Disease Profiles: Monogenetic Non-Diabetic Endocrine Syndromes

Question 1

What is McCune-Albright Syndrome?

Answer 1

Mosaic disease arising from a post-zygotic somatic GNAS mutation; results in constitutive adenylyl cyclase signalling and overproduction of several hormones

Question 2

What is primary pigmented nodular adrenocortical disease

Answer 2

Form of bilateral adrenocortical hyperplasia which can lead to Cushing’s, often occurs in association with Carney complex

Question 3

What is a prophylactic option for a MEN2 patient?

Answer 3

‘Prophylactic’ thyroidectomy in RET mutation carriers, timing of surgery depends on risk status of RET mutation

Question 4

Describe the musculoskeletal manifestations of NF1

Answer 4

Distinctive osseous lesion e.g. sphenoid dysplasia or thinning of long bone cortex, with or without pseudoarthrosis

Scoliosis

Question 5

What is Multiple Endocrine Neoplasia Type 1?

Answer 5

Autosomal dominant mutation resulting in loss or reduced protein function of MEN1 gene - code for a tumour suppressor in endocrine tissues

Question 6

Which form of malignancy is typically the first manifestation of MEN2?

Answer 6

Medullary thyroid cancer

Question 7

Which form of MEN typically causes medullary thyroid cancer, pheochromocytoma and parathyroid tumours?

Answer 7

MEN2a

Question 8

Describe the pathophysiology of MEN2

Answer 8

RET mutations result in activation of receptor tyrosine kinase

Question 9

Describe the cutaneous manifestations of NF1

Answer 9

Cafe-au-lait macules, neurofibromas, axillary or inguinal freckling

Question 10

Describe the ocular manifestations of NF1

Answer 10

Lisch nodules, optic glioma

Question 11

What is Carney Complex?

Answer 11

Rare genetic disorder caused by a PRKAR1A mutation; characterized by multiple neoplasia most often affecting the heart, skin and endocrine system and abnormalities in skin pigmentation

Question 12

Which forms of tumours have been associated with NF1, MEN2a, VHL, and succinate dehydroxinate enzyme mutations?

Answer 12

Pheochromocytoma and paraganglioma

Question 13

What is Multiple Endocrine Neoplasia Type 2?

Answer 13

Autosomal dominant RET gene mutation - proto-oncogene

Question 14

How would you manage primary hyperparathyroidism in MEN2?

Answer 14

Surgical removal of enlarged/overactive parathyroid glands

Question 15

What is Neurofibromatosis Type 1?

Answer 15

NF1 gene mutation which results in tumours along the nervous system

Question 16

Describe the clinical presentation of McCune-Albright Syndrome

Answer 16

Cafe-au-lait skin pigmentation

Polyostotic fibrous dysplasia

Precocious puberty (typically females)

Thyroid nodules

GH excess

Cushing’s syndrome

Question 17

Which form of MEN typically causes MTC and pheochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibres, and intestinal autonomic ganglion dysfunction?

Answer 17

MEN2b

Question 18

What is Von Hippel-Lindau (VHL) syndrome?

Answer 18

Autosomal dominant mutation in VHL gene which leads to accumulation of HIF proteins and stimulation of cellular proliferation, resulting in a range of vascular tumours

Question 19

What determines the timing of the development of medullary thyroid carcinoma in a MEN2 patient?

Answer 19

Determined by specific RET mutation - different variations are associated with different risk levels and earlier or later diagnosis

Question 20

Which form of MEN typically causes parathyroid, pituitary and enteropancreatic tumours?

Answer 20

MEN1