Week 3 Flashcards
What can go wrong with the hypothalamo-pituitary-gonadal axis
Central pathology: can be congenital or acquired
-lack of secretion of LH and FSH
-hypothalamic/pituitary disease
Gonadal damage: can be congential or acquired
-failure of germ cell production
-lack of sex steroid production
Polycystic ovary syndrome
Presentation: female
Menstrual history important
-oligoamenorrhoea
—irregular cycle, <9 periods a year or 42 day cycles
-amenorrhoea
—primary: failure of menarche after age 15
—secondary: absent periods for 6 months after menarche
—infertility
Oestrogen deficiency:
-hot flushes, poor libido, dyspareunia
Hirsutism, acne, androgenic alopecia
Weight
Galactorrhoea
Causes of amenorrhoea
Pregnancy- always exclude
Central causes:
-hypothalamic- weight loss (anorexia), excessive exercise, stress
-pituitary-hyperprolactinaemia (lactation), pituitary tumours
-hypogonadotropic hypogonadism (failure of LH, FSH secretion)
Ovarian causes:
-turners syndrome (45XO)
-premature ovarian failure
Polycystic ovary syndrome
Miscellaneous- thyrotoxicosis, chronic disease, local uterine problems
Leptin
Leptin decreases food intake, energy expenditure up and sympathetic activity up to lose weight
Congenital leptin deficiency:
-severe obesity, hyperphagia, hypogonadotropic hypogonadism
Anterior pituitary hormones
ACTH: regulation adrenal cortex
TSH: thyroid hormone regulation
GH: growth (+)
LH/FSH: reproductive control
PRL: breast milk production
Control of PRL secretion
Synthesised in lactotrophs
Regulation of PRL different to other anterior pituitary hormones
-negative regulation by tonic release of inhibiting factor- dopamine
When you disrupt dopamine- lactation
TRH positive effect- hypothyroidism Increase PRL
Physiological hyperprolactinaemia- stress
Physical or psychological
Post seizure
Greater increase in women
Rarely exceeds 850-1000mU/L
PRL does have circadian rhythm with peak during sleep
Clinical features of hyperprolactinaemia
Usually easy to recognise in pre menopausal women
Less apparent in men and post menopausal women
Pre menopausal women:
-hypogonadism: oligo/amenorrhoea, symptoms of oestrogen deficiency (vaginal dryness, lack libido, lack energy)) associated problems
-galactorrhoea- spontaneous/expressible
Post menopausal women:
-due to hypogonadal status- none of above
Pathological hyperprolactinaemia
PRL-secreting pituitary tumours- prolactinomas
-microadenomas (<1cm diameter)
-macroadenomas (>1cm diameter)
Loss of inhibitory effect hypothalamus derived DA
-pituitary stalk compression/pituitary disconnection
Drugs- DA antagonists
-phenothiazines, metoclopramide, TCAs, verapamil
Hypothyroidism- increased TRH
Premature ovarian insufficiency
Amenorrhoea
Oestrogen deficiency
Elevated LH, FSH (>30IU/L) all <45 years of age
Causes:
Congenital- Turner’s syndrome
-1:2500 live births 45XO
-short stature and gonadal dysgenesis (streak ovaries)
-webbed neck, cubitus valgus, congenital heart disease, hypothyroidism, lymphoedema
Autoimmune (nb thyroid, additions, diabetes)
Iatrogenic- chemotherapy and radiotherapy and surgery
Mutations in FSH receptor, galactossaemia, FMR1 gene permutation
Phenotype of tuners syndrome XO
Short stature
Low hairline
Characteristic facial features
Fold of skin
Construction of aorta
Shield shaped thorax
Poor breast development
Widely spaced nipples
Elbow deformity
Shortened metacarpal IV
Small finger nails
Rudimentary ovaries gonadal streak (underdeveloped gonadal structures)
No menstruation
Brown spots (nevi)
Autoimmune POI
POI is often caused by autoimmune diseases such as Graves’ disease, Addison’s, diabetes
2-10% of POI cases are linked with adrenal autoimmunity. POI precedes Addison’s disease by 8-14 years
The mechanism of autoimmune POI is likely to be due to inflammatory infiltration of follicles and production of anti ovarian Ab, apoptosis and atrophy
The sharing of auto antigens between the ovary and adrenals may explain the link with POI and addisons
Fragile X permutation and POI
1 in 200 females has the genetic change that leads to FXPOI. FXPOI accounts for about 4-6% of all cases of POI in women
Mutations in the FMR1 gene increase a women’s risk of developing FXPOI
FXPOI is inherited in an Xlinked dominant pattern therefore one copy leads to the condition
Management of POI
Diagnosis on serial FSH and E2 levels
Karyotyping and FMR-1 permutation analysis
Screening for autoimmune diseases:
-anti adrenal, TPO, ovarian Abs
Anti mullerian hormone (AMH) produced by gonadal cells
DEXA scan: POI carries 50% risk of osteopaenia. Bone density
Manage with oestrogen replacement- need progesterone added if still has uterus
Polycystic ovary syndrome
Commonest endocrine condition affecting 10% of all pre-menopausal women
-oligomenorrhoea 80%
-hirsutism 30%
-obesity 40%
-infertility 30%- anovulation
-polycystic ovaries on ultrasound
Hyperandrogenism:
-increased testosterone, androstenedione, DHEA
-increased LH/FSH ratio
-not oestrogen deficient (progesterone withdrawal bleed)
Aetiology unknown
Rotterdam diagnostic criteria for PCOS
European society for human reproduction and embryology/american society for reproductive medicine (ESHRE/ASRM)
2 out of 3
-oligo/amenorrhea
-clinical or biochemical signs of hyperandrogenaemia
-polycystic ovaries
Exclusion of other causes of androgen excess/oligo-amenorrhoea (Cushing’s, androgen producing tumours, CAH etc)
Clinical features in PCOS
Anovulation
Insulin resistance
Androgen excess
Obesity- can break cycle
Polycystic ovaries
PCO does not = PCOS
Cysts often peripherally, 2-9mm follicles
>/=20 follicles in at least one ovary
PCO: 20-25% of female population
Acanthosis nigricans
Marker insulin resistance
Darker skin patches: back of neck, armpit etc
Hirsutism
Male hormone dependent hair growth
Upper lip, chin
Anterior neck
Sideburn
Breast
Pubic hair
Ferriman gallwey score of hirsutism
Androgenic alopecia
Male pattern baldness
PCOS and pregnancy
Oligo/amenorrhoea and infertility: commenest 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 OVF protocol with a GnRH trigger injection for egg maturation
A pregnant PCOS woman is always a risk patient
PCOS- what to treat and how
Obesity, oligo/amenorrhoea: metformin, lifestyle
-modification (diet, exercise); MPA 10mg od for 10 days every month if no spontaneous bleed, weight loss pharmacotherapy (avoid prganancy); Bariatric surgery (avoid pregnancy 2 years)
Anovulatory infertility: clomiphene or letrozole-> metformin +IVF. Ongoing trial comparing these treatments. Inositol also insulin sensitiser and can be brought OTC
Hirsutism: Yasmin (pill), vaniqua cream (eflornithine 11.5%), cosmetic removal, spironolactone (antiandrogen)
Anti androgenic oral contraceptives
Dianette: 35microg ethinyl estradiol, cyproteterone acetate, high risk venous thrombosis in leg
Zoely: 2.5mg nomegestrol acetate, 1.5mg estradiol
Yasmin: 30microg ethinyl estradiol, drospirenone