MOD 7

Question 1

Which receptors sense ca levels to produce pth?

Answer 1

If low Ca, CaSR receptors in PT gland sense this and act on various parts of body to increase Ca

Question 2

Effects of PTH on body

Answer 2

Directly: PTH incr Ca reabs in DCT and decr PO4 reabs in PCT, and stim 1a-hydroxylase which converts 25 to 1,25 active vit D (which induces osteoblast then osteoclast act in BONE, and enhances Ca abs via GUT)

Question 3

What does PTHrP (PTH related protein) do?

When is it clinically relevant?

Answer 3

simialr stuff to PTH
-binds to pthrp R in BONE incr osteoblast/clast causing hypercalc, and in kidney tubule

• can be stimulated to be produced by the growth factotrs made by tumor cells such as TGF-B
• examine if sus hypercalc of malig (most common is SCC!)

Question 4

Possible causes of hypercalc?

Answer 4

Endocrine disorders (MOST COMMON) in PTH prod
Malig (elev PTHrP or other factors)
Inflam disorders (eg sarcoidosis)
HIV illness
Drugs (thiazides and lithium, vitamins and sxe)

Question 5

Hypercalcemia caused by inflam disorders?

Answer 5

EG granulomatous disease can cause hypercal such as SARCOIDOSIS (common in NOLA), where a1-OH overexpressed in macros causing incr in vit D (so lots of pts with sacroidosis have hypercalc)

Question 6

Hypercalc caused by HIV?

Answer 6

takes more Ca for CaSR to sense, and then suppress PTH

Question 7

Hypercalc caused by drugs?

Answer 7

Thiazides- incr Ca in PCT causing modest Hypercalc, may look like hyperPTism
Lithium: incr CaSR set point (takes more Ca to be sensed to suppress PTH) causes secondary hyperPTism (persists)–tx is bisphophonates to protect from osteoporosis

Question 8

What is hyperparathyroidism usu from in most patients, and what are some dx levels?

Answer 8

PT gland tumor!

• pts on routine blood test will have incr Ca in urine (too much cant all get abs by kidneys so spills into urine), renal stones (since more Ca)
• elev Ca(blood/urine)/PTH/low PO4, and hgih alkaline phosphatase which is a marker for BONE TURNOVER

Question 9

What does superiosteal (eg phalanges) bone resorption indicate?

Answer 9

Hyperparathyroidism!

Question 10

Sx and assoc issues in hyperPTism?

Answer 10

wrist and hip bone loss (and vert), superiosteal (phalanges etc) bone resorp
-stuff like PUD and GI stuff, OSTEO FIBROTIC CYSTICA (if severe, cystic bones paces fill with brown fibrous “tumor” material whic is really osteoclasts and deposited hemosiderin from hemm causing bone pain)

Question 11

Tx for hyperPTism

Answer 11

surgery to remove PT gland, usu cured, can restore bone loss by giving Ca (bone hungry)

Question 12

Other causes of hyperparathyroidism

Answer 12

Familial primary HPTism -MEN

and Familial Hypocalciuric hypercalcemia

Question 13

Familial primary hyperPTism

MEN-1

Answer 13

This is MEN (Multiple Endocrine Neoplasia) (AD)
MEN 1- mutation in tsg MEN1 (which would noramlly encode menin) causing pit tumors (like prolactinoma), pancreatic endocrine tumors (ZE, vipoma, glucagonoma), or PT adenoma

Question 14

MEN-2A

Answer 14

activation of RET protooncogene which can cause pt hyperplasia, MEDULLARY THYROID CANCER (presents with amyloid in stroma), bilateral pheochromocytoma)

Question 15

Familial Hypocalciuric Hypercalcemia

Answer 15

AD due to loss of function of CASR gene mutation so Ca not sensed (like w lithium pts), so PTH not suppressed, need to screen for this before removing PT gland (dont do surgery if they have it)
-there will be LOW ca in the URINE! bc extra renal uptake by kidneys (unlike pirmary hyperPTism where it would be high)

