Hypocalcaemia

Introduction

This page focuses on hypocalcaemia, a condition characterised by low calcium levels in the blood. Calcium is crucial for nerve function, muscle contraction, and bone health, making early recognition and treatment vital. This guide will cover the clinical manifestations, causes, diagnostic approach, and treatment strategies for hypocalcaemia.

Clinical Manifestations of Hypocalcaemia

Hypocalcaemia often presents with neuromuscular and cardiac symptoms, which can vary in severity based on the rate of onset and the degree of calcium deficiency.

  • Mild Symptoms:
    • Tetany: Increased nerve excitability leads to muscle spasms and cramps.
    • Paresthesias: Tingling, particularly around the mouth (perioral region).
    • Muscle cramps: Stiffness and painful contractions.
    • Confusion or emotional disturbances.
  • Severe Symptoms:
    • Seizures
    • Hypotension
    • Psychosis
    • Prolonged QT interval on ECG (may lead to arrhythmias such as Torsades de Pointes).
    • Carpopedal spasm (Trousseau’s sign).

Two notable bedside signs of hypocalcaemia include:

Sign Name Description Practical Usefulness
Chvostek’s Sign Facial spasm upon tapping the facial nerve anterior to the ear. Low positive predictive value; seen in up to 10% of normal individuals.
Trousseau’s Sign Carpal spasm after inflating a BP cuff above systolic pressure for 3 minutes. Specific but uncomfortable for patients, useful in diagnosing hypocalcaemia.

Corrected Calcium for Albumin

Because calcium in the blood is bound to albumin, it is necessary to correct serum calcium levels when albumin is low. This adjustment provides a more accurate reflection of the ionised (active) calcium.

The formula for corrected calcium is:

Corrected Calcium (mg/dL)=Measured Calcium (mg/dL)+0.8×(4.0−Albumin (g/dL))\text{Corrected Calcium (mg/dL)} = \text{Measured Calcium (mg/dL)} + 0.8 \times (4.0 - \text{Albumin (g/dL)})

Where:

  • 4.0 g/dL is the standard albumin concentration.
  • 0.8 mg/dL is the correction factor for each 1 g/dL of albumin below 4.0.

For mmol/L, a similar correction factor of 0.02 mmol/L for each 1 g/L of albumin below 40 g/L is used.

Aetiologies of Hypocalcaemia

Hypocalcaemia can be divided into PTH-dependent and PTH-independent causes. This categorisation helps streamline the diagnostic approach, as the parathyroid hormone is a central regulator of calcium metabolism.

Category Aetiology Description
PTH-Dependent Hypoparathyroidism Low PTH production due to surgical removal, autoimmune destruction, or genetic disorders (e.g., DiGeorge syndrome).
Hypomagnesaemia Low magnesium impairs PTH secretion and action.
PTH resistance Pseudohypoparathyroidism; end-organ resistance to PTH despite high levels of circulating PTH.
PTH-Independent Vitamin D deficiency Inadequate intake, malabsorption, or lack of sunlight exposure leading to reduced calcium absorption.
Chronic kidney disease (CKD) Impaired conversion of vitamin D to its active form (calcitriol), leading to secondary hyperparathyroidism.
Hyperphosphataemia Tumour lysis syndrome, rhabdomyolysis, or excessive phosphate ingestion causing calcium deposition.
Acute pancreatitis Calcium forms soaps in the pancreas, reducing serum calcium levels.
Medication-induced Bisphosphonates, phenytoin, citrate (from blood transfusions), and EDTA cause calcium chelation or reduce bone resorption.

Key Mechanisms:

  • PTH-dependent hypocalcaemia arises from insufficient PTH secretion or action.
  • PTH-independent hypocalcaemia is due to factors like vitamin D deficiency, kidney disease, or increased calcium binding by phosphate or other chelators.

Diagnostic Approach

To diagnose hypocalcaemia and determine its cause, a systematic evaluation of laboratory markers is crucial. The diagnostic workup typically follows these steps:

  1. Correct serum calcium for albumin to determine the true calcium status.
  2. Measure:
    • PTH: To distinguish PTH-dependent from PTH-independent causes.
    • Vitamin D: Both calcidiol (25-hydroxyvitamin D) and calcitriol (1,25-dihydroxyvitamin D).
    • Phosphate: To assess its relationship with PTH.
    • Magnesium: To rule out hypomagnesaemia, which can impair PTH secretion.
    • Creatinine: To evaluate kidney function, especially in CKD.

Laboratory findings for common causes of hypocalcaemia:

Condition PTH Level Phosphate Magnesium Calcitriol Creatinine
Hypoparathyroidism Low High Normal Low Normal
Hypomagnesaemia Low Normal Low Variable Normal
Vitamin D Deficiency High Normal/Low Normal Low Normal
CKD High High Variable Low Elevated

Treatment Strategies

Management of hypocalcaemia focuses on addressing the underlying cause while providing symptomatic relief through calcium and vitamin D supplementation. Treatments vary depending on severity and aetiology.

  1. Calcium Supplementation:
    • Oral Calcium: Typically calcium carbonate or calcium citrate. Calcium citrate is preferable in patients with low gastric acid (e.g., the elderly).
      • e.g. AdCal (1.5g) 1-2 tablets PO BD; Sandocal 1000 1 tablet PO BD
    • IV Calcium: Indicated in severe cases (e.g., tetany, seizures, or QT prolongation). Calcium gluconate is commonly used for intravenous replacement:
      • 10ml 10% Ca gluconate in 100ml 5% dextrose over 10 min, followed by 100ml 10% Ca gluconate in 1L normal saline or 5% dextrose given at 50-100ml/h
  2. Vitamin D Therapy:
    • Cholecalciferol (Vitamin D3): More effective than Vitamin D2 in raising calcidiol levels. Typical dosing ranges from 600–800 IU daily for mild deficiency, with higher doses in severe cases or malabsorption.
    • Calcitriol: Preferred in patients with CKD or hypoparathyroidism, where conversion of inactive vitamin D is impaired.
  3. Magnesium Supplementation:
    • If hypomagnesaemia is contributing to hypocalcaemia, IV magnesium sulfate (1-2 g) is often required to correct calcium levels. Hypocalcaemia can be refractory to treatment without addressing magnesium deficiency.
  4. Other Treatments:
    • In cases of recalcitrant hypocalcaemia, such as in patients with prior gastric bypass surgery or those resistant to calcium and vitamin D therapy, options include:
      • Thiazide diuretics (which increase renal calcium reabsorption).
      • Recombinant PTH for refractory hypoparathyroidism.

Key Takeaways

  • Physical Manifestations: Hypocalcaemia can present with tetany, paraesthesia, muscle cramps, and in severe cases, seizures and arrhythmias.
  • Aetiologies: The causes of hypocalcaemia can be classified as PTH-dependent (e.g., hypoparathyroidism, PTH resistance) or PTH-independent (e.g., vitamin D deficiency, CKD).
  • Diagnostic Methods: Diagnostic evaluation includes correcting calcium for albumin and measuring PTH, magnesium, phosphate, and vitamin D levels.
  • Treatment Options: Calcium and vitamin D supplementation are the mainstays of treatment, with IV calcium reserved for severe cases. Magnesium must be replaced if deficient.