Lactation, galactarrhoea, prolactinomas

Question 1

Breast development: puberty

Answer 1

Oestrogen, progesterone

GH (via IGF-I)

• increased alveolar buds
• increased lobules

Question 2

Breast development: pregnancy

Answer 2

Oestrogen, progesterone

hCG, prolactin

Alveolar development

• increased ducts and lobules
• differentiated secretory units (acini)
• colostrium accumulates

Question 3

Milk production

Answer 3

Secretory initiation

• progesterone
• occurs during pregnancy
• colostrum

Secretory activation

• decreased progesterone/ oestrogen
• increased prolactin (cortisol, insulin)
• copious milk production after delivery

Question 4

Milk composition

Answer 4

Sugar
- lactose and oligosaccharides

Milk fats
- triglycerides, cholesterol, phospholipids, steroid hormone

Protein
- caseins, lactalbumin, lactoferrin, secretory IgA, lysozyme

Minerals
- Na, K, Cl, ,Ca, Mg, phosphate

Growth factors

Cellular components

• macrophages, lymphocytes, neutrophils, epithelial cells
• phospholipids

Question 5

Lactation (galactopoiesis)

Answer 5

Positive feedback loops

Regular removal of milk

Nipple stimulation

Prolactin (anterior pituitary)

Oxytocin (posterior pituitary)

Question 6

Prolactin

Answer 6

Lactotroph cells
- anterior pituitary

Similar to GH

Similar receptor to GH

• tyrosine phosphorylation
• JAK-STAT signalling

Question 7

Prolactin release

Answer 7

Inhibited by dopamine

Stimulated by 5HT (serotonin), TRH, oxytocin

Question 8

Increased prolactin leads to

Answer 8

Decreased GnRH

Decreased LH and FSH, decreased pulsatility

Decreased oestrogen/ testosterone

Question 9

Oxytocin

Answer 9

Nonapeptide

Synthesised in hypothalamic magnicellular neurons

• supraoptic nucleus
• paraventricular nucleus

Question 10

Oxytocin release

Answer 10

Posterior pituitary
- distal axon terminals of hypothalamic mangocellular neurons

Neurosecretory granules released into capillary system of posterior pituitary

Question 11

Oxytocin function

Answer 11

Afferent signal from receptors in the nipple when the infant suckles ascend to hypothalamus

Increased uterine contraction at birth

Increased smooth muscle activation in breast
- myoepithelial contraction

Increased milk let down

Question 12

The evolutionary perspective

Answer 12

Mammals lactate

• reproductive stratedy producing nutritious secretion from an exocrine gland
• continued nurturing of offspring after birth

Strategies for success

• milk production
• complementary changes in the mothers brain
• same hormones

Question 13

Hyperprolactinaemia presentation in women

Answer 13

Oligo/ amenorrhoea
- increased risk of osteoporosis

Galactorrhoea

Subfertility

May present after stopping the contraceptive pill (coincidental)

Question 14

Hyperprolactinaemia presentation in men

Answer 14

Erectile dysfunction

Decreased libido

Visual symptoms

Headaches

Hypopituitarism

Present later

Galactorrhoea/ gynaecomastia RARE

Question 15

Causes of hyperprolactinaemia

Answer 15

Physiological

• pregnancy
• lactation

Hypothalamic pituitary disease

• micro/ macroPRLoma
• non functioning adenoma

Drugs

Stress

Other

• polycystic ovarian syndrome
• hypothyroidism
• renal failure cirrhosis

Question 16

Drugs that increase prolactin

Answer 16

Antidepressants and antipsychotics

Drugs used for nausea and vertigo

• phenothiazines
• metoclopramide
• domperidone

Mechanism

• inhibition of secretion/ action of dopamine
• stimulation of central serotonin pathway s

Question 17

Investigations

Answer 17

Pregnancy test

Renal function (U&E, creatinine)

Liver function tests

Thyroid function

Prolactin

LH, FSH

Testosterone

MRI pituitary (micro, macro)

Macroadenoma (visual fields, rest of anterior pituitary function tests)

Question 18

Aims of treatment

Answer 18

Restore fertility

Stop galactorrhoea

Restore regular menstrual periods/ libido

• oestrogen/ testosterone needed for bone protection
• can use exogenous oestrogen/ testosterone

Shrink tumour

• recovery of anterior pituitary function
• restore vision

Question 19

PRLoma management (1)

Answer 19

Medical

Dopaminergic drugs

• cabergoline
• bromocriptine

Preserve pituitary function

Side effects (rare)

• fibrotic reactions (pulmonary, pericardial, retroperitoneal)
• psychiatric disturbances

Question 20

PRLoma management (2)

Answer 20

MicroPRLomas

• can take COCP? HRT if fertility not required
• can discontinue treatment in pregnancy
• may involute post-partum
• can trial withdrawal of treatment after 2 years

Idiopathic hyperPRLaemia
- assumed to be a microPRLoma too small to be detected radiogically

Question 21

Non functioning pituitary adenoma management

Answer 21

Compression of the pituitary stalk

• disconnection hyperPRLaemia
• may also occur with hypothalamic masses

May need surgery and radiotherapy

• space occupying effects
• risk loss of pituitary function

[Prolactin] will decrease with dopaminergic drugs
- need to monitor MRI scan and visual fields