Toxic Multinodular Goitre Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: TMNG is a common cause of hyperthyroidism, second only to Graves' disease. It's particularly prevalent in our elderly population, often presenting insidiously with cardiovascular or neuropsychiatric symptoms rather than classic thyrotoxic features. Your job is to pick it up before they go into AF with RVR or heart failure.
High-Yield Definition: "Toxic multinodular goiter is characterized by a heterogeneously functioning goiter, with areas of autonomous function that are TSH-independent, resulting in biochemically overt hyperthyroidism." (Source: UpToDate, 2024).
Clinical One-Liner: An older patient with a long-standing lumpy neck, new-onset atrial fibrillation, and unintentional weight loss.
II. Etiology & Risk Factors
Etiology: The primary driver is chronic iodine deficiency, which leads to follicular cell hyperplasia over decades. This is followed by the development of somatic mutations (often in the TSH receptor gene) within these hyperplastic nodules, causing them to become autonomous and produce thyroid hormone independent of TSH stimulation.
Risk Factors:
Age > 60 years
Female sex
Long-standing simple (euthyroid) multinodular goiter
History of residence in an iodine-deficient region
III. Quick Pathophysiology
Iodine deficiency → Increased TSH stimulation → Diffuse goiter → Focal hyperplasia (nodules) → Somatic mutations in some nodules → TSH-independent (autonomous) hormone production → Gradual development of hyperthyroidism as these nodules grow and produce more hormone. This process takes decades, which is why we see it in older patients.
IV. Classification
There is no formal staging or classification system for TMNG itself. The key clinical distinction is between a non-toxic MNG (normal TFTs) and a toxic MNG (suppressed TSH, high fT4/fT3). The severity is then graded based on the degree of biochemical derangement and the presence of end-organ effects (e.g., atrial fibrillation, heart failure).
V. Clinical Assessment
Red Flags & Immediate Actions
Stridor or Respiratory Distress:
Action: Secure airway (ABCDE approach), sit patient up, give high-flow oxygen, escalate immediately to your senior and the anaesthesia team.
Reason: Potential tracheal compression from a large or retrosternal goiter. This is a life-threatening emergency.
Thyroid Storm (Fever >38.5°C, Tachycardia out of proportion to fever, Altered Mental Status, Severe GI upset):
Action: ABCDE, IV fluids, beta-blockers (Propranolol), start Propylthiouracil (PTU) or Carbimazole, IV Hydrocortisone, and escalate to senior/ICU.
Reason: Decompensated, life-threatening thyrotoxicosis with high mortality.
History
Key Diagnostic Clues: Insidious onset of hyperthyroid symptoms in a patient over 50 with a known goiter for many years. Cardiovascular symptoms often predominate.
Symptom Breakdown:
Common (>50%): Palpitations, atrial fibrillation, unintentional weight loss despite good appetite, heat intolerance, tremor, fatigue, anxiety.
Less Common (10-50%): Dyspnea on exertion, muscle weakness, diarrhea, insomnia.
Rare (<10%): "Apathetic hyperthyroidism" in the very elderly (presenting with depression, lethargy, confusion), compressive symptoms (dysphagia, hoarseness, dyspnea).
Pertinent Negatives:
Absence of eye signs (proptosis, diplopia, ophthalmoplegia) → Argues against Graves'.
Absence of neck pain, fever → Argues against subacute thyroiditis.
No history of amiodarone or recent iodine contrast exposure.
Physical Examination (OSCE Approach)
General Inspection: Patient may appear anxious, tremulous, and thin. Look for signs of weight loss (ill-fitting clothes) and a visible neck mass.
Vitals: Tachycardia (often >100 bpm) or an irregularly irregular pulse (atrial fibrillation). Hypertension (wide pulse pressure).
Disease-Specific Examination (Neck & Thyroid):
Look: Asymmetrical, enlarged thyroid gland. Observe it moving upwards on swallowing.
