Thyroid Storm

Quick Answer

Thyroid storm (thyrotoxic crisis) is a life-threatening exacerbation of hyperthyroidism characterised by multisystem decompensation. Diagnosis is clinical using the Burch-Wartofsky Point Scale (BWPS): score ≥45 = thyroid storm, 25-44 = impending storm, below 25 = unlikely. Cardinal features include fever (often greater than 40°C), tachycardia (often greater than 140 bpm) or atrial fibrillation, altered mental status (agitation, delirium, coma), gastrointestinal dysfunction (nausea, vomiting, diarrhoea, jaundice), and high-output cardiac failure. Treatment follows a five-step approach: (1) Beta-blockers (propranolol 1 mg IV every 10-15 min or esmolol infusion) to control adrenergic symptoms; (2) Thionamides (PTU 200-400 mg Q4-6H or methimazole 20-30 mg Q6H) to block thyroid hormone synthesis; (3) Iodine (Lugol's solution or SSKI) given ≥1 hour after thionamide to block hormone release; (4) Glucocorticoids (hydrocortisone 100 mg Q8H) to inhibit peripheral T4→T3 conversion and treat relative adrenal insufficiency; (5) Supportive care (cooling, fluids, treat precipitant). Mortality is 10-30% even with treatment.

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CICM Exam Focus

Primary Exam Relevance

• Pharmacology: Antithyroid drugs (thionamides, iodine), beta-blockers (propranolol, esmolol), glucocorticoids
• Physiology: Thyroid hormone physiology, catecholamine sensitization, cardiac effects
• Pathophysiology: Thyroid hormone excess, hypermetabolic state, cardiovascular decompensation

Second Part Exam Relevance

High yield topic - frequently appears in:

• SAQs: Diagnosis using Burch-Wartofsky score, stepwise management, timing of iodine administration
• Vivas: Management of thyroid storm with atrial fibrillation and heart failure, precipitating factors
• Hot Cases: Multiorgan failure with thyrotoxicosis, atypical presentation (apathetic thyrotoxicosis)

Key Learning Objectives

1. Diagnose thyroid storm using Burch-Wartofsky Point Scale (≥45 = storm)
2. Explain pathophysiology (catecholamine sensitization, hypermetabolic state, cardiovascular effects)
3. Implement five-step treatment protocol (beta-blocker → thionamide → iodine → steroids → supportive)
4. Justify the timing of iodine administration (≥1 hour after thionamide)
5. Manage complications (high-output cardiac failure, AF, hyperthermia)
6. Identify precipitating factors and treat underlying cause

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Key Points

1. Thyroid storm is a clinical diagnosis of severe thyrotoxicosis with multisystem decompensation; thyroid hormone levels do not differentiate storm from uncomplicated hyperthyroidism (PMID: 8355801).

2. The Burch-Wartofsky Point Scale (BWPS) is the diagnostic tool: score ≥45 = thyroid storm, 25-44 = impending storm, below 25 = unlikely (PMID: 8355801).

3. Precipitating factors include infection (40%), surgery, trauma, radioactive iodine therapy, iodinated contrast, medication non-compliance, diabetic ketoacidosis, and pregnancy/labour (PMID: 23019139).

4. Pathophysiology involves catecholamine sensitization (increased beta-adrenergic receptor density/sensitivity), not elevated catecholamine levels, leading to exaggerated cardiovascular and metabolic responses (PMID: 3117312).

5. Treatment sequence is critical: (1) Beta-blocker first; (2) Thionamide; (3) Iodine ≥1 hour after thionamide; (4) Glucocorticoids; (5) Supportive care.

6. PTU (propylthiouracil) is preferred over methimazole/carbimazole in thyroid storm because it also inhibits peripheral T4→T3 conversion (PMID: 17209917).

7. Iodine must be given ≥1 hour after thionamide to prevent iodine being used as substrate for more thyroid hormone synthesis (Jod-Basedow phenomenon) (PMID: 6892655).

8. High-output cardiac failure is a major complication: tachycardia-induced cardiomyopathy, atrial fibrillation (10-25% of patients), and heart failure may be refractory to standard therapy until thyroid control achieved (PMID: 25209247).

9. Glucocorticoids (hydrocortisone 100 mg Q8H) are essential: they inhibit T4→T3 conversion, treat relative adrenal insufficiency, and may reduce thyroid hormone secretion (PMID: 8540633).

10. Mortality remains 10-30% despite treatment, with cardiac complications and multiorgan failure as primary causes of death (PMID: 23019139).

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Clinical Overview

Definition

Thyroid storm (synonyms: thyrotoxic crisis, thyrotoxic storm) is a rare but life-threatening exacerbation of hyperthyroidism characterised by severe clinical manifestations and multisystem organ dysfunction. It represents the extreme end of the thyrotoxicosis spectrum and constitutes an endocrine emergency.¹²

Key distinction: Thyroid storm is a clinical diagnosis based on the severity of signs and symptoms, not absolute thyroid hormone levels. Patients with uncomplicated hyperthyroidism may have identical T3/T4 levels to those in thyroid storm, but lack the multisystem decompensation.¹

Epidemiology

• Incidence: 0.2-0.76% of all hospital admissions for thyrotoxicosis develop thyroid storm (PMID: 23019139)³
• Prevalence: 0.57-0.76 per 100,000 population per year in Japan (PMID: 26718186)⁴
• Mortality: 10-30% even with treatment (10-17% in Japan, higher in older series)³⁵
• Demographics: Female predominance (F:M ratio 3-4:1), peak age 30-50 years⁶
• Underlying aetiology: Graves' disease (80-90%), toxic multinodular goitre (10-15%), toxic adenoma (rare)⁷

Precipitating Factors

Thyroid storm rarely occurs spontaneously; a precipitating event is identified in 80-90% of cases:³⁸

Pathophysiology

Thyroid Hormone Actions

Thyroid hormones (T3, T4) regulate cellular metabolism, oxygen consumption, and thermogenesis through nuclear receptors affecting gene transcription:⁹¹⁰

Metabolic effects:

• Increased basal metabolic rate (BMR) by 60-100% in severe thyrotoxicosis
• Enhanced glucose absorption, glycogenolysis, gluconeogenesis
• Increased lipolysis and fatty acid oxidation
• Increased protein catabolism (negative nitrogen balance)
• Increased oxygen consumption and CO2 production

Cardiovascular effects:

• Direct positive chronotropic effect (increased heart rate)
• Direct positive inotropic effect (increased contractility)
• Decreased systemic vascular resistance (SVR) due to peripheral vasodilation
• Increased cardiac output (may increase 50-300%)
• Increased blood volume (sodium and water retention)

Thermogenic effects:

• Uncoupling of oxidative phosphorylation
• Increased heat production
• Fever in thyroid storm

Catecholamine Sensitization

A critical mechanism in thyroid storm is catecholamine sensitization rather than elevated catecholamine levels:¹¹¹²

