Endocrinology & Adolescent Gynaecology Flashcards
Which dopamine agonists may be used to inhibit milk production, and which receptors do they act on?
Cabergoline + bromocriptine
Both act on D2 receptors
In what proportion of children does delayed puberty occur?
3%
What are 2 recognised galactagogues (stimulators of milk production)?
- Domperidone
- Metoclopramide
What is the predominant oestrogen during female reproductive years?
Estradiol (except in the early follicular phase when estrone predominantes)
What is the predominant oestrogen during pregnancy?
Estriol
Which drugs can cause an increased prolactin?
Opiates
H2 antagonists e.g. Ranitidine
SSRI’s e.g. Fluoxetine
Verapamil
Atenolol
Some antipsychotics e.g risperidone and haloperidol
Amitriptyline
Methyldopa
How may hyperprolactinaemia alter periods?
Menorrhagia
What are the ratios of testosterone free:albumin-bound:SHBG-bound?
1% free: 19% albumin-bound: 80% SHBG-bound
Which cells are responsible for androgen production in the ovary?
Theca cells
What hormone stimulates theca cells?
LH
Which cell are responsible for aromatisation of androgens into oestrogen?
Granulosa cells
What is leptin release from adipose tissue stimulated by?
Glucocorticoids
High BMI
Long-term hyperinsulinaemia
Excessive food ingestion
What is the most common cause of delayed puberty?
Constitutional delay
What is the definition of puberty in women?
Physical maturation whereby the women becomes capable of sexual reproduction
What is the lifespan of the corpus luteum?
14 days
How many hours after the LH surge does ovulation occur?
24-36 hours
During pregnancy, from where is bHG produced?
Syncytiotrophoblast
At what gestation does the fetal endocrinological system become fully active?
10/40
What tumour marker is used for granulosa cell tumours?
Inhibin
When does the corpus luteum cease to be essential in maintaining a pregnancy?
6/40
What are the physiological effects of progesterone?
- Increased respiratory drive
- Reduced bowel motility
- Increased basal body temperature
What endocrinological manifestation gives rise to the clinical manifestation of PCOS?
Elevated insulin - it is thought to be the insulin that stimulates androgen secretion
What are the stages of female puberty (and order)?
Growth spurt —>
Thelarche (breast development) —>
Adrenarche (pubic hair development) —>
Menarche
At what age is menarche considered precocious puberty?
If occurs prior to age 10
How frequently does GnRH pulse?
Every 90 minutes
What is the action of PTH on bone?
Stimulate osteoclasts, increasing bone resorption and therefore release of calcium
What is the action of PTH on kidneys?
Enhances resorption of calcium and magnesium from the distal tubule
Increases excretion of phosphate
What is the action of PTH on intestine?
Increases absorption of calcium by increasing vit D production
When does the fetus begin to produce PTH?
Week 12
What happens to maternal PTH/calcitonin level in pregnancy?
PTH reduced and calcitonin increased in order to maintain increased calcium transfer to the fetus - the fetus being relatively hypercalcaemic to the mother
Which hormones are secreted by the placenta?
- hCG
- Oestrogen
- Progesterone
- Relaxin
When does the first cleavage division of the fertilised egg take place?
Approx. 30 hours after fertilisation
At what cell stage does the embryo enter the uterus from the fallopian tube?
8 cell stage
What are the characteristics of trophoblast cells?
- Paternal X chromosome inactivation
- Unmethylated DNA
- Ability to form multi-nucleated cells
- Variable expression of MHC1, no MHC2 antigen expression
What are the functions of the trophoblast cells?
- Attachment of the placenta to the uterine wall
- Transport of nutrients and maternal Ig’s
- Elimination of fetal waste
- Synthesis/secretion of hormones
- Barrier between maternal and fetal circulations
- Contact between maternal immune system and conceptus
What are the three stages of implantation?
- Apposition - when decidualisation takes place
- Adhesion - when the zona pellucida is destroyed
- Penetration - the trophoblast produces metalloproteases that digest the ECM, facilitating trophoblast invasion into the uterine decidua
What are the 2 layers of trophoblast?
Outer syncytiotrophoblast - where cellular walls are largely lost
Inner cytotrophoblast - where cell remain recognisibly individual
How many lobules are there to each placenta?
200
What does each placental lobule contain?
A single primary stem villus
Until when does the placenta exceed the weight of the fetus?
Week 17
In humans, where does the placental trophoblast encounter the maternal immune system?
