What are the clinical features of hypocalcemia?

Clinical Features of Hypocalcemia

Hypocalcemia produces a spectrum of clinical manifestations ranging from subtle neuromuscular irritability to life-threatening cardiac arrhythmias and seizures, with severity determined primarily by the rapidity of calcium decline rather than the absolute calcium level. 1

Neuromuscular Manifestations

The hallmark clinical features of hypocalcemia are neuromuscular irritability and tetany, which occur due to increased neuronal excitability when extracellular calcium falls below critical thresholds. 1, 2

Classic Physical Examination Signs

• Chvostek's sign (facial muscle twitching when tapping the facial nerve anterior to the ear) indicates moderate hypocalcemia with neuromuscular irritability 1, 3
• Trousseau's sign (carpopedal spasm induced by inflating a blood pressure cuff above systolic pressure for 3 minutes) is a more specific indicator of moderate hypocalcemia 1, 3
• Tetany with focal or generalized tonic muscle contractions represents severe hypocalcemia requiring urgent treatment 1
• Laryngospasm and bronchospasm are life-threatening complications that can cause airway obstruction in severe hypocalcemia 1

Sensory and Motor Symptoms

• Paresthesias (tingling/numbness) of hands, feet, and perioral region are among the most common early symptoms 1
• Muscle cramps and spasms occur frequently and may be mistaken for musculoskeletal pain 1
• Cramping pain in the lower legs or feet should specifically prompt consideration of hypocalcemia as the underlying cause 1

Neurological and Psychiatric Manifestations

Hypocalcemia affects the central nervous system through altered neurotransmission in the basal ganglia and increased neuronal excitability, producing a wide range of neuropsychiatric symptoms. 4, 5

Seizures and Altered Mental Status

• Seizures may be the first presenting sign of hypocalcemia, particularly in patients with underlying seizure disorders or genetic predisposition 1
• Confusion or altered mental status can occur in severe hypocalcemia 1
• Seizures can occur at any age in patients with underlying parathyroid dysfunction, even without prior history of hypocalcemia 1

Movement Disorders

• Extrapyramidal symptoms including dystonia, myoclonus, tremors, motor tics, and parkinsonism-like symptoms can be induced or worsened by hypocalcemia 4
• Movement disorders are particularly common in patients with 22q11.2 deletion syndrome, who have an 80% lifetime prevalence of hypocalcemia 4

Psychiatric Symptoms

• Irritability and emotional changes are common neurological symptoms 1
• Behavioral changes such as anxiety or depression can be associated with hypocalcemia 1
• Acute psychosis with visual and auditory hallucinations, paranoid delusions, and thought broadcasting can occur in severe cases and resolves rapidly with calcium correction 5
• Symptoms may include weakness, fatigue, memory loss, confusion, delusions, and hallucinations 3

Cardiovascular Manifestations

Calcium is essential for myocardial contractility and cardiac conduction; hypocalcemia produces characteristic ECG changes and increases arrhythmia risk. 1

Electrocardiographic Changes

• Prolongation of the QT interval is the hallmark ECG finding and predicts risk for cardiac arrhythmias including torsades de pointes 1
• A rise of 0.1 pH unit reduces ionized calcium by approximately 0.05 mmol/L, further lengthening the QT interval 1

Arrhythmias and Hemodynamic Effects

• Cardiac arrhythmias including ventricular tachycardia and fibrillation can occur 1
• Ionized calcium below 0.8 mmol/L is linked to cardiac dysrhythmias and mandates immediate correction 1
• Ionized calcium below 0.9 mmol/L predicts higher mortality and transfusion requirements in critically bleeding patients, outperforming fibrinogen, acidosis, or platelet count as a prognostic marker 1
• Cardiomyopathy can rarely be a complication of chronic hypocalcemia 1

Severity Classification

Clinical manifestations correlate with both the absolute calcium level and the rate of decline, allowing stratification into mild, moderate, and severe categories. 1

Mild Hypocalcemia

• Corrected calcium 8.0–8.4 mg/dL or ionized calcium 1.0–1.12 mmol/L 1
• May be asymptomatic or cause only subtle symptoms such as fatigue and mild paresthesias 1

Moderate Hypocalcemia

• Corrected calcium 7.0–8.0 mg/dL 1
• Typically produces Chvostek's and Trousseau's signs, muscle cramps, and paresthesias 1

Severe Hypocalcemia

• Corrected calcium <7.0 mg/dL or ionized calcium <0.75 mmol/L 1
• Causes tetany, seizures, laryngospasm, cardiac arrhythmias, and altered mental status requiring immediate intravenous calcium replacement 1

Special Clinical Contexts and Precipitating Factors

Biological stressors unmask or worsen hypocalcemia in predisposed individuals, particularly those with underlying parathyroid dysfunction. 1, 4

High-Risk Periods

• Surgery, fractures, or injuries increase the risk of symptomatic hypocalcemia 1
• Childbirth, acute illness, puberty, and pregnancy are risk factors 1
• Perioperative periods require targeted calcium monitoring 1

Dietary and Lifestyle Factors

• Decreased oral calcium intake can contribute to hypocalcemia 1
• Alcohol consumption can worsen hypocalcemia 1, 4
• Carbonated beverages, especially colas, may worsen hypocalcemia 1, 4

Special Populations

• Patients with 22q11.2 deletion syndrome have an 80% lifetime prevalence of hypocalcemia due to hypoparathyroidism, which may arise or recur at any age despite apparent childhood resolution 1, 4
• Early neonatal hypocalcemia develops rapidly within the first 24–48 hours after birth due to interruption of placental calcium transfer and immature hormonal regulation 1, 6
• Chronic kidney disease patients are at high risk due to impaired vitamin D activation and phosphate retention 1

Critical Clinical Pitfalls

• Symptoms of hypocalcemia may be confused with primary psychiatric conditions such as depression, anxiety, or psychosis, leading to delayed diagnosis and inappropriate treatment 1, 5
• Foot or leg pain should not be dismissed as purely musculoskeletal without assessing calcium and magnesium levels, particularly in patients with risk factors such as prior neck surgery, chronic kidney disease, genetic syndromes, or bisphosphonate therapy 1
• Hypocalcemia in new-onset seizure patients is uncommon but must be considered, particularly in patients with cancer, renal failure, or malnutrition 1
• Rapid development of hypocalcemia produces more severe symptoms than chronic hypocalcemia at the same absolute calcium level, due to lack of compensatory mechanisms 2, 3