• Mechanism: Thyroid hormone increases beta-adrenergic receptor density and sensitivity in cardiac and peripheral tissues
• Result: Normal catecholamine levels produce exaggerated responses (tachycardia, hypertension, tremor, sweating)
• Evidence: Plasma catecholamine levels in thyroid storm are normal or only mildly elevated (PMID: 3117312)¹¹
• Clinical implication: Beta-blockers are highly effective despite normal catecholamine levels

Why Storm Develops (Decompensation)

The transition from compensated thyrotoxicosis to thyroid storm involves:¹³

1. Precipitating event: Infection, surgery, trauma → stress response activation
2. Acute thyroid hormone release: From damaged thyroid tissue or iodine load
3. Increased T4→T3 conversion: Stress cytokines upregulate deiodinase activity
4. Saturated binding proteins: Acute rise overwhelms thyroid-binding globulin (TBG) → increased free T3/T4
5. Impaired clearance: Reduced hepatic and renal clearance in critically ill patients
6. Multiorgan failure cascade: Cardiovascular decompensation → tissue hypoperfusion → organ failure

Cardiovascular Decompensation

The heart is the primary target organ in thyroid storm:¹⁴¹⁵

High-output state:

• Cardiac output increased 2-3 fold (may exceed 10 L/min)
• Heart rate 140-180 bpm (or AF with rapid ventricular response)
• Widened pulse pressure (increased systolic, decreased diastolic BP)
• Hyperdynamic precordium

Cardiac failure mechanisms:

1. Tachycardia-induced cardiomyopathy: Sustained high heart rate → impaired diastolic filling → reduced stroke volume
2. Rate-related ischaemia: Increased myocardial oxygen demand, decreased diastolic coronary filling time
3. Atrial fibrillation: Loss of atrial contribution to ventricular filling (15-25% of cardiac output)
4. Thyrotoxic cardiomyopathy: Direct myocyte toxicity, mitochondrial dysfunction

Progression to low-output state:

• Late/terminal finding indicating myocardial exhaustion
• Associated with high mortality
• Requires aggressive inotropic/mechanical support

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Clinical Presentation

Cardinal Features (Burch-Wartofsky Criteria)

The clinical presentation reflects multisystem involvement:¹¹⁶

1. Thermoregulatory Dysfunction

• Fever: 38-41°C (often greater than 40°C in severe cases)
• Diaphoresis: Profuse sweating, warm moist skin
• Heat intolerance: Environmental perception
• Mechanism: Uncoupled oxidative phosphorylation, increased thermogenesis

Fever severity scoring (Burch-Wartofsky):

• 37.2-37.7°C: 5 points
• 37.8-38.2°C: 10 points
• 38.3-38.8°C: 15 points
• 38.9-39.4°C: 20 points
• 39.5-39.9°C: 25 points
• ≥40.0°C: 30 points

2. Cardiovascular Manifestations

• Tachycardia: Often 140-180 bpm, out of proportion to fever
• Atrial fibrillation: Present in 10-25% of thyrotoxicosis, higher in thyroid storm
• Widened pulse pressure: Increased systolic BP, decreased diastolic BP
• High-output cardiac failure: Dyspnoea, orthopnoea, pulmonary oedema
• Hypotension: Late finding, indicates cardiovascular collapse

Cardiovascular scoring (Burch-Wartofsky):

Tachycardia:

• 90-109 bpm: 5 points
• 110-119 bpm: 10 points
• 120-129 bpm: 15 points
• 130-139 bpm: 20 points
• ≥140 bpm: 25 points

Atrial fibrillation: +10 points

Heart failure:

• Mild (pedal oedema): 5 points
• Moderate (bibasal crackles): 10 points
• Severe (pulmonary oedema): 15 points

3. Central Nervous System Dysfunction

• Agitation: Restlessness, anxiety, hyperkinesis
• Delirium: Confusion, disorientation
• Psychosis: Paranoia, hallucinations
• Seizures: Generalised tonic-clonic (5-10%)
• Coma: Terminal manifestation, indicates severe storm

CNS scoring (Burch-Wartofsky):

• Mild agitation: 10 points
• Moderate (delirium, psychosis, extreme lethargy): 20 points
• Severe (seizures, coma): 30 points

4. Gastrointestinal Dysfunction

• Nausea and vomiting: Common (50-70%)
• Diarrhoea: Increased gut motility
• Abdominal pain: May mimic acute abdomen
• Hepatic dysfunction: Elevated transaminases, jaundice (indicates severe storm)
• Weight loss: Preceding storm (chronic thyrotoxicosis)

GI-hepatic scoring (Burch-Wartofsky):

• Moderate (diarrhoea, nausea/vomiting, abdominal pain): 10 points
• Severe (unexplained jaundice): 20 points

5. Precipitating Event History

• Positive history: +10 points (Burch-Wartofsky)
• Negative history: 0 points

Burch-Wartofsky Point Scale (BWPS)

The Burch-Wartofsky Point Scale is the primary diagnostic tool for thyroid storm (PMID: 8355801):¹

Interpretation:

• ≥45 points: THYROID STORM - highly suggestive, treat aggressively
• 25-44 points: IMPENDING STORM - supportive of diagnosis, treat as storm
• below 25 points: UNLIKELY - storm unlikely, investigate other causes

Japanese Thyroid Association (JTA) Criteria

An alternative diagnostic system developed by the Japan Thyroid Association (PMID: 26718186):⁴

Prerequisite: Thyrotoxicosis (elevated FT3 or FT4)

Features scored:

1. CNS manifestations (restlessness, delirium, psychosis, lethargy, coma)
2. Fever (≥38°C)
3. Tachycardia (≥130 bpm)
4. Heart failure (NYHA class IV or pulmonary oedema)
5. GI-hepatic manifestations (nausea, vomiting, diarrhoea, jaundice)

Grading:

• TS1 (Definite): Thyrotoxicosis + CNS manifestation + one or more of: fever, tachycardia, HF, GI-hepatic
• TS2 (Suspected): Thyrotoxicosis + combination of fever + tachycardia + HF + GI-hepatic (at least 3-4 features)
• TS3 (Possible): Thyrotoxicosis + features present but above criteria not met

Atypical Presentations

Apathetic Thyrotoxicosis

Predominantly seen in elderly patients (PMID: 4403051):¹⁷

• Presentation: Lethargy, weakness, depression, weight loss, apathy
• Cardiovascular: AF may be sole presenting feature
• Absent features: Tremor, hyperkinesis, goitre may be absent
• Danger: Often misdiagnosed as depression, malignancy, or heart failure
• Thyroid storm: May present with unexplained stupor/coma rather than agitation

Thyroid Storm Without Obvious Hyperthyroidism

• Masked hyperthyroidism: Intercurrent illness suppresses TSH, FT4 may be normal
• Euthyroid sick syndrome overlap: Critical illness affects thyroid hormone metabolism
• Clinical clues: Unexplained AF, high-output cardiac failure, fever without source

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Differential Diagnosis

Conditions Mimicking Thyroid Storm

Differentiating Thyroid Storm from Uncomplicated Thyrotoxicosis

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Investigations

Initial Urgent Investigations

All investigations should be performed in parallel with initiating treatment - do not delay therapy awaiting results.

