Endocrine Pancreas

Question 1

endocrine pancreas

Answer 1

islets of Langerhans, which contain four major and two minor cell types.

The four main types are β, α, δ, and PP (pancreatic polypeptide) cells.

Question 2

The β cells produce

Answer 2

insulin

Question 3

α cells secrete

Answer 3

glucagon, which stimulates glycogenolysis in the liver and thus increases blood sugar.

Question 4

δ cells secrete

Answer 4

somatostatin, which suppresses both insulin and glucagon release.

Question 5

PP cells secrete

Answer 5

pancreatic polypeptide, which exerts several gastrointestinal effects, such as stimulation of secretion of gastric and intestinal enzymes and inhibition of intestinal motility. These cells not only are present in islets but also are scattered in the exocrine pancreas.

Question 6

The two rare cell types

Answer 6

D1 cells and enterochromaffin cells.

D1 cells elaborate vasoactive intestinal polypeptide (VIP), a hormone that induces glycogenolysis and hyperglycemia; it also stimulates gastrointestinal fluid secretion and causes secretory diarrhea.

Enterochromaffin cells synthesize serotonin and are the source of pancreatic tumors that cause the carcinoid syndrome

Question 7

Diabetes Mellitus

Answer 7

Diabetes mellitus is a group of metabolic disorders sharing the common feature of hyperglycemia

In the United States, diabetes is the leading cause of end-stage renal disease, adult-onset blindness and non-traumatic lower extremity amputations resulting from atherosclerosis of the arteries

Question 8

dx of diabetes mellitus

Answer 8

Blood glucose is normally maintained in a very narrow range of 70 to 120 mg/dL

A fasting plasma glucose ≥ 126 mg/dL
A random plasma glucose ≥ 200 mg/dL
2-hour plasma glucose ≥ 200 mg/dL during an oral glucose tolerance test (OGTT) with a loading dose of 75 gm
A glycated hemoglobin (HbA1C) level ≥ 6.5%

Question 9

Impaired glucose tolerance (prediabetes)

Answer 9

A fasting plasma glucose between 100 and 125 mg/dL (“impaired fasting glucose”)
2-hour plasma glucose between 140 and 199 mg/dL following a 75-gm glucose OGTT
A glycated hemoglobin (HbA1C) level between 5.7% and 6.4%

Question 10

Type 1 diabetes

Answer 10

an autoimmune disease characterized by pancreatic β cell destruction and an absolute deficiency of insulin. It accounts for approximately 5% to 10% of all cases, and is the most common subtype diagnosed in patients younger than 20 years of age.

Question 11

Type 2 diabetes

Answer 11

is caused by a combination of peripheral resistance to insulin action and an inadequate secretory response by the pancreatic β cells (“relative insulin deficiency”). Approximately 90% to 95% of diabetic patients have type 2 diabetes, and the vast majority of such individuals are overweight.

nonketotic hyperosmolar coma

amyloid

Question 12

Pathogenesis of Type 1 Diabetes Mellitus

Answer 12

an autoimmune disease in which islet destruction is caused primarily by immune effector cells reacting against endogenous β-cell antigens
The fundamental immune abnormality in type 1 diabetes is a failure of self-tolerance in T cells specific for islet antigens

Question 13

honeymoon period

Answer 13

In the initial 1 or 2 years following the onset of overt type 1 diabetes, the exogenous insulin requirements may be minimal because of ongoing endogenous insulin secretion (referred to as the honeymoon period). Thereafter, any residual β-cell reserve is exhausted and insulin requirements increase dramatically.

Question 14

Clinical Features of Diabetes

Answer 14

Patients with type 2 diabetes are typically older than 40 years and frequently obese.

In some cases, medical attention is sought because of unexplained fatigue, dizziness, or blurred vision.

Most frequently, however, the diagnosis of type 2 diabetes is made after routine blood testing in asymptomatic persons. In fact, in light of the large number of asymptomatic individuals with undiagnosed hyperglycemia in the United States, routine glucose testing is recommended for everyone older than 45 years of age

Question 15

The Classic Triad of Diabetes

Answer 15

The onset of type 1 diabetes is usually marked by the triad of polyuria, polydipsia, polyphagia, and, when severe, diabetic ketoacidosis, all resulting from metabolic derangements

Question 16

Chronic Complications of Diabetes

Answer 16

macrovascular and microvascular disease (chronic hyperglycemia)

Macro­vascular disease causes accelerated atherosclerosis among diabetics, resulting in increased risk of myocardial infarction, stroke, and lower extremity ischemia

Microvascular disease are most profound in the retina, kidneys, and peripheral nerves, resulting in diabetic retinopathy, nephropathy, and neuropathy

Question 17

morphology of pancreatic lesions

Answer 17

reduction in number and size of islets
leukocytic infiltrates in the islets (T lymphocytes)
amyloid deposition within islets in type 2 diabetes
increase in the number and size of islets - in nondiabetic newborns of diabetic mothers.

