SM_190b: Calcium / Parathyroid / Bone Flashcards
Describe Ca homeostasis and actions of PTH
Ca homeostasis and actions of PTH
- Kidney -> Ca, which inhibits PTH
- Bone -> PO4
- Negative feedback from Ca and 1,25 Vitamin D on PTH
Describe etiologies of hypercalcemia
Hypercalcemia
- Vitaminosis D and A
- Immobility
- Thyrotoxicosis
- Adrenal insufficiency
- Milk alkali syndrome, multiple myeloma
- Infections: granulomatous (TB, fungal)
- Neoplasms
- Sarcoidosis
- Thiazides and other meds
- Rhabdomyolysis / renal FHH
- AIDS
- PTH, paraproteinemias
VITAMIN TRAP
PTH dependent hypercalcemia is commonly caused by ___ and ___
PTH dependent hypercalcemia is commonly caused by primary hyperparathyroidism and familial hypocalciuric hypercalcemia
Non-PTH dependent hypercalcemia is commonly caused by ____
Non-PTH dependent hypercalcemia is commonly caused by malignancy
Hypercalcemia presents with ___, ___, ___, and ___
Hypercalcemia presents with stones, bones, groans, and psychogenic overtones
Describe clinical features of hypercalcemia
Hypercalcemia clinical features
- Nephrolithiasis / nephrocalcinosis
- Arthralgias, myalgias, weakness
- Abdominal pain, constipation, nausea / vomiting
- Neurologic impairment: mild to severe
- Polyuria
- Shortened QT interval
- Increased symptoms with higher Ca levels (such as Ca ≥ 12 mg/dL)
(stones, bones, groans, and psychogenic overtones)
Hypercalcemia therapy first line is ____
Hypercalcemia therapy first line is to stop any offending medications / supplements
- Hydration
- Loop diuretics (furosemide) if indicated to induce calciuresis
- IV bisphosphonates (pamidronate, zoledronate)
- Calcitonin
- Glucocorticoids
- Dialysis
____ is the most common outpatient cause of hypercalcemia
Primary hyperparathyroidism is the most common outpatient cause of hypercalcemia
- Commonly in ≥ 50 years old
- Onset in childhood suggests hereditary disorder such as MEN 1 or 2A
Primary hyperparathyroidism is most commonly caused by ___
Primary hyperparathyroidism is most commonly caused by benign solitary parathyroid adenoma
- 85%: benign solitary parathyroid adenoma
- 5%: 2 adenomas present
- 10%: multiple gland hyperplasia (sporadic vs MEN 1 / 2A)
- Parathyroid malignancy is rare
Describe mechanism of primary hyperparathyroidism
Primary hyperparathyroidism mechanism
- Lack of negative feedback from Ca and 1,25 Vitamin D to PTH
Normal to high PTH and high Ca is ___
Normal to high PTH and high Ca is hyperparathyroidism
Low PTH and low Ca is ____
Low PTH and low Ca is hypoparathyroidism
Low PTH and high Ca is ___
Low PTH and high Ca is non-PTH hypercalcemia
Describe lab features of primary hyperparathyroidism
Primary hyperparathyroidism lab features
- High serum Ca with normal to elevated PTH
- Often low phosphorus levels present
- High / normal urine Ca: high serum Ca spills over into urine
Primary hyperparathyroidisim renal manifestations include ____ and ____
Primary hyperparathyroidisim renal manifestations include polyuria and nephrolithiasis / nephrocalcinosis
- Nephrolithiasis / nephrocalcinosis especially if 24 hr urine Ca > 300 mg
Describe bone manifestations of primary hyperparathyroidism
Primary hyperparathyroidism bone manifestations
- Osteoporosis / fractures / low bone mineral density
- Leads to more cortical bone loss (forearm) over trabecular
- Severe manifestations (osteitis fibrosa cystica) are rare: periosteal resorption in distal phalanges, bone cysts / brown tumors
Salt and pepper skull occurs in ____
Salt and pepper skull occurs in Salt and pepper skull occurs in hyperparathyroidism
Describe primary hyperparathyroidism treatment
Primary hyperparathyroidism treatment
- If asymptomatic: observe
- If symptomatic and / or progression likely: surgery
- Calcimimetics (cinacalcet): lower serum Ca by decreasing PTH secretion
Calcimimetics (cinacalcet) lower serum Ca by ____
Calcimimetics (cinacalcet) lower serum Ca by decreasing PTH secretion
Both primary hyperparathyroidism and familial hypocalciuric hypercalcemia have ____ and ____
Both primary hyperparathyroidism and familial hypocalciuric hypercalcemia have high serum Ca and normal to elevated PTH
Describe familial hypocalciuric hypercalcemia
Familial hypocalciuric hypercalcemia
- Autosomal dominant
- One allele of CaSR inactivated
- Hypercalcemia is mild
- Hypocalciuria
- PTH slightly elevated
Describe neonatal severe hyperparathyroidism
Neonatal severe hyperparathyroidism
- Autosomal recessive
- Both CaSR alleles inactivated
- Severe hypercalcemia
- Hypocalciuria
- PTH elevated
Fractional excretion of Ca: FeCa = ____
