophy, or renal disease)
- increased oestrogen (liver disease, hyperthyroidism, obesity, adrenal tumours, or certain testicular tumours)
- medications (digoxin, metronidazole, spironolactone, chemo, goserelin, antipsychotics, or anabolic steroids)
Gynaecomastia investigations
- Only if cause is unknown
- Triple assessment if suspicion of malignancy
- LFTs, U&E’s & then LH & testosterone if cause unknown
** Then management is tailored to the cause
