Multiple endocrine neoplasia

Question 1

What is MEN?

Answer 1

Heridatary cancer syndrome, caused by rare autosomal dominant disorder - Can be sporadic

Question 2

What systems do MEN affect and how?

Answer 2

Tumours or hyperplasias in 2 or more endocrine glands

Question 3

What is the difference between MEN and sporadic endocrine tumours?

Answer 3

There is a collection of endocrine malignancies in MEN compared to sporadi

Question 4

How is MEN screened for and why is it important?

Answer 4

Requires family screening to determine the heridatary consequences in a family. It is important to treat MEN early as they tend to metastasis at a greater rate

Question 5

What are the different classifications of MEN?

Answer 5

MEN1 (wermers syndrome)
MEN2A (Sipple syndrome)
MEN2B
MEN2 - familial medullary thyroid cancer

Question 6

Match the gene mutated to correct MEN

1. MEN1
2. MEN2

A.RET
B.MENIN

Answer 6

1B, 2A

1. Loss of function mutation of a tumour suppressor causing unregulated growth
2. Activation mutation of a proto-oncogene causing activation of RTKs- uncontrolled growth

Question 7

Describe the parts of the endocrine affected in MEN1

Answer 7

Neoplastic lesion in pituitary (adenoma), parathyroid and the pancreatic islet cells (neuroendocrine tumours).

Question 8

State the non-endocrine features of MEN1

Answer 8

lipomas, angiofibromas, collagenomas

Question 9

What three catagories are assessed to diagnose MEN1

Answer 9

Clinical, familial and genetic

Question 10

What is the clinical evaluation in MEN1?

Answer 10

Whether a patient presents with 2 or more MEN-1 associated tumours

Question 11

What is the familila part of diagnosing MEN1?

Answer 11

whether there is a first degree relative with MEN1

Question 12

What is the genetic basis for diagnosing MEN1+

Answer 12

If individual carries the mutation without any clinical manifestation

Question 13

What is the most common biochemical features of MEN1?

Answer 13

• (P) Hyperparathyroidism: common resulting in inappropriate secretion of PTH(hyperglycaemia)
• Hyperglycaemia can manifest in bones, stonesa and moans, poluria, polydipsia
• Investigated by measuring Ca and PTH
• Treat by parathyroidectomy

Question 14

What is the order of enteropancreatic endocrine tumour prevelance?

Answer 14

• Second most common
• Order of prevalence is gastrinoma > Insulinoma > VIPoma > Glucagonoma
• Gastrinoma has the highest associated with the highest increase to morbidity and mortality- due to high propensity to metastasise

Question 15

What is the manifestation, diagnosis and treatment of gastrinomas?

Answer 15

• Manifest as ulcers, diarrhoea and steatorrhoea
• Diagnosis is a plasma gastrin of >114pmol/L+ localisation using somatostating scintigraphy
• Treatment is surgery, PPI, H2 histamine receptor antagonists or chemotherapy

Question 16

What is the manifestation, diagnosis and treatment of insulinoma?

Answer 16

• Typically symptomatic
• Hypoglycaemia: oversecreting insulin
• Diagnosed by unsuppressed insulin with hypoglycaemia and raised C-PEP, low beta-hydroxylation using a 72h fast
• Treat by surgery, diazoxide, or somatostatin analogues

Question 17

What is the screening and treatment of enteropancreatic neuroendocrine tumours?

Answer 17

Biochemically
- annual fasting gut hormones and glucose
Imaging
- annual MRI/CT/endoscopic US

Treatment
- surgery or biotherapies like PPI, H2 histamine receptor antagonist, targeted radionuclide therapy

Question 18

What hormones can be secreted in a pituitary tumour?

Answer 18

• Prolactin(65%)
• GH 25%
• ACTH 5% (cushings)
• non-functioning (10%)

Question 19

What is the most common pituitary tumour?

Answer 19

Adrenal lesions, but do not require treatment as it is non-functioning

Question 20

What is ectopic secretion?

Answer 20

Ectopic (inappropriate secretion of hormones by tissues that do not usually produce that hormone), e.g. due to carcinoid tumours

Question 21

What is the manifestation and diagnosis of pituitary tumours?

Answer 21

Same as for non-MEN pituitary tumours

Question 22

What screening is required for MEN pituitary tumours?

Answer 22

Annual measurement of prolactinand IGF-1. MRI 3-5 years

Question 23

What is the treatment for MEN pituitary tumours?

Answer 23

• Dopamine agonists for prolactin
• Ocreotide/lanreotide for GH
• Transsphenoidal surgery

Question 24

Describe gastric carcinoid in MEN1

Answer 24

Typically found in foregut (carcinoids).

