Endocrine disorders Flashcards
Describe the HPA axis
HPA axis
- FSH and LH are hormones in reproductive pituariary
- act on ovary
- LH acts on theca cells → these make androgens
- peak in LH mid-cycle causes ovulation
- androgens produced get to oestrogen in granulosa cells
- oestrogen feeds back to pituitary
You have negative and positive feedback in this cucle
as you produce more oestrogen it dampens down FSH and LH
what happens if you give continous GnRH
- you suppress FSH and LH
- supresses ovulation
- gove opportunity to give exogenous FSH and control teh growth of follicles without the risk of sponetonous ovulation
would use a GnRH agonsist
Whats the difference between central and gondal pathlogies
- Central pathology
- piruariatry gland and cerebal thing
- Lack of secretion of LH and FSH
- hypo hypothalamic and gonadal
- get no oestrogen → so no cycle
- hypo hypothalamic and gonadal
- Hypothalamic/pituitary disease
- Gonadal damage (secondary)
- Failure of germ cell production
- Lack of sex steroid production
- like oestrogen, failure of ovaries
Central and gondal can be congenital or acquired
What are the causes of ammonhera
- Pregnancy – always exclude
- make sure to always check
- Central causes
- Hypothalamic - weight loss (anorexia), excessive exercise, stress
- problems with FSH, LH
- Pituitary – hyperprolactinaemia (lactation), pituitary tumours
- can be life-threatening if it affects the eyes
- Hypogonadotropic hypogonadism (failure of LH, FSH secretion)
- Hypothalamic - weight loss (anorexia), excessive exercise, stress
- Ovarian causes
- Turner’s syndrome (45 X0)
- Premature ovarian failure
- Polycystic ovary syndrome
- common cause outside of pregnancy
- Miscellaneous – thyrotoxicosis, chronic disease, local uterine problems
What are the causes of hypothalamic amenorrohea and why are the presentations differeng
anoxeria, excerise, bulimia
- people have different baslines when they get amenorrhea
- there’s a cut of when pituarity gland gets cut off
What is lepin
how does it work etc
-Leptin is a peptide hormone released by adipocytes
-Regulates appetite, neuroendocrine function, and energy homeostasis
What is congential leptin defieceny
signs
severe obesity, hyperphagia, hypogonadotropic, hypogonadism
leptin levels fall, food intake foes up, energy expenditure goes down, and reproductive function decreases
What is prolactin
hormone that stimulates lactation
what inhibits prolactin
dophamine
In women that need to breastfeed, what medication can we give to promote this
be given dopamine antagonist to try and promote lactation
When does prolactin levels increase
- Physical or psychological
- breast examination, after exercise
- Post seizure
- Greater increase in women
- reference range for women is different
- if its very high the investigate
- PRL peaks during sleep
- Rarely exceeds 850-1000 mU/L
Clinical features of hyperprolactinaemia
pre menopausal women
- Hypogonadism
- Oligo/amenorrhoea
- symptoms of estrogen deficiency – associated problems
- vaginal dryness etc
- Galactorrhoea – spontaneous/expressible from breas
Clinical features of hyperprolactinaemia
Post menopausal women
Due to hypogonadal status – they dont get the same features as premenopausal women
what can prolactin inhibit
Prolactin inhibits LH & FSH.
So if you have high PRL you will have decreased FSH & LH & Oestrogen/Testosterone production – end up hypogonadal
What is patholgical hyperprolcatnima caused by
Can be due to:
PRL-secreting pituitary tumours - prolactinomas
-Microadenomas (< 1 cm diameter)
-Macroadenomas (≥ 1 cm diameter)
Loss of inhibitory effect of hypothalamus-derived DA (dopamine agonist)
-This is due to Pituitary stalk compression/pituitary disconnection
Drugs – DA antagonists
-Phenothiazines, metoclopramide, TCAs, verapamil
Hyperthyroidism
-Increase in TRH ->increase TSH which can then increase prolactin.
How can we treat patholgical hyperproclatneima
Dopamine agonists to supress PRL, Surgery (to remove pituitary tumour)
What is meant by premature ovarian insuffuicency
when ovaries cannot function well
How do people with POI present
- Amenorrhoea
- Oestrogen deficiency
- Elevated LH, FSH (>30 IU/L) all < 45 years of age
- FSH of 25 would be concerned
- must always repeat after 6-week intervals
- don’t do this test over age of 45
What are the causes of POI
-Turners -> congential
- Autoimmune (nb thyroid, Addisons, diabetes)
- Iatrogenic – chemotherapy and radiotherapy, surgery
- Mutations in FSH receptor, galactosaemia, FMR1 gene premutation (fragile X→ more disposed to this deficiency, can get bigger down generations)
Tuners
symptoms
what is it
1:2500 live births 45XO
symptoms
- Short stature and gonadal dysgenesis (streak ovaries)
- Webbed neck,
- cubitus valgus,
- congenital heart disease,
- hypothyroidism
- lymphoedema
- gains weight easily
How can autoimmune conditions cause POI
- mechanism of autoimmune POI is likely to be due to inflammatory infiltration of follicles and production of anti ovarian Ab,
- this may cause apoptosis and atrophy
- sharing of auto antigens between the ovary and adrenals may explain the link with POI and Addison’s
egg frezzing-> addisons
POI -> precedes addiosns by 8-14 years
POI
Fragile X premutation
what is it, who gets it, what is the mutation etc
1 in 200 females has the genetic change that leads to FXPOI.
