Lactation, Galactorrhoea, Prolactinomas

Question 1

Breast Development in Puberty

• both … and … stimulate the development
• Effects of … hormone via …-1
  
  • develop … buds
  • develop …

Answer 1

• oestrogen, progesterone stimulate the development
• Effects of Growth hormone via IGF-1
  
  • develop alveolar buds
  • develop lobules

Question 2

Breast Development in Pregnancy

• both … and … stimulate the development
• Also produced from the placenta in 1st trimester of pregnancy as well as pro…
• There is …. development
  
  • increased … and lobules
• differentiated … unitis (acini)
• … accumulates

Answer 2

• both oestrogen and progesterone stimulate the development
• Also HCG produced from the placenta in 1st trimester of pregnancy as well as prolactin
• There is alveolar development
  
  • increased ducts and lobules
• differentiated secretory unitis (acini)
• colostrum accumulates

Question 3

Milk Production is known as what?

Answer 3

Lactogenesis

Question 4

Milk production - lactogenesis

1. Secretory initiation

• … hormone helps regulate
• occurs during …
• colostrum

1. Secretory activation

• decreased … and … levels
• increased levels of … (also cortisol, insulin)
• copius milk production after delivery (usually … days post-partum)

Answer 4

Milk production - lactogenesis

1. Secretory initiation

• Progesterone hormone helps regulate
• occurs during pregnancy
• colostrum

1. Secretory activation

• decreased progesterone and oestrogen levels
• increased levels of prolactin (also cortisol, insulin)
• copius milk production after delivery (usually 2-3 days post-partum)

Question 5

Milk Composition (interest only - not for reproduction)

• sugar
  
  • lactose and oligosaccharides
• milk facts
  
  • triglycerides, cholesterol, phospholipids, steroid hormones
• proteins
  
  • casseins, 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)

Answer 5

• sugar
  
  • lactose and oligosaccharides
• milk facts
  
  • triglycerides, cholesterol, phospholipids, steroid hormones
• proteins
  
  • casseins, 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 6

• What feedback mechanism is lactation?
• What is it triggered by?

Answer 6

• positive feedback loop mechanism
• triggered by the regular removal of milk and nipple stimulation

Question 7

What 2 hormones regulate lactation?

Answer 7

• prolactin (anterior pituitary)
• oxytocin (posterior pituitary)

Question 8

• Where is prolactin released from?
• What inhibits it’s release? (1)
• What stimulates it’s release? (3)

Answer 8

• Released from anterior pituitary
• release inhibited by dopamine
• release stimulated by 5HT(Serotonin), TRH, oxytocin

Question 9

What is this diagram representing?

Answer 9

Prolactin secretion/inhibition

Question 10

What does this graph represent an increase of?

Answer 10

prolactin in pregnancy

Question 11

What does this graph represent?

Answer 11

Prolactin levels and suckling

Question 12

What happens to prolactin levels? (1) pregancy, 2) post-partum, 3) baby developing - breastfeeding established)

Answer 12

• increasing during pregnancy
• high post-partum (increased by suckling)
• levels relatively low once breast-feeding is established (80 days postpartum)

Question 13

• Lactational amenorrhoea refers to what?
• Contraceptive efficacy depends on what?

Answer 13

• The time period when a women is breast-feeding and her periods do not resume
• contraceptive efficancy depends on the frequency and duration of breast feeding

Question 14

• Increased prolactin levels have a supressive effect on all levels of what axis?
• What hormone levels decrease? (4)

Answer 14

• gonodal axis
• decreased LH and FSH productiona and pulsatility, decrease oestrogen and testosterone

Question 15

Oxytocin is a … amino acid peptide

Answer 15

• Oxytocin is a nine amino acid peptide

Question 16

Oxytocin is synthesised in hypothalamic … neurons which reside in the ….

• S… nucleus
• P… nucleus

Answer 16

Oxytocin is synthesised in hypothalamic magnicellular neurons which reside in the ….

• supraoptic nucleus
• paraventricular nucleus

Question 17

After oxytocin is synthesised, neurosecretory granules are released into the capillary system of the … …

This is where oxytocin is released from

Answer 17

posterior pituitary - where the distal axons of hypothalamic magnocellular neurons reside

Question 18

Regulation of oxytocin production

• Afferent signal from receptors in the nipple when the infant … ascend to …
• • uterine myometrial … at birth
• • … … activation in breast - ‘myoepithelial contraction’
• • … let-down

role in … behaviour?