Feel: Palpate from behind. The goiter will feel firm and nodular ("lumpy-bumpy"). Note the size, consistency, and mobility of the dominant nodules. There should be no palpable thrill or audible bruit over the gland (unlike Graves'). Check for retrosternal extension by percussion over the manubrium and performing Pemberton's sign.
Pertinent Negatives: No diffuse, smooth enlargement. No tenderness.
Examination for Differentials:
Eyes: Check for ophthalmopathy (proptosis, lid retraction, lid lag). Its absence is a key feature differentiating TMNG from Graves' disease.
Hands/Legs: Look for thyroid acropachy and pretibial myxedema (both specific to Graves'). Check for a fine tremor.
Clinical Pearl
In any elderly patient presenting with new-onset AF, unexplained weight loss, or worsening heart failure, you must actively rule out thyrotoxicosis. Palpate the neck and order a TFT. Don't get tunnel vision on the heart.
VI. Diagnostic Workflow
Differential Diagnosis
Graves' Disease:
Points For: Hyperthyroidism symptoms.
Points Against: Absence of ophthalmopathy/dermopathy, older age of onset, palpable nodules instead of a diffuse goiter.
How to Differentiate: Positive TSH receptor antibody (TRAb) and diffuse, high uptake on thyroid scintigraphy.
Toxic Adenoma (Plummer's Disease):
Points For: Hyperthyroidism, TSH-independent.
Points Against: A single palpable autonomous nodule, not multiple.
How to Differentiate: Thyroid scan shows a single "hot" nodule with suppression of the rest of the gland.
Iodine-Induced Hyperthyroidism (Jod-Basedow effect):
Points For: Hyperthyroidism in a patient with an underlying MNG.
Points Against: No recent history of iodine load (e.g., CT contrast, amiodarone).
How to Differentiate: History is key.
Investigations Plan
Bedside / Initial (First 15 Mins):
ECG: Look for sinus tachycardia or atrial fibrillation with a rapid ventricular response.
First-Line Labs & Imaging:
Thyroid Function Test (TFT): This is the key diagnostic test. Expect suppressed TSH (<0.01 mIU/L) with an elevated free T4 (fT4) and/or free T3 (fT3). Sometimes you see T3-toxicosis (normal fT4, high fT3).
Thyroid Ultrasound: Useful to delineate nodule size, characteristics (e.g., cystic vs. solid), and identify any suspicious features for malignancy (though this is rare in a toxic nodule). Not a functional test.
Confirmatory / Gold Standard:
Thyroid Scintigraphy (99mTc-pertechnetate or I-123 scan): This is the definitive investigation to confirm the diagnosis and differentiate from Graves'. It will show a heterogeneous uptake pattern with multiple areas of increased uptake ("hot" or autonomous nodules) and suppression of tracer uptake in the rest of the thyroid tissue.
VII. Staging & Severity Assessment
Severity is determined clinically and biochemically:
Subclinical Hyperthyroidism: Suppressed TSH, normal fT4/fT3. Common early stage of TMNG.
Overt Hyperthyroidism: Suppressed TSH, elevated fT4/fT3.
Severe/Complicated Thyrotoxicosis: Overt hyperthyroidism with complications such as atrial fibrillation, high-output cardiac failure, or thyroid storm.
VIII. Management Plan
A. Principle of Management
Control Symptoms: Primarily cardiovascular symptoms using beta-blockers.
Restore Euthyroidism: Using anti-thyroid drugs (ATDs).
Provide Definitive Treatment: Ablate or remove the autonomous nodules as ATDs are not a long-term solution.
B. Immediate Stabilisation (The ABCDE Plan)
This is for thyroid storm or severe thyrotoxicosis with haemodynamic compromise.
For most TMNG patients, initial management is on the ward.
Symptom control: Start Propranolol 20-40mg TDS (titrate to heart rate < 90 bpm). Use with caution in asthmatics or decompensated heart failure.
