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Oncology Exam 4
Guest Speaker Liley Hypercalcemia of Malignancy H
| Question | Answer |
|---|---|
| Calcium Homeostasis | -reglulated by 2 sets of hormones (PTH and calcitonin) (PTH tell bones to break down bone tissue) --> increased clast activity; kidneys will hang on to ca2+; tell body to make more Vit D and increase ca2+ levels. Thyroid releases Calcitonin (stop osteolclast acitivty, and let ca2+ go in kidneys and homeostatic process |
| Hypercalcemia Malignancy (HCM) Epidemiology | -Most common metabolic complication associated with malignancy -Affects 2-30% of cancer patients -Occurs in both solid tumors and hematologic malignancies -Most commonly occurs in: Breast cancer, Lung cancer, Multiple myeloma *Breast – bone mets; Lung – PTHrP; Multiple myeloma – in the bones |
| Hypercalcemia Pathophysiology: Develops when normal homeostatic pathway is disrupted by excess of hormones. MOST COMMON CAUSES are? | Hyperparathyroidism OR Hypercalcemia of malignancy (HCM) |
| Hypercalcemia Pathophysiology: Result of any combination of three primary mechanisms consisting of? | -Increased bone resorption (⬆️ osteoclast activity) -Increased GI absorptions (⬆️Vitamin D) -Increased tubular reabsorption at the kidneys |
| HCM Pathophysiology: Osteolytic metastases? | -Tumor cells in bones produce cytokines -Increase osteoclastic bone resorption & suppress osteoblastic bone formation |
| HCM Pathophysiology: Tumor secretion of PTH related protein (PTHrP? | -Increase osteoclastic bone resorption -Increase renal tubular reabsorption -Typically seen in non-metastatic tumors |
| HCM Pathophysiology: Tumor production of Calcitriol? | -Active form of Vitamin D -Less common |
| Calcium Interpretation: What is the normal reference value | -serum Ca: 8.2-10.3 mg/dL -ionized (free) ca2+ 3.3-5.2 mg/dL |
| Calcium Interpretation: Calcium Distribution: | -40% bound to albumin -50% ionized (active form) -10% complexed ions |
| Calcium Interpretation: Must correct serum ca2+ for albumin level < 4 mg/dL. Formula is? | Corrected calcium = 4-serum albumin x 0.8 + measured serum Calcium |
| Practice 1: Corrected calcium Practice: Serum calcium: 11.5 mg/dL; Albumin: 2.5 g/dL. What is the corrected ca2+? | Corrected calcium = (4 – 2.5) x 0.8 + 11.5 Corrected calcium = 12.7 mg/dL |
| Practice 2: Corrected calcium Practice:Serum calcium: 12.3 mg/dL; Albumin: 1.8 g/dL. What is the corrected ca2+? | Corrected calcium = (4 – 1.8) x 0.8 + 12.3 Corrected calcium = 14.06 mg/dL |
| Calcium interpretation: <12 mg/dL: Classification? Symptoms? | Mild hypercalcemia; Asymptomatic or mild symptoms |
| Calcium interpretation: 12-14 mg/dL: Classification? Symptoms? | Moderate hypercalcemia; Tolerable symptoms (chronic), more significant symptoms if acute rise in calcium |
| Calcium interpretation: > 14 mg/dL: Classification? Symptoms? | Severe hypercalcemia; Symptomatic |
| Symptoms of Hypercalcemia are? | -Fatigue -Weakness -Anorexia -Cognitive dysfunction -Abdominal pain -Constipation |
| Signs of Hypercalcemia are? | -Elevated serum calcium levels -Dehydration (secondary to renal compensation of hypercalcemia) -Nephrolithiasis (kidney stones) -EKG changes |
| Other s/sx of hypercalcemia include? | Stones, bones, moans, and groans, and CV |
| Clinical manifestations in systems: Renal "Stones": Toxicity? | -Nephrolithiasis -can get that Nephrogenic diabetes insipidus -Defect in concentrating ability resulting in polyuria and polydipsia -Chronic renal failure |
| Clinical manifestations in systems: Skeletal "Bones": Toxicity? | -Bone pain -Osteoporosis |
| Clinical manifestations in systems: GI "Moans": Toxicity? | -Nausea/vomiting -Anorexia, weight loss -Abdominal pain -Constipation |
| Clinical manifestations in systems: Neuromuscular "Groans": Toxicity? | -Confusion, stupor, coma -Lethargy, fatigue -Weakness -Corneal calcification |
| Clinical manifestations in systems: Cardiovascular: Toxicity? | -Shortened QT interval -T-wave widening -Cardiac arrhythmias |
| Hypercalcemia: Diagnosis? | -Important to determine cause -90% of cases are a result of primary hyperparathyroidism or malignancy -Must rule out underlying malignancy |
| Diagnosis: | -Collect careful hx and physical examination: Clinical features of hypercalcemia; Possible causative diseases; Possible causative medications -Measure serum PTH: Suppressed PTH warrants intensive malignancy workup -Measure serum PTHrP: Confirmatory diagnostic test for humoral hypercalcemia; Not available everywhere; High PTHrP may predict poor response to bisphosphonates |