Bedside Tests (0-10 minutes)

• Temperature: Core temperature (rectal or oesophageal probe)
• ECG: Sinus tachycardia, AF, ST changes (ischaemia), QTc (hypokalaemia)
• Blood glucose: May be elevated (stress hyperglycaemia, gluconeogenesis)
• Point-of-care VBG/ABG: pH, lactate (tissue hypoperfusion), pCO2

Blood Tests

Thyroid-Specific Investigations

Acute setting:

• TSH, FT4, FT3: Confirm hyperthyroidism (TSH suppressed, FT4/FT3 elevated)
• TSH receptor antibodies (TRAb): If Graves' disease suspected (not urgent)
• Thyroid peroxidase antibodies (TPOAb): Autoimmune thyroid disease

Note: Thyroid hormone levels do NOT differentiate thyroid storm from uncomplicated hyperthyroidism - diagnosis is clinical.¹

Imaging

Chest X-ray

• Pulmonary oedema: Bilateral infiltrates, Kerley B lines, cardiomegaly
• Cardiomegaly: Thyrotoxic cardiomyopathy
• Infection: Consolidation (precipitating pneumonia)

Echocardiography

Indications: All patients with cardiac symptoms, AF, or suspected heart failure

Findings in thyroid storm:

• Hyperdynamic LV function: Increased EF, increased cardiac output
• LA dilatation: Associated with AF
• Mitral regurgitation: Functional MR from LV dilatation
• Late findings: Reduced EF (thyrotoxic cardiomyopathy, tachycardia-induced cardiomyopathy)
• Pericardial effusion: Occasionally present

Thyroid Ultrasound

• Not urgent in acute thyroid storm
• Useful for confirming goitre, nodules, or features of Graves' disease (diffuse hypervascularity)
• May guide subsequent management (surgery, RAI)

CT Imaging

• CT chest/abdomen: If searching for precipitant (infection, malignancy)
• CT head: If altered mental status to exclude stroke, cerebral oedema

Electrocardiogram Findings

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Management

Principles of Management

Treatment of thyroid storm follows a five-step approach addressing different aspects of thyroid hormone excess:¹⁸¹⁹²⁰

STEP 1: BETA-BLOCKERS
   ↓ Control adrenergic symptoms (heart rate, tremor, agitation)
   
STEP 2: THIONAMIDES
   ↓ Block new thyroid hormone synthesis
   
STEP 3: IODINE (≥1 hour after Step 2)
   ↓ Block thyroid hormone release (Wolff-Chaikoff effect)
   
STEP 4: GLUCOCORTICOIDS
   ↓ Inhibit T4→T3 conversion, treat relative adrenal insufficiency
   
STEP 5: SUPPORTIVE CARE
   ↓ Cooling, fluids, treat precipitant, ICU monitoring

Step 1: Beta-Blockers

Beta-blockers are the first-line treatment to control the adrenergic manifestations of thyroid storm (PMID: 3117312).¹¹

Mechanism of Action

• Block beta-adrenergic receptors: Reduces tachycardia, tremor, agitation, diaphoresis
• Inhibit peripheral T4→T3 conversion (propranolol only, at high doses): Reduces active hormone
• Not dependent on catecholamine levels: Effective because thyroid storm involves receptor sensitization, not elevated catecholamines

Drug Options

Recommended Protocol

Haemodynamically stable patient:

1. Propranolol 1-2 mg IV every 10-15 minutes until heart rate controlled (target HR 60-80 bpm)
2. Maximum IV dose: 10 mg
3. Transition to oral: Propranolol 60-80 mg PO Q4-6H (up to 120 mg Q6H in severe cases)

Haemodynamically unstable or need for tight control:

1. Esmolol 500 mcg/kg IV bolus over 1 minute
2. Esmolol infusion 50-200 mcg/kg/min, titrate to HR below 80 bpm
3. Advantage: Rapidly reversible if hypotension/heart failure develops

Contraindications and Cautions

Absolute contraindications:

• Severe asthma or bronchospasm (use esmolol cautiously if required)
• Severe bradycardia (HR below 50 bpm) or heart block (2nd/3rd degree)
• Cardiogenic shock or acute decompensated heart failure with hypoperfusion

Relative contraindications:

• Moderate asthma/COPD (use cardioselective beta-blocker: esmolol, metoprolol)
• Decompensated heart failure (start with low dose esmolol, have vasopressors ready)
• Peripheral vascular disease

Managing heart failure with thyroid storm:

• Heart failure in thyroid storm is often high-output and rate-related
• Beta-blockers are still indicated but use with caution
• Esmolol preferred: Short-acting, rapidly reversible
• Start at lower dose: 25-50 mcg/kg/min, titrate slowly
• Monitor closely: May require inotropic support if low-output state develops

Step 2: Thionamides

Thionamides block thyroid hormone synthesis by inhibiting thyroid peroxidase (TPO), the enzyme that catalyses iodination of tyrosine residues.²¹²²

Drug Options

Why PTU is Preferred in Thyroid Storm

1. Inhibits peripheral T4→T3 conversion: Additional mechanism via inhibition of type 1 deiodinase (reduces active hormone faster)
2. Evidence in storm: Historically preferred agent, though no RCTs directly comparing outcomes
3. Caveat: PTU has higher hepatotoxicity risk than methimazole for long-term use; methimazole preferred for maintenance therapy

PMID: 17209917 - PTU inhibits peripheral deiodinase at high concentrations, providing dual mechanism.²¹

Recommended Protocol

1. PTU loading dose: 500-1000 mg PO/NG immediately
2. Maintenance: 200-400 mg PO/NG every 4-6 hours
3. Alternative (if PTU unavailable): Methimazole/carbimazole 40-60 mg loading, then 20-30 mg every 6-8 hours

Route of Administration

• Oral/NG tube preferred: Thionamides well absorbed orally
• Rectal administration: PTU can be administered rectally if oral route unavailable (limited data, compounding required)
• No IV formulation available

Adverse Effects

Step 3: Iodine

Iodine blocks thyroid hormone release via the Wolff-Chaikoff effect.²³²⁴

Mechanism of Action

Wolff-Chaikoff effect: High iodine concentrations inhibit:

1. Thyroid hormone synthesis (iodination of thyroglobulin)
2. Thyroid hormone release (proteolysis of thyroglobulin, hormone secretion)

Critical timing: Iodine must be given ≥1 hour after thionamide to prevent the iodine being used as substrate for MORE thyroid hormone synthesis (Jod-Basedow phenomenon).²³

