Cushing Syndrome; Men And Ai Polygland Syndrome

Front 1

glucocorticoid excess of any etiology

Back 1

cushing syndrome

Front 2

pituitary ACTH excess leading to adrenal stimulation and chronically elevated glucocorticoids

Back 2

cushing disease

Front 3

Cushing syndrome: Effects on metabolism

Back 3

Impaired glucose tolerance to DM in severe cases. Due to cortisol stimulating gluconeogenesis.

Glucocorticoids cause deposition of fat centrally

Protein wasting - causes muscle weakness and thin skin (collagen breakdown) and striae and poor wound healing, causes osteoporosis

Front 4

Cushing syndrome: effects on immune system

Back 4

immunosupprsesion

Front 5

Most common etiology of Cushing syndrome

Back 5

Iatrogenic - excess glucocorticoids given to patients to treat another disease like asthma or inflammatory bowel disease

Front 6

What are the four causes of cushings?

Back 6

1) Iatrogenic (excess corticosteroids given)

2) Primary adrenal adenoma -ACTH indept

3) Cushing disease from pituitary - ACTH dept

4) Ectopic ACTH (tumor)

Front 7

What will the change in the size of the adrenal glands be in the following:

1) Iatrogenic
2) ACTH dept (pituitary)
3) Ectopic ACTH (tumor)
4) ACTH indpt (primary adrenal disease)

Back 7

1) They will shrink because there is less ACTH due to suppression.

2) They will both be enlarged.

3) They will both be enlarged.

4) Only one will be enlarged (the one that's secreting the excess)

Front 8

In ectopic ACTH (from a tumor) what are the most common presenting features and why?

Back 8

Probably won't see the classic Cushing syndrome symptoms if the tumor develops and secretes cortisol too quickly.

Will most likely see the metabolic disturbances first - hyperglycemia and hypokalemia.

Front 9

What is the most common tumor type to produce ectopic ACTH?

Back 9

small cell carcinoma of the lung

Front 10

What is pseudoCushing syndrome?

Back 10

Where the patient looks like Cushings but cortisol can be suppressed. May be elevated cortisol due to stress or alcoholism

Front 11

How to dx and test for Cushing syndrome?

Back 11

1) Confirm hypercortisolism - test levels of cortisol or failure to suppress cortisol.

2) Confirm etiology - primary vs. secondary

Front 12

What will differentiate between ACTH dept vs ACTH indept causes of cortisol excess?

Back 12

Plasma ACTH level - measure in afternoon/evening bc ACTH is usually high in AM.

Front 13

How to establish the source of ACTH in an ACTH-dept cushing syndrome?

Back 13

1) HIGH dose dex suppression - if able to do it, suggests a pituitary tumor. If unable, suggests a "non functional/responsive" cell type - like cancer.
2) Pituitary imaging
3) non-pituitary imaging - looking for ectopic source of ACTH

Front 14

Tx of Cushings

Back 14

1) remove tumor
2) medical therapy - inhibit production of glucocorticoids (ketoconazole, etc)
3) Pituitary irradiation if coming from pituitary

Front 15

3 tests to confirm hypercortisolism

Back 15

1) Low dose dex suppression
2) 24 hour urine free cortisol
3) Midnight salivary cortisol (measures loss of diurnal variation)

Front 16

What is inferior petrosal sampling used to determine?

Back 16

useful to distinguish pituitary vs ectopic ACTH source (will see ACTH in the sample if it's pituitary)

Front 17

Gene for MEN 1 is on chromosome___

Back 17

11

Front 18

What is the oncogene for MEN 2?

Back 18

RET

Front 19

T/F Tumors in MEN patients occur at a younger age than in patients with sporadic tumors

Back 19

T

Front 20

HTN, sweats, headaches: What tumor?

Back 20

pheochromocytoma

Front 21

Familial disorder in which there is a genetic predisposition for affected family members to develop tumors in endocrine organs

Back 21

Multiple Endocrine Neoplasia

Front 22

What are the main tumor types in MEN Type 1?