Fractional excretion of Ca: FeCa = [(UCa x PCr) / (UCr x PCa)] x 100
FeCa ____ in familial hypocalciuric hypercalcemia
FeCa < 1% in familial hypocalciuric hypercalcemia
Look for ___ in familial hypocalciuric hypercalcemia
Look for low urine Ca in familial hypocalciuric hypercalcemia
- Use 24 hour collection: calculate FeCa
- FMHx (autosomal dominant): relative with hypercalcemia, hypercalcemia known in infancy
- Treatment: observation, NO surgery
Humoral hypercalcemia mechanisms are ____, ____, and ____
Humoral hypercalcemia mechanisms are PTHrP, local bone resorption, and ectopic Vitamin D
Describe PTHrP mechanism of humoral hypercalcemia of malignancy
PTHrP mechanism of humoral hypercalcemia of malignancy
- PTh related peptide: factor primarily involved with chondrocyte replication at the growth plate
- Binds to PTH receptor
- Highly expressed in fetus and breast milk
- Commonly produced by squamous cell carcinoma of lung / neck / head and carcinoma of kidney and ovary
Measure PTHrP
Describe local bone resorption mechanism of humoral hypercalcemia of malignancy
Local bone resorption mechanism of humoral hypercalcemia of malignancy
- Via tumor cell production of osteolytic factors
- Multiple myeloma, breast cancer, prostate cancer, lymphoma
Check imaging (bone scan, X-rays)
Describe ectopic Vitamin D mechanism of humoral hypercalcemia of malignancy
Ectopic Vitamin D mechanism of humoral hypercalcemia of malignancy
- Ectopic Vitamin D 1,25-(OH)2 production: due to ectopic production of 1-alpha-hydroxylase, leukomia / lymphoma / renal cell cancer / granulomatous disease (TB, sarcoidosis)
Measure Vitamin D 1,25-(OH)2 level
Evaluation for humoral hypercalcemia of malignancy includes ____, ____, and ____
Evaluation for humoral hypercalcemia of malignancy includes measuring PTHrP, checking imaging (bone scan / X-rays), and Vitamin D 1,25-(OH)2 production
Describe the diagnostic algorithm for hypercalcemia
Diagnostic algorithm for hypercalcemia
Most commonly a low reported Ca is ___
Most commonly a low reported Ca is NOT true hypocalcemia
Correct serum Ca for ____
Correct serum Ca for albumin < 4.0 mg / dL
- Serum Ca is bound to circulating proteins: 40% bound to albumin and other proteins
- Low albumin leads to low total serum Ca measurement but the free (ionized) Ca is normal
Corrected Ca = _____
Corrected Ca = total measured Ca + [(4 - albumin) x 0.8]
- Add 0.8 to the total measured Ca for every 1 point the albumin is below 4
Describe clinical features of hypocalcemia
Hypocalcemia clinical features
- Neuromuscular irritability
- Paresthesias
- Chvostek’s / Trousseai’s signs
- Laryngospasm
- Bronchospasm
- Prolonged QT interval
- Seizures
- Tetany
Hypoparathyroidism can be ____, ____, or ____
Hypoparathyroidism can be destruction, congenital, or functional
- Destruction: surgical, autoimmune, destruction by ionizing radiation / infiltration
- Congenital (abnormal development): DiGeorge, velo-cardio-fascial syndrome
- Functional: hypomagnesemia (PTH secretion is dependent on Mg)
Describe hypocalcemia in renal failure
Hypocalcemia in renal failure
- Loss of renal responsiveness to PTH results in increased urinary Ca loss and decreased P excretion: develop secondary hyperparathyroidism
- Hyperphosphatemia reduces Ca solubility
- Reduced 1-alpha hydroxylase activity with reduced 1,25-(OH)2 Vitamin D production
Loss of renal responsiveness to PTH results in ____ urinary Ca loss and ____ P excretion
Loss of renal responsiveness to PTH results in increased urinary Ca loss and decreased P excretion
Describe treatment for hypocalcemia
Hypocalcemia treatment
- Ca (IV, oral)
- Vitamin D
- Calcitriol (Vitamin 1,25 D): in hypoparathyroidism, Vitamin D resistant rickets, renal failure
- Parathyroid hormone (Natpara)
Describe diagnostic algorithm for hypocalcemia
Hypocalcemia diagnostic algorithm
Rickets / osteomalacia are ____ due to ____, ____, or ____
Rickets / osteomalacia are defect in bone mineralization due to Vitamin D deficiency, Ca deficiency, and P deficiency
- P deficiency: malabsorption, phosphorus wasting conditions
Describe pathogenesis of Vitamin D deficiency in rickets and osteomalacia
Vitamin D deficiency in rickets and osteomalacia
- Chronic low Vitamin D
- Decrease in Ca absorption from gut
- Decrease in serum Ca and increase in PTH (secondary hyperparathyroidism)
- Increased urinary Ca reabsorpion and PO4 excretion
- Increased bone resorption
Serum Ca is preserved at expense of bone
Hypocalcemia and hypophosphatemia present only if severe long-standing Vitamin D deficiency
In Vitamin D deficiency causing rickets and osteomalacia, ____ is preserved at expense of bone
