Investigations
1st investigations to order
total serum calcium
Test
Hypercalcaemia is defined by an elevated serum calcium level. Total serum calcium measurements are influenced by serum albumin levels, and by calcium-binding immunoglobulins as in multiple myeloma.[1] Serum calcium measurements should ideally be obtained from specimens collected without the use of a tourniquet/cuff.
May be included in comprehensive metabolic panel.
Result
elevated
serum ionised calcium
Test
Some sources prefer measurement of serum ionised calcium to total serum calcium plus serum albumin, if available. Measurement of serum ionised calcium should be considered when factors that affect the accuracy of total serum calcium are present, such as abnormal serum albumin levels, and calcium-binding immunoglobulins as in multiple myeloma.[1] Serum calcium measurements should ideally be obtained from specimens collected without the use of a tourniquet/cuff.
Result
elevated
serum albumin
Test
For SI units (calcium in mmol/L; albumin in g/L), the formula for adjusted serum calcium is (0.02 x [normal albumin - patient's albumin]) + serum calcium. Calculation of albumin-adjusted total calcium is not required when ionised calcium is measured.
The formula for adjusted calcium may not be reliable in all circumstances (such as in critically ill patients).
May be included in comprehensive metabolic panel.
Result
variable
comprehensive metabolic panel
Test
May show elevated urea and creatinine in acute kidney injury; elevated bicarbonate level may indicate malignancy or exogenous calcium excess as a cause for hypercalcaemia.
Result
may show elevated urea or bicarbonate
resting ECG
Test
A resting ECG should be done to check the QT interval or other conduction abnormalities.
Result
may show shortened QT interval and dysrhythmias
serum intact parathyroid hormone
Test
Should be ordered for initial biochemical assessment of hypercalcaemia to distinguish between parathyroid hormone (PTH)-mediated hypercalcaemia and non-PTH-mediated hypercalcaemia. Malignancy-associated hypercalcaemia generally leads to appropriate suppression of PTH secretion by the parathyroid gland. However, co-existing malignancy and primary hyperparathyroidism should be excluded. Rare scenarios in which PTH is inappropriately normal or elevated despite the presence of hypercalcaemia include malignancy-associated hypercalcaemia plus concurrent primary hyperparathyroidism, or patients with PTH-secreting tumours.[1][5][24]
Result
elevated in PTH-mediated hypercalcaemia (e.g., primary hyperparathyroidism, tertiary hyperparathyroidism); suppressed in malignancy-associated hypercalcaemia unless concurrent primary hyperparathyroidism is present or ectopic PTH (rare)
serum parathyroid hormone-related peptide
Test
Should be ordered if initial PTH level is low or if PTH level is normal to high despite the presence of a known malignancy. Humoral hypercalcaemia of malignancy results from tumour secretion of parathyroid hormone-related peptide (PTHrP). This mechanism accounts for 80% of cases of malignancy-associated hypercalcaemia. An elevated PTHrP in combination with a suppressed PTH confirms the diagnosis. In rare cases, an elevated PTRHrP in combination with an elevated PTH suggests concurrent humoral hypercalcaemia of malignancy plus primary hyperparathyroidism.[1][5][10][11][24]
Result
elevated in humoral hypercalcaemia of malignancy (PTHrP-mediated hypercalcaemia)
serum phosphorus
Test
In humoral hypercalcaemia of malignancy, PTHrP acts at the level of the kidney to reduce calcium clearance, as well as to reduce the renal phosphorus threshold, leading to hyperphosphaturia and hypophosphataemia.[1][5]
May be included in comprehensive metabolic panel.
Result
low in humoral hypercalcaemia of malignancy (PTHrP-mediated hypercalcaemia)
serum calcitriol (1,25-dihydroxyvitamin D)
Test
Should be ordered if initial PTH level is low in the presence of lymphoma and/or granulomatous disease is suspected. Dysregulated production of calcitriol (1,25-dihydroxyvitamin D) can occur in lymphoma cells or neighbouring normal cells.
Result
elevated in calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcaemia
serum 25-hydroxyvitamin D
Test
Serum 25-hydroxyvitamin D should be checked if intravenous administration of bisphosphonate or subcutaneous denosumab is being considered, as vitamin D deficiency needs to be corrected prior to administration to avoid the risk of hypocalcaemia and, possibly, osteonecrosis of the jaw.[17][18][19][20]
Result
excludes vitamin D deficiency prior to bisphosphonate or denosumab use
Investigations to consider
skeletal survey
Test
A skeletal survey should be done in patients in whom multiple myeloma, bone metastases, or leukaemia is suspected.
Result
may show osteopenia, osteolytic lesions, or pathological fractures
chest x-ray
Test
Hilar and/or paratracheal adenopathy with upper lobe predominant bilateral infiltrates are seen in sarcoidosis. A central mass, hilar lymphadenopathy, or pleural effusion may be seen in lung cancer. May show typical infiltrates, effusions, or cavitation in tuberculosis (TB).
Result
may show typical findings of lung cancer, TB, or sarcoidosis
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