• Non-functioning
• Thymic carcinoids are particularly aggressive and requires screening - requires surgery
• Discovery is of gastric carcinoids are indcidentally

Question 25

What tools/investigations are used in diagnosing gastric carcinoid?

Answer 25

- 5HIAA and chromogranin A are useful follow ups but do not serve as a diagnostic tool - CT/MRI of the chest is required annually + gastroscopic examination - Biopsy every 3 years if evidence for hypergastrinaemia

Question 26

What is the treatment of gastric carcinoid?

Answer 26

In advanced cases surgery and radio+chemo is necessary

Question 27

Screening for MEN1 requires what

Answer 27

Biochemical - calcium, prolactin, gastrin and chromogranin A Genetic - screen germline mutations of MEN1 in patients with a first degree relative with MEN1

Question 28

What is the similarities and difference between MEN2A and B?

Answer 28

Similarities - both tend to develop medullary cell carcinomas and phaeochromocytomas Differences - MEN2A: parathyroid tumours - MEN2B: Marfanoid habitus, mucosal neuromas, and skeletal abnormalities

Question 29

What is present at diagnosis of all MEN2 patients?

Answer 29

Presence of a medullary thyroid carcinoma

Question 30

Describe the tumour formation in MEN2A

Answer 30

The development of phaeocytochromas occurs in 50% of patients and tend to be bilateral, whereas parathyroid adenomas develop in 25% of patients

Question 31

What two variants of MEN2A exist?

Answer 31

Cutaneous lichen amyloidosis and Hirschsprung’s disease.

Question 32

What do MEN2B present with?

Answer 32

Aspects of marfanoid habitus, hallmark mucosal neuromas.

Question 33

What tumours develop in MEN2B and what is their onset?

Answer 33

MTCs form at 12months - require prophylactic removal due to aggressiveness Phaeochromocytoma onset is earlier than 2A

Question 34

Where do MTC manifest?

Answer 34

Parafollicular C-cells of the thyroid, secreting calcitonin | - Least aggressive form is familial MTC and most aggressive is MEN2B

Question 35

What are clinical features of MTC?

Answer 35

thyroid nodule or goitre, diarrhoea and flushing

Question 36

How can MTC cause adrenal dysfunction?

Answer 36

Amyloid deposition

Question 37

Describe the MTC diagnosis

Answer 37

By biochemical or genetic screening or imaging Biochemical - calcitonin measure of >200ng/ml with pentagastrin stimulations (rise <10ng/ml is normal, >100 consistent with C-cell hyperplasia, >200MTC) - CEA (carcinoembryonic antigen measurement) Genetic - RET germ line mutation screen Imaging - ultrasound - metastasises= CT/MRI, seestamibi or scintigraphy

Question 38

How is FNA cytology used in MTC diagnosis?

Answer 38

To exclude malignancy - on thyroid nodules

Question 39

Treatment of MTC

Answer 39

Surgical resection at the hyperplasia stage, suppression with thyroxine and follow up with calcitonin and CEA measurement.

Question 40

Describe phaeochromocytomas

Answer 40

Tumour of adrenal medulla (chromaffin cell) capable of producing mass amounts of catecholamines, metanephrines or methoxytyramine. Often asymptomatic

Question 41

Diagnose phaeochromocytomas

Answer 41

using plasma or urine metanephrines. Then localisation using MRI, CT and scintigraphy is appropriate

Question 42

Treatment of phaeochromocytomas

Answer 42

surgery after alpha and beta blockade (without the blockade the potential of bursting adrenal medulla can cause death)

Question 43

Describe parathyroid disease in MEN2A

Answer 43

Majority are hyperplasias picked up during MTC surgery. Asymptomatic with limited biochemical features, except hypercaliuria - Diagnose like in MEN1: screening using annual Ca and PTH levels

Question 44

What screening is done for MEN2?

Answer 44

Genetic analysis is required - RET gene mutation screen MTC - screen anually till 40 in MEN2A and FMTC - MEN2B require thyroidectomy before 6M Phaeo - Screen every 2 years Hypoparathyroidism - Screen every 2 years MEN2A

Question 45

In diagnosing what is an inappropriate PTH?

Answer 45

If calcium is above ref range then PTH should be low due to serum calciums negative feedback on PTH secretion

Question 46

Test for phaeo

Answer 46

plasma or urine metanephrines

Question 47

Test for MTC

Answer 47

Calcitonin measurement

Question 48

Test for enteropancreatic neuroendocrine tumours

Answer 48

fasting gut hormones and glucose

Question 49

Test for pituitary tumour

Answer 49

Hormone panel

Question 50

Test for foregut carcinoma

Answer 50

5HIAA and ChrA

Question 51

Test for hyperparathyroidism

Answer 51

PTH and calcium