This noon conference covered the differential diagnosis, workup, and treatment of hypercalcemia. Hypercalcemia can be caused by primary hyperparathyroidism, immobilization, vitamin D excess, familial hypocalciuric hypercalcemia, malignancy such as breast cancer or lymphoma, or certain medications. The workup involves measuring serum calcium, parathyroid hormone, vitamin D, and other labs. Treatment depends on the underlying cause but initially involves intravenous normal saline with or without furosemide to rehydrate the patient, followed by calcitonin or bisphosphonates. Denosumab may be used for hypercalcemia of malignancy.

1. Noon Conference
Anton Manyak
2/12/2019

2. © 2016 Virginia Mason Medical Center 2
Objectives
Hypercalcemia
• Differential
• Work up
• Treatment

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Question 1
20-year-old man is hospitalized after sustaining a pelvic fracture in an automobile
accident. One month into his hospitalization, the patient notes nausea and
anorexia. Before the injury, he was in good health and took no medications. Family
history is unremarkable. Current medications are enoxaparin and hydromorphone.
Physical examination reveals an alert, oriented, and thin patient. Blood pressure is
128/78 mm Hg, pulse rate is 88/min, and respiration rate is 16/min. Thyroid
examination reveals no goiter, and the lungs are clear to auscultation. The patient
is immobilized in bed and a pelvic external fixation device is in place. Neurologic
examination findings are unremarkable.
Laboratory studies show albumin 4.4 g/dL (44 g/L), calcium 12.6 mg/dL (3.15
mmol/L), creatinine 1.6 mg/dL (141.4 µmol/L), phosphorus 4.1 mg/dL (1.3
mmol/L), parathyroid hormone 7.1 pg/mL (7.1 ng/L), thyroid-stimulating hormone
0.3 µU/mL (0.3 mU/L), thyroxine (T4), free 1.1 ng/dL (14.2 pmol/L), 1,25-
Dihydroxy vitamin D 35.2 pg/mL (84.5 pmol/L), 25-Hydroxy vitamin D 38 ng/mL
(95 nmol/L).
Which of the following is the most likely cause of his hypercalcemia?
A. Acute kidney injury
B. Fracture-related hypercalcemia
C. Humoral hypercalcemia of malignancy
D. Hypercalcemia of immobilization
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Differential/Work up
• Hyperparathyroidism – primary,
secondary, and tertiary
• Immobilization
• Vitamin D excess – granulomatous
disease
• Familial Hypocalciuric Hypercalcemia
• Malignancy – breast, NSCLC, MM,
RCC, Lymphoma
• Meds – theophylline, thiazide,
lithium 4

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Question 2
A 78-year-old man is evaluated in the emergency department for a
1-week history of weakness, fatigue, nausea, and anorexia. Medical
history is remarkable for recurrent squamous cell carcinoma of the
lung treated with surgery and chemotherapy.
On physical examination, temperature is 37.2°C (99.0°F), blood
pressure is 90/60 mm Hg, pulse rate is 100/min, and respiration rate
is 20/min. Confusion, skin tenting, and bitemporal wasting are noted.
Laboratory studies show blood urea nitrogen 30 mg/dL, calcium 13.5
mg/dL, creatinine 1.9 mg/dL, phosphorus 2.4 mg/dL.
Which of the following is the most appropriate next step in
treatment for this patient?
A. 0.45% saline infusion
B. 0.45% saline infusion and furosemide
C. 0.9% saline infusion
D. 0.9% saline infusion and furosemide
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6. © 2016 Virginia Mason Medical Center
Treatment
1. Normal saline – a lot. Works now
a. Add furosemide ifhypervolemic
2. Calcitonin – works in the 1st 48h
3. Bisphosphonates – work in 2-4 days
a. Long-term use causes jaw necrosis
b. Can’t be used w/ severe renal insufficiency
4. Steroids if suspected granulomatous disease
5. Denosumab – for hypercalcemia of malignancy
refractory to bisphosphonates or w/ severe renal
impairment
a. Can cause profound and prolonged hypocalcemia
6. Dialysis
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7. © 2016 Virginia Mason Medical Center
Illness Scripts
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Primary Hyperparathyroidism
Malignancy-associated
Hypercalcemia
Pathophysiology Inappropriately elevated PTH Bone resorption vs PTHrP production
Epidemiology
Any age but usually 50-65
2F : 1M
Older
Most common: PTHrP
(Couldn’t find too much epidemiologic data on
broad topic)
Clinical
presentation
Bones, moans, stones, and psychiatric overtones
Same, but also weight loss, ?breast mass,
?SOB
Diagnostics
BMP (adjust for albumin)
PTH levels
Urinary calcium
VitD levels
Labs: BMP (adjust for albumin), PTH, PTHrP,
VitD levels, alpha-1 hydroxylase, UPEP/SPEP,
LDH
Imaging: CT Chest, Mammography, Bone scan
Therapeutics NS!!! +/- furosemide -> calcitonin -> bisphosphonates -> denosumab; dialysis?

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References
https://www.uptodate.com/contents/diagnostic-approach-to-
hypercalcemia?search=hypercalcemia&source=search_result&selectedTitle=1
~150&usage_type=default&display_rank=1
https://www.uptodate.com/contents/etiology-of-
hypercalcemia?search=hypercalcemia&topicRef=836&source=see_link
https://www.uptodate.com/contents/treatment-of-
hypercalcemia?search=hypercalcemia&topicRef=836&source=see_link
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683803/
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