Lecture 12: Multiple Endocrine Neoplasia Flashcards
Define MEN-1
MEN-1 consists of hyperplasia or neoplastic transformation of the parathyroid glands, pancreatic islets, and pituitary (3 P’s)
Define MEN-2A
MEN-2A consists of hyperplasia or neoplastic transformation of the thyroid parafollicular cells (medullary thyroid carcinoma [MTC]), parathyroid glands, and adrenal medulla (pheochromocytoma).
Define MEN-2B
MEN-2B consists of hyperplasia or neoplastic transformation of the thyroid parafollicular cells (MTC) and adrenal medulla (pheochromocytoma) with concomitant development of mucosal neuromas.
How many endocrine glands typically involved in MEN; what type of inheritance pattern?
- At least 2 endocrine glands
- Autosomal dominant
Where do MEN tumors arise from; why is this significant?
- Amine precursor and uptake decarboxylation (APUD) group of cells
- A diffuse system of neuroendocrine cells distributed throughout the body (GI, respiratory mucosa, pituitary, parathyroid, pancreatic islets…)
What does APUD denote the capacity of these cells to do; via which enzyme?
Synthesize and/or secrete biogenic amines formed through activity of the enzyme L-dopa decarboxylase
In MEN 1 there is a gene mutation of?
- Menin protein
- Normally functions as a tumor supressor, but mutations lead to unregulated cell division —> tumor formation
What type of tumors are frequently reported in MEN 1 pts?
Carcinoid
What are the 3 means of diagnosing MEN 1?
1) Clinical - 2 or more MEN-1 associated tumors
2) Familial - pt w/ one MEN-1 associated tumor PLUS a first degree relative w/ MEN-1 dx
3) Genetic - asymptomatic carrier of MEN-1 mutation (no biochemical manifestation necessary
What is the most frequently involved organ in MEN 1 and is a result of hyperplasia of?
- Parathyroid gland —> Hyperparathyroidism
- Hyperplasia of ALL 4 glands
What is the second most common manifestation of MEN 1 and what is seen with this?
- Neoplastic transformation of pancreatic islet cells
- Gastrinomas are most frequent (Zollinger Ellison)
- Insulinomas are second most common
- May also see glucagonomas, somatostatinomas, and VIPomas
What is the third most common manifestation of MEN 1 and what is seen with this?
- Pituitary neoplasia causing Hyperprolacinemia
- Females will have galactorreha and amenorrhea
- Males will suffer from impotence
- Some pts may develop tumors secreting ACTH (Cushing syndrome) or GH (acromegaly)
What are the treatment options for MEN-1?
- Surgical resection of hyperplastic PT
- Surgical resection of pituitary adenomas or pharmacotherpay (bromcocriptine for prolactinomas; octreotide for acromegaly)
- Subtotal pancreatectomy (surgery on the pancreas is NOT always possible)
MEN-2 is caused by an activation mutation of?
RET proto-oncogene
What is the most common sign of MEN 2?
- Malignant transformation of the parafollicular (C cells) = Medullary thyroid carcinom (MTC)
- Some patients will develop pheochromocytoma of the adrenal gland
What happens to the parafollicular cells in patients with MEN-2A (sipple syndrome); what is often seen in the patients because of this?
- Characteristically progress through a state of C-cell hyperplasia to nodular hyperplasia to malignant degeneration over a variable period
- MTC also expresses peptides and hormones NOT commonly seen produced by C-cells, including somatostatin, TRH, VIP, POMC, carcinoembryonic antigen (CEA), and neurotensin
What is different about the Pheochromocytomas associated w/ MEN 2A?
Secrete greater amounts of epinephrine than sporadic pheochromocytomas
Cutaneous lichen amyloidosis is often seen with?
- Itchy skin condtion commonly seen with MEN 2A
- Located in the interscapular region or on the extensor surfaces of the extremities
What MEN categories is hyperparathyroidism assosciated with?
- Seen in almost ALL MEN-1 cases
- Associated with MEN-2A, but seen far less frequently
What are the distinguishing pathologies for MEN-2B?
- MTC (also seen in 2A)
- Pheochromocytomas
- Mucosal neuromas
- Intestinal ganglioneuromas (Hirschsprung’s)
- Marafanoid body habitus
We have a saying for Primary Hyperparathyroidism; what is often seen symptom wise?
- “Painful bones, renal stones, abdominal groans, and psychic moans.”
- Bone disease: fractures from osteoporosis
- Renal disease: chronic renal insufficiency –> polyuria and secondary polydipsia
- GI: constipation, nausea, peptic ulcers, pancreatitis, and gallstones
- CNS/Neuromuscular: depression, lethargy, weakness, and fatigue