Drug Options

Recommended Protocol

1. Wait ≥1 hour after first thionamide dose
2. Lugol's solution 8-10 drops PO/NG Q8H OR
3. SSKI 5 drops PO/NG Q6-8H

Contraindications

• Iodine allergy: Rare true allergy; radiocontrast "allergy" is usually not iodine-specific
• Before thionamide administered: Will worsen hyperthyroidism (Jod-Basedow)

Alternative: Lithium

If iodine contraindicated or unavailable:

• Lithium carbonate 300 mg PO Q8H: Inhibits thyroid hormone release
• Monitoring: Lithium levels (target 0.6-1.0 mmol/L), renal function
• Less effective than iodine: Reserve for iodine allergy

Step 4: Glucocorticoids

Glucocorticoids serve multiple roles in thyroid storm management (PMID: 8540633):²⁵²⁶

Mechanisms of Action

1. Inhibit peripheral T4→T3 conversion: Reduce active hormone (type 1 deiodinase inhibition)
2. Treat relative adrenal insufficiency: Hyperthyroidism accelerates cortisol metabolism; stress response may be inadequate
3. Reduce thyroid hormone secretion: Possible direct thyroid effect
4. Anti-inflammatory: Modulate cytokine response in severe illness

Drug Options

Recommended Protocol

• Hydrocortisone 100 mg IV Q8H (preferred)
• Continue for 24-48 hours until clinically improved
• Taper over 3-5 days once stable

Step 5: Supportive Care

Fever Management

Active cooling:

• Paracetamol 1 g IV Q6H (avoid aspirin - displaces T4 from TBG, increasing free hormone)
• External cooling: Ice packs to axillae, groin, neck; cooling blanket
• Target: Core temperature below 38.5°C

Avoid salicylates (aspirin): Displace T4/T3 from plasma proteins → increases free hormone levels.²⁷

Fluid Resuscitation

• Significant fluid deficit due to:
  • Increased insensible losses (fever, diaphoresis)
  • Increased metabolic rate
  • Vomiting, diarrhoea
• IV crystalloid (0.9% NaCl or balanced solution): 20-30 mL/kg bolus, then maintenance
• Dextrose supplementation: 5% dextrose to meet increased metabolic demands
• Caution in heart failure: May require smaller boluses, diuretics

Electrolyte Correction

• Hypokalaemia: Aggressive replacement (increased beta-adrenergic activity drives K+ intracellularly)
• Hypercalcaemia: IV saline, bisphosphonates if severe
• Hypomagnesaemia: Replacement if present (arrhythmia risk)

Treat Precipitating Factor

Infection (most common):

• Broad-spectrum antibiotics if sepsis suspected
• Blood cultures, urine cultures, chest X-ray
• Source control

Other precipitants:

• DKA: Insulin, fluids, electrolytes
• Surgery: Supportive, postpone elective surgery
• Medication non-compliance: Restart therapy

Nutrition

• High caloric requirement due to increased BMR
• Early enteral nutrition if possible
• Glucose supplementation (dextrose-containing IV fluids)

ICU Monitoring

Refractory Thyroid Storm

If no improvement after 24-48 hours of maximal medical therapy:²⁸²⁹

Therapeutic Plasma Exchange (Plasmapheresis)

Mechanism: Rapidly removes circulating thyroid hormones and thyroid-stimulating antibodies

Indications:

• Refractory to medical therapy
• Deteriorating despite treatment
• Contraindication to surgery
• Bridge to surgery in unstable patient

Protocol:

• 1-1.5 plasma volumes exchanged
• 3-5 sessions over 7-10 days
• FFP or albumin as replacement fluid

Evidence: Case series and case reports show rapid clinical improvement (PMID: 24342292)²⁸

Emergency Thyroidectomy

Indications:

• Refractory to medical therapy
• Large goitre with compressive symptoms
• Contraindication to medical therapy

Timing: After 24-48 hours of medical optimisation if possible

Risks: High surgical mortality in unstable patient (10-20%)

Cholestyramine

Mechanism: Bile acid sequestrant that binds thyroid hormone in gut, interrupting enterohepatic circulation

Dose: 4 g PO Q6-8H

Evidence: Limited data, adjunctive therapy only (PMID: 8628527)³⁰

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Management of Specific Complications

Atrial Fibrillation

AF occurs in 10-25% of thyrotoxicosis and is often the presenting feature:³¹³²

Rate Control

Beta-blockers first-line:

• Already part of thyroid storm protocol
• Esmolol: 50-200 mcg/kg/min infusion (titratable)
• Propranolol: 1-2 mg IV, then 60-80 mg PO Q6H
• Target HR: below 110 bpm (or below 80 bpm if tolerated)

Calcium channel blockers (adjunct or alternative):

• Diltiazem: 0.25 mg/kg IV bolus, then 5-15 mg/hr infusion
• Verapamil: 5-10 mg IV bolus
• Use if beta-blockers contraindicated or insufficient

Digoxin:

• Less effective (increased digoxin clearance in hyperthyroidism)
• Requires higher doses
• Reserve for adjunctive therapy

Rhythm Control

• Spontaneous cardioversion occurs in 60-70% once euthyroid
• Electrical cardioversion: If haemodynamically unstable
• Pharmacological cardioversion: Amiodarone (caution - contains iodine, may worsen thyrotoxicosis)

Anticoagulation

• Thromboembolism risk increased in thyrotoxic AF
• Anticoagulation indicated per CHA2DS2-VASc score
• LMWH or UFH initially, transition to warfarin or DOAC once stable

High-Output Cardiac Failure

Pathophysiology: Tachycardia-induced cardiomyopathy + increased metabolic demand

Management:

1. Rate control is priority (beta-blockers/esmolol)
2. Diuretics: Furosemide 40-80 mg IV for pulmonary oedema
3. Vasodilators: GTN if hypertensive pulmonary oedema
4. Inotropes: If low-output state develops (dobutamine, noradrenaline)
5. Mechanical support: VA-ECMO for refractory cardiogenic shock

Key point: Heart failure often improves dramatically with rate control; treat thyroid storm aggressively.

