What are the typical presentation, differential diagnosis (ddx), diagnostic investigations (invx), management (mx), and complications of hypothyroidism and hyperthyroidism?

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Hypothyroidism and Hyperthyroidism: Clinical Presentation, Diagnosis, Management, and Complications

Hypothyroidism

Clinical Presentation (Signs and Symptoms)

Hypothyroidism presents with characteristic symptoms related to decreased metabolic rate, including fatigue, weight gain, cold intolerance, constipation, and dry skin. 1, 2, 3

Common signs and symptoms include:

  • Fatigue and lethargy
  • Weight gain despite unchanged diet
  • Cold intolerance
  • Dry skin (xeroderma)
  • Constipation
  • Bradycardia
  • Delayed relaxation phase of deep tendon reflexes
  • Hoarseness
  • Periorbital puffiness
  • Coarse, cold skin
  • Slow movements
  • Myxedema (non-pitting edema) in severe cases

Atypical presentations may include:

  • Musculoskeletal complaints (myalgia, arthralgia, tendinitis) 4, 5
  • Joint effusions
  • Neurological symptoms (paresthesias, carpal tunnel syndrome)
  • Depression and cognitive impairment

Differential Diagnosis

  • Chronic fatigue syndrome
  • Depression
  • Fibromyalgia
  • Anemia
  • Chronic kidney disease
  • Sleep apnea
  • Medication side effects
  • Chronic autoimmune diseases

Diagnostic Investigations

  • Initial laboratory evaluation consists of serum TSH with reflex testing of free T4 2
  • Elevated TSH with low free T4 confirms overt hypothyroidism
  • Elevated TSH with normal free T4 indicates subclinical hypothyroidism
  • Additional tests to determine etiology:
    • Thyroid peroxidase antibodies (TPOAb) for autoimmune thyroiditis
    • Thyroid ultrasound if structural abnormalities suspected
    • Complete blood count, lipid panel, and metabolic panel to assess complications

Management

  • Levothyroxine (synthetic T4) is the standard treatment for hypothyroidism 6, 2, 3
  • Initial dosing considerations:
    • Adults: 1.6 μg/kg/day (typically 50-100 μg daily)
    • Elderly or those with cardiac disease: Start with 25 μg daily and gradually increase
    • Take on empty stomach, 30-60 minutes before breakfast
  • Monitoring:
    • Check TSH and free T4 levels 6-8 weeks after initiation or dose adjustment
    • Once stable, monitor annually
    • Target TSH within reference range (0.4-4.0 mIU/L)
  • Special considerations:
    • Pregnancy: Increase dose by approximately 30%, monitor TSH monthly 7
    • Elderly: Higher TSH targets acceptable to minimize cardiovascular risk 6
    • Cardiac disease: Start at lower doses and titrate slowly 6

Complications

  • Cardiovascular: Dyslipidemia, diastolic hypertension, increased risk of atherosclerosis
  • Reproductive: Menstrual irregularities, infertility, increased risk of miscarriage
  • Neurological: Cognitive impairment, depression
  • Myxedema coma (rare but life-threatening emergency)
  • Growth and developmental delays in children
  • Pericardial effusions in severe cases 8

Hyperthyroidism

Clinical Presentation (Signs and Symptoms)

Common signs and symptoms include:

  • Warm, moist skin
  • Heat intolerance
  • Nervousness and anxiety
  • Tremulousness
  • Insomnia
  • Weight loss despite increased appetite
  • Diarrhea
  • Tachycardia or atrial fibrillation
  • Proximal muscle weakness
  • Lid lag
  • Fine tremor of outstretched hands 8
  • Exertional dyspnea 8

In Graves' disease specifically:

  • Diffusely enlarged thyroid gland (goiter)
  • Ophthalmopathy (exophthalmos, periorbital edema)
  • Dermopathy (pretibial myxedema)

Differential Diagnosis

  • Anxiety disorders
  • Pheochromocytoma
  • Diabetes mellitus
  • Malignancy
  • Medication side effects (stimulants)
  • Pregnancy
  • Cardiac arrhythmias of other etiologies

Diagnostic Investigations

  • Low TSH with elevated free T4 and/or T3 confirms overt hyperthyroidism 8, 7
  • Additional tests to determine etiology:
    • TSH receptor antibodies (TRAb) for Graves' disease
    • Thyroid peroxidase antibodies
    • Thyroid ultrasound to evaluate for nodules or diffuse enlargement
    • Radioactive iodine uptake scan to differentiate causes (Graves' disease vs. toxic nodular goiter)

Management

  • Initial treatment should include a β-blocker to control symptoms, particularly tachycardia and tremor 8, 7

  • Definitive treatment options:

    1. Antithyroid drugs (methimazole preferred, propylthiouracil in first trimester of pregnancy)

      • First-line for Graves' disease
      • Typically given for 12-18 months
      • Monitor liver function and CBC for adverse effects
    2. Radioactive iodine ablation

      • Often used for toxic nodular goiter
      • Leads to permanent hypothyroidism requiring lifelong levothyroxine
      • Contraindicated in pregnancy
    3. Thyroidectomy

      • Option for patients with large goiters or when other treatments are contraindicated
      • Requires lifelong thyroid hormone replacement
      • Surgical risks include hypoparathyroidism and recurrent laryngeal nerve damage
  • Monitoring:

    • Check thyroid function tests every 4-6 weeks during initial treatment
    • For subclinical hyperthyroidism (low TSH, normal free T4/T3):
      • Monitor every 4-6 weeks if TSH <0.1 mIU/L
      • Monitor every 3 months if TSH between 0.1-0.45 mIU/L 7

Complications

  • Cardiovascular: Atrial fibrillation, heart failure, pulmonary hypertension 8
  • Skeletal: Osteoporosis and increased fracture risk
  • Ophthalmopathy (in Graves' disease)
  • Thyroid storm (life-threatening emergency)
  • Tachycardia-induced cardiomyopathy 8
  • Muscle wasting and weakness
  • Psychiatric manifestations (anxiety, psychosis)

Key Considerations for Both Conditions

  1. Thyroid function tests must be interpreted carefully as acute illness, diet, and medications can alter values 2

  2. Both conditions can have significant cardiovascular effects:

    • Hypothyroidism: Bradycardia, diastolic hypertension, increased vascular resistance
    • Hyperthyroidism: Tachycardia, atrial fibrillation, decreased systemic vascular resistance 8
  3. Elderly patients require special attention:

    • Hypothyroidism: Start with lower doses of levothyroxine
    • Hyperthyroidism: Higher risk of cardiovascular complications 8, 7
  4. Pregnancy considerations:

    • Hypothyroidism: Increase levothyroxine dose by ~30%, monitor TSH monthly
    • Hyperthyroidism: Propylthiouracil in first trimester, methimazole thereafter; avoid radioactive iodine 7, 6
  5. Regular monitoring of thyroid function is essential for both conditions to ensure optimal treatment and prevent complications.

References

Research

Hypothyroidism.

Lancet (London, England), 2024

Research

Unusual presentations of hypothyroidism.

The American journal of the medical sciences, 1997

Research

Hypothyroidism presenting as tendinitis.

The Physician and sportsmedicine, 1997

Guideline

Hyperthyroidism Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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