FXPOI accounts for about 4 to 6 % of all cases of POI in women.
Mutations in the FMR1 gene increase a woman’s risk of developing FXPOI.
It is inherited – so gets worse with going down the generation.
FXPOI is inherited in an X-linked dominant pattern therefore one copy leads to the condition
How do we diagnose and manage POI
- Diagnosis on serial FSH and E2 levels
- do them 6 weeks apart
- Karyotyping and FMR-1 premutation analysis
- Screening for autoimmune diseases:
- anti–adrenal, TPO, ovarian Abs
- Anti Mullerian Hormone (AMH)
- produced by granulosa cells
- produced by resting follicles
- can be used to diagnose women with low ovarian reserve
- can be useful for menopause
- DEXA scan: POI carries 50% risk of osteopenia
- do after 23 which is when we reach
- Manage with oestrogen replacement – need progesterone added if still has a uterus
- oestrogen: bones
- progesterone: protects endometrium
basically hormone replacment for managment
How common is PCOS
Commonest endocrine condition affecting 10% of all pre- menopausal women
What are the signs of PCOS
- Oligoamenorrhoea (80%)
- Hirsutism (30%)
- Obesity (40%)
- Infertility (30%) – anovulation
- Polycystic ovaries on ultrasound
Why do people with PCOS get hyperandrogenism
due to Increased testosterone, androstenedione, (DHEA)
- Increased LH/FSH ratio
- more LH, remember LH stimulates androgens
- levels are normal
- but the ratio between the same is different
People with PCOS are not oestrogen deficent, so what needs to be done
like what do you need to make sure happens and why
think about what oestrogen does physiologically
- NOT oestrogen deficient (prog withdrawal bleed)
- if they are not having periods, need to make sure there’s progesterone release
- helps protect the endometrium
- protects from endometrium abnormalities
- need to have 4 withdrawal bleeds a year
- use a minipill
What is rotterdams critera
Oligo-amenorrhea
clinical or biochemical signs of hyperandrogenameia
polysitic ovaries
2 out of 3 means PCOS
remember to exculde POI, cushings, adrenal tumors, CAH,
What are the clinical features of PCOS
- anovulation
- insulin
- androgen excess
- obesity
all of these things feed into each other -> weight loss may help
PCOS
What sign is a marker of insulin resistance
Acanthosis nigrinacans
What are the risks of PCOS and pregnancy
Oligo-/Amenorrhea & Infertility commonest clinical problem
- Risk of gestational diabetes and pregnancy-related hypertension is ten times increased
- IVF: increased risk of Ovarian Hyperstimulation Syndrome (OHSS) although this can be avoided by using an antagonist
IVF protocol with a GnRH trigger injection for egg maturation
How to treat PCOS
Obesity, oligo/ammenohera: metaformin, lifestyle, bariatric surgery
anvolution
-> metformin + IVF
hirtusim: Yasmin, vaniqua cream, cosemtic removal, sprinolactone
What can people buy over the counter to increase insulin sensitivity
Myo-inositol
can help regulate cycles
What anti-androgenic oral contraceptives can you take
dinette → better ones but no longer first line anymore
zoely
Yasmin
What are the two types of 21 hydroxylase defienecy
what symptoms can you get
- classical form pick up as neonate
- salt wasting
- andorgen excess
- non classical happens at puberty
- can look like PCOS
- premature puberty, hirsutism
- can be subtle
can mimic PCOS
When trying to diagnose PCOS what other thing do you need to check
- do 17 OH progesterone when diagnosing PCOS
- if it’s high means that it’s not being converted into cortisol or aldoestrone
What is complete 46XY
what are the features ans
used to be called Testicular Feminisation
- Female external genetalia
- Short, blind-ending vagina
- No uterus, may have abdominal/inguinal testes
- need to remove testes
- these testes are more at risk of testicular cancer
- Absent prostate, axillary (pubic) hair
- Gynaecomastia – impressive breast development
How do people with 46 XY present
May present as “inguinal hernia” but it is actual testes
Primary amenorrhoea
What are the signs of 46 XY
- Bloods: Elevated LH, Testosterone and E2
- Oestrogen from aromatisation of Testosterone and LH- driven gonad secretion
- T secretion 50% increased vs normal
What condition is hard to differeniate with 46 XY and why
people with 5 alpha reductase deficiency
- cant convert testosterone into DHT
- so tissues cant convert it…
- appear female but have abdominal testes
- present with primary ammenhorrea
