L15 Lactation and prolactinomas Flashcards
Effect of GH on alveolar buds and lobules during puberty
Increase in alveolar buds and lobules via IGF-I
Alveolar development during pregnancy
- Increase in ducts and lobules
- Differentiated secretory units (acini)
- Colostrum accumulates
What is colostrum
- Is the first form of milk produced by the mammary glands of mammals (including many humans) immediately following delivery of the newborn
Hormonal changes prior to secretory activation in lactogenesis
- Decrease in progesterone/oestrogen
- Increase in prolactin (cortisol, insulin)
- Copious milk production after delivery (usually 2-3 days post-partum)
Sugars in breast milk
- Lactose and oligosaccharides
Fats in breast milk
○ triglycerides, cholesterol, phospholipids, steroid hormones
Proteins in breast milk
○ Caseins, lactalbumin, lactoferrin, secretory IgA, lysozyme
Minerals in breast milk
○ Na, K, Cl, Ca, Mg, Phosphate
- Growth factors
Cellular components of breast milk
○ Macrophages, lymphocytes, neutrophils, epithelial cells
○ Phospholipids (membrane fragments)
What is prolactin produced by
- Anterior pituitary
What is oxytocin produced by
- Posterior pituitary
Positive feedback loops - lactation
- Regular removal of milk
- Nipple stimulation
- Prolactin (anterior pituitary)
- Oxytocin (posterior pituitary)
Which cells produce prolactin
- Lactotroph cells located in the anterior pituitary
What are prolactin receptors similar to
- Similarities to GH
- Similar receptor to GH
- Tyrosine phosphorylation
- JAK-STAT signalling
Effects of 5HT, TRH and OXT on the pituitary
5HT, TRH and OXT released by hypothalamus have excitatory effects on the pituitary which causes released of prolactin
Effect of dopamine on prolactin release
- Prolactin release is inhibited by dopamine
What is lactational amenorrhoea
- Lactational amenorrhea is the temporary postnatal infertility that occurs when a woman is amenorrheic (not menstruating) and fully breastfeeding
What does contraceptive efficacy depend on
- Contraceptie efficacy depends on the frequency and duration of breast feeding
Effect of increase in prolactin on other hormone levels
Causes:
- Decrease in GnRH
- Decrease in LH and FSH, decrease in pulsatility
- Decrease in oestrogen/testosterone
Where is oxytocin synthesised
Synthesised in hypothalamic magnicellular neurons
- Supraoptic nucleus
- Paraventricular nucleus
What does the posterior pituitary consist of
- The posterior pituitary is neural tissue and consists only of the distal axons of the hypothalamic magnocellular neurons that make up the neurohypophysis
Where are neurosecretory granules released into from the posterior pituitary
- Neurosecretory granules released into capillary system of posterior pituitary
Where does the afferent signal from receptors in the nipple ascend to when the infant suckles
- Hypothalamus
Effects of oxytocin
+ uterine myometrial contraction at birth
+ smooth muscle activation in breast ( ‘myoepithelial contraction’)
+ milk let-down
Potential role in maternal behaviour
Evolutionary perspective - mammals lactation
- Reproductive strategy involved producing a nutritious secretion from an exocrine gland and encouraging offspring to consume it
- Continued nurturing of offspring after birth with benefits including enhanced brain development
What does the brain respond to during mating and pregnancy
- Brain responds to hormonal changes associated with ovulation, mating, implantation and pregnancy
- Via prolactin and placental lactogens
Body mechanisms - coping with fetal growth
- Fluid retention
- Cardiovascular and respiratory changes
- Altered glucose metabolism
- Altered immune system
How does the body provide support to the fetus
- Uterine growth
- Development of the placenta
Behavioural changes in the mother during pregnancy
- Maternal behaviour
- Adult neurogenesis
- Reduced anxiety
- Increased aggression to protect young
How does the body cope with increased metabolic demands during pregnancy
- Increased appetite and fat deposition
- Loss of menstrual cycle
Hormonal changes during lactation
- Pattern of firing of oxytocin neurons
- Loss of prolactin negative feedback
How does hyperprolactinaemia present in women
- Oligo/amenorrhoea –> increase in risk of osteoporosis
- Galactorrhoea
- Subfertility
- May not have all these symptoms
- May present after stopping contraceptive pill (coincidental)
How does hyperprolactinaemia present in men
- Erectile dysfunction
- Decrease in libido
- Visual symptoms
- Headaches
- Hypopituitarism
- Present later
- Galactorrhoea/gynaecomastia(rare)
Phsyiological causes of hyperprolactinaemia
- Pregnancy
- Lactation
How can hypothalamic-pituitary disease cause hyperprolactinaemia
- Micro/macroPRLoma
- Non-functioning adenoma
Other causes of hyperprolactinaemia
- Drugs
- Stress
- Polycystic ovarian syndrome
- Hypothyroidism (increase in TRH)
- Renal failure, cirrhosis
Drugs that increase PRL levels
- Antidepressants and antipsychotics
- Drugs used for nausea and vertigo
How do drugs increase PRL levels - mechanisms
- 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 (men)
- MRI pituitary
Micro vs macro adenoma
- Micro < 1 cm diameter
- Macro > 1 cm diameter
Tests for a macroadenoma
- Visual fields
- Rest of anterior pituitary function tests
Aims of treatment - hyperprolactinaemia
· 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 of PRLoma management
• RARE:
○ Fibrotic reactions
□ Pulmonary, pericardial, retroperitoneal
○ Psychiatric disturbances
Specific features of microPRLoma treatment
- Can take COCP/HRT if fertility not required
- Can discontinue treatment in pregnancy
- May involute post-partum
- Cn trial withdrawal of treatment after - 2 years (may not recur)
What is idiopathic hyperPRLaemia assumed to be
- Assumed to be a microPRLoma too small to be detected radiologically
Non-functioning pituitary adenoma (NFA) management
• May need surgery & radiotherapy
○ space-occupying effects
○ risk loss of pituitary function
• [prolactin] will ¯ with dopaminergic drugs
○ Need to monitor MRI scan & visual fields
What can an NFA cause compression of
• Compression of the pituitary stalk
○ ‘Disconnection hyperPRLaemia’
○ May also occur with hypothalamic masses
Risk of transphenoidal hypophysectomy
- Risk to vision with further growth
- Potential risk to pituitary growth - including future fertility prospects (though would be amenable to treatment)
