HYPERCALCEMIA

Dr Fatima Sajid
 OUTLINE

 Normal serum calcium values

 Calcium Metabolism
 Etiology of hypercalcemia
 Mechanism of Hypercalcemia of Malignancy
 Clinical manifestations
 Diagnostic approach
 Treatment
 When to admit
 SOURCES

 Current Medical Diagnosis & Treatment 2019

 Manual of Clinical Oncology- A Lippincott Manual 7 th Edition
 Uptodate
 INTERPRETATION OF SERUM CALCIUM

 Normal serum calcium values

 2.2 to 2.7 mmol/L
 8.5 to 10.5 mg/dl
 4.3 to 5.3 mEq/L

 Calcium in serum is bound to proteins, principally albumin

 total serum calcium concentrations in patients with low or high serum
albumin levels may not accurately reflect the physiologically important
ionized (or free) calcium concentration
CALCIUM METABOLISM

2
1
 ETIOLOGY

HYPERCALCEMIA

2. ↑Calcium
1. ↑Bone resorption
Absorption

Hyperparathyroidism Malignancy Hyperthyroidism Hpervitaminosis A Immobilization Pagets Disease

Primary

Secondary/ Tertiary
 ETIOLOGY

HYPERCALCEMIA

2. ↑Calcium
1. ↑Bone resorption
Absorption

↑Calcium Intake Hypervitaminosis D

spontaneous
↑Vit D ( Calcidiol, Endogenous idiopathic excess
CKD
calcitriol, calcipotriol) production production of calcitriol
( macrophages)

Milk Alkali syndrome Malignant lymphoma

Granulomatous
diseases (Wegeners,
sarcoidosisi)
 ETIOLOGY

 Lithium
 Thiazide diuretics - with an underlying increase in bone
resorption
 Theophylline toxicity
 Pheochromocytoma - MEN2 or tumoral production of PTHrP
 Adrenal insufficiency
 Familial hypocalciuric hypercalcemia
 Congenital lactase deficiency
 HYPERCALCEMIA OF MALIGNANCY:
MECHANISMS

Hypercalcemia
Of Malignancy

1,25-
PTHrP Metastases dihydroxyvitamin PTH
D
 HYPERCALCEMIA OF MALIGNANCY:
MECHANISMS
 Tumor secretion of PTHrP- ↑ PTHrp, ↓ PTH, N 1,25-OH Vit D
 Osteolytic metastases with local release of cytokines (including
osteoclast activating factors )- ↓ PTH, PTHrp, 1,25-OH Vit D
 Tumor production of 1,25-dihydroxyvitamin D ( calcitriol)
 Ectopic tumoral secretion of PTH

 Tumors rarely associated with hypercalcemia:

 Small cell
 Colorectal
 Prostate
 CLINICAL MANIFESTATION

 Mild hypercalcemia (calcium <12 mg /dL [3 mmol/L]) may be

asymptomatic
 Serum calcium of 12 to 14 mg /dL (3 to 3.5 mmol/L) may be well
tolerated chronically
 Early symptoms: Polyuria, nocturia, polydipsia, weakness
 Late: NVD, constipation, depression, vision, obtundation, coma
 Acute rise to these concentrations may cause marked symptom
CLINICAL MANIFESTATION
 CLINICAL MANIFESTATION

 Physical Findings
 No specific physical findings of hypercalcemia other than those that
might be related to an underlying disease
 Band keratopathy, a reflection of subepithelial calcium phosphate
deposits in the cornea
DIAGNOSTIC APPROACH

Raised serum
calcium

Check/ repeat (
albumin correction)

Hypercalcemia
confirmed on repeat

Measure PTH
DIAGNOSTIC APPROACH

Measure
PTH

Mid to upper
↑ normal/ minimally ↓
elvated

Primary
Primary Non PTH mediated
hyperparathyroidism
hyperparathyroidism hypercalcemia
likely/ FFH

Measure PTHrp, 1,
25 Vit D, 25 Vit D

PTHrp
DIAGNOSTIC APPROACH

PTHrp

↑ ↓

Hormonal
1, 25 hydroxyVit
hypercalcemia
D
of malignancy

↑ ↓

Lymphoma,
granulomatous 25 hydroxyVit D
diseases
DIAGNOSTIC APPROACH

25 hydroxyVit
D

↑ ↓

Measure SPEP, UPEP,

Vitmain D intoxication
free light chains

Abnormal Normal

Look for other causes:

Multiple myeloma Hyperthyroidism,
Hypervitaminosis A
 DIAGNOSTIC APPROACH

 Albumin-calcium correction
 In hypoalbuminemia, total serum calcium concentration may be normal
when serum ionized calcium is elevated.
 In hyperalbuminemia, pseudohypercalcemia
 Measured serum calcium concentration should be corrected for the
abnormality in albumin

 Calcium = Serum calcium + 0.02 * (Normal albumin – Patient albumin)

 DIAGNOSTIC APPROACH

 Other tests
 Serum phosphate concentration
 Raised in granulamtous disease, Vit D, TSH, milk-alkali, mets, immobilization
 Low in primary hyperPTH and PTHrp
 Urinary calcium excretion
 Raised in hyperparathyroidism and malignancy
 Low in milk-alkali, thiazide and FHH
 ALP
 Raised in hyperPTH and mets
 Normal in multiple myeloma
 Electrolytes
 Serum chloride levels raised in Pri hyperPTH
 Radiographs
 Nephrolithiasis, nephrocalcinosis, subperiosteal bone resorption
 TREATMENT

 INDICATIONS

 Acute rise to >3 with severe symptoms OR >3.5 mmol/L regardless of

symptoms – requires treatment

 degree of hypercalcemia, along with the rate of rise of serum calcium

concentration and determines symptoms
 Asymptomatic or mildly symptomatic (calcium <3 mmol/L) – no
immediate treatment
 3-3.5 mmol/L if chronic – may not require immediate treatment
 TREATMENT

 Mild hypercalcemia ( <3 mmol/L)

 Avoid factors that can aggravate hypercalcemia
 Adequate hydration (6-8 glasses of water per day)

 Moderate hypercalcemia (3-3.5mmol/L)

 If chronic, same as above
 If acute with changes in sensorium, treat as severe

 Severe hypercalcemia (>3.5 mmol/L)

 Immediate and to prevent recurrence
 Three pronged approach
CALCIUM METABOLISM

2
Calcitonin

1
Saline
CALCIUM METABOLISM

3
Bispohosp
honates
 TREATMENT

 Severe hypercalcemia (>3.5 mmol/L)

 Immediate therapy
1. Volume expansion - Isotonic saline at 200 to 300 mL/hour
2. Calcitonin
3. Bisphosphonates

4. Hemodialysis – 4.5-5 mmol/L with neurological symptoms OR

hypercalcemia with renal failure

Preventing recurrence in malignancy

IV ZA or pamidronate every three to four weeks. If refractory Denosumab
 TREATMENT

 Saline therapy
 Rate of saline infusion depends upon several factors
 200 to 300 mL/hour initially then adjusted to maintain the urine output
at 100 to 150 mL/hour
 If fluid overload, stop fluids, start loop diuretic

 Fluid intake/output and weight carefully monitored 2 -3

times/day. Consider CVP
 Electrolytes ( Ca, Mg, K) 8-12 hourly
 Target Serum calcium <3.5
 TREATMENT

 Calcitonin
 4 IU/kg I/M or S/C every 12 hours; doses can be increased up to 6 to
8IU/kg TDS

 Bisphosphonates
 Zoledronic acid (4mg IV in 100ml N/Saline over 15 minutes)
 Pamidronate (60 to 90 mg in 250-500ml N/Saline over 2 hours) in
hypercalcemia related to malignancy
 Doses maybe repeated 7-30 days
 Side effects: Osteonecrosis of jaw
 TREATMENT

 Glucocorticoids
 glucocorticoids (prednisone in a dose of 20 to 40 mg/day)
 In patients with increased calcitriol production

 Denosumab
 Refractory to bisphosphonates or contra indicated

 Calcimimetics
 Cinacelcet in severe hypercalcemia due to parathyroid carcinoma and in
secondary hyperparathyroidism
 TREATMENT

 Disease-specific approach

 Hyperparathyroidism- Correcting hyperparathyroidism, monitoring

complications
 Parathyroid carcinoma- Surgery, followed by medical
 Endogenous calcitriol production- low calcium diet, corticosteroids, and
treatment of the underlying disease
 Ingestion of calcitriol- Stop calcitriol, oral/IV hydration
 Ingestion of calcidiol- Glucocorticoids and ZA or pamidronate
 FHH- Not treated
TREATMENT
THANK YOU