L15 - Lactation and prolactinomas Flashcards
What is the term for milk production?
Lactogenesis
Secretory initiation of lactogenesis
Progesterone
Occurs during pregnancy
Colostrum
Secretory activation of lactogenesis
Decrease in progesterone/oestrogen
Increase in prolactin (cortisol, insulin)
Copious milk production after delivery
-usually 2-3 days post-partum
What is milk composed of?
Sugar
Milk fats
Proteins
Minerals
Growth factors
Cellular components (esp in colostrum)
Other word for lactation
Galactopoiesis
What is lactation and how is it stimulated?
Regular removal of milk
Nipple stimulation
Hormones involved in lactation
Prolactin (anterior pituitary)
Oxytocin (posterior pituitary)
Where is prolactin produced?
Lactotroph cells in the anterior pituitary
What is prolactin similar to?
GH
Similar receptor to GH
- tyrosine phosphorylation
- JAK-STAT signalling
What is prolactin release inhibited by?
Dopamine
What is prolactin release stimulated by?
5HT
TRH
Oxytocin
Prolactin in pregnancy
increases
Prolactin and suckling postpartum
increased up to 80 days postpartum when suckling occurs
What is lactational amenorrhoea?
In the first 6 months after giving birth, if a women exclusively breastfeeds she will not get her period
Therefore it is a temporary contraceptive
What does the contraception efficacy of lactational amenorrhoea depend on?
On the frequency and duration of breast feeding
How does lactational amenorrhoea work?
Increase in prolactin leads to:
- decreased GnRH
- decreased LH and FSH, decreased pulsatility
- decreased oestrogen/testosterone
What is oxytocin and where is it synthesised?
Nonapeptide
Posterior pituitary
-Distal axon terminals of hypothalamic magnocellular neurons
Neurosecretory granules released into capillary system of posterior pituitary
How does oxytocin work?
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 ?
The evolutionary perspective
Mammals lactate
- nutritious excretion from an exocrine gland and encouraging offspring to consume it
- continued nurturing of offspring after birth with benefits including enhanced brain development
Strategies for succes -milk production -complementary changes in the mother's brain =>metabolic =>psycho-social/behavioural -same hormones
How mammals know if they’re pregnant
Brain responds to hormonal changes associated with occupation, mating, implantation & pregnancy
Via prolactin & placental lactogens
Presentation of hyperprolactinaemia in women
Oligo/amenorrhoea
-increases risk of osteoporosis
Galactorrhoea
Sub fertility
May not have all these symptoms
May present after stopping contraceptive pill
-coincidental
Presentation of hyperprolactinaemia in men
Erectile dysfunction
Decreased libido
Visual symptoms
Headaches
Hypopituitarism
Present later
Galactorrhoea/gynaecomastia RARE
Causes of hyperprolactinaemia
Physiological
- pregnancy
- lactation
Hypothalamic-pituitary disease
- micro/macroPRLoma
- non-functioning adenoma
Drugs
Stress
Other
- PCOS
- Hypothyroidism (increase in TRH)
- Renal failure, cirrhosis
Drugs that increase prolactin
Antidepressants and antipsychotics
Drugs used for nausea and vertigo
- Phenothiazines
- Metoclopramide
- Domperidone
Others
Mechanism of prolactin increasing drugs
Inhibition of secretion/action of dopamine
- DA antagonists
- DA receptor blockers
Stimulation of central serotonin (5HT) pathways
-5HT re-uptake inhibitors
Investigations for hyperprolactinaemia
Pregnancy test Renal function -U&E, creatinine Liver function tests Thyroid function Prolactin (repeat) LH, FSH Testosterone
MRI pituitary
- Micro < 1cm diametes
- Macro > 1cm diameter
Macroadenoma
- visual fields
- rest of anterior pituitary function tests
Aims of treatment of hyperprolactinaemia
Restore fertility
Stop galactorrhoea
-Also stop nipple stimulation/;checking’ (oxytocin)
Restore regular menstrual periods/libido
- oestrogen/testosterone needed for bone protection
- can use exogenous oestrogen/testosterone (contraceptive pill/HRT/testosterone)
Shrink tumour (macroadenoma)
- recovery of anterior pituitary function
- restore vision
PRLoma management (1)
Medical
Dopaminergic drugs
- cabergoline
- bromocriptine
Preserve pituitary function
Side-effects -RARE =>fibrotic reactions =>pulmonary. pericardial, retroperitoneal =>psychiatric disturbances
Micro PRLomas management
Can take COCP/HRT if fertility not required
Can discontinue treatment in pregnancy
May involute postpartum
Can trial withdrawal of treatment after approx 2 years (may not recur)
What is ‘idiopathic hyperPRLaemia’?
Assumed to be a microPRLoma too small to be detected radiologically
NFA (non-functioning pituitary adenoma) management
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 decrease with dopaminergic drugs
-need to monitor MRI scan and visual fields (bitempotal hemianopia)
