Hyperthyroidism and thyrotoxicosis

Thyrotoxicosis = the clinical state of excess thyroid hormone in tissues, whatever the cause. Most cases are due to hyperthyroid disorders — most commonly Graves’ disease, toxic multinodular goitre, and toxic adenoma. Thyrotoxicosis without hyperthyroidism occurs with exogenous thyroid hormone, thyroiditis (leak of preformed hormone), and amiodarone. Pituitary-driven (secondary) hyperthyroidism is rare.

Murtagh DxT — anxiety + weight loss + weakness ➜ thyrotoxicosis.

Diagnostic approach

• Thyrotoxicosis is indicated by a low/suppressed TSH; overt disease has a high free T4 (and/or T3), subclinical disease a normal T4.
• If TSH is elevated or inappropriately normal, suspect a pituitary cause — consult endocrinology.
• For subclinical/asymptomatic results, retest TSH and T4 in 6–8 weeks to confirm persistence. Start a beta-blocker early for symptomatic patients.
• TSH-receptor antibody — a significant rise is diagnostic of Graves’. If absent, a radionuclide uptake scan differentiates the other causes.
• Ultrasound is only useful with amiodarone use or known/palpable nodules.

Causes at a glance

Cause	Typical patient	TRAb	Radionuclide scan	Notes
Graves’ disease	Female, 20–60	Elevated (~95%)	Diffuse increased uptake	Diffuse symmetrical goitre; Graves’ ophthalmopathy
Toxic multinodular goitre	Female, >50, long-standing nodular goitre	Absent	Multifocal (“patchy”) uptake	Remission rare without radioiodine/surgery; can be precipitated by iodine (contrast)
Toxic adenoma	Female, 30–50, solitary nodule >3 cm	Absent	Focal uptake with suppression elsewhere	TSH-receptor/G-protein mutation
Painless (sporadic) thyroiditis	Female, 20–50	Usually absent (transient minor rise)	Near-absent uptake	Thyrotoxic 1–2 months → hypothyroid 4–6 months (permanent in ~20%); anti-TPO high titre; can be postpartum

Graves’ ophthalmopathy can be sight-threatening — assess visual acuity, fields and eye closure/corneal protection; refer urgently to ophthalmology (via ED) if any are compromised. Amiodarone-induced thyrotoxicosis can occur up to 12–18 months after ceasing the drug.

Management

Antithyroid drugs

• Carbimazole is first-line. Significant symptoms (AF, weight loss, proximal myopathy) or biochemically severe disease (T3/T4 >2.5× ULN): carbimazole 30–45 mg/day in 2–3 divided doses; mild disease: 10–20 mg/day. Adjust at 4–6 weekly intervals.
• Propylthiouracil (PTU) is reserved for carbimazole intolerance, pre-conception/first-trimester pregnancy, and thyroid storm (rare severe liver injury).
• Both can rarely cause agranulocytosis (usually in the first months) — advise patients to stop the drug and seek urgent review if they develop fever, malaise or infection.

Beta-blockers for symptoms — atenolol 25 mg daily (up to 50 mg), or propranolol 10 mg BD (up to 40 mg BD), titrated to heart rate.

Definitive options (specialist-decided): a 12–18 month antithyroid course then withdrawal and monitoring; long-term antithyroid therapy; radioiodine (usually eventual hypothyroidism; contraindicated in active Graves’ eye disease or current/imminent pregnancy); or thyroidectomy (permanent hypothyroidism).

Thyroid storm — a life-threatening surge of thyroid hormone with fever, tachycardia, vomiting, dehydration, delirium/coma and organ (especially hepatic) dysfunction; may be complicated by stroke. Arrange immediate ambulance transfer to hospital.