C. Definitive Treatment (The Ward Round Plan)
Anti-Thyroid Drugs (ATDs):
Purpose: To render the patient euthyroid before definitive treatment. This is a bridge, not a cure. Spontaneous remission is extremely rare.
Drug: Carbimazole. Start with 15-30mg OD. Check FBC for agranulocytosis at baseline and warn patient about sore throat/fever.
Monitor TFT every 4-6 weeks and titrate dose.
Definitive Treatment Options:
Radioactive Iodine (RAI) Therapy (¹³¹I):
Mechanism: ¹³¹I is selectively taken up by the "hot" nodules, which are then destroyed by radiation. The suppressed normal tissue is spared.
Indication: Often the first-line definitive treatment, especially in elderly patients or those who are poor surgical candidates.
Outcome: High success rate (~80-90%). The main side effect is permanent hypothyroidism (occurs in ~10-40% within 5 years), which is easily managed with levothyroxine.
Surgery (Total or Near-Total Thyroidectomy):
Indication: Patients with large goiters causing compressive symptoms, suspected malignancy, contraindication to RAI (e.g., pregnancy planning), or patient preference.
Pre-op: Patient MUST be made euthyroid with Carbimazole first to prevent intra-operative thyroid storm.
Outcome: Definitive cure. Patient will require lifelong levothyroxine replacement. Risks include recurrent laryngeal nerve injury and hypoparathyroidism.
D. Long-Term & Discharge Plan
Post-RAI: Follow-up TFT at 6 weeks, 3 months, 6 months, then annually. Watch for developing hypothyroidism.
Post-Thyroidectomy: Start levothyroxine immediately post-op. Monitor TFT at 6-8 weeks to titrate dose.
Manage cardiovascular issues (e.g., rate/rhythm control for AF, anticoagulation based on CHA₂DS₂-VASc score).
IX. Complications
Immediate: Thyroid Storm (rare, but high mortality).
Short-Term: Atrial Fibrillation with RVR, High-Output Cardiac Failure.
Long-Term: Osteoporosis due to increased bone turnover, Tachycardia-induced cardiomyopathy.
X. Prognosis
The prognosis is excellent with treatment. Once euthyroidism is achieved, the cardiovascular and metabolic effects are largely reversible. The long-term outcome depends on the management of any residual cardiac issues (like established AF) and adherence to thyroid hormone replacement if required. Untreated, chronic thyrotoxicosis carries significant morbidity and mortality.
XI. How to Present to Your Senior
Use the SBAR format. Be concise.
S (Situation): "Dr, I'm calling about Mr. Lim, a 72-year-old male in Bed 8, who presented with palpitations. His ECG shows new-onset atrial fibrillation with a heart rate of 140."
B (Background): "He has a background of hypertension and a long-standing goiter. On examination, he is alert but anxious, with a palpable, nodular goiter. He has no eye signs. He mentions losing about 5kg over the past 3 months."
A (Assessment): "My impression is new-onset atrial fibrillation secondary to underlying thyrotoxicosis, most likely from a toxic multinodular goiter."
R (Recommendation): "I have sent off a TFT and started him on Metoprolol for rate control. I would like to ask if we should start Carbimazole empirically pending the TFT result, and plan for a thyroid ultrasound and subsequent scintigraphy."
XII. Summary & Further Reading
Top 3 Takeaways
Think of TMNG in any elderly patient with new-onset AF, weight loss, or unexplained heart failure.
The key diagnostic pathway is: Suppressed TSH on TFT → Confirm with a thyroid scan showing multiple "hot" nodules.
Management involves symptom control (beta-blockers), achieving euthyroidism (Carbimazole), followed by definitive treatment (RAI or Surgery).
Key Resources
Malaysian Guideline: Malaysian CPG on the Management of Thyroid Disorders (2019). This should be your primary local reference.
UpToDate: Search for "Toxic multinodular goiter". Excellent, evidence-based overview.
Amboss: Search for "Hyperthyroidism". Good for quick review and differential diagnosis.
