Lactation, Galactorrhoea, Prolactinomas Flashcards
Breast Development in Puberty
- both … and … stimulate the development
- Effects of … hormone via …-1
- develop … buds
- develop …
- oestrogen, progesterone stimulate the development
- Effects of Growth hormone via IGF-1
- develop alveolar buds
- develop lobules
Breast Development in Pregnancy
- both … and … stimulate the development
- Also produced from the placenta in 1st trimester of pregnancy as well as pro…
- There is …. development
- increased … and lobules
- differentiated … unitis (acini)
- … accumulates
- both oestrogen and progesterone stimulate the development
- Also HCG produced from the placenta in 1st trimester of pregnancy as well as prolactin
- There is alveolar development
- increased ducts and lobules
- differentiated secretory unitis (acini)
- colostrum accumulates
Milk Production is known as what?
Lactogenesis
Milk production - lactogenesis
- Secretory initiation
- … hormone helps regulate
- occurs during …
- colostrum
- Secretory activation
- decreased … and … levels
- increased levels of … (also cortisol, insulin)
- copius milk production after delivery (usually … days post-partum)
Milk production - lactogenesis
- Secretory initiation
- Progesterone hormone helps regulate
- occurs during pregnancy
- colostrum
- Secretory activation
- decreased progesterone and oestrogen levels
- increased levels of prolactin (also cortisol, insulin)
- copius milk production after delivery (usually 2-3 days post-partum)
Milk Composition (interest only - not for reproduction)
- sugar
- lactose and oligosaccharides
- milk facts
- triglycerides, cholesterol, phospholipids, steroid hormones
- proteins
- casseins, lactalbumin, lactoferrin, secretory IgA, lysozyme
- minerals
- Na, K, Cl, Ca, Mg, Phosphate
- Growth factors
- Cellular components (Esp in colostrum)
- macrophages, lymphocytes, neutrophils, epithelial cells,
- phospholipids (membrane fragments)
- sugar
- lactose and oligosaccharides
- milk facts
- triglycerides, cholesterol, phospholipids, steroid hormones
- proteins
- casseins, lactalbumin, lactoferrin, secretory IgA, lysozyme
- minerals
- Na, K, Cl, Ca, Mg, Phosphate
- Growth factors
- Cellular components (Esp in colostrum)
- macrophages, lymphocytes, neutrophils, epithelial cells,
- phospholipids (membrane fragments)
- What feedback mechanism is lactation?
- What is it triggered by?
- positive feedback loop mechanism
- triggered by the regular removal of milk and nipple stimulation
What 2 hormones regulate lactation?
- prolactin (anterior pituitary)
- oxytocin (posterior pituitary)
- Where is prolactin released from?
- What inhibits it’s release? (1)
- What stimulates it’s release? (3)
- Released from anterior pituitary
- release inhibited by dopamine
- release stimulated by 5HT(Serotonin), TRH, oxytocin
What is this diagram representing?
Prolactin secretion/inhibition
What does this graph represent an increase of?
prolactin in pregnancy
What does this graph represent?
Prolactin levels and suckling
What happens to prolactin levels? (1) pregancy, 2) post-partum, 3) baby developing - breastfeeding established)
- increasing during pregnancy
- high post-partum (increased by suckling)
- levels relatively low once breast-feeding is established (80 days postpartum)
- Lactational amenorrhoea refers to what?
- Contraceptive efficacy depends on what?
- The time period when a women is breast-feeding and her periods do not resume
- contraceptive efficancy depends on the frequency and duration of breast feeding
- Increased prolactin levels have a supressive effect on all levels of what axis?
- What hormone levels decrease? (4)
- gonodal axis
- decreased LH and FSH productiona and pulsatility, decrease oestrogen and testosterone
Oxytocin is a … amino acid peptide
- Oxytocin is a nine amino acid peptide
Oxytocin is synthesised in hypothalamic … neurons which reside in the ….
- S… nucleus
- P… nucleus
Oxytocin is synthesised in hypothalamic magnicellular neurons which reside in the ….
- supraoptic nucleus
- paraventricular nucleus
After oxytocin is synthesised, neurosecretory granules are released into the capillary system of the … …
This is where oxytocin is released from
posterior pituitary - where the distal axons of hypothalamic magnocellular neurons reside
Regulation of oxytocin production
- Afferent signal from receptors in the nipple when the infant … ascend to …
- uterine myometrial … at birth
- … … activation in breast - ‘myoepithelial contraction’
- … let-down
role in … behaviour?
