7. Parathyroid, Metabolic Bone Disease, Adrenals

Front 1

2 main cell types in parathyroid gland. What do they make?

Back 1

Chief cells- make PTH
Oxiphil cells- no known function (may be degenerative change of chief cells)

Front 2

Function of PTH

Back 2

Increased production when serum calcium is low

ACTIVATES VITAMIN D, Stimulates osteoclasts to liberate Ca from bone, increased Ca absorption from intestine, increased Ca absorption from renal tubule, increases phosphate excretion

Front 3

Symptoms of primary hyperparathyroidism

Back 3

Stones, bones, abdominal groans and psychic moans

Stones- Ca stones in kidney
Bones- Ca leaching from bone
Groans- Calcium --> constipations
Moans- Calcium leads to CNS side effects

Front 4

Mutations seen in sporadic parathyroid adenoma

Back 4

Activation of PRAD1 --> overexpression of cyclin D1

Mutations and resultant inactivation of MEN1

Front 5

mutations seen in familial primary hyperparathyroidism

Back 5

Mutations and inactivation of MEN1
RET mutation --> persistent tyrosine kinase activation (MEN2 syndrome)
CASR- calcium sensing receptor gene mutation

Front 6

Parathyroid adenoma- appearance

Back 6

Gross- solitary, enlarged, well circumscribed brown mass,
Micro- monotonous population of chief cells

Front 7

Parathyroid hyperplasia

Back 7

Enlargement of multiple parathyroid glands, predominately chief cells

Front 8

Parathyroid carcinoma

Back 8

resembles adenoma, but with evidence of invasion or metastasis

Front 9

Bone loss in hyperparathyroidism

End stage disease is called?

Back 9

Leads to bone pain, thinning of cortex more than medullary(trabecular/spongy/cancellous) bone

Osteitis fibrosa cystica

Front 10

Osteitis?
Dissecting osteitis?
Osteitis fibrosa?
Osteitis fibrosa cystica?

Back 10

Osteitis = increased osteoclastic activity
Dissecting osteitis= trabecular bone resorption
Osteitis fibrosa= osteoclast activity followed by osteoblast function --> reactive woven bone
Osteitis fibrosa cystica= Brown tumors, cystic areas of hemorrhage, hemosiderin-macs, granulation tissue

Front 11

Hyperparathyroidism complications due to hypercalcemia

Back 11

Metastatic calcification, nephrolithiasis

Front 12

Secondary hyperparathyroidism- causes

How will the parathyroid glands change?

Back 12

Low serum calcium levels (due to vit D deficiency, renal failure, increased phosphate levels) --> stimulation of parathyroid glands

Chief cell hyperplasia of multiple parathyroid glands

Front 13

Causes of hypoparathyroidism

Symptoms?

Back 13

Surgical excision of parathyroid glands
Congenital absence (digeorge)
Autoimmune (may involve adrenals too)

Hypocalcemic symptoms- tetany, mental status changes, cardiac conduction abnormalities, defective dental development

Front 14

What is osteoporosis?

Back 14

Reduced bone mass that is qualitatively normal, incomplete production followign resorption

Front 15

Factors which can cause osteporosis?

Back 15

Heredity
Increasing age
Decreased estrogen (menopause) --> increased osteoclast activity
Nutrition- calcium and vit D
Lack of weight bearing exercise
Corticosteroids

Front 16

Clinical features of osteoporosis

Back 16

osteopenia with increased risk of fracture (femoral neck, compression of vertebrae)
+ complications- scoliosis, pulmonary embolism

Front 17

components of menopause that contribute to osteoporosis

Components of aging that contribute

Back 17

Meno- decrease estrogen, increase IL1, IL6, TNF-alpha, increase RANK, RANKL, increase osteoclast activity

Aging- decreased replication of osteoprogenitor cells, decreased synthesis of osteoblasts, decreased biologic activity of matrix bound growth factors, reduced physical activity

Front 18

Describe formation of activated vitamin D

Back 18

7-dehydrocholesterol (in foods & sun exposed skin) moves into bloodstream and travels to liver. Here it is converted to 25 (OH)D, then travels to kidney to become 1,25 (OH)D

Front 19

Activation of vitamin D in the kidney is stimulated by?

Back 19

(the conversion in the kidneys is stimulated by low calcitriol, low Ca, low P)

Front 20

What is the most important factor which determines the effect of calcitriol on the bones?

Back 20

Serum calcium trumps everything else

If low, bones are cleaved to increase Ca
If normal, osteoid and epiphyseal cartilage is mineralized

Front 21

Why does Rickets present with an excess of osteoid?