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

Evolutionary perspective of lactation

• Mammals lactate
  
  • … strategy involves producing a nutritious secretion from an exocrine gland & encouraging offspring to consume it
  • continued nurturing of offspring … birth with benefits including enhanced … development
• Strategies for success:
  
  • milk …
  • complementary changes in the mother’s … - metabolic and psycho-social/ behavioural
  • same …

Answer 19

• 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 and psycho-social/ behavioural
  • same hormones

Question 20

Discovering pregnancy

• humans - take a …
• other mammals - brain responds to … changes associated with ovulation, mating, implantation and pregnancy - via … & placental …

Answer 20

• humans - pregnancy test
• other mammals - brain responds to hormonal changes associated with ovulation, mating, implantation and pregnancy - via prolactin & placental lactogens

Question 21

What is hyperprolactinaemia?

Answer 21

The presence of abnormally high levels of prolactin in the blood (unrelated to pregancy and breastfeeding)

Question 22

Presentation of Hyperprolactinaemia - Women

• What is the typical triad?

Answer 22

• oligo / amenorrhoea leading to an increased risk of osteoporosis
• galactorrhoea
• subfertility

They may not have all of these - may present after stopping contraceptive pill - coincidental

Question 23

Presentation of Hyperprolactinaemia - Men

• low testosterone levels may cause 2 things, what are they?
• is presentation earlier or later than women?
• what other 3 symptoms present?
• What is a rare presentation?

Answer 23

• low testosterone levels may cause erectile dysfunction or loss of libido
• presentation is later than women
• visual symptoms, headaches, hypopituitarism
• rare - galactorrhoea/gynaecomastia

Question 24

Causes of Hyperprolactinaemia

• physiological causes include … and …
• what disease can cause it?
• drugs
• stress
• other causes include P.., renal .., or hypo….

Answer 24

• physiological causes include pregnancy and lactation
• what disease can cause it - hypothalamic-pituitary disease (non-functioning adenoma, micro/macroprolactinoma)
• drugs
• stress
• other causes include PCOS, renal failure / cirrhosis or hypothyroidism (increased TRH)

Question 25

_Drugs that increase prolactin_ * Drugs used for n... and * Anti... and Anti...

Answer 25

* Drugs used for **nausea** and **vertigo (phenothiazines, metoclopramide, domperidone)** * Anti**psychotics** and Anti**depressants** * also others

Question 26

nausea and vertigo drugs (phenothiazines, metoclopramide, domperidone) and antidepressants/antipsychotics can increase what?

Answer 26

**prolactin**

Question 28

_Mechanisms of drugs that increase prolactin_ * inhibiton of secretion/action of ... (... antagonists or receptor blockers) * stimulation of ... ... pathways (... re-uptake inhibitors)

Answer 28

* inhibiton of secretion/action of **dopamine - DA antagonists or DA receptor blockers** * stimulation of **central serotonin (5HT)** pathways - 5HT re-uptake inhibitors

Question 29

_Investigations in hyperprolactinaemia_ * ... test * Renal ... (including ..&.. and c....) * Liver function tests * .. function * ... - repeat * Hormones - ... and ... * In men, test ... levels * after this - imaging - ... of pituitary (micro if what size? macro if what size?) * If they have a ... - test visual fields and rest of anterior pituitary function tests

Answer 29

* **pregnancy** test * Renal **function** (including **U&E & Creatinine**) * Liver function tests * .. function * ... - repeat * Hormones - ... and ... * In men, test ... levels * **MRI** of **pituitary** (micro if what size - **\<1cm** macro if what size **\> 1cm**) * Macroadenoma - visual fields, rest of anterior pituitary function tests

Question 30

_Aims of treatment - prolactinoma_ * restore ... * stop ... - also stop stimulation of ... * restore regular ... - women / ... mostly in men (can use exogenous oestrogen and testosterone - needed for protection of ...) * shrink the ... (if macro) to help recover function of ... and restore their ...

