Pediatric Hypocalcemia Workup

Updated: Dec 05, 2016
  • Author: Yogangi Malhotra, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Laboratory Studies

The following should be assessed in patients with hypocalcemia:

  • Total and ionized serum calcium levels
  • Serum magnesium levels
  • Serum electrolyte and glucose levels
  • Phosphorus levels
  • Parathormone levels
  • Vitamin D metabolite (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) levels
  • Urine calcium, magnesium, phosphorus, and creatinine levels
  • Serum alkaline phosphatase levels

Total and ionized serum calcium levels

Measuring ionized calcium level is essential to differentiate true hypocalcemia from a mere decrease in total calcium concentration. A decrease in total calcium can be associated with low serum albumin concentration and abnormal pH.

Serum magnesium levels

Serum magnesium levels may be low in patients with hypocalcemia, which may not respond to calcium therapy if hypomagnesemia is not corrected. Severe hypomagnesemia (0.46 mmol/L) causes hypocalcemia by impairing the secretion and action of parathormone (PTH).

Serum electrolyte and glucose levels

Seizures and irritability in newborns and children can be associated with hypoglycemia and sodium abnormalities. Low bicarbonate levels and acidosis may be associated with Fanconi syndrome and renal tubular acidosis.

Phosphorus levels

Estimating the phosphate level is essential to establish the etiology of hypocalcemia. Phosphate levels are increased in cases of exogenous and endogenous phosphate loading and renal failure and are usually high in patients with hypoparathyroidism. Phosphate levels are low in cases of vitamin D abnormalities and rickets.

Parathormone levels

Hormone studies are indicated if hypocalcemia persists in the presence of normal magnesium and normal or elevated phosphate levels.

Low PTH levels suggest hypoparathyroidism; serum calcium rises in response to PTH challenge. Oppositely, PTH levels are elevated in patients with vitamin D abnormalities and pseudohypoparathyroidism, and calcium levels do not rise in response to PTH challenge.

The N -terminal fragment of PTH is the only biologically active fragment of PTH. It is difficult to measure because of its short half-life of 2-5 minutes. Circulating PTH levels are determined by assaying for intact PTH peptide.

Vitamin D metabolite (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) levels

These may be assessed, along with hormone concentrations, to eliminate uncommon causes of hypocalcemia (e.g., malabsorption, disorders of vitamin D metabolism).

Urine calcium, magnesium, phosphorus, and creatinine levels

These values should be assessed in patients with suspected renal tubular defects and renal failure. Urine should also be evaluated for pH, glucose, and protein.

In patients with renal defects, calcium excretion is high in presence of hypocalcemia. A urine calcium-to-creatinine ratio of more than 0.3 on a spot sample in presence of hypocalcemia suggests inappropriate excretion.

Serum alkaline phosphatase levels

Values are generally elevated in patients with rickets.

A practical approach to investigation of the etiology of hypocalcemia is a classification system based on the level of circulating PTH level in presence of hypocalcemia. A low/undetectable serum PTH level is seen in cases of hypoparathyroidism or hypomagnesemia. A normal PTH level is inappropriate and is seen in cases of abnormally functioning calcium sensing receptor. An elevated PTH level is a normal physiologic response. However, persistent hypocalcemia despite elevated PTH level indicates a vitamin D disorder or end-organ failure as seen in pseudohypoparathyroidism. [14]



Imaging Studies

Chest radiography - Evaluate for thymic shadow, which may be absent in patients with DiGeorge syndrome

Ankle and wrist radiography - Evaluate for evidence of rickets; changes appear at an early stage in the radius and ulna (the distal ends are widened, concave, and frayed)


Other Tests

Additional tests

Additional tests in the diagnosis of hypocalcemia include the following:

  • Malabsorption workup
  • Total lymphocyte and T-cell subset analyses - Findings are decreased in patients with DiGeorge syndrome
  • Electrocardiography - A prolonged QTc (>0.4 s), a prolonged ST segment, and T-wave abnormalities may be observed; measurements of specific intervals are of little value in predicting hypocalcemia (see the image below)
    Electrocardiogram (ECG) findings in severe hypocal Electrocardiogram (ECG) findings in severe hypocalcemia.
  • Karyotyping - To assess for 22q11 and 10p13 deletion
  • Maternal and family screening - This is helpful in familial forms of hypocalcemia, such as those caused by activating mutations of the calcium-sensing receptor