Calcium Disorders: MCCQE1 Preparation Guide

Introduction

Disorders of calcium homeostasis—Hypercalcemia and Hypocalcemia—are high-yield topics for the MCCQE1. As a future Canadian physician, you must demonstrate the Medical Expert competency by accurately interpreting laboratory values, understanding the physiological feedback loops involving Parathyroid Hormone (PTH) and Vitamin D, and initiating appropriate management.

In the Canadian context, given our northern latitude, Vitamin D deficiency plays a significant role in calcium metabolism disorders. This guide is structured to help you master these concepts for your medical licensing exam.

Calcium Homeostasis

Understanding the physiology is crucial for answering “mechanism of disease” questions on the MCCQE1.

The Corrected Calcium Formula

Approximately 40-45% of calcium is bound to albumin. Hypoalbuminemia leads to a falsely low total calcium. Always calculate corrected calcium or check ionized calcium.

// Formula for Corrected Calcium (SI Units)
Corrected Calcium (mmol/L) = Measured Calcium + [0.02 x (40 - Albumin g/L)]

Hypercalcemia

Hypercalcemia is common in hospital settings. For MCCQE1, remember that 90% of cases are caused by either Primary Hyperparathyroidism or Malignancy.

Etiology

A useful mnemonic for MCCQE1 preparation is VITAMINS TRAP:

• Vitamins (A and D toxicity)
• Immobilization
• Thyrotoxicosis
• Addison’s disease
• Milk-alkali syndrome
• Inflammatory disorders (Sarcoidosis - granulomas produce 1,25-Vit D)
• Neoplastic diseases (Malignancy)
• Sarcoidosis
• Thiazides / Theophylline
• Rhabdomyolysis
• AIDS
• Primary Hyperparathyroidism (PHP) / Paget’s disease / Pheochromocytoma

Clinical Presentation

Symptoms correlate with the rapidity of onset and the absolute level.

Diagnostic Approach

Management

Management depends on the severity and symptoms.

1. Severe Hypercalcemia (Ca >3.5 mmol/L) or Symptomatic

This is a medical emergency.

1. Volume Expansion (First Line): IV Normal Saline (0.9% NaCl). Rehydrates and promotes calciuresis.
   • Target: Urine output 100-150 mL/hr.
2. Bisphosphonates: (e.g., Pamidronate or Zoledronic acid).
   • Inhibits osteoclasts. Takes 2-4 days to work.
3. Calcitonin:
   • Rapid onset (hours) but tachyphylaxis develops quickly (works for ~48 hours). Useful as a bridge while waiting for bisphosphonates.
4. Glucocorticoids:
   • Specific for granulomatous disease (Sarcoidosis) or Lymphoma (inhibits 1α-hydroxylase).
5. Dialysis:
   • Last resort for renal failure or life-threatening levels.

2. Primary Hyperparathyroidism

• Surgery (Parathyroidectomy): Definitive treatment.
  • Indications: Symptomatic (stones, fractures), Age <50, Ca >0.25 mmol/L above upper limit, GFR <60, T-score <-2.5.
• Medical: Cinacalcet (calcimimetic) if surgery is contraindicated.

Hypocalcemia

Etiology

Clinical Presentation

Hypocalcemia increases neuromuscular excitability.

• Neuromuscular: Paresthesias (fingertips, perioral), Tetany, Laryngospasm, Seizures.
• Cardiac: Prolonged QT interval (Risk of Torsades de Pointes).
• Physical Exam Signs:
  1. Chvostek’s Sign: Tapping facial nerve anterior to ear causes facial muscle contraction.
  2. Trousseau’s Sign: Inflating BP cuff above systolic pressure for 3 mins causes carpal spasm (more specific than Chvostek’s).

Management

1. Acute Symptomatic (Tetany/Seizures/Arrhythmias):
   • IV Calcium Gluconate (preferred over Calcium Chloride due to less tissue necrosis risk if extravasated).
2. Chronic:
   • Oral Calcium supplements (Calcium Carbonate or Citrate).
   • Active Vitamin D (Calcitriol) if renal failure or hypoparathyroidism (cannot convert Vit D).
   • Correct Magnesium if low.

Canadian Guidelines & Context

1. Vitamin D in Canada

Due to high latitude, Vitamin D deficiency is endemic in Canada.

• Osteoporosis Canada Guidelines: Routine supplementation is often recommended, especially in winter and for the elderly.
• Recommended Intake: Adults <50 years: 400–1000 IU daily; Adults >50 years: 800–2000 IU daily.