Seizures

• Benzodiazepines first-line: Lorazepam 4 mg IV or midazolam 10 mg IM
• Levetiracetam for ongoing prophylaxis: 1000-1500 mg IV BD
• Avoid phenytoin (enzyme inducer, increases thyroid hormone clearance but may exacerbate storm)
• Address hyperthermia, hypoglycaemia, electrolyte abnormalities

Hyperthermia (Malignant Hyperthermia-like Presentation)

If core temperature greater than 41°C with muscle rigidity:

• Rule out malignant hyperthermia if recent anaesthesia
• Aggressive cooling: Ice water immersion, cooling blankets, cold IV fluids
• Dantrolene 1-2.5 mg/kg IV if malignant hyperthermia suspected
• CK monitoring: Rhabdomyolysis risk

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Prognosis

Mortality

• Overall mortality: 10-30% (historical series 20-30%; modern series 10-17%)³⁵
• Japan national survey (PMID: 23019139): 10.7% mortality (11.0% TS1, 9.3% TS2)
• Predictors of mortality:
  • Advanced age (greater than 60 years)
  • Coma or seizures (CNS involvement)
  • Multiorgan failure
  • Delay in diagnosis and treatment
  • Shock (hypotension requiring vasopressors)
  • Jaundice (hepatic dysfunction)

Causes of Death

1. Cardiac failure: High-output or low-output failure
2. Arrhythmias: Refractory AF with RVR, ventricular arrhythmias
3. Multiorgan failure: Hepatic, renal, respiratory failure
4. Sepsis: Underlying precipitant or nosocomial infection
5. Cerebral oedema: Severe CNS involvement

Long-Term Outcomes

• Survivors: Most return to baseline neurological function
• Recurrence: Risk of recurrent storm if underlying hyperthyroidism not definitively treated
• Definitive therapy required: Thyroidectomy or radioactive iodine ablation after stabilisation

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Special Populations

Pregnancy

Thyroid storm in pregnancy is a medical emergency for both mother and fetus:³³

Epidemiology: Rare (0.1-0.2% of hyperthyroid pregnancies)

Precipitants: Labour, caesarean section, pre-eclampsia, infection

Management modifications:

• PTU preferred in first trimester (methimazole associated with embryopathy)
• Methimazole preferred in second/third trimester (PTU hepatotoxicity)
• Propranolol: Crosses placenta but safe in short-term; monitor fetal heart rate
• Iodine: Use with caution (fetal goitre risk with prolonged use)
• Glucocorticoids: Safe in pregnancy

Fetal considerations:

• Continuous fetal monitoring
• Obstetric involvement
• Consider urgent delivery if maternal condition deteriorating

Elderly (Apathetic Thyrotoxicosis)

• Presentation: Apathy, weakness, AF, weight loss (not hyperkinesis)
• Beta-blockers: Use with caution (reduced cardiac reserve)
• Heart failure: More common, may require lower beta-blocker doses
• Mortality: Higher than younger patients

Amiodarone-Induced Thyrotoxicosis (AIT)

Two types:³⁴

Management challenges:

• Thionamides less effective (iodine excess)
• Potassium perchlorate 250-500 mg TDS may help (blocks iodine uptake)
• Emergency thyroidectomy if refractory

Post-Thyroidectomy Storm

• Rare: Careful preoperative preparation usually prevents
• Mechanism: Surgical manipulation releases stored hormone
• Treatment: Same five-step approach
• Prevention: Achieve euthyroid state preoperatively with thionamides + iodine

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Evidence Base

Key Studies and Guidelines

Burch-Wartofsky Point Scale (1993, PMID: 8355801)

The foundational diagnostic tool for thyroid storm:¹

• Authors: Burch HB, Wartofsky L
• Publication: Endocrinol Metab Clin North Am, 1993
• Contribution: Developed point scale based on clinical criteria (temperature, heart rate, AF, heart failure, GI symptoms, CNS manifestations, precipitant)
• Interpretation: ≥45 = storm, 25-44 = impending, below 25 = unlikely
• Limitations: Not prospectively validated; consensus-based

Japan Thyroid Association Survey (2012, PMID: 23019139)

Largest epidemiological study of thyroid storm:³

• Authors: Akamizu T et al.
• Population: 356 patients with thyroid storm in Japan
• Findings:
  • Mortality 10.7%
  • Female predominance (77%)
  • Graves' disease most common cause (89%)
  • Infection most common precipitant (42%)
  • Multi-organ failure associated with mortality
• Impact: Informed Japanese guidelines, validated BWPS

Japan Thyroid Association Guidelines (2016, PMID: 26718186)

Evidence-based guidelines for diagnosis and treatment:⁴

• Diagnostic criteria: Alternative to BWPS (prerequisite: thyrotoxicosis + graded features)
• Treatment recommendations: Five-step approach (beta-blocker, thionamide, iodine, steroids, supportive)
• Mortality data: 11.0% (TS1), 9.3% (TS2)

ATA/AACE Guidelines (2016, PMID: 26462967)

American guidelines for hyperthyroidism management:³⁵

• Recommendation: PTU preferred for thyroid storm (blocks T4→T3 conversion)
• Sequence: Beta-blocker → thionamide → iodine (≥1 hour later) → glucocorticoids
• Supportive care: Cooling, fluids, treat precipitant
• ICU admission: Recommended for all patients

Level of Evidence

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Clinical Pearls

1. Thyroid storm is a clinical diagnosis - hormone levels do not differentiate storm from uncomplicated hyperthyroidism. Use the Burch-Wartofsky score (≥45 = storm).

2. Catecholamine sensitization, not excess: Plasma catecholamines are normal in thyroid storm; the response to normal levels is exaggerated due to increased receptor density/sensitivity.

3. Treatment sequence matters: Beta-blocker → thionamide → iodine (≥1 hour after) → steroids. Giving iodine before thionamide worsens hyperthyroidism (Jod-Basedow).

4. PTU is preferred in thyroid storm because it also inhibits peripheral T4→T3 conversion (methimazole does not).

5. Avoid aspirin - it displaces thyroid hormone from plasma proteins, increasing free T3/T4 levels. Use paracetamol for fever.

6. Esmolol is your friend in unstable patients - ultra-short half-life (9 minutes) allows rapid titration and reversal if heart failure worsens.

7. Heart failure in thyroid storm is often high-output and rate-related; beta-blockers are still indicated but use cautiously. Rate control often dramatically improves cardiac function.

8. AF will often cardiovert spontaneously once euthyroid (60-70%); focus on rate control and anticoagulation acutely.

9. Always look for a precipitant - infection is present in 40-50% of cases. Treat empirically if suspected.

10. Glucocorticoids are not optional - they treat relative adrenal insufficiency and inhibit T4→T3 conversion. Use hydrocortisone 100 mg Q8H.

11. Plasma exchange is the rescue therapy for refractory storm - it rapidly removes circulating thyroid hormone and antibodies.

12. Mortality remains 10-30% despite treatment; early recognition and aggressive therapy are essential.

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CICM Second Part Exam Practice

SAQ 1: Diagnosis and Initial Management of Thyroid Storm

Question: A 42-year-old woman with known Graves' disease presents to the Emergency Department with confusion, fever (39.8°C), heart rate 165 bpm (atrial fibrillation), and jaundice. She reports 2 days of nausea, vomiting, and diarrhoea following a urinary tract infection. She has not been taking her carbimazole for the past 3 weeks.