Question 16

Malignancy Associated Hypercalcemia

Answer 16

usu with cancer
Ca usu hyper than in hyperPTism
High Ca so suppreses PTH levels, but PTHrP levels elev bc tumor (eg squamous and MANY other tumors in all systems have this)

Question 17

Tx for malig assoc hypercalc

Answer 17

Hydrate and give loop diuretics and NaCl like Lasix to cause Ca diuresis, calcitonin short term, and bisphosphonates long term control, gluco corticoids, denosumab if they have kidney disease (anti resorpbtive, works as well as bisphosphonates)

Question 18

Sarcoidosis induced hypercalcemia

Answer 18

v common in NOLA, most hypercalcURIC some hypercalcEMIC

• ELEV VIT D DUE TO EXTRA ENZ prod by macros in sarcoid granuloma
• can suppress by steroids nad chloroquine
• hypercalc can also occur from TB, histo, coccidiomycosis in southwest, bartonella

Question 19

What is sestamibi scan for

Answer 19

Dx for tumor of parathyroid gland!
give them this which is a radiolabeled tech99, taken up by PTH gland. if it disappears quickly its normal if it stays theres a tumor

Question 20

common PT adenoma sx (hyperPTH)

Answer 20

fractures esp in hip spine wrists / cortical areas

Question 21

what cancer can rel PTHrP

Answer 21

SCC (saline and calcitonin can tx, and surg)

Question 22

SPEP is for dx of

Answer 22

multiple myeloma

Question 23

What do sx of High vitamin D and High Ca2?

Answer 23

Possibly Sarcoidosis which incr vit D thus incr Ca2 which decr PTH, tx with CHloroquine

Question 24

What must you always do when looking at Pt Ca level?

