Hyperthyroidism & Thyrotoxicosis

 Definitions

• Thyrotoxicosis:
  A clinical syndrome resulting from excess circulating thyroid hormones (T3, T4), regardless of their source (thyroidal or extrathyroidal).
  ➝ Causes a hypermetabolic state affecting nearly every organ system.

• Hyperthyroidism:
  A subset of thyrotoxicosis caused specifically by excessive hormone production from the thyroid gland itself.

  • Always causes thyrotoxicosis.

  • Thyrotoxicosis, however, can occur without hyperthyroidism (e.g., exogenous hormone intake, destructive thyroiditis).

• Subtypes:

  • Overt hyperthyroidism:

    • ↓ TSH

    • ↑ free T4 and/or T3

    • Patients are symptomatic.

  • Subclinical hyperthyroidism:

    • ↓ TSH

    • Normal free T4 and T3

    • Patients often asymptomatic or mildly symptomatic.

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Etiology of Thyrotoxicosis

1. Hyperfunctioning Thyroid Gland

• Graves disease (most common cause worldwide, especially in iodine-sufficient regions).

• Toxic multinodular goiter (MNG) – autonomous hyperfunctioning nodules.

• Toxic adenoma – a single hyperfunctioning thyroid nodule.

2. Destructive Thyroiditis (thyroid hormone leakage due to gland inflammation)

• Subacute granulomatous thyroiditis (De Quervain) – viral/post-viral, painful goiter.

• Subacute lymphocytic thyroiditis (silent/postpartum thyroiditis) – painless, often autoimmune-related.

• Drug-induced thyroiditis – amiodarone, lithium, interferon, IL-2.

• Radiation/iodine contrast-induced thyroiditis – Jod-Basedow phenomenon.

3. Exogenous Thyrotoxicosis

• Excessive intake of thyroid hormones (intentional or accidental).

• Factitious thyrotoxicosis in eating disorders/body dysmorphia.

• Supplements containing thyroid hormone.

4. Ectopic Hormone Production

• Struma ovarii (ovarian teratoma with thyroid tissue).

• Rare tumors secreting thyroid hormone.

5. Central (Secondary) Causes

• TSH-secreting pituitary adenoma → ↑ TSH + ↑ T4/T3.

• Excess hCG (molar pregnancy, choriocarcinoma, hyperemesis gravidarum) stimulating TSH receptor.

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Pathophysiology

• Excess T3/T4 → upregulation of β-adrenergic receptors and Na+/K+ ATPase activity.

• Results in:

  • Increased basal metabolic rate → hyperthermia, weight loss.

  • Enhanced sympathetic activity → tachycardia, tremor, anxiety.

  • Cardiac effects:

    • ↑ contractility and cardiac output.

    • ↓ systemic vascular resistance.

  • Bone effects: increased osteoclast activity → osteoporosis.

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Clinical Features

General

• Heat intolerance, excessive sweating.

• Weight loss despite ↑ appetite.

• Fatigue, muscle weakness (especially proximal).

• Tremor of outstretched fingers.

• Insomnia, anxiety, restlessness.

Skin & Hair

• Warm, moist, smooth skin.

• Alopecia, thinning of hair.

• Onycholysis (Plummer’s nails).

• Pretibial myxedema (Graves disease).

Eyes

• Graves ophthalmopathy:

  • Lid lag, lid retraction.

  • Exophthalmos, conjunctival injection, periorbital edema.

• Photophobia, diplopia.

  

Cardiovascular

• Tachycardia, palpitations.

• Atrial fibrillation (especially in elderly).

• Systolic hypertension with wide pulse pressure.

• Thyrotoxic cardiomyopathy → heart failure.

GI

• Increased bowel movements, diarrhea.

• Weight loss.

Reproductive/Endocrine

• Women: oligomenorrhea, amenorrhea, infertility.

• Men: gynecomastia, erectile dysfunction, ↓ libido.

• Glucose intolerance.

Neurological/Psychiatric

• Hyperreflexia.

• Nervousness, irritability.

• Depression, emotional instability.

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Diagnosis

Initial Evaluation

• TSH (best screening test).

• Free T4, Total/Free T3: elevated in overt hyperthyroidism.

Additional Tests

• TRAb (TSH receptor antibody) → confirms Graves disease.

• Thyroid scintigraphy / Radioactive Iodine Uptake (RAIU):

  

  • Graves disease: diffuse uptake.

  • Toxic MNG: multiple hot nodules.

  • Toxic adenoma: single hot nodule.

  • Thyroiditis/exogenous: low uptake.

• Ultrasound with Doppler: diffuse hypervascularity in Graves.

• ECG: atrial fibrillation, sinus tachycardia.

• Cholesterol: often low (↑ metabolism).

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Treatment

1. Symptomatic Control

• Beta blockers (propranolol, atenolol, esmolol if HF present).

  • Reduce tachycardia, tremors, anxiety.

  • Propranolol also inhibits peripheral T4 → T3 conversion.

2. Antithyroid Medications

• Methimazole (first-line, except in 1st trimester pregnancy).

• Propylthiouracil (PTU): preferred in thyroid storm and 1st trimester.

  • Mechanism: inhibits thyroid peroxidase → ↓ hormone synthesis; PTU also inhibits peripheral T4 → T3 conversion.

3. Definitive Therapy

• Radioactive iodine ablation (RAIA)

  • First-line definitive therapy in adults.

  • Contraindications: pregnancy, breastfeeding, young children.

• Surgery (thyroidectomy)

  • Indicated for large goiter, suspicion of malignancy, intolerance to meds.

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Special Considerations

• Pregnancy:

  • PTU in 1st trimester, switch to methimazole in 2nd–3rd trimester.

  • RAIA contraindicated.

• Elderly patients:

  • Often present with apathetic hyperthyroidism (weight loss, depression, AF) instead of classic symptoms.

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Complications

1. Thyroid Storm (Thyrotoxic Crisis)

   • Life-threatening acute exacerbation of thyrotoxicosis.

   • Triggers: infection, surgery, trauma, childbirth.

   • Symptoms:

     • Hyperpyrexia (> 40°C), profuse sweating.

     • Severe tachycardia/AF/CHF.

     • Agitation, delirium, coma.

     • Nausea, vomiting, diarrhea.

   • Management:

     • ICU admission.

     • Propranolol (β-blockade).

     • Propylthiouracil (PTU) (blocks hormone synthesis + T4→T3 conversion).

     • Potassium iodide (after PTU, blocks hormone release).

     • Glucocorticoids (hydrocortisone/dexamethasone) (reduce T4→T3 conversion, treat adrenal insufficiency).

     • Supportive: IV fluids, cooling, oxygen, treat trigger.

2. Long-term complications

   • Osteoporosis.

   • Thyrotoxic cardiomyopathy → dilated cardiomyopathy.

   • Infertility.