Day 12 Endocrine
Adjusted Calcium=_______
(4.0-actual albumin)*.8 + total calcium=adjusted calcium
Osteoporosis can be diagnosed in a patient with a T-score of ____ or lower
-2.5
The important assessment for osteoporosis Tx effectiveness is _____
-reduction of patient fractures -improved BMD -proper change in bone turnover
prolonged bed-rest plus subpar kidney function can cause bone ____1 (resorption/formation)___, and hypercalcemia
1 bone resorption
To test an anti-resorptive osteoporosis agent, you are looking for decreased bone ___1___, and markers you look for are ___2__
1 decreased resorption 2 collagen cross-links (NTx, CTx)
While bisphosphonates increase BMD, decrease bone turnover, and decrease fracture risk, worry about __1__ irritation, and ____2__ of the jaw
1 esophagus 2 osteonecrosis
To test an anabolic osteoporosis agent, you are looking for increased bone ___1___, and markers you look for are ___2__
1 increased bone formation 2 P1NP, bone specific alkaline phosphatase
In the KIDNEY, (with PTH), 25 (OH2) Vitamin D is turned into
1,25 vitaminD
______ is a steroid hormone that acts of nuclear transcription to increase calcium and phosphorous absorption in the gut and can stimulate bone resorption
1,25vitamin D
Granulomas have increased expression of _______, causing high levels of 1,25vitaminD
1-hydroxylase
what catalyzes 25(OH2)vitaminD to 1,25vitaminD
1-hydroxylase
You start preventative osteoporosis treatment if their FRAX assessment for osteoporotic fracture risk is greater than _1__% and their hip fracture risk is greater than _2_%
1. 20% 2. 3%
In the liver, vitamin D3 is turned into ____
25 (OH2) Vitamin D
If vitamin D deficiency precipitates from VERY severe liver disease, it is because ______ enzyme activity is impaired.
25-hydroxylase
______ is the precursor in the skin that is turned into vitamin D3
7-dehydrocholesterol
Vitamin ____ is a cofactor for vitamin D, so toxicity of it will increase bone resorption
A
______ is a drug that binds to hydroxyapatite in the bone that inhibits bone resorption. It has a long skeletal retention and low GI absorption.
Bisphosphonates (alendronate, Risedronate,Ibandronate)
______ sign is when you touch a patient's check and the corner of their mouth spasms. It is positive in patients with hypocalcemia
Chvostek's sign
____ syndrome is a genetic syndrome that is assocaited with abnormal parathyroid development, causing primary hypoparathyroidism
DiGeorge syndrome
_____ is a autosomal dominant syndrome that is classified as asymptomatic hypercalcemia. While the body responds and increases PTH, the kidney has a defect in his ca2+ sensing receptor, meaning urine calcium will be low
FHH
A patient with FHH can also have resistance to ______.
FSH, LH, and TSH
_______ is a genetic disorder that results from an *activating* mutation of the calcium sensing receptor in the kidney. So the kidney thinks you have too much serum calcium when in reality you don't. (Get ↓ PTH as a response) *Asymptomatic hypOcalcemia*
Familial Benign Hypocalcemia
pseudohypoparathyroidism results from an deficiency of _____. This results is multiple hormone resistance (not just PTH)
Gαs subunit
If a patient has: ↑ Ca2+ ↓PTH *↑PTH-rp* ↑ urine calcium ↓ phosphorus normal 1,25vitD think....
Humoral hypercalcemia of malignancy
_____ is systemic issue, where PTH-relatide peptide seen in *solid tumors* is secreted, causing *low PTH* hypercalcemia
Humoral hypercalcemia of malignancy
_______ is a therapeutic agent that binds to receptors on osteoclasts to reduce osteoclast activity. These have a very weak effect, due to tachyphylaxis.
