admittomedicine

toxic multinodular goitre

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clinical identity

A cause of hyperthyroidism arising from autonomously functioning thyroid nodules. It is a disease of older adults and often presents with “apathetic” symptoms (cardiovascular predominance) without the autoimmune features of Graves’ disease.

pathophysiology

  • Mechanism: Somatic activating mutations in the TSH Receptor (TSH-R) in specific nodular clones.
  • Evolution: Often evolves from a long-standing non-toxic multinodular goitre (MNG) over decades.
  • Autonomy: These nodules produce T4/T3 independently of TSH stimulation.
    • Toxic Adenoma: Single hyperfunctioning nodule.
    • Toxic MNG: Multiple hyperfunctioning areas.

clinical features

  • Patient Profile: Typically >50 years old with a history of goitre.
  • “Apathetic Hyperthyroidism”: Elderly patients may lack classic sympathetic signs (tremor, anxiety) and present solely with:
    • Atrial Fibrillation (refractory to rate control).
    • Congestive Heart Failure.
    • Weight Loss / Muscle weakness.
  • Compressive Symptoms: Dysphagia, orthopnoea, or voice change due to large goitre size (substernal extension).
  • Absence of Graves’ Features: NO orbitopathy, NO pretibial myxoedema, NO acropachy.

diagnosis

  1. Biochemical: TSH, fT4/fT3.
    • T3 Toxicosis: Isolated elevation of T3 is common in early TMNG.
  2. Antibodies: TRAb Negative (distinguishes from Graves’).
  3. Radioactive Iodine Uptake (RAIU) & Scan:
    • Pattern: Patchy / Heterogeneous uptake.
    • Toxic Adenoma: Single “Hot” nodule with suppression of the rest of the gland.
    • TMNG: Multiple hot and cold areas.
  4. Ultrasound: Useful to assess goitre size and look for suspicious “cold” nodules (malignancy risk).
    • Note: A “hot” nodule is rarely malignant (<1%). A “cold” nodule within a TMNG carries a ~5% malignancy risk and may need FNA.

management

Unlike Graves’ disease, remission does not occur. Management is definitive.

1. radioactive iodine (RAI)

  • First Line for most patients (especially if poor surgical candidates).
  • Mechanism: Preferentially taken up by autonomous (hot) nodules, sparing the suppressed normal tissue.
  • Risk: Lower risk of permanent hypothyroidism compared to Graves’ (since normal tissue is suppressed/spared), but late failure can occur.

2. surgery (thyroidectomy)

  • Indications:
    • Large compressive goitre.
    • Suspicion of malignancy in a co-existing cold nodule.
    • Patient preference or contraindication to RAI.
  • Procedure: Total or near-total thyroidectomy prevents recurrence.

3. antithyroid drugs (ATDs)

  • Role: Stabilization only.
  • Used to achieve euthyroidism prior to surgery or RAI.
  • Long-term use: Generally reserved for elderly/frail patients with limited life expectancy who cannot undergo surgery or RAI.

the iodine load

Patients with TMNG are susceptible to the Jod-Basedow Effect. Exposure to large iodine loads (CT contrast, Amiodarone) provides substrate for the autonomous nodules, and can precipitate acute thyrotoxicosis.