2. Choosing Wisely Canada

• Don’t order population-based screening for Vitamin D deficiency.
• Test only in high-risk populations (osteoporosis, rickets, malabsorption, renal disease).

3. CanMEDS Role: Health Advocate

Physicians should advocate for fall prevention strategies and adequate dietary calcium/vitamin D in elderly populations to prevent fractures associated with calcium metabolic bone disease.

Key Points to Remember for MCCQE1

• Hypercalcemia + Suppressed PTH: Think Malignancy first.
• Hypercalcemia + Elevated PTH: Think Primary Hyperparathyroidism.
• Familial Hypocalciuric Hypercalcemia (FHH): Benign condition. Do not remove parathyroids. Differentiate from Primary Hyperparathyroidism using Urine Calcium (Low in FHH).
• ECG Changes:
  • Hypercalcemia = Short QT.
  • Hypocalcemia = Prolonged QT.
• Alkalosis: Causes acute hypocalcemia (Albumin binds more calcium in alkalotic states, lowering ionized calcium). This is why hyperventilation causes paresthesias.
• Magnesium: Always check Mg levels in hypocalcemia. Hypomagnesemia causes PTH resistance and inhibits PTH secretion.

Sample Question

Clinical Scenario

A 68-year-old female presents to the Emergency Department with a 3-day history of profound weakness, confusion, and polyuria. Her daughter reports that the patient has been increasingly lethargic and constipated. Past medical history is significant for breast cancer diagnosed 3 years ago, treated with lumpectomy and radiation. She is not currently on medication.

Physical Examination:

• BP: 100/60 mmHg
• HR: 104 bpm
• Signs of severe dehydration (dry mucous membranes, decreased skin turgor).
• Neurologic exam shows disorientation to time and place but no focal deficits.

Laboratory Results:

• Total Calcium: 3.6 mmol/L (Normal: 2.20–2.60 mmol/L)
• Albumin: 38 g/L (Normal: 35–50 g/L)
• Creatinine: 140 µmol/L (Baseline: 80 µmol/L)
• PTH: < 0.5 pmol/L (Normal: 1.6–6.9 pmol/L)

Which one of the following is the most appropriate initial management step?

• A. Intravenous pamidronate
• B. Intravenous normal saline
• C. Intravenous furosemide
• D. Subcutaneous calcitonin
• E. Hemodialysis

Explanation

The correct answer is:

• B. Intravenous normal saline

Detailed Explanation: This patient presents with severe symptomatic hypercalcemia (Calcium > 3.5 mmol/L with confusion and dehydration). The suppressed PTH suggests a non-parathyroid cause, likely Hypercalcemia of Malignancy given her history of breast cancer (likely bone metastases or PTHrP secretion).

1. Volume Resuscitation (Option B): Patients with severe hypercalcemia are almost always profoundly dehydrated due to nephrogenic diabetes insipidus (hypercalcemia impairs the kidney’s ability to concentrate urine) and poor intake. The first priority is to restore intravascular volume with isotonic saline (0.9% NaCl). This improves GFR and promotes the excretion of calcium (calciuresis).
2. Bisphosphonates (Option A): While IV bisphosphonates (e.g., pamidronate, zoledronic acid) are the mainstay of therapy for hypercalcemia of malignancy, they take 24–72 hours to reach peak effect. They should be started after or concurrent with hydration, but hydration is the immediate life-saving step.
3. Loop Diuretics (Option C): Furosemide should not be used until the patient is fully volume resuscitated, as it can worsen dehydration and electrolyte abnormalities. It is reserved for patients with fluid overload or heart failure.
4. Calcitonin (Option D): Calcitonin works rapidly (within hours) but has a weak effect and develops tachyphylaxis quickly. It is often used as an adjunct to bisphosphonates but is not the sole initial resuscitation step compared to fluids.
5. Hemodialysis (Option E): This is reserved for patients with severe renal failure or life-threatening hypercalcemia refractory to other measures.

Takeaway for MCCQE1: Always hydrate first in severe hypercalcemia.

References

1. Medical Council of Canada. (n.d.). MCCQE Part I Clinical Decision-Making and Multiple-Choice Question Objectives.
2. Osteoporosis Canada. (2023). Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada.
3. Choosing Wisely Canada. (n.d.). Endocrinology and Metabolism.
4. Goltzman, D. (2023). Approach to Hypercalcemia. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA.
5. Toronto Notes. (2023). Endocrinology: Calcium Disorders. Toronto Notes for Medical Students, Inc.