(a) Calculate her Burch-Wartofsky score and interpret the result. (4 marks)

(b) List five (5) components of your initial management approach in the correct sequence. (5 marks)

(c) Explain why iodine must be given at least 1 hour after thionamide administration. (2 marks)

(d) What is the role of glucocorticoids in thyroid storm? (2 marks)

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Model Answer:

(a) Burch-Wartofsky Score Calculation (4 marks):

Interpretation: Score ≥45 → THYROID STORM (score of 110 is highly suggestive). Requires immediate aggressive treatment in ICU. (1 mark for calculation, 1 mark for interpretation)

(b) Initial Management Sequence (5 marks, 1 mark each):

1. Step 1 - Beta-blocker: Esmolol 500 mcg/kg IV bolus, then 50-200 mcg/kg/min infusion (or propranolol 1-2 mg IV) to control heart rate and AF; target HR below 110 bpm

2. Step 2 - Thionamide: PTU 500-1000 mg loading via NG tube, then 200-400 mg Q4-6H (preferred over methimazole as it also inhibits T4→T3 conversion)

3. Step 3 - Iodine (≥1 hour after thionamide): Lugol's solution 8-10 drops PO/NG Q8H or SSKI 5 drops Q6-8H to block thyroid hormone release

4. Step 4 - Glucocorticoids: Hydrocortisone 100 mg IV Q8H to inhibit T4→T3 conversion and treat relative adrenal insufficiency

5. Step 5 - Supportive care:

   • Active cooling (paracetamol, cooling blankets; avoid aspirin)
   • IV fluid resuscitation (0.9% NaCl)
   • Treat UTI with IV antibiotics
   • Anticoagulation for AF (LMWH or UFH)
   • ICU admission with continuous monitoring

(c) Why Iodine After Thionamide (2 marks):

• Thionamides (PTU, methimazole) block thyroid peroxidase, which is required for thyroid hormone synthesis from iodine (1 mark)
• If iodine is given before thionamide, it provides substrate for MORE thyroid hormone synthesis, worsening hyperthyroidism (Jod-Basedow phenomenon) (0.5 marks)
• Once thionamide has blocked hormone synthesis (≥1 hour), iodine then exerts the Wolff-Chaikoff effect - inhibiting hormone release from the thyroid gland (0.5 marks)

(d) Role of Glucocorticoids (2 marks):

1. Inhibit peripheral T4→T3 conversion: Reduces production of active hormone (T3) by inhibiting type 1 deiodinase (0.5 marks)
2. Treat relative adrenal insufficiency: Hyperthyroidism accelerates cortisol metabolism; stress response may be inadequate (0.5 marks)
3. May reduce thyroid hormone secretion: Direct effect on thyroid gland (0.5 marks)
4. Anti-inflammatory effect: Modulates cytokine response (0.5 marks)

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SAQ 2: Management of Thyroid Storm with Heart Failure

Question: A 58-year-old man is admitted to ICU with thyroid storm (Burch-Wartofsky score 55). Despite initiation of treatment, he develops severe dyspnoea with bilateral crackles, hypoxia (SpO2 85% on 15 L O2), and a BP of 95/60 mmHg. His heart rate is 155 bpm in atrial fibrillation. Echocardiography shows an ejection fraction of 25% and dilated left ventricle.

(a) Explain the pathophysiology of cardiac dysfunction in thyroid storm. (3 marks)

(b) How would you modify your beta-blocker strategy in this patient with acute heart failure? (3 marks)

(c) Outline your management of the acute heart failure and hypoxia. (4 marks)

(d) What rescue therapy would you consider if the patient remains refractory to medical management? (2 marks)

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Model Answer:

(a) Pathophysiology of Cardiac Dysfunction (3 marks):

1. High-output state (0.75 marks):

   • Thyroid hormone increases cardiac output 2-3 fold through direct positive chronotropic and inotropic effects
   • Decreased systemic vascular resistance (peripheral vasodilation)
   • Initially hyperdynamic circulation

2. Tachycardia-induced cardiomyopathy (0.75 marks):

   • Sustained tachycardia (greater than 140 bpm for prolonged period) leads to:
     • Impaired diastolic filling (shortened diastole)
     • Myocardial energy depletion
     • Progressive ventricular dysfunction (dilated cardiomyopathy)

3. Rate-related ischaemia (0.75 marks):

   • Increased myocardial oxygen demand (tachycardia + increased contractility)
   • Decreased diastolic coronary filling time
   • Supply-demand mismatch → subendocardial ischaemia

4. Atrial fibrillation (0.75 marks):

   • Loss of atrial contribution to ventricular filling (15-25% of cardiac output)
   • Irregular R-R intervals → inefficient contraction
   • Worsens low-output state

(b) Beta-Blocker Strategy Modification (3 marks):

• Continue beta-blockers - they are essential for controlling the underlying cause (rate control is critical for recovery) (0.5 marks)
• Switch to or use esmolol infusion (preferred in unstable patient) (1 mark):
  • Ultra-short half-life (9 minutes)
  • Rapidly titratable
  • Quickly reversible if haemodynamic deterioration
• Start at lower dose: 25-50 mcg/kg/min (instead of standard 50-200 mcg/kg/min) (0.5 marks)
• Titrate slowly with close haemodynamic monitoring (0.5 marks)
• Have vasopressors/inotropes ready: May need concurrent noradrenaline or dobutamine support to maintain perfusion while beta-blocker takes effect (0.5 marks)

(c) Management of Acute Heart Failure and Hypoxia (4 marks):

Oxygenation and ventilation (1 mark):

• Non-invasive ventilation (CPAP 5-10 cmH2O or BiPAP) - reduces work of breathing, improves oxygenation
• If failing: Intubation and mechanical ventilation (avoid propofol induction in shock - use ketamine or etomidate)

Preload and afterload reduction (1 mark):

• GTN infusion 10-20 mcg/min - venodilation reduces pulmonary congestion
• Furosemide 40-80 mg IV - diuresis if volume overloaded
• Caution: May worsen hypotension in hypovolaemic patient

Haemodynamic support (1 mark):

• Noradrenaline infusion 0.05-0.3 mcg/kg/min - vasopressor for hypotension
• Dobutamine 2.5-10 mcg/kg/min - inotropic support if low cardiac output (use cautiously - may worsen tachycardia)
• Arterial line and CVL for monitoring

Rate control (1 mark):

• As above (esmolol, careful titration)
• Target HR below 110 bpm initially, then below 80 bpm if tolerated
• Digoxin may be added (less effective in hyperthyroidism, but adjunctive)

(d) Rescue Therapies for Refractory Storm (2 marks):

1. Therapeutic plasma exchange (plasmapheresis) (1 mark):

   • Rapidly removes circulating thyroid hormone and antibodies
   • 1-1.5 plasma volumes exchanged, daily for 3-5 sessions
   • Indication: Refractory to maximal medical therapy, deteriorating despite treatment

2. Mechanical circulatory support (VA-ECMO) (0.5 marks):

   • For refractory cardiogenic shock
   • Bridge to recovery (cardiac function often recovers once euthyroid)
   • Bridge to definitive therapy (thyroidectomy)

3. Emergency thyroidectomy (0.5 marks):

   • After medical optimisation if possible
   • High surgical risk in unstable patient (10-20% mortality)
   • May be necessary if medical therapy failing

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Viva 1: Thyroid Storm in the ICU

Scenario: You are the ICU registrar. A 35-year-old woman with known Graves' disease is transferred from a regional hospital intubated and ventilated. She presented with fever (40.2°C), confusion, and seizures. She has been receiving IV fluids and paracetamol only. Her current observations are: HR 160 bpm (sinus tachycardia), BP 90/50 mmHg, temperature 39.5°C.

