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Internal MedicineEndocrinologyFatigue

Fatigue: An Endocrine and Internal Medicine Approach for MCCQE1

Introduction

Fatigue is one of the most common presenting complaints in Canadian primary care, accounting for a significant portion of visits to family physicians. For MCCQE1 preparation, understanding fatigue requires a broad differential diagnosis with a specific focus on distinguishing organic disease (endocrine, neoplastic, infectious) from functional or psychiatric causes.

In the context of Endocrinology, fatigue is a cardinal symptom of thyroid dysfunction, adrenal insufficiency, and metabolic derangements. As a future Canadian physician, you must apply the CanMEDS roles—particularly Medical Expert and Communicator—to navigate this subjective complaint effectively.

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Canadian Context: In Canada, the approach to fatigue emphasizes a “Choosing Wisely” strategy. Avoid the “shotgun” approach to laboratory testing. Instead, use a targeted, evidence-based strategy to minimize unnecessary healthcare costs and patient anxiety.

MCCQE1 Objectives

According to the Medical Council of Canada, a candidate should be able to:

  1. Define the problem (differentiate true fatigue from sleepiness, dyspnea, or muscle weakness).
  2. Construct a comprehensive differential diagnosis including physical, psychological, and social causes.
  3. Select appropriate investigations based on the clinical presentation.
  4. Manage the condition using non-pharmacologic and pharmacologic means.

Differentiating Fatigue

Before investigating, clarify what the patient means by “tired.”

FeatureFatigue (Lassitude)Daytime Sleepiness (Hypersomnolence)Weakness
DefinitionA subjective feeling of lack of energy or exhaustion.The inability to stay awake or alert during the day.Reduction in the force-generating capacity of muscle.
Key Question”Do you feel worn out even after sleeping?""Do you fall asleep while driving or watching TV?""Do you have trouble lifting your arms or climbing stairs?”
Common CausesHypothyroidism, Depression, Anemia, Malignancy.Obstructive Sleep Apnea (OSA), Narcolepsy.Myasthenia Gravis, Myopathy, Stroke.

Etiology: The Differential Diagnosis

For MCCQE1 preparation, categorize causes to organize your thinking. While psychiatric causes (depression/anxiety) are the most common etiology in primary care, organic causes must be ruled out.

  • Hypothyroidism: Weight gain, cold intolerance, constipation, dry skin.
  • Hyperthyroidism: (Apathetic in elderly) Weight loss, palpitations, heat intolerance.
  • Diabetes Mellitus: Polyuria, polydipsia, weight loss.
  • Adrenal Insufficiency (Addison’s): Hyperpigmentation, hypotension, salt craving.
  • Hypercalcemia: “Bones, stones, groans, and psychiatric overtones.”
  • Panhypopituitarism: History of head trauma or postpartum hemorrhage (Sheehan’s).

Mnemonic for Causes of Fatigue

A useful mnemonic for Canadian medical students is TIRED:

  • T - Thyroid / Tuberculosis / Tumor
  • I - Infection (Endocarditis, HIV, Mono, Hepatitis) / Inflammation
  • R - Rheumatologic / Renal failure
  • E - Electrolytes (Ca, Na, K) / Endocrine (Diabetes, Addison’s)
  • D - Depression / Diet / Drugs

Clinical Approach

Step 1: Detailed History

Focus on the onset, duration, and course.

  • Duration: Acute (<1 month), Subacute (1-6 months), Chronic (>6 months).
  • Sleep History: Snoring, witnessed apneas (STOP-BANG questionnaire).
  • Review of Systems: Focus on “B symptoms” (fever, night sweats, weight loss) for malignancy.
  • Social History: Substance use, occupational hazards, life stressors.

Step 2: Physical Examination

Perform a targeted exam looking for signs of organic disease.

  • General: Pallor (anemia), Jaundice (liver), BMI (OSA vs. malignancy).
  • Neck: Thyromegaly, nodules, lymphadenopathy.
  • Cardio/Resp: Murmurs (endocarditis), signs of heart failure.
  • Abdomen: Organomegaly.
  • Neuro: Focal deficits, muscle bulk/tone (myopathy), delayed relaxation of reflexes (hypothyroidism).
  • Skin: Hyperpigmentation (Addison’s), butterfly rash (SLE).

Step 3: Targeted Investigations

Do not order a “full body scan” or indiscriminate panels.

  • Basic Labs: CBC, Ferritin, TSH, Electrolytes, Creatinine, Glucose (HbA1c), Liver enzymes.
  • If indicated: Monospot, HIV serology, ESR/CRP (if age >50 or inflammatory signs), Chest X-ray (if respiratory symptoms).
  • Endocrine Specific: If TSH is abnormal, follow up with T4/T3. If Addison’s suspected, 8 AM Cortisol.

