genetics of endocrine

Question 1

what are monogenic disorders?

Answer 1

-disorders caused due to defect in a single gene

Question 2

what are polygenic disorders?

Answer 2

-disorders caused due to defect in multiple genes

Question 3

what are the 6 different patterns of monogenic inheritence?

Answer 3

• AD
• AR
• XLD
• XLR
• Y linked
• mitochondrial

Question 4

what does MEN1 affect (multiple endocrine noeplasia type 1)?

Answer 4

MAINLY 3 Ps
Pituitary
Parathyroid
Pancreas

angiofibromas= common!!

but can also have:

• gastric carcinoma
• thymic/ bronchial carcinoids
• adrenal

Question 5

is MEN1 autosomal dominant or recessive?

Answer 5

MEN1 is autosomal dominant inheritance

Question 6

what does MEN1 gene mutation typically result in?

Answer 6

-loss/reduced protein function

Question 7

is MEN 2 (multiple endocrine neoplasia type 2) autosomal dominant or recessive?

Answer 7

autosomal dominant

Question 8

what are the 2 types of MEN2 and which is more common?

Answer 8

MEN2a (more common)

MEN2b

Question 9

what type of cancer occurs in almost every patient with MEN2?

Answer 9

MTC

medullary thyroid cancer

Question 10

what mutation is associated with MEN2?

Answer 10

RET proto oncogene mutation

Question 11

what type of MEN is associated with pheochromocytoma?

Answer 11

MEN2

Question 12

what is neurofibromatosis type 1 characterised by?

Answer 12

• axillary freckling
• cafe au lait patches
• neurofibromas
• optic gliomas
• scoliosis

Question 13

what mutation causes neurofibromatosis type 1?

Answer 13

-mutation in NF1 gene

Question 14

what type of MEN is associated with parathyroid hyperplasia?

Answer 14

MEN2A and MEN1

Question 15

what is phaechromocytoma?

Answer 15

-a rare tumour of the adrenal medulla

Question 16

how may patients present if there is a MEN1 mutation causing a tumour in the parathyroid?

Answer 16

-may present with hypercalcaemia due to parathyroid hyperplasia

Question 17

how may patients present if they have a MEN1 mutation causing a pituitary adenoma?

Answer 17

• If affecting mammotrophs (prolactin cells) may present with hyperprolactinaemia
• if affecting somatotrophs may present with excess GH
• if affecting corticotrophins may present with excess cortisol through excess ACTH

Question 18

what is diagnostic criteria for MEN1 mutation?

Answer 18

-presence of two or more MEN1 tumour type

Question 19

what are some investigations done if suspected MEN1?

Answer 19

• serum calcium (to detect asymptomatic hypercalcaemia)
• CT or MRI
• unlike MEN2 there is no clear evidence of benefit of using DNA testing in general screening

Question 20

what is the management for parathyroid hyperplasia caused by MEN1 mutation?

Answer 20

PARATHYROIDECTOMY

-this is indicated when there are pathological features of excess PTH and raised Ca levels for example by osteopenia, nephroliathiasis (kidney stones) and symptomatic hypercalcaemia

Question 21

what is management for pituitary adenoma caused by MEN1 mutation?

Answer 21

both surgical and medical options available

Transsphenoidal surgery!

Question 22

what is the main cause of mortality in MEN1 mutations?

Answer 22

-pancreatic tumours :(

Question 23

what is the management for insulinomas?

Answer 23

• may be treated pharmacologically with diazoxide (inhibits insulin release)
• surgery

Question 24

what does diazoxide do?

Answer 24

inhibits insulin release

Question 25

what is the treatment for a gastrinoma?

Answer 25

- PPIs | - surgical excisions in those who do not maintain symptomatic relief

Question 26

what does MEN2A cause?

Answer 26

- phaechromocytoma - medullary thyroid cancer - parathyroid hyperplasia

Question 27

what does MEN2B cause?

Answer 27

- phaeochromocytoma - medullary thyroid cancer - neuroma and ganglioneuroma - marfanoid habitus

Question 28

how many phaechromocytoma present?

Answer 28

- sweating - increase BP - irregular HB - anxious (basically increase in adrenaline as it affects chromaffin cells in adrenal )glands

Question 29

how does medullary thyroid cancer typically present when there is a MEN2 mutation?

Answer 29

-bilateral and multifocal

Question 30

how is MEN2 diagnosed?

Answer 30

-if there is presence of two or more MEN2 tumours OR -if there is presence of RET oncogene mutation

Question 31

what should be done if someone is found to have a RET oncogene mutation?

Answer 31

- genetic testing of family | - screen patient and their family for tumours

Question 32

what should be done if someone presents with MTC (medullary thyroid cancer)?

Answer 32

-screen for other tumours associated with MEN2

Question 33

who is a prophylactic thyroidectomy offered to?

Answer 33

-patients with MEN2

Question 34

what is treatment for parathyroid hyperplasia in a patient with MEN2 mutation?

Answer 34

parathyroidectomy

Question 35

what is treatment for patient with phaechromocytoma due to MEN2 mutation?

Answer 35

- unilateral or bilateral adrenalectomy | - patients with adrenalectomy should be given synthetic glucocorticoids and mineralocorticoids

Question 36

what is the treatment for a patient with MEN2 mutation who has developed MTC?

Answer 36

-thyroidectomy and lymph node dissection