In Vitamin D deficiency causing rickets and osteomalacia, serum Ca is preserved at expense of bone
Rickets / osteomalacia clinical features are ____, ____, and ____
Rickets / osteomalacia clinical features are skeletal deformities, bone pain / fragility / fractures, and muscular hypotonia / weakness
- Bone pain, fragility, fractures: effect of secondary hyperparathyroidism
Descibe Vitamin D sources
Vitamin D sources
- Sun: need UVB rays to make Vitamin D
- Diet
- Limitations: where you live, body surface exposure, sunscreen, skin cancer risk, naturally dark skin tone, older age (less efficient at making Vitamin D)
Describe major causes of Vitamin D deficiency
Vitamin D deficiency causes
- lack of intake exposure
- Decreased skin synthesis
- Decreased bioavailability: intestinal malabsorption (Celiac), obesity
- Increased intestinal losses
Vitamin D 25-OH represents the ____ and should be measured to ____
Vitamin D 25-OH represents the storage form and should be measured to diagnose Vitamin D deficiency
Vitamin D 1,25-(OH)2 is the ____ form
Vitamin D 1,25-(OH)2 is the active form
- Due to secondary hyperparathyroidism: Vitamin D converted to this form
- Body tries to maintain this level in the normal range as much as possible
Describe treatment of rickets / osteomalacia
Rickets / osteomalacia
- Vitamin D2 (ergocalciferol): prescription
- Vitamin D (cholecalciferol): over the counter
- Ca: diet / supplements
- Calcitriol (Vitamin D 1,25(OH)2) if indicated: prescription
- Phosphate (if indicated)
Osteoporosis is ___
Osteoporosis is compromised bone strength prediposing to increased risk of fracture
- Bone strength: bone density and bone quality
Osteoporosis is T-score ____
Osteoporosis is T-score ≤ -2.5
(DXA)
(osteopenia is -2.5 < x < 1)
Describe pathogenesis of osteoporosis
Pathogenesis of osteoporosis
- Resorption > formation, increased bone loss, low peak bone mass
- Poor bone quality, low bone density, propensity to fall
Peak bone mass is ____
Peak bone mass is maximum bone mass or density achieved during a lifetime
- Strongest predictor of BMD in old age is BMD at younger age
- Skeletal sites reach maturity at different ages
___ is used to measure bone strength
DXA is used to measure bone strength
- T-score: SD compared to young adults
- Z-score: SD compared to age/sex-matched controls
As age increases, bone density ____ and fracture risk ____
As age increases, bone density decreases and fracture risk increases
Describe osteoporosis prevention
Osteoporosis prevention
- Maximize peal bone density achieved in adolescence: physical activity, adequate Ca and Vitamin D
- Minimize other causes: amenorrhea / hypogonadism, tobacco, alcohol, medications, eating disorders
- Health lifestyle interventions possible at any age
Antiresorptive osteoporosis therapy consists of ____, ____, ____, ____, and ____
Antiresorptive osteoporosis therapy consists of bisphosphonates, denosumab, selective estrogen receptor modulators, estrogen, and calcitonin
(post-menopausal women, men ≥ 50 years old)
Anabolic therapy for osteoporosis includes ____, ____, and ____
Anabolic therapy for osteoporosis includes teriparatide, abaloparatide, and romosozumab
(postmenopausal women, men ≥ 50 years old)
Paget’s disease is ____ caused by ____
Paget’s disease is hyperdynamic bone remodeling caused by increased osteoclast and osteoblast activity
- Etiology: viral (paramyxovirus)
- Often asymptomatic
- Detection by elevated alkaline phosphattase or incidental radiologic exam
Severity of Paget’s disease correlates with ___
Severity of Paget’s disease correlates with rise in alkaline phosphatase level
- Alkaline phosphatase is not specific to bone: osteoblasts, liver or intestine
- If of bone origin: represents any state of high bone turnover
Describe clinical features of Paget’s disease
Paget’s disease clinical features
- Characteristic features on radiograph and bone scan
- Degenerative changes: pain, nerve compression / entrapment, hearing loss
- Labs: normal serum Ca, normal P, normal PTH, high alkaline phosphatase
- Bony deformities
- Pathologic fracture with minimal trauma
- Increased bone vascularity: high output CHF
- Small risk of osteosarcoma development
Paget’s Disease therapy involves ___
Paget’s Disease therapy involves treatment to relieve symptoms and prevent complications
- NSAIDs / PT for pain
- Bisphosphonate therapy: cyclic oral or IV therapy highly effective in normalizing alkaline phosphatase levels and diminishing disease progression
- Calcitonin shown to decrease disease progression