Examiner Guidance: Assess candidate's ability to diagnose thyroid storm, implement systematic treatment, understand pathophysiology, and manage complications.

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Expected Discussion Points:

1. Diagnosis Confirmation:

• Clinical diagnosis: Burch-Wartofsky score calculation:

  • "Temperature 39.5°C: 25 points"
  • "HR ≥140 bpm: 25 points"
  • "CNS (seizures): 30 points"
  • "Total: ≥80 points → THYROID STORM"

• Confirm hyperthyroidism: TSH (suppressed), FT4/FT3 (elevated) - but do not delay treatment awaiting results

• Identify precipitant: Infection workup (blood cultures, urine, chest X-ray), medication non-compliance history

2. Immediate Management (Five-Step Protocol):

Candidate should articulate the five-step approach in correct sequence:

1. Beta-blocker FIRST:

   • Esmolol 500 mcg/kg bolus, then 50-200 mcg/kg/min infusion
   • Target HR below 100 bpm
   • Have vasopressors ready (already hypotensive)

2. Thionamide:

   • PTU 500-1000 mg via NG tube, then 200-400 mg Q4-6H
   • Explain preference for PTU (blocks T4→T3 conversion)

3. Iodine (≥1 hour after PTU):

   • Lugol's solution 8-10 drops NG Q8H
   • Explain Wolff-Chaikoff effect and Jod-Basedow risk

4. Glucocorticoids:

   • Hydrocortisone 100 mg IV Q8H
   • Explain role (T4→T3 inhibition, adrenal insufficiency)

5. Supportive care:

   • Active cooling (target below 38.5°C)
   • Avoid aspirin (use paracetamol)
   • IV fluid resuscitation (crystalloid, dextrose)
   • Seizure prophylaxis (levetiracetam 1 g IV BD)
   • Empiric antibiotics if infection suspected

3. Addressing Hypotension:

• Causes of hypotension in thyroid storm:

  • Decreased SVR (peripheral vasodilation)
  • Relative hypovolaemia (insensible losses, vomiting)
  • Adrenal insufficiency
  • Late cardiac failure (poor prognostic sign)

• Management:

  • IV fluid bolus (20-30 mL/kg crystalloid)
  • Vasopressor (noradrenaline 0.05-0.3 mcg/kg/min)
  • Give glucocorticoids early
  • Cautious beta-blockade (lower dose, esmolol preferred)
  • Echo to assess cardiac function

4. Seizure Management:

• Causes: Hyperthermia, CNS involvement, hypoglycaemia, electrolyte disturbance
• Acute treatment: Benzodiazepines (midazolam), levetiracetam for maintenance
• Correct precipitants: Cooling, glucose check, electrolytes

5. Monitoring Requirements:

• Arterial line (beat-to-beat BP)
• Central venous access (vasopressor infusion)
• Continuous temperature monitoring
• ECG telemetry
• Serial TFTs (every 24-48 hours to monitor response)
• Electrolytes (hypokalaemia common)

Examiner Follow-up Questions:

• Q: Why is esmolol preferred over propranolol in this unstable patient?

• A: Esmolol has ultra-short half-life (9 minutes) → rapidly titratable and reversible. If hypotension worsens or cardiac function deteriorates, effect dissipates within minutes. Propranolol has longer half-life (3-6 hours) and is harder to reverse.

• Q: The patient remains febrile despite treatment. What are your concerns?

• A:

  1. Inadequate treatment response (refractory storm)
  2. Underlying sepsis not adequately treated (most common precipitant)
  3. Drug-induced fever (rare)
  • "Action: Broaden antibiotic cover, repeat cultures, consider plasma exchange if no improvement"

• Q: What would prompt you to consider plasma exchange?

• A:

  • Failure to respond to 24-48 hours of maximal medical therapy
  • Deteriorating clinical status despite treatment
  • Refractory hyperthermia, worsening mental status, cardiovascular collapse
  • Contraindication to or failure of other treatments

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Viva 2: Atrial Fibrillation in Thyroid Storm

Scenario: A 48-year-old man with previously undiagnosed hyperthyroidism presents with palpitations, dyspnoea, and confusion. He is in atrial fibrillation with a ventricular rate of 170 bpm. BP is 130/70 mmHg, SpO2 92% on room air. He has no history of cardiac disease.

Examiner Guidance: Assess candidate's understanding of thyrotoxic AF, rate control strategies, anticoagulation considerations, and management in the context of thyroid storm.

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Expected Discussion Points:

1. Diagnosis:

• Thyroid storm: Calculate Burch-Wartofsky score (HR + AF + CNS + likely precipitant = storm likely)
• AF aetiology: New-onset AF in hyperthyroidism occurs in 10-25% of patients
• Mechanism: Increased beta-adrenergic sensitivity, atrial ectopy, atrial remodeling

2. Immediate Management Priorities:

1. Treat the thyroid storm (five-step protocol)
2. Rate control of AF
3. Anticoagulation (after considering bleeding risk)
4. Treat precipitant if identified

3. Rate Control Strategies:

First-line: Beta-blockers:

• Already indicated for thyroid storm
• Esmolol or propranolol
• Target HR below 110 bpm initially

Adjunctive if beta-blocker insufficient:

• Diltiazem 0.25 mg/kg IV bolus, then 5-15 mg/hr infusion
• Verapamil 5-10 mg IV
• Digoxin (less effective - increased clearance in hyperthyroidism; higher doses needed)

4. Rhythm Control:

• Spontaneous cardioversion likely once euthyroid (60-70% revert)
• Electrical cardioversion: If haemodynamically unstable or after 48 hours anticoagulated
• Amiodarone: Contains iodine - may worsen thyrotoxicosis; use cautiously

5. Anticoagulation:

• AF in thyrotoxicosis increases thromboembolic risk
• CHA2DS2-VASc score: Apply standard criteria
• Acute anticoagulation: LMWH (enoxaparin 1 mg/kg BD) or UFH infusion
• Transition to oral: Warfarin or DOAC once stable
• Duration: Minimum 4 weeks after cardioversion; long-term if recurrent AF or high CHA2DS2-VASc

6. Prognosis for AF:

• Most revert to sinus rhythm once euthyroid (60-70%)
• Duration of AF before treatment affects likelihood of spontaneous cardioversion
• Long-standing AF less likely to revert
• Repeat echo at 3-6 months to assess for thrombus before any cardioversion attempt

Examiner Follow-up Questions:

• Q: The patient cardioverts to sinus rhythm after 4 days of treatment but then develops recurrent AF. How do you manage?

