Hereditary Endocrinopathy

Question 1

What types of tumors are associated with MEN1? (Hint: “3 P’s”

Answer 1

Parathyroid (100% by age 50), Pancreas (60%), Pituitary (40%)

Question 2

What skin findings can be associated with MEN1?

Answer 2

facial angiofibromas (85%), collagenomas (70%), lipomas (30%), cafe au laid macules (38%), confetti-like hypopigmented macules (6%), gingival papules (6%)

Question 3

What is the inheritance pattern and de novo rate of MEN1?

Answer 3

Autosomal dominant
10% de novo rate

Question 4

What are some managements for MEN1?

Answer 4

Subtotal/total parathyroidectomy (hyperparathyroidism)
Autotransplantation of parathyroid tissue (hyperparathyroidism)
Medical therapy or transsphenoidal surgery (pituitary tumors)
Medical therapy or surgery (gastro-entero-pancreatic tract tumors)
Thymectomy (carcinoid tumors)
Surgical removal for adrenocortical tumors

Question 5

What are the 3 subtypes of MEN2 syndrome?

Answer 5

MEN2A
FMTC (Familial medullary thyroid carcinoma)
MEN2B

Question 6

What is the gene, inheritance pattern, and de novo rate for MEN2A and MEN2B?

Answer 6

RET gene
Autosomal dominant
5% de novo in MEN2A
50% in MEN2B

Question 7

What percentage of people with MEN2 syndrome have MEN2A?

Answer 7

70-80%

Question 8

What are the clinical features of MEN2A?

Answer 8

95% have medullary thyroid carcinoma by early adulthood, 50% have pheochromocytoma, 20-30% get hyperparathyroidism

Question 9

What are the clinical features of FMTC?

Answer 9

100% get medullary thyroid carcinoma by middle age, no pheo or hyperparathyroidism

Question 10

What are the clinical features of MEN2B?

Answer 10

100% get medullary thyroid cancer by early childhood, 50% get pheochromocytomas, and it’s uncommon but unreported percentage for hyperparathyroidism.
Have distinctive facial appearance (marfanoid habitus, mucosal neuromas, prominent lips over time, neuromas of the eyelids)
40% get diffuse ganglioneuromatosis of GI tract
95% have RET mutation Met918Thr

Question 11

Describe paragangliomas

Answer 11

neuroendocrine tumors in the adrenal medulla or ganglia of sympathetic/parasympathetic nervous system

Question 12

Describe pheochromocytomas

Answer 12

neuroendocrine tumor located IN the adrenal gland

Question 13

What are some genes associated with pheo/PGL?

Answer 13

VHL, SDHD, SDHB, RET, ND1, SDHC, SDHA

Question 14

If a paraganglioma is in the parasympathetic system, what is expected?

Answer 14

Head/neck tumor, usually nonfunctional
Described as glomus tumors, includes carotid body paraganglioma, vagal paraganglioma, and jugulotympanic paraganglioma

Question 15

If a paraganglioma is in the sympathetic system, what is expected?

Answer 15

Extra-adrenal paraganglioma, typically functional
includes pelvic, abdominal, thoracic tumors, pheochromocytoma
produce catecholamines (fight or flight response)

Question 16

What are red flags for hereditary PGL/pheo?

Answer 16

Young age of diagnosis (under 45)
bilateral tumors
multifocal tumors
malignant paraganglioma (5-20% are malignant)
Family history of PGL/Pheo

Question 17

What role does maternal imprinting play in SDHD?

Answer 17

SDHD inherited from mother is silenced

Child who inherits SDHD variant from mom should not develop tumors, but if they inherit SDHD variant from dad then they are at risk to develop tumors.

Question 18

What are the management recommendations for PGL and Pheos?

Answer 18

No guidelines for asymptomatic carriers
Identify specialist for personalized surveillance plan (endocrinologist or oncologist)
Whole-body MRI every 2-3 years
Annual biochemical evaluation (blood or urine) suggested 5-10 years or 5 years before youngest diagnosis
Surgery is primary treatment for PGL/Pheo