Back 22

3 Ps

Parathyroid

Pancreas and duodenum (enteropancreatic or pancreaticoduodenal endocrine tumors (PET’s))

Pituitary

Front 23

What is often the initial presentation of MEN Type 1?

Back 23

Hypercalcemia. Due to PTH secretion

Front 24

What is the normal gene product of MEN 1 on chromosome 11?

Back 24

MENIN, a predominantly nuclear protein, which interacts with factors in transcription and cellular proliferation.

MENIN functions to suppress cellular proliferation in endocrine tissues but can promote proliferation in the hematopoietic system.

Menin is a tumor suppressor.

Front 25

Pattern of inheritance of MEN1

Back 25

Autosomal dominant.
Inherit one bad and one good copy.

Then it only takes one "hit" for the good copy to go bad --> development of the syndrome.

Front 26

MEN 1 Gene Carriers: What kind of screening?

Back 26

Annual screening biochemically for calcium, PTH, gastrin, glucose, pancreatic polypeptide, prolactin, IGF-1, insulin, proinsulin


Periodically get imaging.

Front 27

All 3 types of MEN2 have what in common?

Back 27

Medullary Thyroid Cancer

Front 28

What is Medullary Thyroid Cancer
?

Back 28

Cancer of C-cells (parafollicular cells) of thyroid, derived from neural crest.

Front 29

Difference between MEN 2A and MEN 2B

Back 29

Both have medullary thyroid cancer and pheochromocytoma.

2A: Also has hyperparathyroidism. Non-endocrine Hirschsprungs, Cutaneous lichen amyloidosis


2B: Mucosal neuromas, marfanoid habitus

Front 30

Gene responsible for MEN 2 is on Chromosome ___

Back 30

10

Front 31

T/F
Defective RET gene that causes MEN Type 2 is inherited in autosomal dominant fashion

Back 31

T

Front 32

What is the normal gene product/function of RET, the gene that is mutated in MEN type 2?

Back 32

RET is essential for the development of the parasympathetic, sympathetic and enteric nervous systems and the kidney.

Gene product is RET protein, which is a receptor tyrosine kinase.

ONE mutated copy is sufficient to cause disease.

Front 33

Hirschsprung’s disease: what is it?

Back 33

dz—inactivating mutation –absent enteric ganglia, children present with megacolon

Front 34

Why is it important to ID gene carriers of MEN 2?

Back 34

To remove the thyroid before medullary thyroid cancer can develop.

Front 35

All new cases of Medullary Thyroid Cancer and Pheochromocytoma should undergo testing for ___ gene

Back 35

RET

Front 36

T/F For MEN, Patients have to have tumors in all organs to be considered affected.

Back 36

F

Front 37

Autoimmune Polyglandular Syndrome: Defn

Back 37

Autoimmune disease that affects >1 gland.

Front 38

Autoimmune Polyglandular Syndrome Type 1: What gene mutation?

Back 38

AIRE (autoimmune regulator) gene located on chromosome 21. This gene is involved in thymic suppression of T-cells that recognize self. Abnormality in the gene allows this population of T-cells to infiltrate and disrupt organ function

Front 39

Autoimmune Polyglandular Syndrome Type 1: Most common components

Back 39

Chronic mucocutaneous candidiasis *
Hypoparathyroidism *
Primary adrenal insufficiency *

Front 40

Autoimmune Polyglandular Syndrome Type 2: what gene mutation?

Back 40

only about 50% are familial

Front 41

Autoimmune Polyglandular Syndrome Type 1: Most common components

Back 41

<b>Primary adrenal insufficiency</b>: most important

Autoimmune thyroid disease
Type 1 DM
Primary hypogonadism

Front 42

medullary thyroid cancer and pheochromocytoma: characteristics of what?

Back 42

MEN 2 (A and B)