15. Lactation, galactorrhoea, prolactinoma

Question 1

Breast development in puberty

Answer 1

Puberty

• oestrogen, progesterone
• GH (via IGF-I):
  
  • increase in alveolar buds
  • increase in lobules

Question 2

Breast development in pregnancy

Answer 2

Oestrogen, progesterone
hCG, prolactin
Alveolar development:
- increase in ducts & lobules
- Differentiated secretory units (acini)
- Colostrum accumulates

Question 3

Milk production

Answer 3

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

Question 4

Milk composition

Answer 4

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)

Question 5

lactation

Answer 5

Lactation (galactopoiesis)
Positive feedback loops

Regular removal of milk
Nipple stimulation

Prolactin (anterior pituitary)
Oxytocin (posterior pituitary)

Question 6

prolactin

Answer 6

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

Question 7

What does an increase in prolactin lead to?

Answer 7

Increase in Prolactin leads to:
· Decrease in GnRH
· Decrease in LH and FSH, decrease in pulsatility
· Decrease in oestrogen / testosterone

Question 8

oxytocin synthesis

Answer 8

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

Question 9

oxytocin action

Answer 9

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 ?

Question 10

Evolutionary perspective

Answer 10

• 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!

Question 11

How do other mammals know they’re pregnant?

Answer 11

Brain responds to hormonal changes associated with ovulation, mating, implantation & pregnancy
via prolactin & placental lactogens

Question 12

hyperprolactinoma presentation in women

Answer 12

triad of hyperprolactinoma:
oligo / amenorrhoea
galactorrhoea
subfertility

osteoporosis

May not have all these symptoms
May present after stopping contraceptive pill
- coincidental

Question 13

hyperprolactinoma presentation in men

Answer 13

Erectile dysfunction
decreased libido

visual symptoms
headaches
hypopituitarism

Present later
Galactorrhoea / gynaecomastia RARE

Question 14

hyperprolactinoma causes

Answer 14

Physiological
- Pregnancy
- Lactation
Hypothalamic-pituitary disease
- Micro / macroPRLoma
- Non-functioning adenoma
Drugs
Stress
Other
- Polycystic ovarian syndrome
- Hypothyroidism (increase in TRH)
- Renal failure, cirrhosis

Question 15

Drugs that increase prolactin (and can cause hyperprolactinoma)

Answer 15

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

Question 16

hyperprolactinoma investigations

Answer 16

• 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

Question 17

aims of treating prolactinoma

Answer 17

• 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

Question 18

PRLoma management

Answer 18

‘MEDICAL’
Dopaminergic drugs
Cabergoline
(Bromocriptine)
Preserve pituitary function
Side-effects
RARE:
Fibrotic reactions
Pulmonary, pericardial, retroperitoneal
Psychiatric disturbances

Question 19

microprolactinoma management

Answer 19

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)

Question 20

what is idiopathic hyperPRLaemia?

Answer 20

Assumed to be a microPRLoma too small to be detected radiologically

Question 21

Non-functioning pituitary adenoma (NFA) management

Answer 21

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

Question 22

Triad of prolactinoma

Answer 22

oligo/mennorhea, galactorrhea, subfertility