MEN 1 Syndrome (27)

Question 1

What is hyperplasia?

Answer 1

Increase in the number of cells in tissue or organ in response to a stimulus

Question 2

How many parathyroid glands are mostly affected in hyperplasia?

Answer 2

All 4 glands

Question 2

What is the microscopic picture of parathyroid hyperplasia?

Answer 2

• The most common pattern seen is that of chief cell hyperplasia, which may involve the glands in a diffuse or multinodular pattern.
• Less commonly, the constituent cells contain abundant water-clear cells (“water-clear cell hyperplasia”).
• In many instances, there are islands of oxyphils, and poorly developed, delicate fibrous strands may envelop the nodules.

Question 3

Why did the patient (MEN 1 Syndrome) develop stupor, confusion, and hypoglycemia (1.2 mmol/l)?

Answer 3

Insulinoma

Question 4

What are the other causes of unresponsive hypoglycemia?

Answer 4

• Abnormal insulin sensitivity,
• Diffuse liver disease,
• Inherited glycogenoses,
• Ectopic production of insulin by certain retroperitoneal fibromas and fibrosarcomas

Question 5

What cell is insulinoma derived from?

Answer 5

β-cell of islets of Langerhans’

Question 6

What is the clinical picture of insulinoma?

Answer 6

• Confusion
• Stupor
• Loss of consciousness (blood glucose 2.5 mmol/L or less)
• These episodes are precipitated by fasting or exercise
• Promptly relieved by feeding or parenteral administration of glucose.

Question 7

What is the biochemical diagnosis of insulinoma?

Answer 7

• High circulating levels of insulin (<10 μU/mL)
• High insulin-to-glucose ratio

Question 8

What is another pathology that could be suspected in this patient with insulinoma + parathyroid hyperplasia?

Answer 8

Pituitary adenoma (MEN 1)

Question 9

What are the 3 gene mutations in insulinoma?

Answer 9

• MEN1, which causes familial MEN syndrome, type 1, also is mutated in a number of sporadic neuroendocrine tumors
• Loss-of-function mutations in tumor suppressor genes such PTEN and TSC2 (which results in activation of the oncogenic mammalian TOR (mTOR) signaling pathway
• Inactivating mutations in two genes, alpha-thalassemia/mental retardation syndrome, X-linked (ATRX) and death-domain associated protein (DAXX), which have multiple cellular functions, including telomere maintenance.

Question 10

What is the two-hit hypothesis?

Answer 10

Most loss-of-function mutations that occur in tumor suppressor genes are recessive in nature. Thus, in order for a particular cell to become cancerous, both of the cell’s tumor suppressor genes must be mutated. This idea is known as the “two-hit” hypothesis.

Question 11

What is telomere?

Answer 11

A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes.

Question 12

What is apoptosis?

Answer 12

Programmed cell death.