Question 18

Diabetic Macrovascular Disease

Answer 18

Myocardial infarction, caused by atherosclerosis of the coronary arteries, is the most common cause of death in diabetics

Gangrene of the lower extremities, as a result of advanced vascular disease, is about 100 times more common in diabetics than in the general population

Question 19

Diabetic Ocular Complications

Answer 19

Diabetes-induced hyperglycemia leads to acquired opacification of the lens, a condition known as cataract. The most profound histopathologic changes of diabetes are seen in the retina.

Question 20

Clinical Manifestations of Chronic Diabetes

Answer 20

Macrovascular complications such as myocardial infarction, renal vascular insufficiency, and cerebrovascular accidents are the most common causes of mortality in long-standing diabetes.

Diabetic nephropathy

Visual impairment, sometimes even total blindness,

distal symmetric polyneuropathy of the lower extremities that affects both motor and sensory function

by enhanced susceptibility to infections of the skin and to tuberculosis, pneumonia, and pyelonephritis.

Question 21

Pancreatic Neuroendocrine Tumors

Answer 21

The preferred term for tumors of the pancreatic islet cells (“islet cell tumors”) is pancreatic neuroendocrine tumors or PanNETs.

The three most common and distinctive clinical syndromes associated with functional pancreatic endocrine neoplasms are:

(1) Hyperinsulinism
(2) Hypergastrinemia and the Zollinger-Ellison syndrome
(3) Multiple endocrine neoplasia (MEN)

Question 22

Unequivocal criteria for malignancy

Answer 22

metastases, vascular invasion, and local infiltration.

Question 23

functional status of the tumor has some impact on prognosis

Answer 23

approximately 90% of insulin producing tumors are benign, while 60% to 90% of other functioning and nonfunctioning pancreatic endocrine neoplasms are malignant. Fortunately, insulinomas are the most common subtype of pancreatic endocrine neoplasms.

Question 24

Hyperinsulinism (Insulinoma)

Answer 24

β-cell tumors (insulinomas) are the most common of pancreatic endocrine neoplasms, and may produce sufficient insulin to induce clinically significant hypoglycemia

hypoglycemic episodes, - the blood glucose level falls below 50 mg/dL of serum.

The clinical manifestations: confusion, stupor, and loss of consciousness. These episodes are precipitated by fasting or exercise and are promptly relieved by feeding or parenteral administration of glucose.

Question 25

insulinoma morphology

Answer 25

pale to red-brown nodules located anywhere in the pancreas
look like giant islets, with preservation of the regular cords of monotonous cells and their orientation to the vasculature
Deposition of amyloid (pink) is characteristic

Question 26

Insulin to glucose ratio

with insulinomas

Answer 26

While up to 80% of islet cell tumors demonstrate excessive insulin secretion, the hypoglycemia is mild in all but about 20%, and many cases never become clinically symptomatic.

The critical laboratory findings in insulinomas are high circulating levels of insulin and a high insulin-to-glucose ratio. Surgical removal of the tumor is usually followed by prompt reversal of the hypoglycemia.

Question 27

Zollinger-Ellison Syndrome (Gastrinomas)

Answer 27

hypersecretion of gastrin
are just as likely to arise in the duodenum and peripancreatic soft tissues as in the pancreas (so-called gastrinoma triangle).

Zollinger and Ellison first called attention to the association of pancreatic islet cell lesions, hypersecretion of gastric acid and severe peptic ulceration, which are present in 90% to 95% of patients.

Question 28

Clinical Features of gastrinomas

Answer 28

More than 50% of the patients have diarrhea; in 30%, it is the presenting symptom.

Treatment of Zollinger-Ellison syndrome involves control of gastric acid secretion by use of H+K+-ATPase inhibitors and excision of the neoplasm.

Total resection of the neoplasm, when possible, eliminates the syndrome. Patients with hepatic metastases have a shortened life expectancy, with progressive tumor growth leading to liver failure usually within 10 years

Question 29

α-cell tumors

Answer 29

glucagonomas

• -> increased serum levels of glucagon
• syndrome consisting of mild diabetes mellitus,
• skin rash (necrolytic migratory erythema),
• anemia.

most frequently in perimenopausal and postmenopausal women; extremely high plasma glucagon levels.

Question 30

δ-cell tumors

Answer 30

somatostatinomas) are associated with diabetes mellitus, cholelithiasis, steatorrhea, and hypochlorhydria. They are exceedingly difficult to localize preoperatively. High plasma somatostatin levels are required for diagnosis.

Question 31

VIPoma

Answer 31

(watery diarrhea, hypokalemia, achlorhydria, or WDHA syndrome) induces a characteristic syndrome that is caused by release of vasoactive intestinal peptide (VIP) from the tumor. Some of these tumors are locally invasive and metastatic. A VIP assay should be performed on all patients with severe secretory diarrhea.

Question 32

Pancreatic carcinoid tumors producing serotonin

Answer 32

and an atypical carcinoid syndrome are exceedingly rare. Pancreatic polypeptide-secreting endocrine tumors present as mass lesions as even high plasma levels of this hormone fail to cause symptoms.