Prolactin + multiple endocrine neoplasia

What is the prolactin axis?

• dopamine inhibits prolactin secretion and thyrotropin releasing hormone stimulates prolactin release

What stimulates prolactin?

• nipple stimulation

• thyrotropin-releasing hormone

• elevated oestrogen during pregnancy

• stress

• sleep

What inhibits prolactin?

• dopamine inhibits secretion of prolactin

• progesterone inhibits effect of prolactin on breast tissue, hence why milk isn’t produced during pregnancy, but when progesterone levels fall after birth, prolactin can carry out it’s effects

What is the relevance of antipsychotics and prolactin?

Dopamine antagonists (e.g., antipsychotic medications) inhibit dopamine receptors, which can allow prolactin levels to rise, causing gynaecomastia (glandular breast tissue enlargement in males) and galactorrhea (breast milk production).

What are the actions of prolactin?

• stimulates milk production

• glandular breast tissue development

• inhibits GnRH from hypothalamus→ inhibiting FSH/LH→ causing amenorrhoea

What are the actions of oxytocin?

• oxytocin levels rise during pregnancy

• oxytocin inhibits dopamine promoting prolactin production

• stimulates uterine contraction

What is a prolactinoma?

benign pituitary adenoma secreting prolactin

How does hyperprolactinaemia present?

males- gynaecomastia, impotence loss of libido, galactorrhoea

females- amenorrhoea, galactorrhoea, infertility

How does hypothyroidism cause hyperprolactinaemia?

In hypothyroidism, low thyroid hormones mean reduced negative feedback on the hypothalamus, resulting in elevated thyrotropin-releasing hormone (TRH). This elevated TRH stimulates excessive prolactin release by the pituitary.

What can cause hyperprolactinaemia?

• pregnancy

• prolactinomas

• hypothyroidism

• dopamine antagonists

How is prolactinoma investigated?

bloods: high prolactin >5000mU/L

MRI pituitary

How is prolactinoma managed?

1. dopamine agonists, eg: cabergoline or bromocriptine

2. transsphenoidal surgery

What is a microprolactinoma?

<10mm on MRI

What is a macroprolactinoma?

<10mm MRI

What can cause hypoprolactinaemia?

Sheehan’s syndrome is a rare complication of postpartum haemorrhage, where the drop in circulating blood volume leads to avascular necrosis of the pituitary gland. Low blood pressure and reduced perfusion of the pituitary gland lead to ischaemia in the pituitary cells and cell death. It only affects the anterior pituitary gland. Hormones produced by the posterior pituitary (oxytocin and antidiuretic hormone) are spared

What is a multiple endocrine neoplasia syndrome?

autosomal-dominant disorder causing endocrine glands to grow benign, malignant or noncancerous growths

What is MEN 1?

three P’s

• parathyroid- hyperparathyroidism and raised calcium

• pituitary

• pancreas- insulinoma, gastrinoma )leading to peptic ulceration)

commonly presents with hypercalcaemia

What gene is affected in MEN 1?

MEN 1 on chromosome 11

What tissues are affected in MEN 2a?

• parathyroid (however less than 20% get raised calcium)

• pheochromocytoma

• medullary thyroid cancer

What gene is affected in MEN 2a/b?

RET proto-oncogene on chromosome 10

What tissues are affected in MEN2b?

• pheochromocytoma

• medullary thyroid

• Marfanoid habitus

• neuromas

How is MEN 1 investigated?

1. screening of 1st/2nd degree relatives

2. full gut hormone screen, serum calcium, serum prolactin, genetic mutation

What is a Marfanoid habitus?

• long limbs

• arachnodactyly

• high arched palate

• hyperlaxity- increased flexibility of joints

• crowded teeth

How is MEN managed?

genetic counselling and surgery to remove affected tissue