L12 - Endo aspects of male hypogonadism COPY Flashcards
TESTOSTERONE
i) what type of hormone is it?
ii) name three places it is secreted from - where is most derived from?
iii) which two plasma proteins does most testosterone bind in the blood? approx what % is free hormone?
i) steroid hormone
ii) secreted from testes (most), ovary and adrenals (little)
iii) binds albumin (>50%) and SHBG (sex hormone binding globulin)
- about 2% is present as a free hormone
THE TESTES
i) what is the name of the two anatomical units contained by the testes?
ii) which two hormones are synthesied by sertoli cells? which unit are these found in?
iii) which hormones do leydig cells produce? which unit are these cells found in? name one other cell type also found here
i) seminiferous tubules and an interstitium
ii) anti mullerian hormone and inhibin B are synth by sertoli cells
- sertoli cells are found in the seminiferous tubules
iii) leydig cells produce androgens
- found in the interstitium alongside peritubular myoid cells
ANDROGEN SYNTHESIS
i) what molecule are they synthesised from? (a)
ii) what facilitates the conversion of this molecule to pregnelone? (b)
iii) what does pregnelone produce? (c and d)
iv) what type of reaction occurs to make estradiol from testosterone? (e)
v) which enzyme catalyses testos to DHT?
i) cholesterol
ii) LH
iii) pregnelone produces DHEA and progesterone
iv) testos to oestradial is aromatisation and needs FSH
v) 5 alpha reductase
THE HYPOTHALAMIC PITUITARY TESTICULAR AXIS
i) release of which hormone from the hypothalamus causes LH and FSH secretion from the pituitary?
ii) what are FSH and LH composed of structurally?
iii) what is LH predominantly involved in?
iv) what is FSH predominantly involved in? (2)
v) which two structures does testos feed back to? what does this cause?
i) release of gonadotrophin releasing hormone causes LH and FSH to be secreted from PG
ii) FSH and LH are two glycoprotein chains
iii) LH is involved in release of testosterone
iv) FSH involved in spermatogenesis and inhibin B secretion
v) testos feeds back to the HT and PG to reduce LH release
TESTOSTERONE - MECHANISM OF ACTION
i) can it cross the cell membrane?
ii) what conversion takes place inside the andogren target cell before it binds the androgen receptor? what is this mediated by?
iii) what process converts some testosterone to oestrogens?
- what effects do these have in relation to androgens?
iv) where is the androgen receptor found?
i) yes
ii) testos to DHT via 5a reductase before it binds the androgen receptor
iii) testos to oestrogens via aromatisation
- can have indep, opposite or synergistic effects to androgens
iv) in the nucleus
ACTION OF TESTOSTERONE
i) what hormone secretion does it regulate in the hypothalamic pituitary system?
ii) how does it affect spermatogenesis?
iii) what effect does it have in embryogenesis?
iv) what role does it play in puberty?
v) how does it affect lean body mass and decrease fat mass
vi) is testos concentration higher in the testes or the blood?
vii) what effect does taking exogenous testosterone have on sperm production? why?
i) regulates gonadotrophin secretion (LH and FSH)
ii) initiates and maintantains spermatogenesis
iii) specifies the male phenotype in embryogenesis
iv) promotes sexual maturation at puberty and maintains this after
v) increases lean body mass and decreases fat mass
vi) higher testos in the testes than blood (needed for spermatogen)
vii) exogenous testos can inhibit sperm produc as you need it in the testes (not the blood) to make sperm
MALE HYPOGONADISM - OVERVIEW
i) what is it?
ii) where is the disease in primary and secondary hypogonadism?
iii) in primary - what are the testosterone, serum LH and FSH levels? why?
iv) in secondary - what are the testosterone, serum LH and FSH levels?
i) decrease in one or both of the two major testes functions - sperm production and testosterone production
ii) primary - testes
secondary - hypothalamus or pituitary
iii) primary - low testos and high LH/FSH as there is no negative feedback on them
iv) secondary - low testos and LH/FSH are normal or low
CAUSES OF HYPOGONADISM
i) give six causes of primary HG
ii) give six causes of secondary HG
i) (testes problem) kleinfelter syndrome (2 or more X chromos in men), cryptorchidism (undesc testes), infection, radiation, trauma, torsion
ii) (HT/PG problem) congenital GnRH deficiency, hyperprolactinaemia, use of GnRH analog eg in prostate cancer, excess opioid use, androgen use, anorexia nervosa, pit disorder
CLIN FEATURES/SYMPTOMS/SIGNS OF HYPOGONADISM
i) what is seen in the first and third trimester?