Back 21

Vitamin D deficiency --> decreased Ca & P reabsorption in intestine --> activation of PTH --> resorption of bone/liberation of Ca & P

PTH also leads to increase renal wasting of P

As a result, there is more Ca (still relatively small amount) in the blood but less P. For this reason, the osteoid doesn't get mineralized as quickly.

Front 22

The overgrowth of cartilage in rickets give rise to what?

Back 22

frontal bossing, rachitic rosary, pigeon breast deformity, bowing of legs (as children age & begin to walk, pressure on cartilage --> bending)

Front 23

Lack of mineralization in kids? In adults? Associated features in adults?

Back 23

Rickets

Osteomalacia

Loss of bone density, increased susceptibility to fractures, kyphoscoliosis, bone pain,

Front 24

Severe vitamin D deficiency can lead to what muscular manifestations

Back 24

Hypocalcemic tetany

Front 25

Bone disease in white adults? Pathogenesis

Sites of involvement

Characterized by?

Back 25

Paget's disease of bone

Paramyxovirus (Measles) or other viral infection of osteoclasts (may also have genetic susceptibility)

multiple bones, usually axial skeleton and large bones of extremities

Disorganized and excessive bone formation

Front 26

Bone in Pagets disease of bone is _______

What compounds are identified which indicated the turbulent activities at the level of the bone?

Back 26

coarse, thick, disorganized (tile like arrangement)

-Increased serum alkaline phosphatase (due to increased osteoblastic activity)
-Increased hydroxyproline in serum and urine (due to increased collagen breakdown)

Front 27

Complications of Pagets disease of bone

Back 27

Bone pain, skeletal deformities, neural deficits (due to skull overgrowth), increased risk of fractures, cardiac failure, secondary sarcomas (due to excess osteoblast activity)

Front 28

Regions of adrenal cortex, products produced there

What color surrounds the adrenal gland? Why?

Back 28

Zona glomerulosa- makes aldosterone
Zona fasciculata- makes cortisol
Zona reticularis- makes sex hormones (androstenedione and DHEA)

Yellow, because the hormones produced there are biproducts of cholesterol

Front 29

Cushings syndrome vs Cushings disease

Back 29

Syndrome refers to elevated cortisol levels

Disease is a specific subtype which is caused by a central tumor (ACTH producing pituitary microadenoma)

Front 30

Ectopic CRH or ACTH --> cushing's syndrome. Where does it come from?

Back 30

The ectopic source is often a small cell carcinoma of the lung.

Front 31

ACTH independent cushings syndrome- what causes that?

Back 31

An adrenal mass that produces increased cortisol, REGARDLESS of ACTH levels

Front 32

How can we differentiate between ectopic cushings syndrome and cushings disease?

Back 32

High dose dexamethasone (high affinity cortisol)

If Cushings disease, dex will bind and inhibit ACTH release from pituitary --> decreased cortisol

If ectopic, ACTH is coming from another source and cortisol won't be decreased (effect on pituitary is minimal since it is largely atrophied due to excess cortisol)

Front 33

What is the crooke hyaline change

Back 33

Seen in ACTH producing cells in Cushing's syndrome. The inhibition of these cells caused by excess cortisol leads to degeneration and keratin filament accumulation

Front 34

Adrenal gland- what is the cause of the cushing syndrome if:

1. adrenal cortex atrophies (except glomerulosa)
2. diffuse adrenal cortex hyperplasia
3. Adrenal cortical neoplasm

Back 34

1. Taking exogenous cortisol- decreases ACTH (glomerulosa is spared because it's not under ACTH control)
2. ACTH dependent cushing syndrome
3. Neoplasm + atrophy of non-neoplastic adrenal cortex

Ex- huge zona fasiculata (neoplasm making cortisol inhibiting ACTH --> atrophy of zona reticularis)

Front 35

Symptoms of Cushings syndrome

Back 35

Obesity, moon face, buffalo hump, hirsuitism, weakness, emotional changes

Front 36

Primary hyperaldo- effect on renin levels?

Causes?

Back 36

Decreases Renin

Idiopathic- ZG overproduces
Adenoma- (Conn Syndrome)- rest of adrenal is fine- no impact on ACTH sensitivity
Rare glucocorticoid responsive hyperaldosteronism- ZG becomes responsive to ACTH

Front 37

Most common type of adrenal mass which can produce more than 1 hormone?

Back 37

Carcinoma

Front 38

Congenital adrenal hyperplasia- inheritance? Most common adrenal cause? Manifestations?

