pituitary tumours

Question 1

What are the anterior pituitary cells, their hormones, and their functioning tumours?

Answer 1

Lactotrophs - prolactin - prolactinoma. Gonadotrophs - LH/FSH - gonadotrophinoma. Somatotrophs - GH - acromegaly. Coritcotrophs - ACTH - cushings. Thyrotrophs - TSH - TSHoma

Question 2

What are functioning pituitary tumours?

Answer 2

tumours of cells in the pituitary

Question 3

How are pituitary tumours classified?

Answer 3

1. size - microadenoma <1cm, macroadenoma >1cm. Can sit in sella (sellar) or above sella (supra-sellar). Can invade cavernous sinus or not. Can compress optic chiasm or not.2. function - can secrete excess hormone (functioning adenoma) or not (non-functioning adenoma) 3. benign or malignant - most are benign. Mitotic index measured by Ki67 index - benign less than 3%.

Question 4

What is hyperprolactinaemia and what does it cause?

Answer 4

increased prolactin. Prolactin binds to prolactin receptors on kisspeptin neurones in hypothalamus inhibiting kisspeptin release which is needed for GnRH pulsatility, shutting off the GnRH axis and therefore causing decreased LH/.FSH/oestrogen/progesterone leading to amenorrhea, subfertility, decreased libido etc.

Question 5

What is the most common functioning pituitary adenoma?

Answer 5

prolactinoma

Question 6

What is prolactinoma and how is it diagnosed?

Answer 6

Tumour of lactotrophs leading to elevated prolactin. Prolactin >5000 mU/L –> proportional to tumour size

Question 7

How does prolactinoma present?

Answer 7

Galactorrhea, menstrual disturbance, decreased libido, subfertility

Question 8

What are other causes for a raised prolactin?

Answer 8

1. physiological - stress, exercise, nipple wall stimulation, venepuncture, breast-feeding/pregnancy. 2. pathological - primary hyperthyroidism, PCOS, CKD (excretion problem) 3. iatrogenic - SSRI, antipsychotics, anti-emetics, high dose oestrogen, opiates

Question 9

Why are false positives common with prolactin (serum) and what to do to overcome this?

Answer 9

1. venupunture stress - can increase prolactin - use cannulated series that takes measurements every 20 minutes with indwelling cannula –> usually should decrease over time, if it doesn’t problematic. 2. macroprolactin - usually prolactin is monomer but macroprolactin (sticky prolactin) is polymer form - prolactin + IGG complex - detected as elevated prolactin - need other method to distinguish

Question 10

how is prolactinoma diagnosed

Answer 10

Confirm elevated prolactin + pituitary MRI

Question 11

What is first line treatment for prolactinomas?

Answer 11

Medical treatment –> dopamine agonist (cabergoline) - to shrink prolactinoma and normalise serum PRL. Dose adjusted for tumour size.

Question 12

How do dopamine receptor agonists work?

Answer 12

Dopamine usually binds on D2 receptors on lactotrophs. Dopamine receptor agonists bind on D2 receptors on lactotrophs, inhibiting prolactin release.

Question 13

How does GH act/bind/cause?

Answer 13

GH can bind directly to body tissues for growth & dev, but also via IGF-1 made in liver (IGF-2 mostly fetal development) which can bind on receptors on body tissues for growth.

Question 14

What does increased GH cause in children and in adults and why?

Answer 14

In children causes gigantism because epiphyseal plate unfused. In adults causes acromegaly because physis is fused so affects soft tissue instead.

Question 15

How does acromegaly present and why?

Answer 15

Presents slowly with sweatiness, macroglossia, prognathism, increase in hand and feet size, CV problems (affects vasculature), hypertension, impaired glucose tolerance/diabetes mellitus (causes insulin resistance), increased prolactin, obstructive sleep apnoea and snoring

Question 16

How is growth hormone tumour diagnosed?

Answer 16

Serum GH and IGF1.oral glucose tolerance test - given glucose - failed suppression of GH confirms diagnosis (usually should decrease)

Question 17

why growth hormone tumours sometimes cause high prolactin?

Answer 17

Because GH tumours often have D2 receptors

Question 18

What is the first line treatment for GH tumours. What other treatments can be used and what are their side effects?

Answer 18

First line is surgery - trans-sphenoidal pituitary surgery. Can give treatments to shrink tumour - somatostatin analogues (ocreotide) but can switch off many pathways, dopamine agonsits (cabergoline) for the prolactinaemia or radiotherapy (slow)

Question 19

What is the difference between cushings syndrome and disease?

Answer 19

Cushings syndrome is elevated cortisol or other glucacortidoid. Cushings disease is due to corticotroph adenoma secreting ACTH

Question 20

What are the causes of cushings syndrome? How can they be separated?

Answer 20

1. ACTH dependent - (pituitary adenoma) functional corticotroph adenoma secreting ACTH, ectopic ACTH (lung cancer). 2. ACTH independent - exogenous steroid use or adrenal adenoma/carcinoma

Question 21

What are symptoms of cushings?

Answer 21

Fat pads, proximal myopathy, pruple striae, red cheeks, impaired glucose tolerance, bruising, pendulous abdomen, cns symtpoms (low mood)

Question 22

How is cushings diagnosed? What is cortisols biochemical feature and how is it different in cushings. What are other investigations?

Answer 22

sually cotisol is diurnal but in cushings it is not so it will constantly be high even at midnight. Give oral dexamethosone to try to switch off cortisol - normally will switch off but in cushings will not. Once elevated cortisol is confirmed, measure ACTH. If ACTH is high pituitary dependent so do pituitary MRI. ACTH independent steroid by mouth

Question 23

What are non-functioning pituitary adenomas and what can they present with and why? What is the treatment for it?

Answer 23

Pituitary adenomas that do not produce excess hormone but can damage surroudning structures. Can press on optic chiasm causing bitemporal hemianopia. Can present with hypopituitarism by affecting other pituitary cells from producing hormones. Can present with prolactin elevation as dopamine cant go down stalk. Treatment needed is trans-sphenoidal pituitary surgery for large tumours, especially if visual disturbances present.