L15 - Lactation, Glactorrhoea, Prolactinomas Flashcards
BREAST DEVELOPMENT
how and what hormones happen during puberty and what does this cause
also pregnancy
• Puberty — oestrogen, progesterone ---GH (via IGF-I) • INCR alveolar buds • INCR lobules
Pregnancy — oestrogen, progesterone ---hCG, prolactin — Alveolar development • INCR ducts & lobules • Differentiated secretory units (acini) • Colostrum accumulates
milk production - lactogenesis
secretory initiation and activation
what hormones for each
— Secretory intitiation
• Progesterone
• Occurs during pregnancy
• Colostrum
— Secretory activation • DECR progesterone / oestrogen INCR prolactin (cortisol, insulin) • Copious milk production after delivery — Usually 2-3 days post-partum
milk composition
sugar, milk fats, proteins, minerals, growth factors, minerals, growth factors, cellular components - esp in colostrum
lactation
aka?
what stimulates
Lactation (galactopoiesis)
Positive feedback loops
Regular removal of milk
Nipple stimulation
Prolactin (anterior pituitary)
Oxytocin (posterior
pituitary)
Prolactin
what cells secrete and where
what is it similar to and in what ways
what is it release inhibited by and stimulated
how do levels change in pregnancy? suckiling?
Lactotroph cells
— anterior pituitary
Similarities to GH
Similar receptor to GH
— Tyrosine phosphorylation
— JAK-STAT signaling
prolactin inhib by dopamine
release stim by 5HT (serotonin), TRH, oxytocin
progressively incr in preg
also after suckling
Lactation
how does this effect periods and what is this called
what does this thing depend on
how and why does this happen
Lactational amenorrhoea
— Contraceptive efficacy depends on the frequency and duration of breast feeding
INCR Prolactin leads to:
— decr GnRH
—decr LH and FSH, decr pulsatility
— decr oestrogen / testosterone
OXYTOCIN
where is it synthesised
how and where does it go
in hypothalamic magnicellular neurones
- –supraoptic nucleus
- –paraventricular nucleus
Posterior pituitary
— Distal axon terminals
of hypothalamic
magnocellular neurons
Neurosecretory
granules released into
capillary system of
posterior pituitary
oxytocin
what happens when infant suckles
what else can incr / activate this hormone
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 ?
how does the brain respond to having a baby? what is this via
— Brain responds to hormonal changes associated with ovulation, mating, implantation & pregnancy — via prolactin & placental lactogens
HYPERPROLACTINAEMIA
presentation? w/ m
WOMEN • oligo / amenorrhoea ---incr risk osteoporosis • galactorrhoea • subfertility • May not have all these symptoms •May present after stopping contraceptive pill — coincidental
MEN • Erectile dysfunction • DECR libido • visual symptoms • headaches • hypopituitarism • Present later • Galactorrhoea / gynaecomastia RARE
CAUSES of HYPERPROLACTINOMA
•Physiological
- –Pregnancy
- –Lactation
•Hypothalamic-pituitary
disease
—Micro / macroPRLoma
—Non-functioning adenoma
• Drugs • Stress • Other ----Polycystic ovarian syndrome ----Hypothyroidism (INCR TRH) ----Renal failure, cirrhosis
what drugs increase prolactin?
what is the mechanism of these
Antidepressants and
antipsychotics
Drugs used for nausea & vertigo
— Phenothiazines
— Metoclopramide
— Domperidone
Others
Mechanisms — Inhibition of secretion / action of dopamine • DA antagonists • DA receptor blockers
— Stimulation of central serotonin (5HT) pathways • 5HT re-uptake inhibitors nausea & vertigo
what investigations would you take for suspected hyperprolactinoma?
Pregnancy test Renal function — U&E, creatinine Liver function tests Thyroid function Prolactin (repeat) LH, FSH Testosterone (men)
MRI pituitary
— Micro < 1 cm diameter
— Macro > 1 cm diameter
Macroadenoma
— Visual fields
— Rest of anterior pituitary function tests
what are the aims of treatment?
Restore fertility
Stop galactorrhoea
— Also stop nipple stimulation / ‘checking’ (oxytocin)
Restore regular menstrual periods / libido
— Oestrogen / testosteone needed for bone protection
— Can use exogenous oestrogen / testosterone
(contraceptive pill / HR T / testosterone)
Shrink tumour (macroadenoma) — Recovery of anterior pituitary function — Restore vision
how to manage a PRLoma?
medical? what drugs? what do they do and what is the side effect
what about a microPRLoma
and idiopathic hyperPRLoma?
‘MEDICAL’
Dopaminergic drugs
Cabergoline
(Bromocriptine)
Preserve pituitary function
Side-effects RARE: Fibrotic reactions -----Pulmonary, pericardial, retroperitoneal Psychiatric disturbances
MicroPRLomas --- Can take COCP / HRT if fertility not required — Can discontinue treatmment in pregnancy --May involute post- partum — Can trial withdrawal of treatment after 2 years (may not recur)
‘Idiopathic
hyperPRLaemia’
— Assumed to be a
microPRLoma too small to be detected radiologically
management of NFA
what is it what does it cause
what does it need? what are u trying to prevent
how can you decr prolactin and what would u want to monitor
Non-functioning pituitary
adenoma
— Compression of the pituitary stalk
• ‘Disconnection hyperPRLaemia’
• May also occur with hypothalamic masses
— May need surgery & radiotherapy
• space-occupying effects
• risk loss of pituitary function
— [prolactin] will with dopaminergic drugs
• Need to monitor MRI scan & visual fields
CASE: abnormal CT scan, macroPRLoma, bitemporal hemianopia normal TSH low FT4 & FSH (for post menopause) vvv high PRL cortisol ok
what would this be?
what would this be
2ary hypothyroidism
—-> pointing to hypothalamus
CASE: galactorhhoea 2.5 year 2-4 year on COCP no other meds no PMH / FH
raised PRL
TSH and FT4 normal
LH and FSH low
what could this be and how would you manage this
the low LH and FSH is cos shes on the pill
microprolactinoma
manage
continue COCP
avoid nipple stim / checking
may need cabergoline to conceive — discontinue when preg confirmed
CASE: 8 month 2ary amenorrhoea negative preg test no meds wants kids raised PRL normal thyroid TSH and LH normal
what could this be and how would you manage this
non funct pit adenoma
causing incr prl and decr DA
—not high enough for prolactinoma: size of swelling and PRL level determines this
transphenoidal hypophysectomy
—- but risk to vision and with further growth
potential risk yo pituitary function – incl future fertility. treatment woudl fix
CASE: galactorrhoea 4 week regular menstrual cycle long H of anxiety and depression TH: risperidone, trazodone duloxetine
PRL high for age
FSH higher, but normal for age
thyroid normal
MRI: structurally normal pit
what is it? management?
reasurre:
medication induced hyperprolactinoma
noo treatment
- –risk to mental health
- –regular MP to protect bones
avoid nipple stim / checking