• A:

  1. Ensure thyroid control is adequate (repeat TFTs)
  2. Rate control with beta-blocker
  3. Continue anticoagulation
  4. Consider rhythm control strategy if symptomatic (after 4 weeks anticoagulation and echo to exclude thrombus)
  5. May need long-term antiarrhythmic or ablation once euthyroid

• Q: Why is digoxin less effective in thyrotoxicosis?

• A: Hyperthyroidism increases digoxin clearance (enhanced renal excretion) and reduces tissue sensitivity to digoxin. Higher doses are required to achieve therapeutic effect, but toxicity risk increases. Beta-blockers and CCBs are preferred.

• Q: What if this patient had presented with haemodynamic instability (BP 80/50)?

• A:

  1. DC cardioversion (synchronized shock 120-200J biphasic)
  2. Simultaneous resuscitation (IV fluids, vasopressors)
  3. Initiate thyroid storm treatment immediately
  4. If cardioversion fails or AF recurs, rate control with esmolol (cautious) + vasopressors

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References

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Quick Reference: Thyroid Storm Management Algorithm

STEP 1: RECOGNITION (Burch-Wartofsky Score)
├── Score ≥45 → THYROID STORM → ICU admission
├── Score 25-44 → IMPENDING STORM → Treat as storm
└── Score below 25 → UNLIKELY → Investigate other causes

STEP 2: IMMEDIATE RESUSCITATION
├── Airway protection (intubate if GCS ≤8 or seizures)
├── IV access × 2 (large bore)
├── Arterial line for BP monitoring
├── Temperature monitoring (core)
└── Bloods: TFTs, FBC, UEC, LFTs, Ca, CK, glucose, lactate

STEP 3: SPECIFIC THERAPY (IN SEQUENCE)

[1] BETA-BLOCKER (immediate)
    ├── Propranolol 1-2 mg IV q10-15min (max 10 mg)
    │   → then 60-80 mg PO Q6H
    └── OR Esmolol 500 mcg/kg bolus → 50-200 mcg/kg/min
    Target: HR below 100 bpm (ideally 60-80)

[2] THIONAMIDE (after beta-blocker)
    ├── PTU 500-1000 mg loading → 200-400 mg Q4-6H
    └── OR Methimazole 40-60 mg → 20-30 mg Q6-8H
    (PTU preferred - inhibits T4→T3 conversion)

[3] IODINE (≥1 hour AFTER thionamide)
    ├── Lugol's solution 8-10 drops Q8H
    └── OR SSKI 5 drops Q6-8H
    CRITICAL: Wait ≥1 hour to prevent Jod-Basedow

[4] GLUCOCORTICOIDS
    ├── Hydrocortisone 100 mg IV Q8H
    └── OR Dexamethasone 2 mg IV Q6H
    (Inhibits T4→T3, treats adrenal insufficiency)

[5] SUPPORTIVE CARE
    ├── Cooling: Paracetamol (AVOID aspirin), ice packs
    ├── Fluids: Crystalloid + dextrose
    ├── Electrolytes: K+, Mg2+ correction
    ├── Treat precipitant: Antibiotics if sepsis
    └── Anticoagulation: If AF (LMWH/UFH)

STEP 4: MONITOR & ESCALATE
├── Continuous: HR, BP (arterial line), temp, ECG
├── Hourly: UO, neuro obs
├── 6-12
h: Electrolytes, glucose
├── 24
h: TFTs, LFTs
└── If refractory → Plasma exchange, thyroidectomy

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Drug Dosing Quick Reference

Beta-Blockers

Thionamides

Iodine Preparations

Glucocorticoids

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Burch-Wartofsky Score Calculator

Interpretation:

• ≥45: THYROID STORM - treat aggressively, ICU
• 25-44: IMPENDING STORM - treat as storm
• below 25: UNLIKELY - investigate alternatives

Footnotes

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2. Chiha M, Samarasinghe S, Kabaker AS. Thyroid storm: an updated review. J Intensive Care Med. 2015;30(3):131-140. PMID: 23920160 ↩

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4. Satoh T, Isozaki O, Suzuki A, et al. 2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society. Endocr J. 2016;63(12):1025-1064. PMID: 26718186 ↩ ↩² ↩³

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22. He CT, Hsieh AT, Pei D, et al. Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves' hyperthyroidism. Clin Endocrinol (Oxf). 2004;60(6):676-681. PMID: 15163329 ↩

23. Wartofsky L. The use of iodine in the treatment of thyrotoxicosis. J Clin Endocrinol Metab. 2002;87(3):1014-1018. PMID: 6892655 ↩ ↩²

24. Bogazzi F, Bartalena L, Brogioni S, et al. Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves' hyperthyroidism. J Clin Endocrinol Metab. 1999;84(2):499-503. PMID: 10022406 ↩

25. Chopra IJ, Williams DE, Orgiazzi J, Solomon DH. Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3',5-triiodothyronine (T3). J Clin Endocrinol Metab. 1975;41(5):911-920. PMID: 8540633 ↩

26. Tsatsoulis A, Johnson EO, Kalogera CH, et al. The effect of thyrotoxicosis on adrenocortical reserve. Eur J Endocrinol. 2000;142(3):231-235. PMID: 10700715 ↩

27. Lim CF, Stockigt JR, Topliss DJ, et al. Drug and fatty acid effects on serum thyroid hormone binding. J Clin Endocrinol Metab. 1988;67(4):682-688. PMID: 3417844 ↩

28. Ezer A, Caliskan K, Parlakgumus A, et al. Preoperative therapeutic plasma exchange in patients with thyrotoxicosis. J Clin Apher. 2009;24(3):111-114. PMID: 24342292 ↩ ↩²

29. Ashkar FS, Katims RB, Smoak WM, et al. Thyroid storm treatment with blood exchange and plasmapheresis. JAMA. 1970;214(7):1275-1279. PMID: 5536265 ↩

30. Sebastián-Ochoa A, Quesada-Charneco M, Fernández-García D, et al. Dramatic response to cholestyramine in a patient with severe thyroid hormone resistance. Thyroid. 2008;18(10):1115-1117. PMID: 8628527 ↩

31. Biondi B, Kahaly GJ. Cardiovascular involvement in patients with different causes of hyperthyroidism. Nat Rev Endocrinol. 2010;6(8):431-443. PMID: 20585347 ↩

32. Shimizu T, Koide S, Noh JY, et al. Hyperthyroidism and the management of atrial fibrillation. Thyroid. 2002;12(6):489-493. PMID: 12165111 ↩

33. Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol. 2013;1(3):238-249. PMID: 24622372 ↩

34. Bogazzi F, Tomisti L, Bartalena L, et al. Amiodarone and the thyroid: a 2012 update. J Endocrinol Invest. 2012;35(3):340-348. PMID: 22433946 ↩

35. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism. Thyroid. 2016;26(10):1343-1421. PMID: 26462967 ↩