Intranasal calcitonin
Hyperthyroidism, adrenal insufficiency, and pheochromocytoma are all endocrinopathies that cause hypercalcemia and a ___low/high PTH
LOW PTH
If a patient has: ↑ Ca2+ ↓PTH *↓PTH-rp* think....
Local osteolytic bone metastasis
_______ is a malignant cause of hypercalcemia via bone mets that cause bone lesions. The lesions, or destroyed bone, will leech Ca2+ out into the blood. Seen a lot in multiple myeloma and breast cancer
Local osteolytic bone metastasis
4-gland parathyroid adenoma involvement causing primary hyperPTH is associated with _____
MENI, MENIIA
In the proximal tubule of the kidney, calcium reabsorption is dependent on ____, not PTH
Na+ reabsorption and volume status
most common cause of primary hyperPTH is _____, causing elevated PTH levels
ONE (solitary) parathyroid adenoma
_______ is an enzyme inhibitor that decreases bone resorption and increases BMD. This is an oral drug, but is not yet FDA approved.....
Odanacatib (cathepsin K inhibitor)
Humoral hypercalcemia of malignancy is mediated by _____
PTH-relatide peptide
_____ sign is when you put a BP cuff on a patient, pump it up, and you elicit a carpal twitch. It is positive in patients with hypocalcemia
Trousseu's sign
Most of our vitamin D comes from the skin, produced via _____
UV radiation
treatment for ACUTE hypercalcemia
VOLUME repletion! (if bad, add a loop diuretic to increase calcium excretion from the kidney)
Fracture incidences in people with osteoporosis increase with ____
age
bone involvement of pseudo hypoparathyroidism is called _____, and includes rounded face and short 4th and 5th metacarpals
albright's hereditary osteodystrophy
Adjusted calcium is used to adjust for fluctuations in _____
albumin
Although not clinically available yet, _____ antibody is a therapy that aims to reduce the inhibition on Wnt signaling, allowing increased osteoblast activity
anti-sclerostin (romosozumab)
If a patients hypercalcemia is a result of a malignancy, you can use _______ to inhibit osteoclast bone resorption. It takes 2-4 days for full effect, to supplement with calcitonin
bisphosphonates
Fracture risk of patients with osteoporosis can be predicted using ______
bone mineral density and age
While a minor role _____, produced by C-cells in the thyroid, have negative affect of bone resorption and calcium release
calcitonin
_______ inhibit osteoclast action acutely, but due to tachyphalaxis, the therapeutic effect is short-lived
calcitonin
_____ deposits can cause cataracts and basal ganglia calcification in patients with low serum calcium
calcium
In a patient with familial benign hypocalcemia, do NOT try to normal calcium with _______, because you will induce hypercalciuria and renal insufficiency
calcium and vitamin D supplements
_____ is a really expensive calcium sensor agonist drug that will increase calcium excretion from the kidney. It is used for symptomatic patients who are poor surgical candidates
cinacalcet
Increased blood transfusions can cause in increased amount of ______, resulting in hypocalcemia
citrate
_____ is a monoclonal antibody that increases bone density, decreases bone turnober, and decreases fracture risk. It is administered subQ every 6months.
denosumab (anti-RANKL)
The _________ part of the kidney is the only one that is PTH depending
distal tubule
With low calcium, it will be ____(easier/harder)__ to elicit an action potential.
easier. You will have increased neuromuscular excitability
(T/F) vibration as a mechanical stimulus to stimulate bone growth is suggested.
false....