- The villous syncytiotrophoblast is bathed in maternal bloods
- The extravillous cytotrophoblast interacts with uterine tissue
How many ml of amniotic fluid is present at 8 weeks
15ml
Where is the amnion situated?
Between the inner cell mass and the trophoblast (the chorion)
How many layers are there to the amnion?
- Cuboidal epithelium
- Basement membrane
- Compact layer
- Fibroblast layer
- Spongy layer of mucoid reticular tissue (remnant of extraembryonic coelom)
How many cells thick is the trophoblast layer?
2-10 cells thick
How many layers are there in the chorion?
- Fibroblasts
- Reticular layer
- Basement membrane
- Trophoblast layer
What hormones are hCG structurally similar to?
LH
FSH
TSH
What is it that makes hCG, LH, FSH and TSH structurally similar?
They share an ALPHA subunit
The beta subunit varies between them
What type of hormones are LH and FSH?
Glycoprotein hormones
At what gestation does hCG peak?
Week 12
What are the divisions of the anterior pituitary?
Pars distalis
Pars tuberalis
What are the divisions of the posterior pituitary?
Pars nervosa
Infundibular stalk/infundibulum
Median eminence
What are the three types of hypothalamic neurosecretory cells?
Magnocellular neurons - release AVP or oxytocin
Hypophysiotropic neurons - release TRH, CRH, somatostatin, GHRH, GnRH and dopamine
Projection neurons
What is another name for the anterior pituitary?
Adenohypophysis
What is another name for the posterior pituitary?
Neurohypophysis
What are the cell types of the adenohypophysis?
Acidophils
Basophils
Chromophobes
Which nuclei are magnocellular neurons found in?
Supraoptic or paraventricular nuclei
Which nuclei are hypophysiotropic neurons found in?
Paraventricular and arcuate nuclei
Which nuclei are projection neurons found in?
Paraventricular and arcuate nuclei
What is the embryological origin of the anterior pituitary?
Rathke pouch - an evagination of ectodermal cells of the oropharynx in the primitive gut
At what gestation does the anterior pituitary become recognisable?
Weeks 4-5
What is the embryological origin of the posterior pituitary?
Neural crest cells
From what cell type are FSH and LH secreted?
Gonadotrophs
What is the earliest sign of puberty in boys?
An increase in testicular volume by 4ml, or 2.5cm
When is puberty considered precocious?
In girls, before the age of 8
In boys, before the age of 9
What is SHBG?
A serum glycoprotein that binds to androgens and oestrogens
Hormones must be unbound (free) to function; if SHBG levels are high, there will be less free hormone to function
Where is SHBG synthesised?
By the liver (primarily), brain, uterus, testes and placenta
Is SHBG binding affinity higher for androgens or oestrogens?
Androgens
What is the binding affinity - in order of strength - of SHBG?
Dihydrotestosterone
Testosterone
Androstenediol
Oestradiol
Oestrone
What causes increased SHBG?
- OCP (oestrogens)
- Pregnancy (oestrogens)
- Hyperthyroidism
- Liver cirrhosis
- Anorexia
- AEDs
What causes decreased SHBG?
- Androgens
- PCOS
- Hypothyroidism
- Obesity
- Cushing’s
- Acromegaly
Is SHBG higher in men or women?
Women
This prevents systemic exposure to androgens which cause masculinisation
Approximately 69% of circulating oestrogen is bound to SHBG, 30% to albumin leaving the remainder ‘free’
Where in females are androgens produced?
Ovary = 25%
Adrenal glands = 25%
Peripheral conversion of androstenedione = 50%
Which is the most active oestrogen of the natural oestrogens?
Oestradiol
In what form does the kidney excrete oestrogen?
Oestriol glucuronide
Where in the body is progesterone stored?
Adipose tissue
In plasma what does progesterone bind to?
Corticosteroid-binding globulin - CBG
Albumin
What are the pre-ovulatory levels of progesterone?
<2ng/ml
What are the post-ovulatory levels of progesterone?
5ng/ml
What is the term level of progesterone?
100-250ng/ml
At term how much progesterone is produced by the placenta?
250mg/day
What inhibits lactation, and prevent uterine contraction until term?
Progesterone
What hormones are produced in the arcuate nuclei of the hypothalamus?
Dopamine and GnRH
Where are the only place FSH receptors are found?
Granulosa cells
Which hormone is responsible for resumption of meiosis by the oocyte?
LH
What are the physiological causes of hyperprolactinaemia?
Pregnancy
Lactation
Exercise
Stress
What are the pharmacological causes of hyperprolactinaemia
TRH
Oesotrogen
Dopamine antagonists
Verapamil
Cimetidine
What are the pathological causes of hyperprolactinaemia?
