Endocrine - Endocrine Syndromes

Question 1

What is MEN 1 associated with?

Answer 1

PARATHYROID ADENOMA (90%)

ENTEROPANCREATIC TUMOUR (30-70%)

PITUITARY ADENOMA (5-15%)

Question 2

What enteropancreatic tumours are seen in MEN1?

Answer 2

Gastrinoma:

• Zollinger Ellison Syndrome with elevated fasting serum gastrin levels
• although beware because hypercalcaemia also causes hypergastrinaemia

Insulinoma (10-30%):

• hypoglycaemic symptoms and weight gain
• elevated c peptide and proinsulin
• treat with octreotide

Glucagonoma (<3%)

• skin rashes (necrolytic migratory erythema), weight loss, anaemia and stomatitis
• treat with surgery, somatostatin analogues and 5-fluorocil

VIP-oma (<1%)
- present with watery diarrhoea, HYPOkalaemia and achlorhydria

Question 3

What non-pancreas/pituitary/parathyroid tumours are seen in MEN1?

Answer 3

Adrenocortical tumours (20-70%)
Lipoma (30%)
Meningioma (8%)
Facial angiofibroma (90%)

Question 4

What are the mutation and features of MEN2a?

Answer 4

Mutation in RET proto-oncogene

Pheochromocytoma (>50%)
Parathyroid adneoma (10-25%)
Medullary thyroid cancer (90%)

often with cutaneous lichen amyloidosis in upper back

Question 5

What are the mutation and features of MEN2b?

Answer 5

Mutation in RET proto-oncogene

Pheochromocytoma (>50%)
Medullary thyroid carcinoma (90%)
Marfanoid, mucosal neuromas and megacolon

Question 6

What are the mutation and features of MEN4?

Answer 6

Mutation in CDKN1B

Same as MEN1: pancreatic, parathyroid and pituitary

Associated tumours:

• gonadal
• renal
• adrenal
• thyroid

Question 7

Which MEN syndromes are associated with MEN1 gene?

Answer 7

MEN1

Question 8

Which MEN syndromes are associated with RET proto-oncogene?

Answer 8

MEN2a and MEN2b

Question 9

Which MEN syndromes is associated with CDKN1B mutation?

Answer 9

MEN4

Question 10

What are the demographic and genetic features of Autoimmune Polyendocrine Syndrome Type 1 (=APECED)

Answer 10

Early onset in infancy
Siblings often affected
M=F

Genetics:

• AIRE gene on Ch21
• Autosomal recessive

Question 11

Autoantibodies seen in Autoimmune Polyendocrine Syndrome Type 1 (=APECED)

Answer 11

Anti-type 1 IFN
Anti-IL17
Anti-IL22

Question 12

Features of Autoimmune Polyendocrine Syndrome Type 1 (=APECED)

Answer 12

Endocrine Features:

• Addison’s disease
• Hypoparathyroidism
• Hypogonadism
• Graves Disease
• Type 1 Diabetes

Non-Endocrine Features:

• Mucocutaneous candidiasis
• Chronic active hepatitis
• Pernicious anaemia
• Vitiligo
• Asplenism
• Ectodermal dysplasia
• Alopecia
• Malabsorption syndromes
• IgA Deficiency

Question 13

What are the demographic and genetic features of Autoimmune Polyendocrine Syndrome Type 2

Answer 13

Onset 20-60yrs
Multigenerational
F>M

Genes:
HLA-DR3 and DR4
MICA
PTNP22
CTLA4

Question 14

Features of Autoimmune Polyendocrine Syndrome Type 2

Answer 14

Endocrine features:

• Addison’s
• Type 1 diabetes
• Graves Disease
• Hypogonadism

Non-Endocrine Features:

• Coeliac disease
• Dermatitis herpetiformis
• Pernicious anaemia
• Alopecia
• Vitiligo
• Myaesthenia gravis
• IgA deficiency
• Parkinson’s Disease
• Idiopathic thrombocytopenia

Question 15

In what hereditary syndromes is pheochromocytoma seen?

Answer 15

MEN2A
MEN2B

Neurofibromatosis Type 1

Von-Hippel Lindau Disease
- mutated VHL with risk of pheo 10-20%

Familial Paraganglioma Syndrome
= carotid body catecholamine releasing tumour
- risk of pheo 20%
- mutated SDHB and SDHD

Question 16

What can precipitate pheochromocytoma symptoms?

Answer 16

NON-MEDICATIONS:
Exercise
Surgery
Pregnancy
Urination

MEDICATIONS:
Metoclopramide
TCAs
Opioids

Question 17

What biochemical tests do you use to investigate for pheochromocytoma?

Answer 17

Urine catecholamines/metanephrines

Plasma metanephrines
BUT lack specificity and sensitivity in:
- aging
- acute illness
- medications: TCAs, antipsychotics, alcohol, panadol

Question 18

How is pheochromocytoma treated?

Answer 18

MEDICAL:
Alpha blockade (phenoxybenzamine)

Beta blockade
(propranolol)

Crisis control
(phentolamine / nitroprusside)

SURGERY: removal