Transcript MEN II-A

Multiple Endocrine Neoplasia
MEN I/MEN II
Todd A. Nickloes, DO, FACOS, FACS
Associate Professor
Division of Trauma/Critical Care
Department of Surgery
University of Tennessee Medical Center-Knoxville

MEN I
◦ Involves the 3 P’s
 Pituitary
 Parathyroid
 Pancreatic islet cells

MEN II
◦ MEN II-A
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Parathyroid hyperplasia
◦ MEN II-B




Medullary carcinoma of thyroid
Pheochromocytoma
Ganglioneuromatosis (mucosal neuromas)
Marfanoid habitus
MEN I/MEN II

MEN I
◦ Involves the 3 P’s
 Pituitary
 Parathyroid
 Pancreatic islet cells

MEN II
◦ MEN II-A
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Parathyroid hyperplasia
◦ MEN II-B




Medullary carcinoma of thyroid
Pheochromocytoma
Ganglioneuromatosis (mucosal neuromas)
Marfanoid habitus
MEN I/MEN II

MEN I
◦ Involves the 3 P’s
 Pituitary
 Parathyroid
 Pancreatic islet cells
MEN I

Parathyroid
◦ Hyperparathyroidism occurs in over 90% of pts.
 Typically first detectable abnormality
 Nephrolithiasis/Hypercalcemia
◦ Usual presentation:
 25-35 y/o presents with predominantly urinary complaints
◦ Nephrolithiasis
◦ Polyuria
◦ Hypercalcemia
◦ Muscle weakness
◦ Anorexia/Nausea
 Not as in primary hyperparathyroidism (more on this later)
◦ Postmenopausal women
◦ Nephrolithiasis
◦ Hypertension
◦ Osteoporosis
◦ Emotional disturbances
MEN I

Parathyroid
◦ This is a multi-glandular process
 Diffuse hyperplasia
 Metachronous development of multiple adenomas
 4 gland enlargement
◦ Not as in primary HPT
◦ Single adenoma
 Preop sestimibi will reveal diffuse glandular involvement
MEN I

Parathyroid
◦ Autosomal dominant
 Genetic testing
◦ Found on MENIN gene
◦ Chromosome 11q13
 Family screening
◦ should be accomplished on 1st degree relatives
◦ early teen years
◦ Include serum
◦ Calcium
◦ Glucose
◦ Gastrin
Fasting Insulin
Pancreatic Polypeptide
Growth Hormone
VIP
Prolactin
b-human Gonadotropin
◦ Annual calcium screening should occur in 1st degree relatives
MEN I
◦ Parathyroid
 There is no curative operation
◦ Preferred corrective strategy employs 3.5 gland excision
◦ Optional total parathyroidectomy with autotransplantation to forearm
◦ Achieves cure > 90% of cases
◦ Recurrent hyperparathyroidism
 after autotransplantation to forearm ~ 50% recurrence
 Resection of autotransplanted material
 Hypoparathyroidism postop occurrence < 5%
 Treated with oral supplementation
MEN I

MEN I
◦ Involves the 3 P’s
 Pituitary
 Parathyroid
 Pancreatic islet cells
MEN I

Pituitary
◦ Occur in 40% of MEN I pts
 Most commonly benign prolactin secreting adenomas
 May produce
◦ Growth hormone
◦ ACTH
◦ rarely nonfunctional adenomas
 Presenting symptoms
◦ Headache
◦ Diplopia
◦ Symptoms associated with hormone overproduction
 Galactorrhea, Gynecomastia
 Acromegally
 Cushing’s Syndrome
◦ thin skin/stretch marks
◦ proximal muscle weakness
◦ hyperglycemia
MEN I

Pituitary
◦ Bromocriptine mesylate





Dopamine agonist
First line therapy
Inhibits prolactin production
Reduces tumor bulk
Cabergoline is second line therapy for pts unable to tolerate
Bromocriptine mesylate
◦ Trans-sphenoidal hypophysectomy for medical failures
 3 months of therapy
 Failure to improve prolactin levels or diplopia
 Cabergoline more effective in tumor shinkage
MEN I

MEN I
◦ Involves the 3 P’s
 Pituitary
 Parathyroid
 Pancreatic islet cells
MEN I

Pancreatic islet cells
◦ Poses most difficult clinical challenge
 Pancreas is diffusely involved
◦ Islet cell hyperplasia
◦ Multifocal tumors
 Accounts for most morbidity and mortality
◦
◦
◦
◦
◦
Gastrinoma (Zollinger-Ellison)
Vasoactive intestinal polypeptidoma (VIPoma)
Insulinoma
Glucagonoma
Somatostatinoma
 90% found in gastrinoma triangle and are malignant
◦ Junction of cystic duct and CBD
◦ Junction of 2nd and 3rd portions of duodenum
◦ Junction of body and neck of pancreas
 Therapy directed at palliation of symptoms and the malignant process
MEN I
Junction of cystic duct and
CBD
Junction of 2nd and 3rd
portions of duodenum
Junction of body and neck
of pancreas
Gastrinoma Triangle

