L15 - Lactation and prolactinomas

Question 1

What is the term for milk production?

Answer 1

Lactogenesis

Question 2

Secretory initiation of lactogenesis

Answer 2

Progesterone

Occurs during pregnancy

Colostrum

Question 3

Secretory activation of lactogenesis

Answer 3

Decrease in progesterone/oestrogen

Increase in prolactin (cortisol, insulin)

Copious milk production after delivery
-usually 2-3 days post-partum

Question 4

What is milk composed of?

Answer 4

Sugar

Milk fats

Proteins

Minerals

Growth factors

Cellular components (esp in colostrum)

Question 5

Other word for lactation

Answer 5

Galactopoiesis

Question 6

What is lactation and how is it stimulated?

Answer 6

Regular removal of milk

Nipple stimulation

Question 7

Hormones involved in lactation

Answer 7

Prolactin (anterior pituitary)

Oxytocin (posterior pituitary)

Question 8

Where is prolactin produced?

Answer 8

Lactotroph cells in the anterior pituitary

Question 9

What is prolactin similar to?

Answer 9

GH

Similar receptor to GH

• tyrosine phosphorylation
• JAK-STAT signalling

Question 10

What is prolactin release inhibited by?

Answer 10

Dopamine

Question 11

What is prolactin release stimulated by?

Answer 11

5HT

TRH

Oxytocin

Question 12

Prolactin in pregnancy

Answer 12

increases

Question 13

Prolactin and suckling postpartum

Answer 13

increased up to 80 days postpartum when suckling occurs

Question 14

What is lactational amenorrhoea?

Answer 14

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

Question 15

What does the contraception efficacy of lactational amenorrhoea depend on?

Answer 15

On the frequency and duration of breast feeding

Question 16

How does lactational amenorrhoea work?

Answer 16

Increase in prolactin leads to:

• decreased GnRH
• decreased LH and FSH, decreased pulsatility
• decreased oestrogen/testosterone

Question 17

What is oxytocin and where is it synthesised?

Answer 17

Nonapeptide

Posterior pituitary
-Distal axon terminals of hypothalamic magnocellular neurons

Neurosecretory granules released into capillary system of posterior pituitary

Question 18

How does oxytocin work?

Answer 18

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 19

The evolutionary perspective

Answer 19

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

Question 20

How mammals know if they’re pregnant

Answer 20

Brain responds to hormonal changes associated with occupation, mating, implantation & pregnancy

Via prolactin & placental lactogens

Question 21

Presentation of hyperprolactinaemia in women

Answer 21

Oligo/amenorrhoea
-increases risk of osteoporosis

Galactorrhoea

Sub fertility

May not have all these symptoms

May present after stopping contraceptive pill
-coincidental

Question 22

Presentation of hyperprolactinaemia in men

Answer 22

Erectile dysfunction

Decreased libido

Visual symptoms

Headaches

Hypopituitarism

Present later

Galactorrhoea/gynaecomastia RARE

Question 23

Causes of hyperprolactinaemia

Answer 23

Physiological

• pregnancy
• lactation

Hypothalamic-pituitary disease

• micro/macroPRLoma
• non-functioning adenoma

Drugs

Stress

Other

• PCOS
• Hypothyroidism (increase in TRH)
• Renal failure, cirrhosis

Question 24

Drugs that increase prolactin

Answer 24

Antidepressants and antipsychotics

Drugs used for nausea and vertigo

• Phenothiazines
• Metoclopramide
• Domperidone

Others

Question 25

Mechanism of prolactin increasing drugs

Answer 25

Inhibition of secretion/action of dopamine - DA antagonists - DA receptor blockers Stimulation of central serotonin (5HT) pathways -5HT re-uptake inhibitors

Question 26

Investigations for hyperprolactinaemia

Answer 26

``` 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

Question 27

Aims of treatment of hyperprolactinaemia

Answer 27

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

Question 28

PRLoma management (1)

Answer 28

Medical Dopaminergic drugs - cabergoline - bromocriptine Preserve pituitary function ``` Side-effects -RARE =>fibrotic reactions =>pulmonary. pericardial, retroperitoneal =>psychiatric disturbances ```

Question 29

Micro PRLomas management

Answer 29

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)

Question 30

What is 'idiopathic hyperPRLaemia'?

Answer 30

Assumed to be a microPRLoma too small to be detected radiologically

Question 31

NFA (non-functioning pituitary adenoma) management

Answer 31

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)