Answer 24

correct it for albumin! so if low alb<4, ADD to Ca level

Question 25

``` What will Ca2+ levels, PTH levels, and general causes be in: Primary hyperPTHism SEcondary hyperPTHism Malignancy Inflamm ```

Answer 25

prim- High PTH causing high Ca from adenoma Sec- ??? from RF Malig- High Ca from PTHrP thus low PTH Inflam- high Ca from VIt D but low PTH (eg sarcoid etc)

Question 26

What can cause HYPOcalcemia?

Answer 26

PT issues, or Vit D deficiency

Question 27

Vit D deficiency causes

Answer 27

nutritional, sunlight, malabs, gastric bypass, cirrhosis, CKD, rickets

Question 28

PT issues that can cause hypocalc

Answer 28

hypo after surg, autoimm, gen pseudohypo, removal of PT causing hungry bone syndrome, drugs like bisphoshpoantes IV or denosumab sclerotic mestastases etc

Question 29

what does Ca/PO4, 24h urine ca, alk phos, and pth look like in vitamin D def labs>

Answer 29

low Ca and/or PO4 low urine Ca elev alk phos and PTH

Question 30

Radiographic findings in hypOcalc

Answer 30

skeletal pseudo fracture (break that doesn go thru entire thickness of bone)

Question 31

Vit D def tx

Answer 31

- ergocalciferol, vit D - creon suppl in pacnreatic insuff - tube feeding with cholecalciferol

Question 32

Rickets

Answer 32

can cause VITAMIN D DEF - bone pain, delayed growth, fracture and BOWING OF LEGS due to weak bones, hypotonia, cavities, not enough sunlight - Type I is defect in 1a enz, low 1,25, tx with Ca and calcitriol - Type II is defect in vit D rec binding of 1,25, 1,25 lvls high, tx with ergocalc, cholecal or calcitriol, Ca and PO

Question 33

Pseudohypoparathyroidism

Answer 33

RESISTANCe to PTH (body isnt responding), so hypocalc, hyperphos, elev PTH (more in females), 3 types 1a 1b 2

Question 34

1a pseudo

Answer 34

Albright's hereditary osteodystrophy AD, renal res to PTH, also to TSH gonadotropin and GHRH -sx: short 4th metacarpal, knuckle dimples -gene mut GNAS on 20q13 (GNAS is noramlly where PTH binds)

Question 35

1b pseudo

Answer 35

renal res to PTH again, many have TSH, no 1a phenotypic changes but DELAYED ERUPTION OF TEETH AND HYPOPLASIA OF DENTAL ENAMAL, also gnas assoc

Question 36

psuedo 2

Answer 36

TISSUES res to PTH, no skeletal or phenotypic changes

Question 37

Pseudo-psuedohypoparathyroidism

Answer 37

Phenotypic change of psuedohypoparathyroidism, but NO actual renal or skel resistance to pth!

Question 38

Most common cause of hypocalc?

Answer 38

Vit D Def

Question 39

Dif between psuedo and psuedopsuedo hypoparathyroidism

Answer 39

psuedo have RES to PTH whereas pseudopsuedo dont

Question 40

Common reasons for secondary osteo?

Answer 40

VIT D DEF hypercalciuria malabs hypogonadism in men

Question 41

Osteomalacia sx>

Answer 41

muscle weakness and bone pain esp hips, softening of bones caused by impaired bone met -inadeuqate levls of avail phos, ca or vit D, INADEQUATE BONE MINERALIZATION (RICKETS in kids), has bowing of the legs

Question 42

What will be positive in Celiacs pt when they eat gluten?

Answer 42

tTG-IgA IgA (anti endomysial antibody and abs against tissue translutaminase) both can cause anemia due to malabs and low albumin, low vit D causing elev PTH sx

Question 43

DXA scan

Answer 43

tests bone density, if negative may mean (-2.5 or less without fracture) osteoporosis (or could be celiacs with elev PTH from lack of vit D abs) which can cause osteomalacia (both cause low bone density)

Question 44

What bone dis can severe prolonged Vit D def cause?

Answer 44

Osteomalacia

Question 45

What do bisphosphonates do>

Answer 45

Tx for osteoporosis to decr bone RESORBP

Question 46

Dx of osteomalacia

Answer 46

biopsy of bone! rare so need hx (eg why isnt pt getting enough nutrients, is it celiacs or lack of vit d, nursing home etc)

Question 47

What coudl cause high PTH with hgih Ca? | How would you dx?

Answer 47

Hyperparathyroidism (primary or tertiary, secondary may not cause high Ca and may be kidney issue) Familial hypocalciuric hypercalcemia (but would be low in urine) Dx with sestamibi scan (cpd abs by overactive PTH gland)

Question 48

HyperpTH sx?

Answer 48

Stones, Bones, Groans etc

Question 49

FHH (familial hypOcalciuric hypercalcemia)

Answer 49

looks similar to hyperPTH, due to inactivating mutations in CASR gene, kidneys taking up more Ca -phenotype normal but hallmark is LOW URINE CA EXXCRETION and bone density may be normal, AD

Question 50

What might high ALP (hyperphosphatasia?) indicate

Answer 50

Pagets disease of the bone

Question 51

What might low ALP (Hypophosphatasia) cause (sx)

Answer 51

teeth fall out, fractures,

Question 52

What is GGT test for?

Answer 52

blood test to det cause of elev ALP | If bone disease, ONLY ALP will be elev! not ggt, otherwise if it is itll be liver dis or smth

Question 53

Paget's disease of the bone sx appearnce on CT pop

Answer 53

Osteoitis deformans--localized disorder of bone remodling, excessive boen resrption then formation of new woven bone which is more sus to fracture - sx: bone pain, joint pain etc, bowing, excessive warmth due to hypervasc, neurologic, common remodeling dis after osteoporosis, more common in older white males, - Cotton wool appearance on CT

Question 54

Paget's disease of the bone mutation

Answer 54

SQSTM1 gene mut (KNOW!)