MEN I
◦ Involves the 3 P’s
 Pituitary
 Parathyroid
 Pancreatic islet cells

MEN II
◦ MEN II-A
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Parathyroid hyperplasia
◦ MEN II-B




Medullary carcinoma of thyroid
Pheochromocytoma
Ganglioneuromatosis (mucosal neuromas)
Marfanoid habitus
MEN I/MEN II

MEN II
◦ MEN II-A
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Parathyroid hyperplasia
MEN II-A

Medullary carcinoma of thyroid
◦ Present in all pts
◦ Autosomal dominant syndrome
 Gain-of-function mutation in RET proto-oncogene
 Prophylactic thyroidectomy indicated for all RET-mutation carriers upon
discovery1
◦ Greatest survival benefit if thyroidectomy completed < 5 yoa for MEN II-A2
◦ Age specific progression from C cell hyperplasia to medullary thyroid cancer to nodal
metastasis
◦ After primary resection – recurrence in over 50% pts
 No recurrence/nodal metastasis in pts < 14 yoa
 Re-operation for locally recurrent disease
 No accepted adjuvant therapy for metastatic disease


1Machens et al. N Engl J Med 2003;349:1517
2Brandi ML, et al. J Clin Ednocrinol Metab 2001;86:5658
MEN II-A

MEN II
◦ MEN II-A
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Parathyroid hyperplasia
MEN II-A

Pheochromocytoma
◦ Present in 40-50% of pts
◦ Biochemical testing recommended in all:
 Medullary thyroid cancer pts
 MEN II pts
 Includes
◦ 24 hour urinary catecholamines/metanephrines/VMA
◦ Plasma metanephrines
◦ Discontinue antihypertensives 24 hours prior to collection
MEN II-A

MEN II
◦ MEN II-A
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Parathyroid hyperplasia
MEN II-A

Parathyroid hyperplasia
◦ Arises in 25-35% of pts
◦ Similar to MEN I
 Diffuse/multiglandular
 Metachronous development of multiple adenomas
 Preferred corrective strategy employs 3.5 gland excision
MEN II-A

MEN I
◦ Involves the 3 P’s
 Pituitary
 Parathyroid
 Pancreatic islet cells

MEN II
◦ MEN II-A
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Parathyroid hyperplasia
◦ MEN II-B




Medullary carcinoma of thyroid
Pheochromocytoma
Ganglioneuromatosis (mucosal neuromas)
Marfanoid habitus
MEN I/MEN II

MEN II
◦ MEN II-B
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Ganglioneuromatosis (mucosal neuromas)
 Marfanoid habitus
MEN II-B

MEN II
◦ MEN II-B
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Ganglioneuromatosis (mucosal neuromas)
 Marfanoid habitus
MEN II-B

Medullary carcinoma of thyroid
◦ Present in all pts
◦ Autosomal dominant syndrome
 Gain-of-function mutation in RET proto-oncogene
 Prophylactic thyroidectomy indicated for all RET-mutation carriers upon
discovery1
◦ Greatest survival benefit if thyroidectomy completed < 1 yoa for MEN II-B2
◦ Age specific progression from C cell hyperplasia to medullary thyroid cancer to nodal
metastasis
◦ After primary resection – recurrence in over 50% pts
 No recurrence/nodal metastasis in pts < 14 yoa
 Re-operation for locally recurrent disease
 No accepted adjuvant therapy for metastatic disease


1Machens et al. N Engl J Med 2003;349:1517
2Brandi ML, et al. J Clin Ednocrinol Metab 2001;86:5658
MEN II-B

MEN II
◦ MEN II-B
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Ganglioneuromatosis (mucosal neuromas)
 Marfanoid habitus
MEN II-B

Pheochromocytoma
◦ Present in 40-50% of pts
◦ Biochemical testing recommended in all:
 Medullary thyroid cancer pts
 MEN II pts
 Includes
◦ 24 hour urinary catecholamines/metanephrines/VMA
◦ Plasma metanephrines
◦ Discontinue antihypertensives 24 hours prior to collection
MEN II-A

MEN II
◦ MEN II-B
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Ganglioneuromatosis (mucosal neuromas)
 Marfanoid habitus
MEN II-B
Multiple mucosal
neuromas
Ganglioneuromatosis (mucosal neuromas)
Multiple mucosal
neuromas
Ganglioneuromatosis (mucosal neuromas)
Multiple mucosal
neuromas
Ganglioneuromatosis (mucosal neuromas)

MEN II
◦ MEN II-B
 Medullary carcinoma of thyroid
 Pheochromocytoma
 Ganglioneuromatosis (mucosal neuromas)
 Marfanoid habitus
MEN II-B
00000062
Unknown
Mild ptosis
Prominent nose and lips
Macrognathia
MEN II-B
00000062
Unknown
Prominent corneal nerves
MEN II-B
Prominent lips
Mucosal neuromas
MEN II-B