Concept: MEN - Multiple Endocrine Neoplasia

Question 1

What is MEN - Multiple Endocrine Neoplasia?
How does it occur?
How is it diagnosed?

Answer 1

Tumour growth in endocrine glands of body
It is caused by the genetic mutation of 1 of 2 genes, MEN 1 or RET. You only need 1 to have the disease
Diagnosed via genetic testing

Note: MEN 1 typically prevents division while RET typically promotes. => mutation either disables MEN 1 or boosts RET

Question 2

What are the main endocrine glands of the body?

Answer 2

Pituitary (Ant and Post)
Thyroid
Parathyroid
Adrenal
Pancreas
(gonads kinda but not related here)

Question 3

What hormones are regulated by the anterior and posterior pituitary?

Answer 3

Anterior: TSH, ACH, FSH+LH, GH, Prolactin, Melanocyte-stimulating hormone
Posterior: ADH and Oxytocin
Note: Remember than an increase in one (e.g. prolactinoma) will cause decreased production in others. E.g. increase in TSH will cause hypomenorrhea because reduced FSH and LH. Boom!

Question 4

What hormones are produced by the thyroid gland?

Answer 4

Thyroid hormone and Calcitonin

Question 5

What is the function of calcitonin?

Answer 5

Reduces calcium in serum => Raised in hypercalcemia

Question 6

State the action of the Parathyroid hormone

Answer 6

Reduces Phosphate
Increases calcium => raised in hypocalcemia (by increasing calcium absorption in gut and increasing osteoclast activity => weak bones => Bone mineral disease) Just me flexin

Question 7

What hormones are produced by Adrenal glands?

Answer 7

Epinephrine and Norepinephrine (main for MEN)
Others: Cortisol, aldosterone

Question 8

Give the 4 main hormones produced by the pancreas and their main function

Answer 8

Insulin -> decreases glucose
Glucagon -> increases glucose
Gastrin -> increased HCL (thats why Gastrinoma/Zollinger Ellison syndrome, it is a neuroendocrine tumour of the pancreas and duodenum)
Vasoactive intestinal peptide -> Relaxes gut wall

Question 9

What is the most common tumour among the MEN population in general?

Answer 9

Parathyroid carcinoma

Question 10

What neoplasms are associated with MEN 1?
With MEN 2, 2A occurs 95% of the time and MEN 2B 5%. What neoplasms are associated with MEN 2A and 2B?

Answer 10

MEN 1: 3Ps Parathyroid, Pancreas, Pituitary
MEN 2A: Medullary thyroid cancer, Pheochromocytoma, Parathyroid
MEN 2B: Medulary thyroid cancer, Pheochromocytoma, Multiple Neuromas

Question 11

A patient with Parathyroid carcinoma presents to the OPD.
What are expected findings in bloods?
What genetic mutation might she have

Answer 11

Increased PTH => increased calcium => hypercalcemia (constipation, abdominal pain, loss of appetite + B symptoms)
Mutation to MEN 1 or RET causing MEN 1 or MEN2A respectively

Question 12

A patient with pancreatic carcinoma presents to OPD
What serology may be performed to detect pancreatic cancer? (outside RCSI)
What are expected blood findings?
What genetic mutation might she have?

Answer 12

CA19-9

Increased Amylase
If insulinoma, hypoglycemia
If Glucagonoma. hyperglycemia
If Gastrinoma, PUD, upper GI bleed etc…

Mutation to MEN 1 causing MEN 1

Question 13

A patient with pituitary adenoma presents to OPD
What are the 2 most common types of pituitary adenoma? What symptoms/clinical features might they present with for each?
What are some general symptoms/clinical features of any pituitary adenoma?
What genetic mutation might they have?

Answer 13

Prolactinoma: Galactorrhea, Gynacomastia, irregular menstruation, acne, vaginal dryness
GH adenoma: Gigantism in children and Acromegaly in adults

In general:
Neoplastic B symptoms: Pyrexia, Night seats, unintentional Weight loss
Mass Effect: Headache, nausea, vomiting, Diplopia, hemianopia, brain ischemia

Mutation to MEN 1 causing MEN 1

Question 14

A patient with a central neck mass presents to OPD. It is raised on swallowing. They have a family hx of MEN.
What genetic mutation is she likely to have?
What type of thyroid carcinoma is it likely to be? How would you confirm?

Answer 14

RET mutation causing either MEN 2A or MEN 2B

Medullary thyroid Ca, cancer of the parafollicular C cells => diagnosed via raised Calcitonin

Why dont these patients have hypocalcemia given calcitonin is raised and it reduces serum calcium? It is because of the activity on PTH which would balance it out well but nothing balances out the hyperthyroidism.

Question 15

What is Pheochromocytoma?
What hormones are elevated? What symptoms occur as a result?
What genetic mutation is associated with it?

Answer 15

Pheochromocytoma is an adenoma of the adrenal glands => increased NE and epinephrine => increased SNS activity => HTN, sweating, anxiety, diarrhea, palpitations, arrythmia, tachycardia
Mutation to RET causing MEN 2A or 2B

Question 16

Multiple neuromas is associated with what genetic mutation?
Where are these neuromas typically found?

Answer 16

RET mutation causing MEN 2B only
Typically on the tongue, lips, and roof of mouth