Endocrine Part II

Question 1

What is the Incretin effct?

Answer 1

oral intake of food leads to secretion of multiple hormones that play a role in glucose homeostasis & satiety

Question 2

what are the hormones released during Incretin effect and where are they secreted from?

Answer 2

Glucose-dependent insulinotropic polypeptide - K cells in the proximal small intestine

Glucagon-like peptide-1 = L cells in the distal ileum and colon

Question 3

What mediates glucose u[tale by GLUT4 to the plasma membrane?

Answer 3

AKT - principle effector of the PI3K pathway
CBL - direct phosphorylation target of the Insulinr eceptor

Question 4

What are the chances of u developing DM with first-degree relatives with DM?

Answer 4

5 to 10 fold higher risk

Question 5

What are adipokines that decrease blood glucose by INC insulin sensitivity in peripheral tissues?

Answer 5

Leptin & Adiponectin

Question 6

What adipokine is reduced in obesity thus contributing to insulin resistance?

Answer 6

Adiponectin

Question 7

What can happen when there is an excessive FFA?

Answer 7

impedes insulin signaling directly within peripheral tissues or indirectly through the release of pro-inflammatory cytokines

Question 8

what happens if there is excess FFAs within macrophages and B cells?

Answer 8

Activates Inflammasome –> secretion of the cytokine IL-1B

Question 9

What is the function of IL-1B and IL-1?

Answer 9

IL-1B = mediates secretion additional pro-inflammatory cytokines

IL-1 and other cytokines = released into the circulation and act on the major sites of Insulin action to promote Insulin resistance

Question 10

What are diff mechanisms that promote B cell dysfunction?

Answer 10

1. Excess FFA compromising B cell function and Insulin release
2. Impact of chronic hyperglycemia
3. Abnormal “incretin effect” which leads to reduced secretion of GIP & GLP-1
4. Amyloid deposits in the islets
5. Genetics

Question 11

what are the monogenic forms of DM?

Answer 11

Genetic defects in B cell function
Genetic defects in Insulin action

Question 12

What are the genetic defects in Insulin action?

Answer 12

Type A insulin resistance = Acanthosis nigricans
Lipoatrophic DM = hyperglycemia w/ loss of adipose tissue

Question 13

What are the 4 harmful effects of persistent hyperglycemia?

Answer 13

1. Formation of advanced glycosylation end product
2. Activation of protein kinase C
3. Oxidative stress and disturbances in the polyol pathway
4. Hexosamine pathway and formation of fructose-6-phosphate => exacerbates end organ damage

Question 14

What is the histological presentation in DM type I & II?

Answer 14

Type I = INC in # of Islet cells, leukocytic infiltrates in the islets
Type II = Subtle reduction in islet cell mass, amyloid deposit in the islets –> expression of B cell exhaustion

Question 15

What happens in diabetic macrovascular disease?

Answer 15

Endothelial dysfunction
- Accelerated atherosclerosis = Coronary artery (MI)
- Hyaline atherosclerosis: arterioles in Small BVs in the kidney

Question 16

What histologic presentation is seen in diabetic microangiopathy disease?

Answer 16

Diffuse thickening of the BM –> capillaries of skin, skeletal muscle, retina, glomeruli, renal medulla

Question 17

What are the 3 lesions formed from diabetic nephropathy?

Answer 17

1. Glomerular lesion
2. Renal vascular lesion
3. Pyelonephritis

Question 18

What is Kimmelstiel-Wilson lesion?

Answer 18

nodular glomerulosclerosis

Question 19

What happens if renal vascular lesion & pyelonephritis progress?

Answer 19

Renal vascular lesion = arteriosclerosis
Pyelonephritis= necrotizing papilitis

Question 20

What condition in the kidneys can occur if there is long standing DM? WHat does it look like (gross)?

Answer 20

Nephrosclerosis
- Diffuse granular transformation of the surface
- marked thinning of the cortical tissue
- irregular depression
- incidental cortical cyst

Question 21

What are the different diabetic ocular complications?

Answer 21

Cataract –> disturbance of polyol pathway
Glaucoma
Retinal vasculopathy of DM

Question 22

What are the complications of diabetic peripheral neuropathy?

Answer 22

diabetic foot
ulceration
gangrene –> ischemia –> infection –> necrotic –> amputation

Question 23

What are the clinical manifestation of chronic disease?

Answer 23

Macrovascular complication –> MI, renal vascular insufficiency, CVA
Visual impairment –> total blindness
Neuropathy –> distal symmetrical neuropathy
Autonomic neuropathy –> neurogenic bladder
INC susceptibility to infection

Question 24

What are the different pancreatic endocrine tumors?

