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Internal MedicineEndocrinologyHyperthyroidism (Graves’ Disease)

Hyperthyroidism (Graves’ Disease)

Must-Not-Miss / Red Flags

  • Thyroid storm: hyperpyrexia, tachycardia >140, delirium, vomiting – Burch‑Wartofsky score ≥45
  • Graves’ orbitopathy: severe proptosis with optic nerve compression or corneal ulceration
  • Agranulocytosis: absolute neutrophil count <500 – rare side effect of methimazole
Patient Explanation
“Your thyroid gland is overactive, speeding up your body’s metabolism. We’ll give you medication to calm it down and discuss long‑term options.”
Board Fact
“TSH is the most sensitive screening test for thyroid function; a low TSH with elevated free T4/T3 confirms hyperthyroidism.”
ICD-10
E05.00

Definition & Core Concept

Graves’ disease is an autoimmune disorder characterized by TSH receptor antibodies (TRAb) that stimulate the thyroid gland, causing hyperthyroidism, diffuse goiter, and often ophthalmopathy and dermopathy.

Epidemiology & Risk Factors

  • Most common cause of hyperthyroidism (60‑80%)
  • Female‑to‑male ratio 5‑10:1; peak incidence 20‑50 years
  • Associated with other autoimmune conditions (vitiligo, T1DM, pernicious anemia)

Pathophysiology (Rule of 3)

  1. Genetic susceptibility + environmental trigger (stress, infection) → loss of immune tolerance
  2. B‑cell production of TRAb → TSH receptor stimulation → increased thyroid hormone synthesis and release
  3. Excess T3/T4 → increased metabolic rate, sympathetic overactivity

Clinical Presentation

  • Hypermetabolic symptoms: weight loss despite increased appetite, heat intolerance, sweating, tremors, palpitations, anxiety
  • Diffuse, painless goiter; possible thyroid bruit
  • Extrathyroidal: ophthalmopathy (proptosis, lid lag), pretibial myxedema (dermopathy)

Diagnostic Workup

TSH: suppressed (<0.01 mIU/L). Free T4 and free T3: elevated. TRAb (TSH receptor antibodies): positive. Radioactive iodine uptake scan: diffusely increased uptake. Thyroid ultrasound: diffuse enlargement with hypervascularity.

Management Protocol

  1. Antithyroid drugs: Methimazole 5‑30 mg daily (preferred) or Propylthiouracil (PTU) in first trimester pregnancy
  2. Beta‑blockers: Propranolol 20‑80 mg TID for symptomatic relief
  3. Definitive therapy: Radioactive iodine (RAI) ablation or total thyroidectomy after euthyroidism achieved
  4. Thyroid storm: PTU load + Lugol’s iodine, corticosteroids, beta‑blockers, cooling, supportive care

Complications & Prognosis

  • Thyroid storm (mortality 10‑30%)
  • Agranulocytosis (0.2‑0.5% with antithyroid drugs)
  • Hypothyroidism after RAI or surgery (expected, easily managed)
  • Progressive ophthalmopathy

ICU Criteria

ICU admission for thyroid storm with multi‑organ dysfunction.

Clinical Vignette

A 28‑year‑old woman presents with palpitations, 10‑lb weight loss over 2 months, and bilateral proptosis. TSH is <0.01, free T4 4.2 ng/dL (normal 0.8‑1.8). TRAb is positive. Radioactive iodine uptake shows 60% at 24 hours.

Pearls & Pitfalls

  • Methimazole is preferred over PTU due to less hepatotoxicity, except in first trimester of pregnancy (PTU preferred).
  • All patients on antithyroid drugs must be counseled to stop the drug and seek immediate medical attention if they develop fever, sore throat, or mouth ulcers (signs of agranulocytosis).

Discharge & Follow-Up

Monitor free T4 and TSH every 4‑6 weeks during titration. After RAI or surgery, lifelong levothyroxine replacement. Eye evaluation for Graves’ orbitopathy.

Literature & Guidelines

ATA 2024 Guidelines for Hyperthyroidism. PMID: 38672340.

Personal Clinical Notes