ii) what is seen at puberty?
iii) what are the effects on sexual development, desire, erections and body hair?
iv) what effect does it have on the testes?
v) how many it affect fertility?
vi) how is height, fracture rate and muscle bulk affected?
vii) give four other less specific symptoms
i) first trimester - female genitalia to ambiguous genetalia
third trimester - micropenis
ii) puberty - failure to undergo/complete puberty
iii) decreased sex dev, desire, erection, body hair
iv) causes small or shrinking of the testes (<5ml)
v) may cause low or zero sperm counts
vi) decreased height and muscle bulk with higher fracture rate
vii) non spec symptoms - low mood, low energy/motivation, poor concentration, mild anaemia, increase BMI
CONDITIONS ASSOC WITH HYPOGONADISM
may be associated with:
i) what are the three most common assoc conditions
ii) medication that affects T cell production - give two examples
iii) which immunodeficient condition?
iv) which respiratory condition
v) give six relevant aspects of the PMH
i) infertility, T2DM and osteoporosis
ii) glucocorticoids/opioids
iii) HIV related weight loss
iv) COPD
v) when puberty occured, major illness, nutritional deficiencies, drug hx (androgens), sexual probs, recent body changes, testicles problems/changes
EXAMINATION FOR HYPOGONADISM
i) give four key things to look for
ii) what are five signs of severe HG?
iii) what may a large arm span indicate?
iv) what blood investigations may be done? (4)
v) what other things may be analysed? (4)
i) amount of body hair (has it changed), breast exam, size/consistency of testicles, size of penus
ii) loss of body hair, reduced muscle bulk, osteoporosis, small or soft testicles
iii) large arm span can indicate kleinfelter syndrome (RF for primary HG)
iv) serum testos - do before 9am and fasting as it peaks in the morning
LH/FSH, SHBG (to calc free testos), LFT
v) semen analysis, karyotyping, pit func, MRI/DEX for bones
GUIDELINES ON SCREENING
i) what does the initial screen test? why?
ii) name two factors that can affect testosterone levels
iii) what confirmation test can be done?
iv) when should a patient not be screened? why is this?
v) if testos is low what three things need to be excluded for a dx of HG?
vi) what protein should be analysed to see if it is altered?
i) initial screen tests morning total testosterone because levels are highest in the morning
ii) time of day and age can affect testosterone
iii) confirmatory test = repeat morning testos
iv) dont screen patients with acute/subacute illness as this may temporarily be lowering the testos
v) low testos - need to exclude acute illness, nutrition deficiency and drugs
vi) analyse SHBG
SEX HORMONE BINDING GLOBULIN
i) around what % of testos is physiol bound to SHBG?
ii) name five things that lower SHBG
iii) give three drugs that lower SHBG
iv) name four things that raise SHBG
v) why can free testosterone be normal in some patients with HG?
vi) which situation would benefit from treatment in relation to SHBG and free testos levels?
i) 44% of total bound to protein
ii) lower SHBG - moderate obesity, nephrotic syndrome, hypothyroidism, drugs
iii) drugs = glucocorticoids, progestins, androgenic steroids
iv) ageing, hepatic cirrhosis, hyperthyroidism, anticonvulsants, oestrogen tx and hiv
v) normal free testos may be seen as the body is trying to compensate
vi) benefit from tx is high SHBG and low free testos
FURTHER INVESTIGATION ONCE LOW TESTOS CONFIRMED
i) what does low/normal FSH and LH indicate? what three other things should be measured?
ii) what does high LH and FSH indicate? what three other things should be measured/screened for?
iii) what other investigation could be done?
i) low/normal FSH and LH = secondary HG
- measure prolactin, iron sats and other pit homrones
ii) high FSH and LH indicates primary HG
- look at karyotype, screen for klinefelter syndrome or other testicular insults
iii) can also do an MRI
TREATMENT FOR HYPOGONADISM
i) what is given? name the two most common routes of admin
ii) what effect can this treatment have on sperm count?
iii) what dose level should the patient be initially started on?
iv) name three side effects
v) name a condition that may develop on this treatment
i) testosterone - gel or injection
ii) can decrease sperm count - need high testos in the testes for spermatogenesis
iii) low dose - patient may have had low testosterone for an extended period of time
iv) acne, hair loss, polycythaemia
v) prostatic hyperplasia