Pituitary tumour
Chest wall lesions
Spinal cord lesions
Liver failure
Chronic renal failure
When does adrenal androgen production begin in males/females?
Males = 7-9 years old
Females = 6-7 years old
When does the growth spurt in boys begin relative to girls?
2 years later
When is the bone mineralization in boys/girls respectively?
Boys = 17.5 years old
Girls = 14-16 years old
Which tumours secrete hCG
Choriocarcinoma
Germ cell tumour
Hydatiform mole
When do menses return after pregnancy?
Breastfeeding women = 28 weeks postpartum
Non-breast feeding women = 9 weeks postpartum
When does steroidogenesis start in the fetus?
7 weeks
When are the testes seen in the fetus?
6 weeks
When are the ovaries seen in the fetus?
7-8 weeks
When does testosterone production begin in the fetus?
10 weeks
When does oestrogen production begin in the fetus?
20 weeks
In what form does the kidney excrete progesterone?
Pregnanediol glucuronide
How does the LH surge at ovulation cause rupture of the mature oocyte?
Acts on theca externa
Activation of what causes puberty?
Activation of the HPG axis
What changes to the HPG axis occur as puberty progresses
- Before the onset of puberty, GnRH release is inhibited by neurotransmitters such as GABA and neuropeptide-Y
- Puberty begins when central GnRH inhibitory mechanisms decline; the exact mechanism behind this is poorly understood
- Neurotransmitters implicated include glutamate, kisspeptin and leptin
- Nocturnal GnRH pulse frequency increases first, leading to FSH release and the development of ovarian follicles
- As puberty progresses, GnRH pulsatility extends to day time release as well; diurnal variation is eventually lost
- GnRH receptors also become more sensitive
- Increasing ovarian follicular activity results in oestrogen synthesis and development of sexual secondary characteristics
What neurotransmitters are implicated in the activation of GnRH release at the onset of puberty?
Glutamate, kisspeptin and leptin
Does GnRH release begin nocturnally or in the daytime at the onset of puberty?
Nocturnally
Pre-puberty, what are the relative LH / FSH levels?
FSH>LH
At puberty, what are the relative LH / FSH levels?
LH>FSH
When does ovulation occur in puberty?
During early puberty, LH levels are insufficient to cause ovulation; the majority of cycles are therefore anovulatory
By 4-5 years post menarche, LH surges achieve dominant follicle rupture; the majority of cycles are ovulatory (>80%)
Which Tanner stage marks the beguinning of puberty?
Tanner stage 2
Boys = testicular volume >3mls
Girls = breast bud development
When is puberty considered delayed in boys?
Absence of testicular enlargement (<4mls) by age 14
When is puberty considered delayed in girls?
Absence of breast bud development by age 13
When is secondary referral required for girls with amenorrhoea?
Age ≥13 with absent menstruation and no secondary sexual characteristics
Age ≥15 and absent menstruation and with normal secondary sexual characteristics
How is leptin related to puberty?
- Leptin is believed to be one of the hormones associated with activating the HPG axis during puberty
- Leptin is a protein hormone released by adipocytes
- Some studies suggest a minimum body weight of around 47 kg is required to activate puberty
- This may explain why girls with a higher body mass start experience menarche at an earlier age
- Girls with low body mass (and therefore low leptin levels) often experience anovulatory cycles and a delay in menarche onset
What is the average age of menarche in the UK?
12
What many amenorrhoea, but cyclical pelvic pain suggest?
Haematocolpos, caused by a genital tract malformation
What are the possible causes of hypothalamic dysfunction that may cause amenorrhoea?
Stress
Depression
Weight loss
Level of exercise
Chronic systemic illness
What cause of amenorrhoea is associated with anosmia?
Kallman syndrome
What are the signs of virilisation, that may indicate an androgen-secreting tumour as a cause of amenorrhoea?
Clitoromegaly
Hirsutism
What are the clinical features of decreased endogenous oestroegn?
Reddened or thin vaginal mucosa
Breast development is a good marker for ovarian oestrogen production
What are the clinical features of androgen insensitivity?
Absence of axillary and pubic hair with normal breast development
Testes may be palpable in the inguinal canal or labia
What do high levels of testosterone warrent investigation for?
Androgen insensitivity (46XY genotype, female phenotype)
Late-onset congenital adrenal hyperplasia
Cushing’s syndrome
Androgen-secreting tumour
(moderate increase seen in PCOS)
