Hypocalcemia

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

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 algorithm

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