Monogenetic Non-Diabetic Endocrine Syndromes Flashcards
MEN1, MEN2
What are the three main tumour sites involved in MEN Type 1?
(1) Parathyroid glands
(2) Pancreas (gastroenteropancreatic tract)
(3) Anterior pituitary
What is the inheritance pattern of MEN1?
Autosomal dominant
Which gene is mutated in MEN1 and on what chromosome is it located?
MEN1 gene on chromosome 11q13
What is the classic triad for MEN1?
“3 Ps” – Pituitary, Parathyroid, Pancreas
What type of pancreatic tumour is commonly seen in MEN1?
Insulinoma
What are the leading causes of death in MEN1 patients?
- Malignant pancreatic neuroendocrine tumours
- Thymic carcinoids
When should genetic testing for MEN1 be considered?
(1) When the patient has ≥2 MEN1-associated tumours
(2) A family history of MEN1
(3) Suspicious clinical features
(4) or is a first-degree relative of someone with a known MEN1 mutation.
By what age should asymptomatic individuals at risk be tested for MEN1?
By age 5
What is the primary goal of MEN1 management?
To prevent early morbidity and mortality from MEN1-associated tumours while preserving quality of life
What genetic mutation causes MEN Type 2?
RET proto-oncogene mutation on chromosome 10q
= autosomal dominant
What are the two main subtypes of MEN Type 2?
MEN2A (Sipple syndrome) and MEN2B
What is unique to MEN2A compared to MEN2B?
Parathyroid hyperplasia
What tumours are common to both MEN2A and MEN2B?
Medullary thyroid cancer (MTC) and phaeochromocytoma
What is unique to MEN2B compared to MEN2A?
(1) Mucosal neuromas
(2) Marfanoid habitus
(3) Medullated corneal fibres
(4) Intestinal autonomic ganglion dysfunction
Which subtype of MEN2 is more common?
MEN2A
What is the typical first manifestation of MEN2?
Medullary thyroid cancer (MTC)
What are the symptoms of metastatic MTC?
Neck mass, diarrhoea, flushing, and ectopic ACTH (not common)
= Cushing’s syndrome
How is MEN2-associated pheochromocytoma typically present?
- Often bilateral
- May occur in childhood
- Diagnosed by elevated plasma or urinary metanephrines
What is the management of pheochromocytoma in MEN2?
Surgical resection with pre-operative alpha blockade
How common is primary hyperparathyroidism in MEN2?
Occurs in about 30% of patients, especially in MEN2A
What is the significance of early RET mutation testing in MEN2?
Allows early detection and prophylactic treatment (eg, thyroidectomy)
= which can prevent morbidity and mortality from MTC
What kind of RET mutations are seen in MEN2B?
Usually de novo activating point mutations in the catalytic domain of the RET enzyme
Which gene is responsible for MEN type 2?
RET gene
Which 4 abnormalities occur in MEN2B?
- Medullary thyroid cancer
- Mucosal neuromas
- Marfanoid habitus
- Phaeochromocytoma
What is the gene responsible for MEN type 1?
MEN1 gene
A 50-year-old woman is referred to the ENT surgeon to screen her for thyroid cancer. She is the sister of a patient recently diagnosed with medullary thyroid cancer. The family history is suggestive of familial medullary thyroid cancer as 2 other first-degree relatives are also affected. She is otherwise clinically well and looks normal
An ultrasound suggests malignant features and a FNAC confirms the diagnosis
The patient reports to the ENT Doctor that she has been experiencing sweats, flushing and palpitations recently. She is referred to the Endocrinologists for further investigation
What test should be done next?
Plasma metanephrines
Likely MEN2
The best test with the highest sensitivity for picking this up is a plasma metapnephrines test. Once the diagnosis is confirmed genetic testing for the RET proto-oncogene should also take place
MEN-1 is associated with what?
- parathyroid hyperplasias
- adenomas
- gastrinomas
- insulinomas
- prolactinomas
A 26-year-old male with a history of medullary thyroid cancer in childhood presents to A&E with a one-month history of intermittent palpitations, sweating, nausea and flushing. He is otherwise fit and well and does not drink alcohol or take any recreational drugs. There is a strong family history of thyroid cancer
On examination, he is flushed and his blood pressure is 190/95 mmHg. Bloods show a calcium level of 3.00 mmol/L
What is the most likely underlying diagnosis?
Multiple Endocrine Neoplasia-2a (MEN2A)
A 30-year-old male presents to A&E after his partner found him at home drowsy, confused and verbally aggressive. He has had two similar episodes in the last month after going to the gym. She reports he previously had surgery on a gland in his neck and takes cholecalciferol, calcium carbonate and cabergoline
On arrival, his capillary blood sugar is 2.5mmol/L which improves with treatment. A C-peptide is sent, paired with a serum glucose of 2.0mmol/L, and the result is in the normal range. Other investigations are normal.
What is the most likely diagnosis?
Multiple Endocrine Neoplasia type 1
An 18-year-old male presents with a lump on his neck, which he notices while shaving
On examination, it is noted that the patient is particularly tall and thin with arachnodactyly and a high-arched palate. He has mucosal neuromas on the lips, tongue, and eyelids. A 2cm thyroid nodule is palpable
Which hormone is likely to be elevated in this case and why?
Calcitonin
= This patient has clinical signs typical of type 2 multiple endocrine neoplasia (MEN2). MEN2 is caused by autosomal-dominant mutations that can be inherited or occur sporadically. Tumours typically arise from RET proto-oncogene mutations causing medullary thyroid cancer and/or phaeochromocytoma
A 35-year-old man presented with a history of recurrent peptic ulcers and hypercalcaemia
Genetic testing revealed a mutation in a tumour suppressor gene on chromosome 11
What is the most likely diagnosis?
Multiple Endocrine Neoplasia Type 1 (MEN 1)
A 32-year-old woman is admitted with haematemesis. She has a one-year history of recurrent peptic ulceration which has been unresponsive to ranitidine and omeprazole. She also complains of a milky white discharge from her breasts, and excessive thirst and urination. Endoscopy reveals a 3cm, actively bleeding ulcer in the duodenum. Blood tests reveal hypercalcaemia.
What is the most likely diagnosis?
MEN1