Answer 24

Hyperinsulinism (Insulinomas)
Zollinger-Ellison syndrome (Gastrinomas)

Question 25

What are the presentation of Insulinomas?

Answer 25

Solitary tumors w/ amyloid deposits --> Focal or diffuse hyperplasia of the Islets Hypoglycemia

Question 26

What is the presentation of Zollinger-Ellison syndrome?

Answer 26

Gastrin-producing tumors --> gastric acid hypersecretion & peptic ulceration

Question 27

What are other rare pancreatic neuroendocrine tumors?

Answer 27

a-cell tumors (Glucagonomas) --> produce Glucagon Delta-cell tumors (Somatostatinomas) --> produces Somatostatin VIPomas --> watery diarrhea, hypokalemia, achlorhydria/WDH syndrome Pancreatic carcinoids -> produces Serotonin

Question 28

what are the clinical manifesations of Cushing syndrome?

Answer 28

Truncal obesity, moon facies, and accumulation of fat in the posterior neck & back (buffalo hump)

Question 29

What are the lab tests done to diagnose Cushing syndrome?

Answer 29

Increased 24-h urine free-cortisol concentration Loss of normal diurnal pattern of cortisol secretion

Question 30

What is a cell pathognomonic to Cushing’s dynrome?

Answer 30

Pituitary-Crooke’s hyaline change

Question 31

In what type of CUshing syndrome can we see diffuse hyperplasia?

Answer 31

ACTH-dependent Cushing syndrome

Question 32

What type of hyperplasia are seen in the adrenal glands?

Answer 32

Macronodular hyperplasia - lipid-poor & lipid-rich cells Micronodular hyperplasia - w/ atrophic intervening areas

Question 33

What can cause Cushing syndrome to be malignant or benign?

Answer 33

Primary adrenococortical neoplasms

Question 34

WHat are the histological features of an adrenal cortical adenoma?

Answer 34

Neoplatic cells are vacuolated bcos of the presence of intracytoplasmic lipids There is mild nuclear pleomorphism Mitotic activity & necrosis are not seen

Question 35

What are the 2 kinds of hyperaldosteronism?

Answer 35

Primary & Secondary hyperalodsteronism

Question 36

What is the cause of primary hyperalosteronism?

Answer 36

Autonomous overproduction of aldosterone with resultant suppression of the RAAS & DEC plasma renin activity

Question 37

What causes secondary hyperaldosteronism?

Answer 37

Aldosterone release occurs due to activation of RAAS —> INC levels of plasma renin —> DEC renal perfusion, Arterial hypovolemia & edema, Pregnancy

Question 38

What is the most common manifestation of primary hyperaldosteronism?

Answer 38

BP Elevation

Question 39

What is the most common underlying cause of primary hyperaosteronism?

Answer 39

Bilateral idiopathic hyperaldosteronism w/ bilateral nodular hyperplasia

Question 40

What condition cayses Adrenocortical neoplasm?

Answer 40

Conn syndrome Aka solitary aldosterone-secreting adenoma

Question 41

What is an uncommon cause of primary familial hyperalodsoteronism?

Answer 41

Glucocorticoid-remediable hyperalodsteronism

Question 42

What is the gross morphology of Aldosterone-producing adenomas?

Answer 42

Solitary small, well-circumscribed lesions, mroe often found on the L than on the R Buried within the gland, is not visibly enlarged

Question 43

What are the special cells seen in Aldosterone-producing adenomas?

Answer 43

Lipid-laden cortical cells

Question 44

WHat is a characteristic feature of aldosterone-producing adenomoas?

Answer 44

Spironolactone bodies

Question 45

What is the most important clinical consequence of hyperaldosteronism?

Answer 45

Hypertension

Question 46

What are the long-term effects of hyperaldosteronism-induced HTN?

Answer 46

CV compreomise, stroke, MI

Question 47

What confirms diagnosis of primary hyperaldosteronism?

Answer 47

Elevated ratios of plasma aldosterone concentration to plasma renin activity

Question 48

What are different adrenogenital syndrome?

Answer 48

C-21 hydroxylase deficiency 21-Hydroxylae deficiency - impaired synthesis of both cortisol & aldosterone

Question 49

What are the cause sof C21 hydroxylase deficiency?

Answer 49

Adrenocortical neoplasms Congenital adrenal hyperplasia

Question 50

What causes congenital adrenal hyperplasia? What is its effect?

Answer 50

Autusomal recessive inherited metab errors Effect: INC production of androgens (virilization), INC secretion of ACTH

Question 51

What is the msot common cause of congenital adrenal hyperplasia & what are its 3 primary features?

