Endocrine syndromes

Question 1

Inheritance of MEN-1

Answer 1

Autosomal dominant
Mutation in tumour suppressor gene MEN-1
Codes for MENIN protein

Question 2

Manifestations of MEN-1

Answer 2

Primary hyperparathyroidism (in 90%)
Pancreatic neuroendocrine tumours (in 60-70%)
Pituitary tumours (in 20-30%)

Question 3

Types of pancreatic neuroendocrine tumours in MEN-1

Answer 3

Gastrinoma - most common, excess gastrin leads to increased acid production with oesophagitis, duodenal ulcers, diarrhoea

Insulinoma - second most common, fasting hypoglycaemia, raised insulin/c-peptide

Glucagonoma - hyperglycaemia, skin rash, stomatitis

VIPoma - watery diarrhoea, hypokalaemia, hypochlorydia, metabolic acidosis

Somatostatinoma - weight gain, diabetes, gallstones, steatorrhoea

Question 4

Causes of increased gastrin

Answer 4

Achlorydia
H2 antagonists
PPIs
Hypercalcaemia
Small bowel resection
Gastric outlet obstruction

Question 5

Inheritance of MEN-2

Answer 5

Autosomal dominant

Genetic mutation in RET proto-oncogene

Question 6

Manifestations of MEN-2a

Answer 6

Medullary thyroid cancer
Phaechromocytoma in 50%
Hyperparathyroidism

Question 7

Manifestations of MEN-2b

Answer 7

Medullary thyroid cancer - aggressive
Phaeochromocytoma
Mucosal neuromas - on tip of tongue
Marfanoid habitus

NO hyperparathyroidism

Question 8

Features of von Hippel Lindau

Answer 8

Autosomal dominant
Mutation in VHL tumour suppressor gene
Phaechromocytoma, renal cell carcinoma, islet cell tumour, hemangioblastoma of CNS

Question 9

Features of Neurofibromatosis Type 1

Answer 9

Autosomal dominant
Mutation in NF1
Neurofibromaa, cafe au lait spots, axillary and inguinal freckling, iris hamartomas, phaeochromocytoms in 2%

Question 10

Features of Carney syndrome

Answer 10

Mutation in PPKAR1a

Myxoma of heart, skin and breast, peripheral nerve schwanomma, pituitary tumours

Question 11

Features of Polyglandular autoimmune syndrome type1

Answer 11

Autosomal recessive
Also known as APECED - defect in AIRE gene which is important for T cell selection
Hypoparathyroidism, chronic mucocutaneous candidiasis, adrenal insufficiency, primary hypogonadism

Question 12

Features of polyglandular autoimmune syndrome type 2

Answer 12

More common than type 1
Polygenic inheritance, HLA-DR3/4
Adrenal insufficiency, autoimmune thyroid disease, primary hypogonadism, autoimmune hypophysitis
Myasthenia gravis, ITP, Sjogrens, vitiligo

Question 13

Features of crow-fukase syndrome (aka POEMS)

Answer 13

Polyneuropathy
Organomegaly
Endocrinopathy - T2DM, hypothyroidism, adrenal insufficiency
M-proteins - monoclonal bands
Plasmacytomas