Describe the hypothalamic testes axis in males
LH/FSH drives things
Leydig cells produce testosterone, LH acts on these
Sertoli cells produce AMH, inhibition
you also get spertamgenous
testosterone gives negative feedback to reduce FSH and LH
- testosterone decreases with age
How can hypogonadism present in men
Delayed puberty
- Psychological effects
- Loss of libido and reduced sexual behaviour
- Lack of sex drive versus erectile impotence
- Gynaecomastia
- Loss of body hair, reduced shaving frequency, thin skin
- Decreased muscle mass, female fat distribution
- Osteoporosis
- Infertility +/- reduced testicular volume
Causes of
Primary gonadal failure
Primary gonadal failure
- Trauma – surgery and torsion
- Chemotherapy and radiotherapy
- Undescended testes (cryptorchidism) (10% at birth)
- Infections, Inflammation & Infiltration
- Orchitis (mumps)
- can cause insufficiency
- Iron overload
- inhertied disease
- Varicocele
- warm up testes and cause spermatic damage
- Chromosomal abnormalities
- Klinefelter’s syndrome
- Systemic diseases
- Liver cirrhosis
- Renal failure
- Thyroid dysfunction
- Myotonic dystrophy
what causes secondary gondal failure
– Pituitary tumours
– Hyperprolactinaemia
-Hypothalamic disorders:
like, Craniopharyngioma (brain tumour)
Kallman’s syndrome
GnRH therapy
-Systemic disease
-Obesity (lots of oestrogen production which may inhibit FSH and LH)
-Androgen use & abuse
How do we investigate hypogondism
what tests, exmaination
- LH, FSH, Testosterone
- Is Testosterone low? (Remember age)
- Negative feedback
- Is Testosterone low? (Remember age)
– High LH, FSH indicates primary gonadal failure
– Low LH, FSH suggests secondary cause
- Further investigations to establish cause
- eg Liver function, prolactin, karyotype (looking at chromosomes), imaging etc
Klienfelters syndrome
how common, what chromsomes, what symptoms
Affects 1:1000 males
47 XXY
Leads to Primary hypogonadism – “firm pea-sized” testes
Feminisation – Azoospermia (no sperm in sample),
Gynaecomastia
Reduced secondary sexual hair
Osteoporosis
Eunuchs – tall stature
Reduced IQ in 40%
20-fold increased risk of breast cancer
muscular dystrophy
talk about symptoms, genetics etc
- Autosomal dominant
- Progressive muscular weakness
- Myotonia
- Mental impairement
- Frontal baldness
- Cataracts
- Primary gonadal failure
Kallmans
talk about common, genetics, symptoms
- Idiopathic hypogonadotropic hypogonadism
- 1:10,000 - M:F = 4:1
- Anosmia in 75%
- Failure of migration of GnRH neurons to hypothalmus
Genetics
* X-linked, autosomal recessive or autosomal dominant
* Mutations in Kal-1, FGF-Receptor 1, prokineticin
* GnRH-Rec and G-protein coupled receptor 54 (normosmic)
*
How can we treat men with fertlity problems
**Testoerone replacement
**
- can give tablets
- give injections 3 monthly (intramsuclar)
- patches are withdrawn
- subdermal implants every 6 months (on abdomen or buttocks)
What are the conerns around testosterone replacement
-Behaviour: High testosterone can result in person becoming aggressive
-Need to do Annual PSA, FBC (can get high levels of red cells in blood), Lipids (can get high),
-BP monitors over 50 yrs
-High PSA can lead to prostate hyperplasia and prostate cancers.
Need to make sure testosterone is in normal range
What can androgen abuse cause
Hypogonadism
-Side effect of androgen abuse is very small testicles.
-Exogenous testosterone will inhibit FSH and LH production – this means you do not get sperm production
other side effects
Psychological changes (aggression, sex drive)
Prostate cancer
Atrophy of testes
Azoospermia - infertility
Polycythaemia (too many red cells)
Cardiovascular death
Men how are not proudcing LH, FSH will be given hormones stimulate spermatgoensis + produce testostrone
Exogneoius testsotorne is given to protect cCV system and bones -> but they will not make sperm due to supression
What do you need to look at when investigating endocrine causes of male infertlity
assessment – history + examination
- Seminal Fluid analysis
- LH, FSH, Testosterone
- Increased FSH – germ cell failure – numbers game, IVF, ICSI etc (may need endocrine input if primary gonadal failure)
- Normal FSH, normal sized testes – think of obstructive uropathy
- Low FSH, LH, Testosterone – ENDOCRINE causes
- Pituitary/hypothalamic disease
- Replace with LH (HCG 2000units/twice weekly and FSH 75IU x3/week – injections)
- Spermatogenesis may take >12 months