Answer 51

21 hydroxylase deficiency 1. Salt losing adrenogenitalism - salt-wasting, hyponatremia, and hyperkalemia (acidosis, HTN, CV collapse, death) 2. Simple virilizing adrenogenitalism syndrome w/o salt-wasting - ambigous genitalia 3. Nonclassic or late onset adrenal virilism - more common & partial def of 21-hydroxylase function

Question 52

What are the 3 conditions caused by adrenocortical hypofunction?

Answer 52

Primary & Secondary adrenal insufficiency Addison’s disease (Primary chronic adrenocortical insufficiency)

Question 53

What conditions cause primary adrenal insufficiency?

Answer 53

- rapid withdrawal of steroids - massive adrenal hemorrhae (Waterhouse-Friederichson syndrome) - loss of cortical cells - metab failure in hormone production

Question 54

What are cause sof secondary adrenal insufficiency?

Answer 54

Hypothalami pituitary disease = neoplasm, inflammation Hypothalamic pitutiary suppression = long-term steroid administration, steroid-producing neoplasms

Question 55

What are diff conditions that can cause Addison’s disease?

Answer 55

Autoimmune adrenalitis TB, AIDS infections Metastastic tumors Genetic causes: CAH, Adrenoleukodystrophy

Question 56

What are conditionc of Primary Chronic Adrenocortical insufficiency/Addison’s dis?

Answer 56

Autoimmune polyendocrine syndrome type 1 Autoimmune polyendocrine syndrome type 2

Question 57

In 90% of Addison’s dis, what is the secondary condtion?

Answer 57

Tuberculous adrenalitis

Question 58

What causes skin pigmentation in Addison’s dis?

Answer 58

Elevated levels of Pro-opiomelanocortin

Question 59

What are the 3 grps of autonomic NS found in extra-adrenal paraganglia?

Answer 59

Branchiomeric Intravagal Aortico-sympathetic

Question 60

What are neoplasms derived from chromaffin cells?

Answer 60

Pheochromocytoma

Question 61

What are the clinical manifestations of Pheochromocytoma?

Answer 61

Extra-adrenal -> Paragangliomas Sporadic Bilateral Sporadic adrenal pheochromocytoma Malignant adrenal pheochromocytoma

Question 62

What are Paragangliomas?

Answer 62

Pheochromocytomas that develop in extra-adrenal parganglia

Question 63

What is the gross morphology of Pheochromocytoma?

Answer 63

Small, circumscribed lesions condined to the adrenal medulla, to large hemorrhagic mass Well-demarcated large tumors

Question 64

WHat is the histologic morphology of Pheochromocytoma?

Answer 64

CLusters of polygonal to SPINDLE-shaped chromaffin cells or chief cells surrounded by supporting sutentanicular rash “Salt & Pepper” chromatin

Question 65

What cells in Pheochromocytoma are stained with antibodies against S-100?

Answer 65

Peripheral sustentacular cells

Question 66

What is the definitive dx of malignancy of Pheochromocytoma?

Answer 66

Excusively on the presence of metastasis

Question 67

What are endocine tumors arising in the contect of MEN syndromes? Wjat are the distinct features of this condition?

Answer 67

Multiple endocrine neoplasms Distinct features: - younger age - arise in multiple endocrine organ syndronously/metachronously - multifocal in one organ - usually prceded by an asymptomatic stage of hyperplasia

Question 68

What are the 3 multiple endocrione neoplasms?

Answer 68

MEN 1 MEN 2A MEN 2B

Question 69

WHat condition is aka Wemer’s syndrome & caused by germline mutations in the MEN1 tumor suppressor gene?

Answer 69

MEN 1

Question 70

What does MEN1 do?

Answer 70

Encodes a protein called Menin

Question 71

What is the purpose of Menin?

Answer 71

It blocks tracriptional activation by JunD when menin partners with JunD

Question 72

What are the abnormalities of MEN1?

Answer 72

3Ps PTG Pancreas, Pitutiary gland

Question 73

WHat is the most common manifestation of MEN-1?

Answer 73

Primary hyperparathyroidism

Question 74

What is the most commn site of gastrinomas in indiviudal with MEN-1?

Answer 74

Duodneum

Question 75

What condition is aka Sipple syndrome tha thas Pheochromcytoma, Medullar carcinoma of the thyroid Caused by germinal mutation in the RET proto-oncogene on chromosome 10q11.2?

Answer 75

Men-2A

Question 76

What is a common presentation in MEN-2A?

Answer 76

Medullary carcinoma asosci w. foci of C-cell hyperplasia

Question 77

What is the difference betw MEN-2A & MEN-2B?

Answer 77

Hyperparathyroidism is not present in MEN-2B