Endocrinology Part 4 Flashcards
What does calcitonin do in the kidney?
Small decrease in Ca2+ and PO4 reabsorption
How is calcitonin controlled?
Stimulation of CSR increases calcitonin secretion
What stimulates the osteoclast?
PTH binds PTHR-1 on osteoblast which produces osteoid, OPG, and RANKL –> RANKL binds RANK on the osteoclast –> osteoclast releases H+ and proteases
Why is salmon calcitonin used over human calcitonin?
Salmon calcitonin is less likely to breakdown and has increased affinity for the receptor
What hormone can reduce RANKL production and increase OPG production?
Estrogen –> by directly increasing PTH
Starting with cholecalciferol how is Vitamin D activated?
Cholecalciferol –> 25 hydroxylase in the liver ==> calcifediol –> 1-alpha-hydroxylase in the kidney ==> calcitriol (active)
How does vitamin D affect Ca2+ and PO4?
Increase both Ca2+ and PO4 by increasing abosrption in the GI tract
What can excess vitamin D cause?
Hypercalcemia, increase RANKL expression = more resorption
What does vitamin D do in the kidney?
Small increase in Ca2+ and PO4 reabsorption
How is vitamin D synthesis controlled?
PTH increases activation of 1-alpha-hydroxylase which increase concentration of activated vitamin D
What is the MOA of teriparatide?
PTH analog –> leads to increased bone formation
How is teriparatid supplied?
Injectable
What are the adverse effects of teriparatid?
Muscle/bone pain
Osteosarcoma
What is the MOA of calcitonin?
MOA of calcitonin? How is it supplied? What are the adverse effects?
Decrease osteoclast function –> leads to decreased bone resorption, overactive remodeling, and Ca2+
How is calcitonin supplied?
Injectable and nasal spray
What are the AE of calcitonin
Low incidence of N/V
What is the MOA of bisphosphonates?
Decrease osteoclast function –> leads to decreased bone resorption and overactive remodeling
How are bisphosphonates supplied?
Oral and injectable
What are the AE of bisphosphonates?
Esophagitis
jaw necrosis,
atypical femur fractures
What is the MOA of raloxifene?
SERM –> agonist to ER in bone and liver (decrease resorption, increase formation, decrease LDL), antagonist to ER breast and uterus
How is raloxifene supplied?
Oral
What are the AE of raloxifene
Inc risk of thromboembolism & hot flashes
MOA of cinacalcet
Calcimimetic –> increases activation of the CSR to decrease PTH
How is cinacalcet supplied?
Oral
What are the adverse effects of cinacalcet?
HypOcalcemia
How do loop diuretics affect calcium?
Decrease renal Ca2+ reabsorption
How do thiazide diuretics affect calcium?
Increase renal Ca2+ reabsorption
What can excess calcium supplementation cause?
HypERcalcemia
Constipation
Kidney stones
What is the MOA of denosumab?
Monoclonal antibody to RANKL –> decrease bone resorption
How is denosumab supplied?
Injectable
What are the AE of denosumab?
Risk of infections/malginancies
What are the symptoms of hypercalcemia?
Ion channel inhibition
Kidney
Cardiovascular
Soft tissue calcification Bone loss
HypERcalcemia - ion channel inhibition sx
Constipation N/V dec DTR's Depression Lethargy Confusion Memory loss
HypERcalcemia - kidney sx
Polyuria
Polydipsia
Kidney stones
HypERcalcemia - CV sx
BradyC
Sinus arrest
Dec QT
HypERcalcemia - soft tissue calcification sx
Pruritus Crunchy skin Pain/swelling joins Inflammation Risk of thromboembolism
What can cause hypercalcemia?
Parathyroid tumor excreting excess PTH
Humoral hypercalcemia of malignancy releasing PTHrP
Bone tumor releasing RANKL
Excess vitamin D
Hyperthyroidism
Lithium
Thiazide diuretics
How can hypercalcemia be treated?
Surgery of tumor, hydration, bisphosphonates, calcitonin, furosemide
Cinacalcet for PT tumor
High dose denosumab for bone tumor
What are the symptoms of hypocalcemia?
Muscle spasms Tetany Inc DTR's Paresthesia Hallucinations Seizures HF Inc QT Dry skin Brittle nails Hair loss
What can cause hypocalcemia?
Hypoparathyroidism (low PTH)
Psuedohypoparathyroidsim (low PTHR-1)
Vitamin D deficiency
Ca2+ complex formation due to blood transfusion or muscle damage
How can hypocalcemia be treated?
Treat the cause, give Ca2+/vitamin D supplementation, thiazide diuretics, off-label use of teriparatide
What is rickets?
rickets?
Inadequate mineralization of bone in children (thin cortical bone)
What are the symptoms of rickets?
the symptoms of rickets?
Short bones, deformities, fractures
What is osteomalacia? symptoms?
Inadequate mineralization of bone in adults (thin cortical bone)
Causes bone pain and fractures
What can cause inadequate mineralization of bone?
Vitamin D deficiency/activation problems,
low Ca2+,
low PO4-
How can inadequate mineralization be treated?
Treat the cause (ie. if caused by dilantin , d/c the drug)
Ca2+/vitamin D supplementation
What is Paget’s disease?
Localized hyperactive remodeling causing bone swelling, pain, fractures, and increased risk of sarcoma
What can cause Paget’s disease?
Genetics or a virus
How can Paget’s disease be treated?
Bisphosphonates and calcitonin
What is renal osteodystrophy?
Chronic renal failure coupled with excessive bone resorption
What can cause renal osteodystrophy?
Decreased activation of vitamin D –> decreases Ca2+ absorption in GI –> decreases fre e Ca2+ –> increases PTH –> increases resorption
Increased PO4 retention –> binds free Ca2+ –> increases PTH –> increases resorption
How can renal osteodystrophy be treated?
Ca2+ and activated vitamin D supplementation
Cinacalcet
Sevelamer
What is osteoporosis?
Loss of cortical bone resulting in thin/weak bone –> causes vertebral fractures, kyphosis, hip fractures, and wrist/forearm fractures
What can cause primary osteoporosis?
Menopause and age
considered normal
What can cause secondary osteoporosis?
Excess PTH Thyroid hormones Glucocorticoids Immobilization Chronic phenytoin Barbituates Heparin use
How can primary osteoporosis be diagnosed?
Measure BMD (Bone Mineral Density)
T > 2.5 sd below normal = osteoporosis
2.5 > T > 1 sd below normal = osteopenia
How is primary osteoporosis treated?
Excercise, fall prevention, diet
Ca2+/vitamin D supplementation
Bisphosphonates
Estrogens, raloxifene
Calcitonin
Teriparatide
Low dose denosumab
