multiple endocrine neoplasia syndrome

Question 1

definition

Answer 1

hereditary tumour syndromes of various neoplastic patterns. characterised by development of multiple endocrine tumours e.g. parathyroid adenomas, pituitary adenomas, enteropancreatic neuroendocrine tumours, facial lipomas, facial angiofibromas, medullary thyroid cancers, phaechromocytomas

Question 2

signs and symptoms

Answer 2

Presenting complaints can include any of the symptoms of any of the characteristic tumours.

Pituitary adenomas may present with headaches and visual field defects, or symptoms related to anterior pituitary hormone excess including galactorrhoea, low libido and oligo/amenorrhoea (due to a prolactinoma), sweating and increased ring/shoe size with or without diabetes mellitus (due to acromegaly), central adiposity, easy bruising, slow wound healing, emotional lability, proximal myopathy with or without hypertension and/or diabetes mellitus (due to Cushing’s disease), or symptoms of anterior pituitary hormone deficiency (due to a non-functioning pituitary adenoma).

Phaeochromocytomas may present with episodic headaches, sweating, palpitations, and hypertension.

Pancreatic lesions are often asymptomatic and may present with symptoms of peptic ulceration and diarrhoea (gastrinomas), recurrent hypoglycaemia (insulinomas), or diabetes with or without a rash (glucagonoma).

Question 3

MEN1 and MEN2

Answer 3

MEN1 more common than MEN2

MEN1
tumours typically arise from mutations in the tumour suppressor gene MEN1, which encodes the protein menin.[1] Diagnosis is based on patients having 2 or more of the MEN1-associated tumours listed below, or 1 associated tumour and a first-degree relative with the condition, or on the basis of genetics alone with a diagnosed pathogenic mutation of MEN1.[
Endocrine:
Parathyroid adenomas
Pituitary adenomas
Gastrinomas and other enteropancreatic tumours
Neuroendocrine/carcinoid tumours from bronchial/gastric/thymic origin
Adrenal cortical tumours
CNS tumours, including meningiomas[1]
Thyroid tumours (although these may occur with similar frequency to the background population).[1]

Non-endocrine:
Cutaneous tumours
Lipomas
Facial angiofibromas.[2][3]
Primary hyperparathyroidism is commonly associated with MEN1. At least 90% of patients develop primary hyperparathyroidism by 50 years of age.[4][5]

MEN2
Tumours typically arise from RET proto-oncogene mutations causing medullary thyroid cancer and/or phaeochromocytoma. Subgroups of MEN2 include MEN2A, MEN2B, and familial medullary thyroid cancer.

Patients with MEN2A (also known as Sipple’s syndrome) may have:
Medullary thyroid cancer
Phaeochromocytoma
Multigland parathyroid adenomas with hyperparathyroidism
Hirschsprung’s disease as an associated feature
Cutaneous lichen amyloidosis as an associated feature.[2][6][7]

Patients with MEN2B may have:
Medullary thyroid cancer
Phaeochromocytoma
Marfanoid body habitus
Mucosal intestinal ganglioneuromatosis.

Question 4

explain the general areas affected by MEN 1 and MEN 2 simply

Answer 4

MEN 1

• adrenal cortex (aldosterone, cortisol, DHEAS)
• pituitary
• parathyroid
• gastrinoma

MEN 2

• phaeochromocytomas (adrenal medulla - A, NA)
• thyroid medullary (parafollicular cells)

Question 5

investigations

Answer 5

MEN 1

• serum prolactin
• 24hr urine calcium
• insulin like growth factor 1 (IGF-1) (pituitary releases growth hormones -> IGF 1 made in liver)
• fasting serum gastrin

MEN 2

• plasma metanephrine
• 24hr urinary metanephrine and catecholamines
• 24hr urine calcium
• thyroid biopsy
• serum carcinoembryonic antigen (up in medually thyroid cancer)
• calcitonin