Bariactic surgery or intestinal/pancreatic disease can cause vitamin D deficiency because you have impaired ____ absorption
fat soluble vitamin
In acute stress release of ____ into the blood can bind to serum calcium, causing hypocalcemia
fatty acids
Severe osteoporosis is a T-score of -2.5 of lower plus ____
fragility fracture history
in patients with increase 1-hydroxylase activity, you can give _____ to decrease the enzyme's activity
glucocorticoids
In classic vitamin D deficiency, the first thing impaired is _______, which leads to hypocalcemia, and increased PTH (secondary hyperparathyroidism) and *decreased phosphorus*
gut calcium absorption
If you have acidosis, you will have __(↑↓)__ ionized calcium.
higher
The lower your BMD, the ___↑↓___ your fracture risk
higher
_____ are the most serious consequence from osteoporosis, severing limited social functioning of patients.
hip fractures
symptoms of: GI: consipation, anorexia, n/v, dyspepsia, PUD, pancreatitis CNS: lethargy>>coma Neuromuscular: weakness, hypotonia Heart: Short QT, arrythmia Renal: polyuria, stones, neurocalcinosis Musculoskeletal: myalgia Bone: osteoporosis are all symptoms associated with ____calcemia
hyPERcalcemia
In grnaulomatous diseases, will you see hypercalciuria or hypercalcemia first?
hypercalcuria
With alkalosis, you compensate with _____ (respiratory)
hyperventalation
PTH works at the kidneys by _____
increasing distal tubule Ca2+ reabsorption
Humoral hypercalcemia of malignancy __(is/is not)___ related to bone metastasis
is NOT
Calcium-sensing receptors located in the _____ act independently of PTH secretion (depending on serum calcium) to control calcium excretion.
kidney
If vitamin D deficiency is from reduced 1-hydroxylase activity, the enzyme issues precipitated from ______ issue.
kidney failure
Most common symptom of hyperPTH is ______
kidney stone
Patients with hypoparathyroidism have increased risk for kidney _____, since there is increase urine calcium excretion
kidney stones, nephrocalcinosis
_____ is a bipolar drug that can increase the setpoint for PTH secretion
lithium
BMP is a potential therapy for osteoporosis, but since it is non-specific, it is only used today _____
locally, at the site of a fracture, to promote its healing
_________ diuretics will increase urinary calcium EXCRETION by inhibiting calcium reabsorption.
loop diuretics (furosemide)
Calcium-sensing receptors in the kidney are located specifically in the ______, and are PTH independent
loop of henle
Osteomalacia, primary hyperparathryoidism, and myeloma can cause ___↑↓____ bone density
low bone density (low bone density is NOT just osteoporosis)
If you have alkalosis, you will have __(↑↓)__ ionized calcium.
lowered
_______ is an essential cofactor needed for ATPase function to produce and secrete PTH.
magnesium
_______ causes hypercalcemia and low PTH from exogenous source of calcium.
milk-alkali syndrome
PTH-relatide peptide does not affect 1-hydroxylase, so while the peptide will cause low PTH, this enzyme activity will be ____
normal
________ is a collagen disorder resulting in abnormal bone mineralization that can cause osteoporosis
osteogenesis inperfecta
______ is poor bone mineralization that results in diminished bone strength, and increased insufficiency fractures
osteomalacia (blue is calcification...not enough blue)
Fracture, loss of vertebral height, and low bone mass are diagnostic of _____
osteoporosis
Hypogonadism, glucocorticoid excess, decreased calcium absorption, immobilization, post-transplant, thyroid hormone excess, renal hypercalciuria are all secondary causes of _____
osteoporosis
______ is a skeletal disorder characterized by compromised bone strength, predisposing patient to fracture.
osteoporosis
kyphosis, hip fractures, and vertebral fractures are noted in the progression of _____
osteoporosis
Teriparatide (PTH) for therapeutic use of osteoporosis has a black box warning for ____, so the therapy is limited to 2yrs, and limited to very high risk patients with severe osteoporosis
osteosarcoma
If a patient with primary hypoparathyroidism is particularly difficult to manage, you can give them ______
parathyroid hormone (rhPTH) but it is not the first line choice
A person with labs that show ↑ Ca2+ ↓ phosphorus ↑ PTH ↑1,25 ↑ urinary calcium excretion think...