Pituitary cause?

Clinical features?

Back 38

AR
21-OH deficiency
Decreased cortisol --> increased ACTH --> adrenal cortical hyperplasia and increased androgens

Corticotroph hyperplasia- Increased ACTH

Decreased glucocorticoids +/- decreased mineralocorticoids & EXCESS ANDROGENS

Front 39

If a patient is taking high dose steroids, should the patient be weaned off the dose or should it be stopped abruptly? Why?

Back 39

Adrenal cortex gets used to exogenous corticosteroids and produces less. As a result, rapid withdrawl can lead to cortical insufficiency (adrenal crisis). Patients should taper down to allow their adrenal cortex to ramp up production.

Front 40

Adrenal hemorrhage caused by secondary infarction? (3)

Back 40

1. Newborns after difficult delivery
2. Hemorrhagic diathesis (DIC, anticoagulant therapy)
3. Bacterial sepsis (N. meningitidis--> Waterhouse-Friderichsen Syndrome)

Front 41

Addison disease- common cause

What do the adrenals look like?

Back 41

Adrenal cortex insufficiency

CC- Autoimmune adrenalitis- Autimmune polyendocrine syndrome type 1, AIRE gene mutations (autoimmune regulator)

Adrenals are small and filled with lymphocytes

Front 42

Other causes of Addison disease

Back 42

Infections (often in AIDS pts)- mycobacterium tuberculosis, histoplasma capsulatum, CMV, MAC --> destruction of adrenal gland (by organism and immune response)

Metastases
Congenital disorders

Front 43

Features of Addison disease

Back 43

Weakness, fatigue, NV, hypotension, hyponatremia, hypoglycemia, hyperkalemia, hyperpigmentation

Front 44

Secondary hypoadrenalism- do these patients have hyperpigmentation? What do the levels of adrenal hormones look like?

Back 44

Decreased ACTH secretion (not due to feedback) --> decreased cortisol and androgens, but no decrease in Aldosterone

Front 45

Adrenal cortical neoplasm- most common finding?

Name if cortisol producing?
If aldosterone producing?

What does the rest of the gland look like?

Back 45

Nothing, they are most often nonfunctional/benign. Cells are eosinophilic and vacuolated.

Cushing syndrome
Conn syndrome

Atrophic- due to feedback

Front 46

Adrenal carcinoma- what does it look like? What type of hormone profile do we expect to see?

How does it spread?

Back 46

Large infiltrative mass with hemorrhage and necrosis. Cells are anaplastic.

Most notably, often produces excess ANDROGENS.

Often spreads lymphatically and hematogenously

Front 47

What cells produce catecholamines? What are they derived from? Which catecholamine is produced more by these cells?

Back 47

Chromaffin cells, neural crest origin. Produce epinephrine more than norepinephrine.

Front 48

10% rule of pheochromocytoma

Back 48

10%:

arise outside adrenal paraganglion system
Are bilateral
Are malignant
Are not associated with HTN
Are familial
Arise in kids

Front 49

Of the rare familial pheos, what mutations are involved?

What is unique about the mass in a pheo?

Clinical features?

Back 49

MEN2A & 2B

Can turn dark brown due to catecholamine oxidation. May contains necrotic pockets.
Small clusters of neuroendocrine cells are separated by highly vascular connective tissue

HTN, palpitations, headache, sweaty

Front 50

Neuroblastoma- what is a neuroblast?

Who is affected by this?

Mostly familial or sporadic?

Where is it located?

Describe macro/microscopic appearance.

Back 50

An intermediate in the development of sympathetic neurons.

Usually children <5
Sporadic mostly
Adrenal medulla
Macro- soft, lobulated, calcifications and hemorrhage
Micro- Homer-Wright pseudorosettes (like medulloblastoma) with neurofilaments in center

Front 51

What types of transformation can be seen in a neuroblastoma?

Back 51

Neuroblastoma (malignant) --> ganglioblastoma (intermediate pronosis) --> ganglioneuroma (benign- fully matured cells)

Front 52

Spread of neuroblastoma

Back 52

Lymphatic and hematogenous

Front 53

Clinical findings in neuroblastoma

Prognostic indicators

Back 53

Increased urine homovanillic acid and vanillylmandelic acid (similar to pheo)

Age- >18 months is unfavorable
Stage- localized malignancies or mets restricted to liver, skin, bone marrow- favorable
Presence of ganglionic maturation- favorable
Hyperdiploidy- favorable, near diploidy- unfavorable
N-myc- unfavorable
1q/11q loss, 17 q gain- unfavorable