| Hypercalcemia Treatment Goals include? | -Lower serum calcium levels -Treat complications -Treat underlying disorder/malignancy |
| Aggressive Hydration: Normal Saline: | -Increases intravascular volume -Enhances urinary excretion of calcium -Immediate onset of action -Lowers serum calcium 1-1.5 mg/dL over first 24 hours |
| Aggressive Hydration: Monitor fluid status: | -Urine output 100-150 mL/hr -Caution in populations at increased risk of volume overload (heart failure, CKD, cirrhosis) -May need to administer loop diuretics with fluids |
| Discontinue Contributing Medications: Offending medications include? | -Thiazide diuretics -Lithium -Vitamin A intoxication (including analogs used to treat acne) -Calcium supplementation -Vitamin D supplementation -Calcium-containing antacids |
| Stop Bone Resorption by using what agents? | -Calcitonin -Bisphosphonates -Denosumab |
| Calcitonin Drug info? | -Inhibits bone resorption by interfering with osteoclast activity -Increases urinary calcium excretion -Weak effects, quick onset of action Onset of action: 4 to 6 hours Reduction in serum calcium: 1-2 mg/dL -Useful in combination with fluids for initial management Symptomatic Severe hypercalcemia (> 14 mg/dL) $$$$ |
| Calcitonin: Salmon calcitonin 4 to 8 IU/kg IM or SQ every 12 hours. This can? | -Can increase frequency up to every 6 to 8 hours -Nasal route--> not efficacious for hypercalcemia ⭐️ |
| Calcitonin: Tachyphylaxis may develop causing? (more than a week--> throw it out ⭐️) | -Downregulation of calcitonin receptors -Efficacy limited to ~48 to 72 hours |
| Bisphosphonates: Drug info? | -Adsorb to surface of bone hydroxyapatite -Interfere with osteoclast activity -Osteoclast apoptosis -Inhibits calcium release from bone -More potent than calcitonin -Onset of action: 48 to 72 hours |
| Pamidronate (Aredia): Drug info? | -Moderate hypercalcemia (Corrected Ca2+ 12-13.5 mg/dL) 60 to 90 mg IV as a singe dose administered over 2 to 24 hours -Severe hypercalcemia (Corrected Ca2+ >13.5 mg/dL) 90 mg IV as a single dose administered over 2 to 24 hours -Minimum of 7 days should elapse before administering second dose -Normalizes calcium in 60-70% of patients |
| Zoledronic acid (Zometa): Drug info? ⭐️ ⭐️know brand name for Exam | -Corrected Ca2+ > 12 mg/dL 4 mg IV as a single dose over 15 to 30 minutes -Minimum of 7 days should elapse before administering second dose -Normalizes calcium in 80-90% of patients *Hypercalcemia tx--> Zometa *minimum amount of team before it can be repeated--> 7 days |
| Denosumab (Xgeva): Drug info? ⭐️ (EXAM) | -RANK Ligand (RANKL) inhibitor -Prevents activation of osteoclasts--> reduction of bone resorption -FDA approved for treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy -Not first line treatment -Increasing evidence that denosumab may be as effective as IV bisphosphonate -May reduce risk of recurrence *brand name is different than for tx of Osteoporosis |
| Denosumab Dose? Onset of Action? Response? | D: 120 mg subcutaneously every week for 4 weeks, then monthly Onset: 3 to 10 days R: Normalized calcium in at least 70% of patients |
| Treatment recommendations: Mild HCM (<12 mg/dL)--> | -Ensure adequate hydration (can be oral) -Remove offending agents that may worsen HCM |
| Treatment recommendations: Moderate HCM (12-14 mg/dL)--> | -Chronic & asymptomatic OR mildly symptomatic Same as mild HCM -Acute increase in serum calcium or symptomatic Adequate IV hydration + IV bisphosphonate OR denosumab *target 100-150 ml/hr |
| Treatment recommendations: Severe HCM (>14 mg/dL)--> | -Adequate IV hydration + calcitonin + IV bisphosphonate OR denosumab *1 from each category |
| Treatment recommendations: Refractory HCM on IV bisphosphonate)--> | -Adequate IV hydration + denosumab |
| Treatment recommendations: Dialysis? | -Acute, life-threatening hypercalcemia OR -Unable to tolerate aggressive IV hydration |
| Summary of Hypercalcemia | -Result of osteolytic metastases, tumor PTHrP production, or calcitriol production -Correct serum calcium for low albumin (< 4 g/dL) -Classified as mild, moderate, or severe -Hydration is key (oral or IV depending on severity and presence of symptoms) -Bisphosphonates are recommended for moderate HCM (symptomatic) -Calcitonin + bisphosphonates are recommended for severe HCM |
Created by:
Xander635
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