Sandbox hypocalcemia

# Overview
Hypocalcemia, defined as a total serum calcium level (adjusted for albumin) of < 8.4 mg/dL (2.1 mmol/L) or an ionized Ca++ level of < 4.6 mg/dL (1.15 mmol/L), may manifest as an asymptomatic laboratory abnormality or a life-threatening condition requiring emergent correction.  Common causes of hypocalcemia include hypoalbuminemia, advanced chronic kidney disease, hypoparathyroidism, and vitamin D deficiency.  Patients with acute hypocalcemia usually experience symptoms of neuromuscular excitability (e.g., circumoral tingling and muscle cramping) and should receive intravenous calcium gluconate.  Chronic hypocalcemia may present as fatigue, weakness, neuropsychiatric disturbances, papilledema, and cataracts. In conjunction with oral calcium supplementation, treatment of longstanding hypocalcemia should be directed toward the underlying cause.

# Diagnostic Criteria
- The normal range of serum total calcium concentration in adults is 8.610.3 mg/dL (2.152.57 mmol/L).
- The normal range of ionized Ca++ concentration in adults is 4.655.28 mg/dL (1.161.32 mmol/L).
- Hypocalcemia is defined as a total serum calcium level (adjusted for albumin) of < 8.4 mg/dL (2.1 mmol/L) or an ionized Ca++ level of < 4.6 mg/dL (1.15 mmol/L).
- Adjustment of total serum calcium concentration for changes in plasma albumin level:

# Causes

## Common
- Hypoparathyroidism following parathyroidectomy or irradiation
- Vitamin D deficiency due to malabsorption, low dietary intake, or insufficient exposure to ultraviolet light
- Autoimmune disorders (e.g., activating antibodies against calcium-sensing receptors, autoimmune polyendocrine syndrome type 1)

## Rare
- Parathyroid hormone resistance
- Vitamin D resistance
- Hypomagnesemia
- Osteoblastic metastasis
- Autosomal dominant hypocalcemia

## Miscellaneous
- Excess phosphate absorption caused by enemas
- Massive phosphate release caused by tumor lysis syndrome, rhabdomyolysis, or crush injury
- Foscarnet
- Bisphosphonates
- Massive transfusion of large volumes of citrate-containing blood
- Acute pancreatitis
- Gadolinium salts in contrast media
- Critical illness
- Hungry bone syndrome
- Fanconi syndrome

# FIRE: Focused Initial Rapid Evaluation
Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.
Abbreviations:
amp, ampule;
D5W, 5% dextrose in water;
ECG, electrocardiography;
IV, intravenous;
QTc, corrected QT interval.

# Complete Diagnostic Approach

## Laboratory Differential Diagnosis of Hypocalcemia
Abbreviations:
ADHP, autosomal dominant hypoparathyroidism;
CKD, chronic kidney disease;
Cr, creatinine;
Def, deficiency;
HP, hyperphosphatemia;
HPTH, hypoparathyroidism;
PHP, pseudohypoparathyroidism;
VDDR, vitamin D-dependent rickets.

## Treatment of Chronic Hypocalcemia
- In conjunction with oral calcium supplementation, treatment of longstanding hypocalcemia should be directed toward the underlying cause.

### Oral Calcium Supplementation
- Dose: 5001000 mg of elemental calcium per day (maximum: 2000 mg QD)
- Goal: correction of serum calcium concentration to the low-normal range
- Check calcium levels once or twice per week
- Urinary calcium excretion should be monitored after the initiation of therapy.  Frank hypercalciuria (> 300 mg/day) is associated with impaired kidney function and development of nephrocalcinosis.

### Vitamin D Supplementation
- Calcitriol is the optimal modality in hypocalcemic patients associated with hypoparathyroidism, pseudohypoparathyroidism, and chronic kidney disease, as these states are characterized by a deficiency of 1,25(OH)2D.
- Dose: 0.250.50 mcg (capsule) or 1 mcg/mL (oral solution)
- Ergocalciferol is the preferred form in hypocalcemic patients associated with vitamin D malabsorption.
- Dose: 50,000 to 200,000 IU daily, concomitantly with calcium, six times per day.
- After treating vitamin D deficiency, recheck 25(OH)D in 1214 weeks.

# Dos
- Serum concentration of total calcium should be adjusted for  changes in plasma albumin level:
- For hypoparathyroidism, urinary and serum calcium and serum phosphate are measured weekly until stable levels are achieved.
- Intravenous calcium should be administered with caution in hypocalcemic patients receiving digoxin due to its membrane-sensitizing effects on excitable tissues.

# Don'ts
- Do not administer intravenous calcium gluconate in mild, chronic hypocalcemic state. IV therapy should be reserved for severe, symptomatic hypocalcemia.
- Calcium ions from the intravenous solutions may precipitate phosphate or bicarbonate and form insoluble salts.  If phosphate or bicarbonate administration is necessary, a separate IV line in another limb should be established.
- Hypocalcemia associated with hyperphosphatemia (as in tumor lysis syndrome or massive trauma) should not be treated with calcium until hyperphosphatemia is corrected.  Hemodialysis may be considered in this setting.