Hyperthyroidism

History

• Symptoms: Palpitations, weight loss, heat intolerance, hyperhidrosis, muscle weakness, vision changes, tremors, diarrhoea, anxiety.

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Examination

Physical findings:

• Cardiovascular: Irregular heart rate (HR), atrial fibrillation, sinus tachycardia.

• Neuromuscular: Tremors, proximal muscle weakness, hyperreflexia.

• Thyroid: Presence of goitre/nodules.

• Eye Signs: Proptosis/exophthalmos, lid lag, reduced extraocular movements, periorbital oedema (specific to Graves’ disease).

• Skin: Pretibial myxoedema (Graves’ specific), fine hair, thin skin, excessive sweating (hyperhidrosis).

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Diagnosis

Laboratory Tests:

• TSH receptor antibodies (TRAb): Confirms Graves’ disease but may be negative in mild cases (~10%).

  • Three Types:

    • Stimulating: Increases iodide uptake and thyroid hormone production.

    • Blocking: Inhibits TSH activity, seen in hypothyroidism.

    • Neutral: No effect on TSH binding, may induce cell stress.

  • TRAb levels decline with antithyroid therapy but persistently high levels may indicate relapse risk.

• Thyroid function tests:

  • TSH levels: Low in primary hyperthyroidism.

  • FT3/FT4: Increased levels; normal free T4 but elevated T3 suggests T3 toxicosis.

• Additional tests:

  •  thyroid antibodies:

    • TPO (thyroid peroxidase) antibodies: Indicates autoimmune thyroid disease.

    • Thyroglobulin (TG) antibodies.

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Imaging:

Thyroid scintigraphy (Technetium-99m or RAI uptake):

• Used to identify functional status and structure of thyroid tissue.

• Findings:

  • Diffuse uptake: Graves' disease.

  • Multifocal uptake: Toxic multinodular goitre (TMNG).

  • Focal uptake: Toxic adenoma.

  • Reduced uptake: Thyroiditis or exogenous thyroxine ingestion.

Thyroid ultrasound with Doppler: Can assess vascularity in Graves' disease or detect nodules if radioactive iodine is contraindicated.

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When to Treat Subclinical Hyperthyroidism

• Definition: TSH < 0.5 with normal T3 and T4.

• Complications: Osteoporosis, atrial fibrillation.

• Indications for Treatment:

  • TSH 0.1–0.5 if high risk of cardiac or osteoporosis complications, age >65 years, postmenopausal (observe or treat).

  • TSH <0.1 in healthy individuals (observe or treat).

  • Monitoring: Serial TSH, T3, T4 every 6 months if observing.

Treatment (Include Pertinent Side Effects and Pros/Cons of Each Treatment)

• Thionamides (Carbimazole, Propylthiouracil):

  • Mechanism: Inhibit thyroid hormone synthesis.

  • Dosing:

    • Carbimazole: 10–45 mg/day depending on severity.

    • Propylthiouracil (PTU): Used in pregnancy (first trimester), thyroid storm, or if allergic to carbimazole.

  • Side Effects:

    • Minor: Rash, nausea.

    • Major: Agranulocytosis, hepatotoxicity (more with PTU).

  • Pros/Cons:

    • Pros: Non-invasive, reversible.

    • Cons: Risk of relapse, agranulocytosis, hepatotoxicity (monitor liver function).

• Radioiodine Ablation:

  • Indication: Preferred in TMNG, large goitres, or Graves' with persistent high TRAb post-antithyroid therapy.

  • Mechanism: Destroys thyroid tissue using radioactive iodine.

  • Side Effects: Hypothyroidism (late onset), acute thyrotoxicosis (7–10 days post-treatment).

  • Contraindications: Pregnancy, severe orbitopathy, breastfeeding (48-hour post-ablation hold).

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Thyroidectomy:

• Indication: Large goitre, suspicion of malignancy, or failed medication and radioiodine treatment.

• Preoperative Preparation: Antithyroid medication 1–2 weeks before surgery.

• Complications: Hypoparathyroidism, recurrent laryngeal nerve palsy, airway obstruction due to haematoma.

• Post-op Management: Lifelong thyroxine replacement.

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Beta Blockers (e.g., Propranolol):

• Indications: Symptomatic relief for tachycardia, tremor, and anxiety.

• Contraindications: Asthma, heart block, diabetes mellitus.

• Alternatives: Diltiazem if beta-blockers contraindicated.

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Differentials

• Conditions:

  • Toxic multinodular goitre, toxic adenoma, Graves' disease, thyroiditis (subacute, postpartum), exogenous thyroxine ingestion, amiodarone-induced thyrotoxicosis, TSH-secreting pituitary adenoma.

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Notes:

• Graves’ Specific Signs:

• Thyroid acropachy, ophthalmopathy, pretibial myxoedema.

• Management of orbitopathy includes corticosteroids or surgical decompression for severe cases.

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Prognosis

Graves' disease:

• After 2 years of antithyroid medication, 25% may achieve remission, while others may relapse or develop hypothyroidism.

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Complications

Cardiovascular:

• Atrial fibrillation, heart failure, myocardial infarction (thyroid storm).

Bone health:

• Increased risk of osteoporosis and fractures due to accelerated bone turnover.

Eye Disease:

• Thyroid eye disease (Graves' orbitopathy): can progress despite control of hyperthyroidism.

• Management includes lubricating eye drops, systemic corticosteroids for severe cases, and surgery in refractory cases.

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Special Considerations

Subclinical Hyperthyroidism:

• TSH <0.5 mU/L with normal T3 and T4.

• Treatment indicated if TSH <0.1 mU/L in patients >65 years, postmenopausal women, or those with cardiovascular risk.

• Observe with serial TFTs if asymptomatic and lower risk.

Thyroid Storm:

• Life-threatening exacerbation of hyperthyroidism.

• Presentation: Fever, tachycardia (often atrial fibrillation), diarrhoea, agitation.

• Management: Resuscitation, beta-blockers, PTU, iodine solution, glucocorticoids.

Pregnancy:

• Hyperthyroidism may improve in later pregnancy due to reduced HCG levels.

• Graves' disease:

  • Monitor TRAb levels in the 3rd trimester due to risk of fetal hyperthyroidism.

  • PTU is preferred in the first trimester, transitioning to carbimazole thereafter.

• Gestational Hyperthyroidism (transient thyrotoxicosis due to elevated HCG in first trimester):

  • Usually self-limiting, no treatment required.

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Notes:

Definitions:

• Thyrotoxicosis: Clinical syndrome of elevated thyroid hormones from any cause.

• Hyperthyroidism: Overproduction of thyroid hormones specifically due to a hyperfunctioning thyroid gland.

Risk of Complications from Antithyroid Drugs:

• Regular monitoring is essential to detect early signs of agranulocytosis and hepatotoxicity.

• Patients should be advised to seek medical help if they experience severe sore throat or fever.

Beta-blocker Precautions:

• Propranolol is generally preferred, but atenolol may be used based on specific guideline recommendations.