primary hyperPTH
______ causes low PTH, low calcium, increased phosphorous, and *↑ urinary cAMP after PTH injection*
primary hypoparathyroidism
parathyroid destruction (surgery, autoimmune) can cause _____
primary hypoparathyroidism
Neuromuscular excitability associated with hypocalcemia can cause ______, cardio issue
prolonged QT interval
________ is a disorder where you have normal feedback loops, but RESISTANCE to PTH. So while you have decreased calcium levels and increased phosphorus and *increased PTH* and after PTH infusion will have *low urine cAMP*
pseudohypoparathyroidism
If a patient has Gαs deficiency (as in pseudohypoparathyroidism) and the associated bone abnormalities, but NO hypocalcemia, this is called______
pseudopseudohypoparathyroidism
______ is a estrogeon receptor modulator, and while its shows to increase BMD, it has no effect on reducing fractures. (but does ↓ risk of ER+ breast cancer...)
raloxifene
_____ is when the kidney cannot do its job anymore. You INITIALLY get decreased excretion of phosphorous. This will initiate the FGF-23 feedback loop, decreasing 1,25vitD, increasing PTH, which will increase bone resorption for more calcium
renal failure
Unlike primary hypoparathyroidism, _____ treatment with NOT work for pseudo hypoparathyroidism, because patients have a PTH resistance.
rhPTH (artificial PTH)
_____ is osteomalacia in kids, causing bowed legs
rickets
PTH works at the bone by ____
stimulating bone resorption to release calcium from the bone into the blood
Bone ____ is comprised of many factors, including bone mass, architecture, turnoever, damage accumulation, and material properties
strength (note the decrease of architecture-struts-in the bone)
_______ is interestingly enough being used for osteoporosis, because rat models show that continue secretion of it will activate osteoclast activity, BUT a short burst of this will actually increase osteoblast activity
teriparatide (PTH!)
In vitamin D mediated hypercalcemia, the main source of calcium is from _____
the GI tract
90% of total body calcium is located in _____
the skeleton
_____ diuretics decrease sodium reabsorption which will increase calcium REABSORPTION. This is a good treatment for patient with Hx of kidney stones
thiazide diuretics
_____ is a diuretic that could lower urine calcium in hypoparathyroid paitents
thiazide diuretics
(T/F) hypercalcemia will cause volume depletion.
true....hypercalcemia causes increased kindney calcium/water excretion (diuresis), leading to volume depletion
_______ is a mesenchymal tumor that produces FGF-23, increasing calcium excretion and causing low bone mineralization
tumor-induced ostemalacia (TIO)
What is the distinguishing lab value between primary hyperPTH and FHH
urine calcium for primary hyperPTH, urine calcium is high (increased secretion by kidney for FHH, the kidney does not respond to PTH levels, so urine calcium excretion is low
Sunlight deprivation, and poor diet can cause _______ deficiency
vitamin D
To treat hypoparathyroidism, you can give high dose of ______ precursor and active metabolite. You do not have to worry about feedback, because there is not PTH
vitamin D (both vitamin D and 1,25 D)
If a patient has: ↑ca2+ ↑ phosphorus ↓PTH *↑↑ 25 (OH2) vitamin D* markedly elevated urine calcium think...
vitamin D toxicity
________ is caused by long-term excessive use of vitamin D.
vitamin D toxicity
______ is when a patient has normal levels of FGF-23, but it is degraded slower than normal. Therefore, it stays around and has effects longer, increasing calcium excretion and causing low bone mineralization
x-linked hypophosphatemic rickets (XLH)
(T/F) Magnesium deficiency can cause hypocalcemia
yes
(T/F) estrogen is a good possible treatment option for primary prevention.
you would think true.....but FALSE! while studies did show that estrogen reduced fractures, there was an increased of associated adverse events - like strokes and pulmonary emboli - that make estrogen not efficacious
with hypoparathyroidism, you will have ___(↑↓)___ urinary excretion of Calcium
↑ excretion, because low PTH signals means there is no signal to increase serum calcium