Step 4: Management

Treat the underlying cause. If no organic cause is found:

  • Validate the patient’s symptoms (Communicator role).
  • Screen for depression/anxiety explicitly.
  • Encourage sleep hygiene, graded exercise therapy, and balanced diet.

Canadian Guidelines

Choosing Wisely Canada

Choosing Wisely Canada provides specific recommendations relevant to fatigue and MCCQE1:

  1. Don’t order annual screening blood tests unless directly indicated by the risk profile or clinical presentation. However, fatigue is an indication for targeted testing (TSH, CBC, Ferritin).
  2. Don’t order ANA testing as a screening tool in patients without specific signs or symptoms of systemic lupus erythematosus or another connective tissue disease.
  3. Don’t routinely use Vitamin D screening in low-risk adults.

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)

If fatigue persists for >6 months and is not explained by other conditions, consider ME/CFS. Canadian consensus criteria require:

  1. Fatigue
  2. Post-exertional malaise
  3. Sleep dysfunction
  4. Pain
  5. Neurological/Cognitive manifestations

Key Points to Remember for MCCQE1

High-Yield MCCQE1 Concepts

  • Most common cause: In primary care, the most common causes are psychiatric (depression/anxiety) or idiopathic.
  • Hypothyroidism: Always screen with TSH. Remember that in the elderly, hypothyroidism can present solely as confusion or fatigue (“Myxedema Madness”).
  • Ferritin: Ferritin is the most sensitive test for iron deficiency. Normal Hb does not rule out iron deficiency as a cause of fatigue.
  • Sleep Apnea: High BMI + Hypertension + Snoring = High suspicion for OSA. Gold standard Dx is Polysomnography.
  • Red Flags: Unintentional weight loss, night sweats, localized lymphadenopathy, age >50 with new fatigue (think malignancy or Giant Cell Arteritis).
  • Addison’s Disease: A “can’t miss” diagnosis. Look for a patient with fatigue, weight loss, and hyperpigmentation (especially palmar creases/buccal mucosa).

Sample Question

Scenario

A 34-year-old female presents to her family physician with a 4-month history of worsening fatigue. She reports feeling “drained” all the time and has difficulty concentrating at work. She has gained 4 kg over this period despite a decreased appetite. She also complains of feeling colder than her family members and has noticed her hair becoming brittle. She has no significant past medical history and takes no medications. Her menstrual periods have become heavier and more irregular. Physical examination reveals a heart rate of 56 bpm and delayed relaxation of the Achilles tendon reflex.

Question

Which one of the following initial investigations is most appropriate to confirm the diagnosis?

  • A. Polysomnography (Sleep Study)
  • B. Serum Ferritin
  • C. Serum Thyroid Stimulating Hormone (TSH)
  • D. Morning Serum Cortisol
  • E. Nuclear Medicine Thyroid Scan

Explanation

The correct answer is:

  • C. Serum Thyroid Stimulating Hormone (TSH)

Detailed Explanation: The clinical presentation is classic for hypothyroidism.

  • Key Symptoms: Fatigue, weight gain despite poor appetite, cold intolerance, brittle hair, menorrhagia, and “brain fog” (difficulty concentrating).
  • Key Signs: Bradycardia (HR 56) and delayed relaxation of deep tendon reflexes (Woltman’s sign) are highly specific for hypothyroidism.
  • Investigation: The initial screening test for thyroid dysfunction is TSH. In primary hypothyroidism, TSH will be elevated.

Why other options are incorrect:

  • A. Polysomnography: Indicated for Obstructive Sleep Apnea (snoring, witnessed apneas, daytime somnolence), not the metabolic picture described here.
  • B. Serum Ferritin: While anemia/iron deficiency causes fatigue and menorrhagia, the cold intolerance, bradycardia, and reflex changes point more strongly to a thyroid etiology. TSH is the best answer to confirm the specific diagnosis suggested by the full clinical picture.
  • D. Morning Serum Cortisol: Used to investigate Adrenal Insufficiency (Addison’s). Addison’s typically presents with weight loss, hyperpigmentation, and hypotension, not weight gain and bradycardia.
  • E. Nuclear Medicine Thyroid Scan: This is used to investigate a thyroid nodule or to distinguish types of hyperthyroidism (e.g., Graves’ vs. Thyroiditis). It is not an initial test for hypothyroidism.

References

  1. Medical Council of Canada. Objectives for the Qualifying Examination Part I. Available at: mcc.ca 
  2. Choosing Wisely Canada. Family Medicine: Thirteen Things Physicians and Patients Should Question. Available at: choosingwiselycanada.org 
  3. Towards Optimized Practice (TOP) Alberta. Investigation and Management of Fatigue in Adults.
  4. Canadian Medical Association Journal (CMAJ). Approach to the adult patient with fatigue.
  5. Toronto Notes 2024. Endocrinology & Family Medicine Chapters.
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