15. Lactation, galactorrhoea, prolactinoma Flashcards
Breast development in puberty
Puberty
- oestrogen, progesterone
- GH (via IGF-I):
- increase in alveolar buds
- increase in lobules
Breast development in pregnancy
Oestrogen, progesterone hCG, prolactin Alveolar development: - increase in ducts & lobules - Differentiated secretory units (acini) - Colostrum accumulates
Milk production
Secretory intitiation
- Progesterone
- Occurs during pregnancy
- Colostrum
Secretory activation:
- decreased progesterone / oestrogen
- increased prolactin (cortisol, insulin)
- Copious milk production after delivery
- Usually 2-3 days post-partum
Milk composition
Sugar
· Lactose & oligosaccharides
Milk fats
· triglycerides, cholesterol, phospholipids, steroid hormones
Proteins
· Caseins, 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)
lactation
Lactation (galactopoiesis)
Positive feedback loops
Regular removal of milk
Nipple stimulation
Prolactin (anterior pituitary)
Oxytocin (posterior pituitary)
prolactin
Lactotroph cells in anterior pituitary
Similarities to GH
Similar receptor to GH
- Tyrosine phosphorylation and JAK-STAT signalling
Prolactin release inhibited by dopamine
Prolactin release stimulated by 5HT (serotonin), TRH, oxytocin
What does an increase in prolactin lead to?
Increase in Prolactin leads to:
· Decrease in GnRH
· Decrease in LH and FSH, decrease in pulsatility
· Decrease in oestrogen / testosterone
oxytocin synthesis
Nonapeptide
Synthesised in hypothalamic magnicellular neurons
- Supraoptic nucleus
- Paraventricular nucleus
Posterior pituitary
- Distal axon terminals of hypothalamic magnocellular neurons
- Neurosecretory granules released into capillary system of posterior pituitary
oxytocin action
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
• 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
○ Psycho-social / behavioural
Same hormones!
How do other mammals know they’re pregnant?
Brain responds to hormonal changes associated with ovulation, mating, implantation & pregnancy
via prolactin & placental lactogens
hyperprolactinoma presentation in women
triad of hyperprolactinoma:
oligo / amenorrhoea
galactorrhoea
subfertility
osteoporosis
May not have all these symptoms
May present after stopping contraceptive pill
- coincidental
hyperprolactinoma presentation in men
Erectile dysfunction
decreased libido
visual symptoms
headaches
hypopituitarism
Present later
Galactorrhoea / gynaecomastia RARE
hyperprolactinoma causes
Physiological - Pregnancy - Lactation Hypothalamic-pituitary disease - Micro / macroPRLoma - Non-functioning adenoma Drugs Stress Other - Polycystic ovarian syndrome - Hypothyroidism (increase in TRH) - Renal failure, cirrhosis
Drugs that increase prolactin (and can cause hyperprolactinoma)
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
hyperprolactinoma investigations
• 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
aims of treating prolactinoma
• 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 / HRT / testosterone)
• Shrink tumour (macroadenoma)
• Recovery of anterior pituitary function
Restore vision
PRLoma management
‘MEDICAL’ Dopaminergic drugs Cabergoline (Bromocriptine) Preserve pituitary function Side-effects RARE: Fibrotic reactions Pulmonary, pericardial, retroperitoneal Psychiatric disturbances
microprolactinoma management
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)
what is idiopathic hyperPRLaemia?
Assumed to be a microPRLoma too small to be detected radiologically
Non-functioning pituitary adenoma (NFA) management
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
Triad of prolactinoma
oligo/mennorhea, galactorrhea, subfertility
