Multiple endocrine neoplasia Flashcards
What is MEN?
Heridatary cancer syndrome, caused by rare autosomal dominant disorder - Can be sporadic
What systems do MEN affect and how?
Tumours or hyperplasias in 2 or more endocrine glands
What is the difference between MEN and sporadic endocrine tumours?
There is a collection of endocrine malignancies in MEN compared to sporadi
How is MEN screened for and why is it important?
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
What are the different classifications of MEN?
MEN1 (wermers syndrome)
MEN2A (Sipple syndrome)
MEN2B
MEN2 - familial medullary thyroid cancer
Match the gene mutated to correct MEN
- MEN1
- MEN2
A.RET
B.MENIN
1B, 2A
- Loss of function mutation of a tumour suppressor causing unregulated growth
- Activation mutation of a proto-oncogene causing activation of RTKs- uncontrolled growth
Describe the parts of the endocrine affected in MEN1
Neoplastic lesion in pituitary (adenoma), parathyroid and the pancreatic islet cells (neuroendocrine tumours).
State the non-endocrine features of MEN1
lipomas, angiofibromas, collagenomas
What three catagories are assessed to diagnose MEN1
Clinical, familial and genetic
What is the clinical evaluation in MEN1?
Whether a patient presents with 2 or more MEN-1 associated tumours
What is the familila part of diagnosing MEN1?
whether there is a first degree relative with MEN1
What is the genetic basis for diagnosing MEN1+
If individual carries the mutation without any clinical manifestation
What is the most common biochemical features of MEN1?
- (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
What is the order of enteropancreatic endocrine tumour prevelance?
- 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
What is the manifestation, diagnosis and treatment of gastrinomas?
- 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
What is the manifestation, diagnosis and treatment of insulinoma?
- 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
What is the screening and treatment of enteropancreatic neuroendocrine tumours?
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
What hormones can be secreted in a pituitary tumour?
- Prolactin(65%)
- GH 25%
- ACTH 5% (cushings)
- non-functioning (10%)
What is the most common pituitary tumour?
Adrenal lesions, but do not require treatment as it is non-functioning
What is ectopic secretion?
Ectopic (inappropriate secretion of hormones by tissues that do not usually produce that hormone), e.g. due to carcinoid tumours
What is the manifestation and diagnosis of pituitary tumours?
Same as for non-MEN pituitary tumours
What screening is required for MEN pituitary tumours?
Annual measurement of prolactinand IGF-1. MRI 3-5 years
What is the treatment for MEN pituitary tumours?
- Dopamine agonists for prolactin
- Ocreotide/lanreotide for GH
- Transsphenoidal surgery
Describe gastric carcinoid in MEN1
Typically found in foregut (carcinoids).
- Non-functioning
- Thymic carcinoids are particularly aggressive and requires screening - requires surgery
- Discovery is of gastric carcinoids are indcidentally
What tools/investigations are used in diagnosing gastric carcinoid?
- 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
What is the treatment of gastric carcinoid?
In advanced cases surgery and radio+chemo is necessary
Screening for MEN1 requires what
Biochemical
- calcium, prolactin, gastrin and chromogranin A
Genetic
- screen germline mutations of MEN1 in patients with a first degree relative with MEN1
What is the similarities and difference between MEN2A and B?
Similarities
- both tend to develop medullary cell carcinomas and phaeochromocytomas
Differences
- MEN2A: parathyroid tumours
- MEN2B: Marfanoid habitus, mucosal neuromas, and skeletal abnormalities
What is present at diagnosis of all MEN2 patients?
Presence of a medullary thyroid carcinoma
Describe the tumour formation in MEN2A
The development of phaeocytochromas occurs in 50% of patients and tend to be bilateral, whereas parathyroid adenomas develop in 25% of patients
What two variants of MEN2A exist?
Cutaneous lichen amyloidosis and Hirschsprung’s disease.
What do MEN2B present with?
Aspects of marfanoid habitus, hallmark mucosal neuromas.
What tumours develop in MEN2B and what is their onset?
MTCs form at 12months - require prophylactic removal due to aggressiveness
Phaeochromocytoma onset is earlier than 2A
Where do MTC manifest?
Parafollicular C-cells of the thyroid, secreting calcitonin
- Least aggressive form is familial MTC and most aggressive is MEN2B
What are clinical features of MTC?
thyroid nodule or goitre, diarrhoea and flushing
How can MTC cause adrenal dysfunction?
Amyloid deposition
Describe the MTC diagnosis
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
How is FNA cytology used in MTC diagnosis?
To exclude malignancy - on thyroid nodules
Treatment of MTC
Surgical resection at the hyperplasia stage, suppression with thyroxine and follow up with calcitonin and CEA measurement.
Describe phaeochromocytomas
Tumour of adrenal medulla (chromaffin cell) capable of producing mass amounts of catecholamines, metanephrines or methoxytyramine. Often asymptomatic
Diagnose phaeochromocytomas
using plasma or urine metanephrines. Then localisation using MRI, CT and scintigraphy is appropriate
Treatment of phaeochromocytomas
surgery after alpha and beta blockade (without the blockade the potential of bursting adrenal medulla can cause death)
Describe parathyroid disease in MEN2A
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
What screening is done for MEN2?
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
In diagnosing what is an inappropriate PTH?
If calcium is above ref range then PTH should be low due to serum calciums negative feedback on PTH secretion
Test for phaeo
plasma or urine metanephrines
Test for MTC
Calcitonin measurement
Test for enteropancreatic neuroendocrine tumours
fasting gut hormones and glucose
Test for pituitary tumour
Hormone panel
Test for foregut carcinoma
5HIAA and ChrA
Test for hyperparathyroidism
PTH and calcium
