Hypocalcemia
Low ionized calcium producing neuromuscular irritability; correct magnesium first if low.
Also known as: hypocalcemia, tetany, Chvostek sign, Trousseau sign, low calcium
Overview
Total calcium <8.5 mg/dL (corrected for albumin) or ionized calcium <4.65 mg/dL. Symptoms generally appear with ionized Ca <4.0 mg/dL, but acuity and chronicity matter more than absolute number.
Epidemiology
Common in hospitalized patients — present in up to 88% of ICU patients. Causes vary by setting: post-thyroidectomy in surgical patients, vitamin D deficiency in outpatients, pancreatitis and sepsis in critical care, hypomagnesemia in alcohol use and PPI users.
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Risk factors
- Hypoparathyroidism (post-surgical most common; autoimmune; DiGeorge)
- Vitamin D deficiency (low sunlight, malabsorption, CKD)
- Hypomagnesemia (alcohol, diuretics, PPIs, refeeding)
- Acute pancreatitis (saponification with necrotic fat)
- Massive transfusion (citrate binds calcium)
- Tumor lysis, rhabdomyolysis (hyperphosphatemia binds calcium)
- CKD (decreased 1,25-OH vitamin D; phosphate retention)
- Sepsis, critical illness
- Drugs: bisphosphonates, denosumab, calcitonin, foscarnet, fluoride toxicity, PPIs (via Mg loss)
- Pseudohypocalcemia from hypoalbuminemia — correct calcium (add 0.8 mg/dL per 1 g/dL albumin deficit) or measure ionized calcium
Pathophysiology
Calcium is regulated by PTH, vitamin D, and calcitonin. PTH increases bone resorption, renal calcium reabsorption, and 1-alpha-hydroxylation of vitamin D. Vitamin D increases intestinal absorption. Hypocalcemia results from failure of any of these mechanisms, increased calcium binding (citrate, phosphate, fat), or shifts in protein/pH (acidosis raises ionized Ca; alkalosis lowers it).
Clinical presentation
Symptoms
- Perioral and acral paresthesias (early)
- Muscle cramps, carpopedal spasm, tetany
- Anxiety, irritability, depression, confusion
- Seizure, laryngospasm, bronchospasm (severe)
- Symptoms more pronounced with rapid drops and alkalosis
Signs / physical exam
- Chvostek sign — twitch of upper lip / nasolabial fold with tapping over facial nerve anterior to ear (low sensitivity; positive in ~10% of normals)
- Trousseau sign — carpal spasm after 3 min of BP cuff inflation above SBP (more specific)
- Prolonged QTc on ECG; risk of torsades
- Stridor, laryngeal spasm in severe disease
- Hyperreflexia, papilledema, seizure in extreme cases
Classic findings
Patient on POD 1 after total thyroidectomy with perioral tingling, positive Trousseau, and prolonged QT.
Differential diagnosis
- Hypoalbuminemia (pseudohypocalcemia) — Total Ca low but ionized Ca normal; correct for albumin or measure ionized
- Hypoparathyroidism — Low PTH, low Ca, high phosphate; postsurgical most common
- Pseudohypoparathyroidism — HIGH PTH (resistance), low Ca, high phosphate; Albright osteodystrophy phenotype
- Vitamin D deficiency — Low 25-OH vitamin D; elevated PTH (secondary); low/normal Ca, low phosphate
- Hypomagnesemia — Mg <1.0; impairs PTH secretion and action; correct first
- Acute pancreatitis — Acute hypocalcemia with abdominal pain, elevated lipase; saponification
- CKD — Elevated phosphate, low 1,25-OH vitamin D, secondary HPT
- Hungry bone syndrome — After parathyroidectomy in long-standing severe HPT; profound Ca, PO4, Mg drop
- Citrate toxicity (massive transfusion) — Acute setting; ionized Ca low with normal total
- Tumor lysis / rhabdomyolysis — Hyperphosphatemia binds calcium
Diagnostic workup
Diagnostic criteria
Confirmed low ionized Ca + workup to identify underlying cause via PTH, magnesium, phosphate, vitamin D.
Labs
- Total calcium, corrected for albumin; ALWAYS confirm with ionized calcium in symptomatic or severe cases
- Magnesium (correct first if low — PTH is impaired by hypomagnesemia)
- Phosphate (low in vitamin D deficiency; high in hypoparathyroidism, CKD, tumor lysis)
- PTH (low or inappropriately normal in hypoparathyroidism; high in vitamin D deficiency, CKD, pseudohypoparathyroidism)
- 25-OH vitamin D, 1,25-OH vitamin D
- BMP (creatinine, glucose, albumin)
- Lipase (pancreatitis), CK (rhabdomyolysis)
- Uric acid, LDH (tumor lysis)
Imaging
- ECG — prolonged QT (>460 ms in men, >470 in women), risk of torsades
- Head CT/MRI in chronic disease (Fahr syndrome basal ganglia calcification)
- Slit-lamp for cataracts in chronic disease
- Renal ultrasound if longstanding (nephrocalcinosis from over-treatment)
Diagnostic algorithm
| Etiology | Ca | PTH | Phosphate | 25-OH vitamin D | Mg |
|---|---|---|---|---|---|
| Hypoparathyroidism | Low | Low / inappropriately normal | High | Normal | Normal |
| Pseudohypoparathyroidism | Low | HIGH | High | Normal | Normal |
| Vitamin D deficiency | Low / normal | High (2°) | Low | LOW | Normal |
| Hypomagnesemia | Low | Low / inappropriate | Variable | Variable | LOW |
| CKD | Low / normal | High | High | Low (1,25) | Variable |
| Acute pancreatitis | Low | Variable | Variable | Normal | Often low |
| Hungry bone | Low | Variable | Low | Variable | Low |
Complications
- Acute: tetany, laryngospasm, seizure, prolonged QT and arrhythmia (torsades de pointes)
- Heart failure, hypotension
- Chronic: cataracts, basal ganglia calcification (Fahr syndrome), parkinsonism, dementia
- Nephrolithiasis / nephrocalcinosis from over-replacement
- Osteomalacia or rickets (vitamin D deficiency)
- Hungry bone syndrome (post-parathyroidectomy)
PANCE pearls
- ALWAYS check and correct magnesium first — hypomagnesemia produces hypoparathyroid-like state.
- Check ionized calcium in any acute or severe presentation — total calcium misleads in albumin disturbance and alkalosis.
- Alkalosis (hyperventilation, blood gas analysis) shifts calcium to protein-bound form — produces tetany at normal total calcium.
- Treat acute symptomatic hypocalcemia with IV calcium gluconate; calcium chloride only via central line (vesicant).
- Chvostek can be positive in normal people; Trousseau is more specific.
- Post-thyroidectomy hypocalcemia is usually transient (recovery in days to weeks) but can be permanent. Monitor closely first 48-72 h.
References
- Endocrine Society 2016 — Management of Hypoparathyroidism: Summary Statement and Guidelines (Brandi et al., J Clin Endocrinol Metab 2016)
- ESE 2015 — European Society of Endocrinology Clinical Guideline: Treatment of Chronic Hypoparathyroidism (Bollerslev et al., Eur J Endocrinol 2015)
- AACE 2003 — American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism — and supplemental electrolyte guidance
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