- Afferent signal from receptors in the nipple when the infant suckles ascend to hypothalamus
- uterine myometrial contraction at birth
- smooth muscle activation in breast - myoepithelial contraction
- milk let-down
role in maternal behaviour?
Evolutionary perspective of lactation
-
Mammals lactate
- … strategy involves producing a nutritious secretion from an exocrine gland & encouraging offspring to consume it
- continued nurturing of offspring … birth with benefits including enhanced … development
-
Strategies for success:
- milk …
- complementary changes in the mother’s … - metabolic and psycho-social/ behavioural
- same …
-
Mammals lactate
- reproductive strategy involves producing a nutritious secretion from an exocrine gland & encouraging offspring to consume it
- continued nurturing of offspring after birth with benefits including enhanced brain development
-
Strategies for success:
- milk production
- complementary changes in the mother’s brain - metabolic and psycho-social/ behavioural
- same hormones
Discovering pregnancy
- humans - take a …
- other mammals - brain responds to … changes associated with ovulation, mating, implantation and pregnancy - via … & placental …
- humans - pregnancy test
- other mammals - brain responds to hormonal changes associated with ovulation, mating, implantation and pregnancy - via prolactin & placental lactogens
What is hyperprolactinaemia?
The presence of abnormally high levels of prolactin in the blood (unrelated to pregancy and breastfeeding)
Presentation of Hyperprolactinaemia - Women
- What is the typical triad?
- oligo / amenorrhoea leading to an increased risk of osteoporosis
- galactorrhoea
- subfertility
They may not have all of these - may present after stopping contraceptive pill - coincidental
Presentation of Hyperprolactinaemia - Men
- low testosterone levels may cause 2 things, what are they?
- is presentation earlier or later than women?
- what other 3 symptoms present?
- What is a rare presentation?
- low testosterone levels may cause erectile dysfunction or loss of libido
- presentation is later than women
- visual symptoms, headaches, hypopituitarism
- rare - galactorrhoea/gynaecomastia
Causes of Hyperprolactinaemia
- physiological causes include … and …
- what disease can cause it?
- drugs
- stress
- other causes include P.., renal .., or hypo….
- physiological causes include pregnancy and lactation
- what disease can cause it - hypothalamic-pituitary disease (non-functioning adenoma, micro/macroprolactinoma)
- drugs
- stress
- other causes include PCOS, renal failure / cirrhosis or hypothyroidism (increased TRH)
Drugs that increase prolactin
- Drugs used for n… and
- Anti… and Anti…
- Drugs used for nausea and vertigo (phenothiazines, metoclopramide, domperidone)
- Antipsychotics and Antidepressants
- also others
nausea and vertigo drugs (phenothiazines, metoclopramide, domperidone) and antidepressants/antipsychotics can increase what?
prolactin
Mechanisms of drugs that increase prolactin
- inhibiton of secretion/action of … (… antagonists or receptor blockers)
- stimulation of … … pathways (… re-uptake inhibitors)
- inhibiton of secretion/action of dopamine - DA antagonists or DA receptor blockers
- stimulation of central serotonin (5HT) pathways - 5HT re-uptake inhibitors
Investigations in hyperprolactinaemia
- … test
- Renal … (including ..&.. and c….)
- Liver function tests
- .. function
- … - repeat
- Hormones - … and …
- In men, test … levels
- after this - imaging - … of pituitary (micro if what size? macro if what size?)
