Hypercalcemia of Malignancy Flashcards
What is Humoral Hypercalcemia of Malignancy (HHM)?
Caused by PTHrP production by tumors, stimulates bone resorption and renal calcium reabsorption, occurs in 80% of cases.
What is Local Osteolytic Hypercalcemia (LOH)?
Caused by cytokine production in osteolytic bone metastases, leads to local bone resorption and calcium release, occurs in 20% of cases.
What is Calcitriol-Mediated Hypercalcemia?
Caused by tumor production of 1,25(OH)2 vitamin D (calcitriol), stimulates intestinal calcium absorption and bone resorption, occurs in less than 1% of cases.
What is PTHrP?
Parathyroid Hormone–Related Peptide, homologous to the first 13 amino acids of PTH, binds to PTH/PTHrP receptor increasing bone resorption and decreasing renal calcium excretion.
Which cancer is most commonly associated with HHM?
Squamous cell carcinoma of the lung.
Name other cancers associated with HHM.
- Squamous cell carcinomas (head, neck, esophagus)
- Adenocarcinomas (breast, kidney, bladder, pancreas, ovary)
- Non-Hodgkin’s lymphoma
- Chronic myelogenous leukemia
What cancers are commonly associated with LOH?
- Breast cancer with skeletal metastases
- Multiple myeloma
- Lymphoma
What mechanism is involved in LOH?
Cytokines such as PTHrP, DKK1, interleukins, and prostaglandins stimulate local bone resorption.
Which cancers cause Calcitriol-Mediated Hypercalcemia?
Most commonly Hodgkin’s and non-Hodgkin’s lymphomas.
What are the diagnostic features of HHM?
Low PTH, high PTHrP, normal/low calcitriol.
What are the diagnostic features of LOH?
Low PTH, low PTHrP, normal/low calcitriol.
What are the diagnostic features of Calcitriol-Mediated Hypercalcemia?
Low PTH, low PTHrP, high calcitriol.
What initial tests are included in the diagnostic approach for hypercalcemia?
- PTH
- Creatinine
- CO2
- Phosphorus
If PTH is low, what should be suspected?
Malignancy.
What is the definition of a hypercalcemic crisis?
Serum calcium >14 mg/dL with symptoms.
List symptoms of hypercalcemic crisis.
- Nausea
- Vomiting
- Dehydration
- Mental status changes
- Acute kidney injury
- ECG changes (shortened QT interval, heart block, ST changes)
What are general treatment measures for hypercalcemia?
- Saline infusion (200–300 mL/hr)
- Calcitonin (4 IU/kg SQ/IM every 6–12 hours for 48 hours)
- Bisphosphonates (Zoledronic Acid, 4 mg IV over 15–30 minutes)
- Denosumab (120 mg SQ every 4 weeks if refractory)
- Dialysis for refractory cases
What treatment is specific for Calcitriol-Mediated Hypercalcemia?
Glucocorticoids (Prednisone 60 mg daily for 10 days).
What is the prognosis for hypercalcemia of malignancy?
Generally poor, median survival is 30 days, correlates with advanced malignancy.
What factors can improve outcomes in hypercalcemia of malignancy?
Response to antitumor therapy may improve outcomes.
Fill in the blank: HHM is caused by ______ from solid tumors.
[PTHrP]
Fill in the blank: LOH is caused by ______ from bone metastases.
[cytokines]
True or False: Calcitriol-Mediated Hypercalcemia is caused by PTHrP.
False.
