12. Multiple Endocrine Neoplasia Flashcards
What are multiple endocrine neoplasia (MEN) syndromes?
3 autosomal dominant disorders where at least 2 endocrine glands simultaneously undergo neoplastic transformation and become hyperfunctional. These neoplastic tumors can be benign or malignant.
What are the clinical features of MEN?
depend on endocrine gland involved
Each MEN is autosomal dominant with a _____ degree of penetrance and ________ expressivity.
- High degree of penetrance (if you have gene, you will express the disorder).
- Variable expressivity (the level at which a trail appears differs from person -> person)
Types of MENs?
Type 1
Type 2A and 2B
What is the prevelence of MEN syndromes?
- MEN 1: 2-20/100,000 people
- MEN 2 is less common than MEN 1. Of MEN 2, 2A is the most common and 2B is the rarest.
How can so many various endocrine organs be affected in these syndromes?
MEN tumors arise from APUDS (amine precursor uptake and decarboxylation) cells, which make up our endocrine organs.
- Convert AA –> [biogenic amines or peptides] via L-DOPA decarboxylase, which act as hormones or neurotransmitter.
- A mutation in APUD cells can cause neoplastic tumors of related cell types in different endocrine organs.
What the common features of APUD cells?
- Make biogenic amines: by uptake of amine precursors and amine (DOPA) decarboxylase
- Make small polypeptide hormones
- Make membrane-bound neurosecretory granules.
MEN-1 are associated with what tumors?
1. Parathyroid adenoma (most common: 95%)
2. Pancreatic endocrine tumors
3. Puitary adenoma
4. Carcinoid tumors
MEN-2A are associated with what tumors?
- Medullary thyroid carcinoma (parafollicular cells)- 100%
- Bilateral phaeochromacytoma (on adrenal medulla)
- Parathyroid adenoma
MEN-2B are associated with what tumors?
1. Medullary thyroid carcinoma (100%)
2. Mucsal neuromas (100%)
3. Phaeochromacytomas
MEN-1 consists of hyperplasia or neoplastic transformation of the
THREE P’s
- parathyroid glands
- pancreatic islets
- pituitary.
MEN-2A consists of hyperplasia or neoplastic transformation of the
- thyroid parafollicular cells (medullary thyroid carcinoma [MTC]),
- parathyroid glands
- _adrenal medulla (_pheochromocytoma).
MEN-2B consists of hyperplasia or neoplastic transformation of the ______, _____, ____.
- thyroid parafollicular cells (MTC)
- adrenal medulla (pheochromocytoma)
- mucosal neuromas.
Not parathyroid
Assx condition with pancreas, pituitary adenoma in MEN 1
- ZE syndrome
- Pituitary adenoma that can cause acromegaly, cushing syndrome, galloctorrhea.
Assx condition with parathyroid neoplasm MEN 1
- Hyperparathyroidism
- Hypercalcemia
Assx conditions with MEN IIa
1. Hyperparathyroidism
2. Hypercalcemia
3. Medullar carcinoma
4. Increased calcitonin
5. Increased catecholamines
Assx conditions with MEN IIb
- Mucosal nodules
- Marafanoid body. habitus
- medullary carcinoma
- Increased calcitonin
- Increased catecholamines.
MEN type 1 is also called what?
Wermer syndrome
What. is MEN type 1, Wermers syndrome?
A mutation in the MEN1 gene, which encodes the menin protein, a tumor supressor. Thus, a mutation would cause unregulated division -> tumor in the 3 P’s: pancreas, parathyroid and pituiary.
_______ tumors are also frequently reported in MEN 1 patients.
Where do they occur?
Carcinoid tumors
Men-> thymus
Women-> bronchial carcinoids
How can we diagnose MEN Type 1?
Three means:
- Clinical: two or more MEN assx tumors
- Familial: patient with one MEN-1 associated tumor and a 1st degree relative with MEN 1
- Genetic: an asymptomatic carrier of MEN-1 mutation with no biochemical manifestions.
Discuss MEN- 1 and the parathyroid glands
- In MEN-1, the most involved organ is the parathyroid gland. All 4 glands will have hyperplasia.
- First manifestation of syndrome: hyperparathyroidism, however it may not. be detected until a clinical sx of the pituitary or pancreas is noticed.
What is the second most common manifestation of MEN1?
Neoplastic tumors of pancreatic islet cells that can be benign or malignant.
The 2nd most common manifestation of MEN-1 is pancreatic islet tumor that can be benign or malignant.
- What is the most frequent manifestation?
- What is the 2nd most common type of functional pancreatic tumor?
- Gastrinomas: 1/3 of patients with gastrinomas have MEN1.
- Insulinomas
Patients with MEN-1 can have pituitary adenomas.
Describe the types and results of them
- Prolactin secreting pituitary tumors are the most common in MEN1; causing galactorrhea and amenorrhea in W and impotence in M).
- ACTH pituitary adeomas -> Cushing
- GH secreting tumors -> acromegaly
What is gallactorrhea
amenorrhea
and impotence?
Gallactorrhea- milk discharge
Amenorrhea- no menstruation (period)
impotence- cant get an erection
What is the 3rd most common manifestation of MEN-1
Symptoms of hyperprolactinemia: d/t. a prolactin secreting pituitary adenoma causing gallactorrhea, amenorhea and impotence.
Patients with MEN-1 syndrome have ____________ of both functional and nonfunctional adrenal cortical hyperplasias/ adenomas.
increased frequency.
Tx for MEN1
- Surgical resection of hyperplastic parathyroid tissue
- Surgical resection of pituitary adenoma or give meds, such as bromocriptine for prolactinomas (a DA AGO -> nihibits prolactin)
- Subtotal pancreatectomy (remove as many multifolcal tumors in pancreas). However, if pancreas is affected surgery will not cure.
What causes MEN type 2?
MEN type 2 -> d/t a mutation in RET protooncogene, which codes for receptor tyrosine kinase that is needed for cell growth. Mutation will increase growth.
What. is the most common sign of MEN2?
Medullary thyroid carcinoma [MTC] of the parafollicular C cells, which secrete calcitonin.
50% of ppl with MEN-2 develop what?
Pheochromacytomas
Which is worse: MEN 2A or 2B
2B: Average age of death is 30
2A is 60.
MEN-2A is also called what?
Sipple syndrome
In MEN-2A, describe what happens to the parafollicular cells.
- Go from a state of C-cell hyperplasia -> nodular hyperplasia -> malignant degeneration over time.
- MTC will also express peptides that C-cells usually dont excrete: somatostatin, TRH, VIP, POMC (so hyperpigmentation) etc.
In MEN-2A, describe the pheochromacytomas.
These will secrete more EPI than sporadic pheos
What MEN disorder where we might see a itchy skin condition and what is it called?
MEN2A- Cutaneous lichen amyloidosis
Describe the MTCs in MEN-2B.
More aggressive, forming metastatic lesions