- If they have a … - test visual fields and rest of anterior pituitary function tests
- pregnancy test
- Renal function (including U&E & Creatinine)
- Liver function tests
- .. function
- … - repeat
- Hormones - … and …
- In men, test … levels
- MRI of pituitary (micro if what size - <1cm macro if what size > 1cm)
- Macroadenoma - visual fields, rest of anterior pituitary function tests
Aims of treatment - prolactinoma
- restore …
- stop … - also stop stimulation of …
- restore regular … - women / … mostly in men (can use exogenous oestrogen and testosterone - needed for protection of …)
- shrink the … (if macro) to help recover function of … and restore their …
- restore fertility
- stop galactorrhoea - stop nipple stimulation
- restore regular menstrual periods, libido - men mainly (Can use exogenous oestrogen/testosterone - both are needed for bone protection)
- shrink the tumour if macro - restore vision and recover function of anterior pituitary
Prolactinoma management ‘medical’
- … drugs - such as cabergoline, bromocriptine
- preserve … function
- side-effects -which are rare: … reactions (pulmonary, pericardial, retroperitoneal), … disturbances
- dopaminergic drugs - such as cabergoline, bromocriptine
- preserve pituitary function
- side-effects -which are rare: fibrotic reactions (pulmonary, pericardial, retroperitoneal), psychiatric disturbances
Microprolactinoma management
- can take … if fertility not required
- can discontinue treatment in …
- may … post-partum
- can trial withdrawal of treatment after approximately … years - may not recur
- can take oral contraceptive if fertility not required
- can discontinue treatment in pregnancy
- may involute post-partum
- can trial withdrawal of treatment after approximately 2 years - may not recur
What is idiopathic hyperprolactinaemia?
assumed to be microprolactinoma too small to be detected radiologically
Non-functioning pituitary adenoma - can cause high …
- compression of the pituitary … - leading to d… hyperprolactinaemia, may also occur with … masses
- may need surgery and … - space-occupying effects, risk loss of …
- prolactin will decrease with what drugs?
- do we need to monitor it? if so, how?
- compression of the pituitary stalk - leading to disconnection hyperprolactinaemia - may also occur with hypothalamic masses
- may need surgery and radiotherapy - space occupying effects - risk loss of pituitary function
- prolactin will decrease with what drugs - dopaminergic drugs
- do we need to monitor it - yes - MRI scan and visual fields
Case study : 63 year old women, abnormal CT head scan
What prolactinoma does she have?
Macroprolactinoma - visual field affected greatly - compression on optic chiasm
Case study : 63 year old women, abnormal CT head scan
- Is she hypothyroid, euthyroid, hyperthyroid?
- TSH is normal - what does this tell us? (diagnosis?)
- LH and FSH, what do these tell us?
- Free T4 is low - hypothyroid (level is 7.1)
- TSH normal - tells us that the patient does not have primary hypothyroidism - if it was, TSH would be very high - therefore pituitary problem (secondary hypothyroidism)
- LH and FH low - usually high due to ovarian failure - not high = pituitary problem
What are abnormal cortisol levels a sign of? (In which axis is there a problem)?
problem with hypothalamic pituitary adrenal axis
What would have happened to prolactin levels between these MRI scans?
decreased
- Are her prolactin levels elevated?
- TSH normal? FT4 normal?
- LH and FSH ?
- Testo - ? SHBG - ?
- - taking oral contraceptive pill….
- What is her diagnosis?
- prolactin - Yes - upper limit of normal is around 500
- TSH and FT4 normal
- LH and FSH - suppressed
- Testo - normal SHBG - very high
- as she is taking pill - LH and FSH is low - not pituitary failure - oestrogen treatment suppresses these hormones
If fertility isnt relevant after diagnosis of a microprolactinoma, can the pill be continued?
yes - avoid nipple stimulation, but may require cabergoline to conceive - also discontinue if fall pregnant
Beth - 8 months of secondary amenorrhoea
- negative pregancy tests
- no regular medication
- no PM Hx/ Family Hx of note
- would like children but not yet
- What is her possible diagnosis?
- prolactin moderately elevated (upper limit 500)
- LH and FSH normal
- TSH normal FT4 normal
- scan shows non-functioning pituitary adenoma - stalk compressing optic chiasm - increases the prolactin level - not a macro, cells not making prolactin - it is non functioning - just being compressed
non-functioning pituitary adenoma - what treatment?
- transphenoidal hypophysectomy - risk to vision with further growth
- there is a risk to pituitary function - including future fertility prospects - would be amendable to treatment
Carol - 48
- Galactorrhoea
- regular 4-week menstrual cycle
- long Hx of depression and anxiety, meds include risperidone, trazodone, duloxetine (antipsychotic and antidepressant)
- is her prolactin raised? LH/FSH? TSH? FT4?
- whats the diagnosis?
- prolactin sustained and elevated
- FSH and LH - levels normal for her age
- TSH and FT4 - normal
- pituitary - normal structure
- result = medication-induced hyperprolactinaemia