Answer 30

* restore **fertility** * stop **galactorrhoea - stop nipple stimulation** * restore regular **menstrual periods,** **libido** - men mainly (Can use exogenous oestrogen/testosterone - both are needed for bone protection) * shrink the **tumour if macro - restore vision and recover function of anterior pituitary**

Question 31

_Prolactinoma management 'medical'_ * ... drugs - such as cabergoline, bromocriptine * preserve ... function * side-effects -which are rare: ... reactions (pulmonary, pericardial, retroperitoneal), ... disturbances

Answer 31

* **dopaminergic** drugs - such as cabergoline, bromocriptine * preserve **pituitary** function * side-effects -which are rare: **fibrotic** reactions (pulmonary, pericardial, retroperitoneal), **psychiatric** disturbances

Question 32

_Microprolactinoma management_ * can take ... if fertility not required * can discontinue treatment in ... * may ... post-partum * can trial withdrawal of treatment after approximately ... years - may not recur

Answer 32

* can take **oral contraceptive** if fertility not required * can discontinue treatment in **pregnancy** * may **involute** post-partum * can trial withdrawal of treatment after approximately **2 years** - may not recur

Question 33

What is idiopathic hyperprolactinaemia?

Answer 33

assumed to be **microprolactinoma** too **small** to be detected **radiologically**

Question 34

_Non-functioning pituitary adenoma - can cause high ..._ * compression of the pituitary ... - leading to d... hyperprolactinaemia, may also occur with **...** masses * may need surgery and ... - space-occupying effects, risk loss of ... * prolactin will decrease with what drugs? * do we need to monitor it? if so, how?

Answer 34

* compression of the pituitary **stalk** - leading to **disconnection** hyperprolactinaemia - may also occur with **hypothalamic** masses * may need surgery and **radiotherapy - space occupying effects - risk loss of pituitary function** * prolactin will decrease with what drugs - **dopaminergic drugs** * do we need to monitor it - **yes - MRI scan and visual fields**

Question 35

_Case study : 63 year old women, abnormal CT head scan_ _What prolactinoma does she have?_

Answer 35

Macroprolactinoma - visual field affected greatly - compression on optic chiasm

Question 36

_Case study : 63 year old women, abnormal CT head scan_ * Is she hypothyroid, euthyroid, hyperthyroid? * TSH is normal - what does this tell us? (diagnosis?) * LH and FSH, what do these tell us?

Answer 36

* **Free T4** is low - **hypothyroid** (level is 7.1) * TSH normal - tells us that the patient does not have primary hypothyroidism - if it was, TSH would be very high - therefore pituitary problem **(secondary hypothyroidism)** * LH and FH low **- usually high due to ovarian failure - not high = pituitary problem**

Question 37

What are abnormal cortisol levels a sign of? (In which axis is there a problem)?

Answer 37

problem with hypothalamic pituitary adrenal axis

Question 38

What would have happened to prolactin levels between these MRI scans?

Answer 38

decreased

Question 39

* Are her prolactin levels elevated? * TSH normal? FT4 normal? * LH and FSH ? * Testo - ? SHBG - ? * **- taking oral contraceptive pill....** * **What is her diagnosis?**

Answer 39

* prolactin - Yes - upper limit of normal is around **500** * TSH and FT4 **normal** * LH and FSH - **suppressed** * Testo - normal SHBG - **very high** * **as she is taking pill - LH and FSH is low - not pituitary failure - oestrogen treatment suppresses these hormones**

Question 40

If fertility isnt relevant after diagnosis of a microprolactinoma, can the pill be continued?

Answer 40

yes - avoid nipple stimulation, but may require cabergoline to conceive - also discontinue if fall pregnant

Question 41

_Beth - 8 months of secondary amenorrhoea_ * negative pregancy tests * no regular medication * no PM Hx/ Family Hx of note * would like children but not yet * What is her possible diagnosis?

Answer 41

* prolactin moderately elevated (upper limit 500) * LH and FSH normal * TSH normal FT4 normal * scan shows non-functioning pituitary adenoma - stalk compressing optic chiasm - increases the prolactin level - not a macro, cells not making prolactin - it is non functioning - just being compressed

Question 42

non-functioning pituitary adenoma - what treatment?

Answer 42

* **transphenoidal hypophysectomy** - risk to vision with further growth * there is a risk to pituitary function - including future fertility prospects - would be amendable to treatment

Question 43

_​Carol - 48_ * Galactorrhoea * regular 4-week menstrual cycle * long Hx of depression and anxiety, meds include risperidone, trazodone, duloxetine (antipsychotic and antidepressant) * is her prolactin raised? LH/FSH? TSH? FT4? * whats the diagnosis?

Answer 43

* prolactin sustained and elevated * FSH and LH - levels normal for her age * TSH and FT4 - normal * pituitary - normal structure * result = medication-induced hyperprolactinaemia