Thyroid Storm : a Life-Threatening Thyrotoxicosis

(Therapeutical Guidelines with Formula TS 41668-24-6)

2005 (30)
Askandar Tjokroprawiro
Diabetes and Nutrition Center Airlangga University School of Medicine - Dr. Soetomo Teaching Hospital, Surabaya

Workshop and Hands on Experiences V Thyroid Surgery

Surabaya, 22-24 August 2005
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Thyroid Storm (TS) = Thyroid Crisis (TC)

(Summarized : 2005)

I Clinical Patterns - Differentials II Pathogenesis : Several Proposed Theories

III Essentials to Know: No Laboratory Tests are Diagnostic, Etc.

IV 24 Precipitants of TS or TC : Originals (13) & New Ones (11) V BW-Score = Burch-Wartofsky Score : Dx for TS or TC

VI Treatment : - Supportive Care - Specific Measures : FORMULA TS 41668-24-6

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Thyroid Storm (TS) = Thyroid Crisis (TC)

I Clinical Patterns and Differentials
(Summarized : Tjokroprawiro 2005) CLINICAL PATTERNS : a Life Threatening Clinical Extreme of Thyrotoxicosis

1 General Symptoms : - Fever (>38.5 0C, Frequently >40 0C) Tachycardia >120/min
- Profuse Sweating, Respiratory Distress, Fatigue

2 Signs of Thyrotoxicosis : Orbital Signs, Goiter

3 Neurologic : Agitation, Psychosis, Seizures, Coma

4 Cardiovascular : Tachycardia disproportionates to Fever Increased BP with Wide Pulse Pressure, CHF, AF

5 GI Symptoms : Diarrhea, Vomiting, Abdominal Pain, Jaundice

DIFFERENTIALS: CNS Infections, Malignant Hyperpyrexia, Sepsis, Adrenergic Drugs, Etc.
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II Pathogenesis of Thyroid Storm (TS)

(Summarized : Tjokroprawiro 2005)

Exact Pathogenesis is Not Fully Understood

FT3 and FT4 Correlate Poorly with Severity of Condition
(Condition is Essentially an Inability of End-Organs to Modulate their Response to Excess TH)

The Proposed Theories

1 TS : Relatively High Free-TH (Thyroid Hormone)

2 Activated Adrenergic Receptor : - Dramatic Response of TS to Beta-Blockers - Pseudoephedrine as a Precipitant

3 A Rapid Rise of TH-levels : - Drop in Binding Proteins Postoperatively - Vigorous Palpation of Thyroid Gland 4 Presence of a Unique Catecholamine - like Substances in Thyrotoxicosis and a Direct Sympathomimetic Effect of TH (Structural Similarity to Catecholamine)
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III A Essentials to Know about Thyroid Storm

(Summarized : Tjokroprawiro 2005)

1 Never Forget (!) that the Dx for TS is Clinically Based 2 No Laboratory Tests are Diagnostic 3 Special Attention :
Should Positive Clinical Pattern of TS has been Confirmed, Never Delay Treatment to Await Laboratory Results
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III B Thyroid Laboratory Studies in Thyroid Storm

(Summarized : 2005)

1 Results of Thyroid Studies : Consistent with Hypertyroidism These are Useful if Pts has not been Diagnosed Previously 2 Test Results may not come back quickly Usually, such Results are unhelpful for Immediate Management 3 Usual Findings : Increased FT3 and FT4, Decreased TSHS TSH is not Suppressed if the Etiology is Excess TSH Secretion

4 LFT : Non Specific Abnormalities : ALT, AST, LDH, CK, Alkaline Phosphatase, Serum Bilirubin
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IV A Precipitants of Thyroid Storm

The Following Factors are Known to Precipitate
(Singhal 2003, 2004; Summarized : 2005)

1 Infection 2 Surgery 3 Trauma 4 R/ Radioactive Iodine

5 Pregnancy 6 Anticholinergic and Adrenergic Drugs f.e. Pseudoephedrine 7 TH Ingestion 8 Diabetic Ketoacidosis

Mortality : - In the Past 90% - Today < 20% (Better Control, Early Treatment)
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IV B 24 Known Cumulative Precipitans of Thyroid Storm

Burch et al 1993, Tietgens et al 1995, Hall et al 1999, Turner et al 2003, Greenspan et al 2004 (Summarized : Tjokroprawiro 2005)
1 Infection 2 Thyroid Surgery 3 Non-Thyroid Surgery 4 Iodinated Contrast Dyes 14 Hypoglycemia 15 Sympathomimetic Drugs : Pseudoephedrine , Amiodarone , etc

5 Withdrawal of Antithyroid Drug Therapy 17 Congestive Heart Failure 6 Radioiodine Therapy 18 Toxemia of Pregnancy 7 Diabetic Ketoacidosis 8 9 Parturition Severe Emotional Stress 19 Bowel Infarction 20 Tooth Extraction 21 TH Ingestion 22 Burn Injury 23 Sepsis 24 Childbirth

16 "Healthy Food" Preparation Containing Sea weed or Kelp

10 Pulmonary Embolism 11 Cerebral Vascular Accident 12 Trauma : Fracture, etc.

13 Vigorous Thyroid Palpation

No 1 - 13 are Known Precipitants presented by Burch and Wartofsky-1993

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Effect of Pregnancy on Thyroid Function

Turner et al 2003, Becker 2004, Greenspan et al 2004
(Summarized : Tjokroprawiro 2005)

Normal : 1 TSH

WNL. But, 13.5% T-1, 4.5% T-2, 1.2% T-3

II Decreased Iodide Stores : 1 Renal Clearance 2 Transplacental Transfer to Foetus

T = Trimester

III Increased : 1 Thyroid Size by 10-20% (hCG Stimulation and Relative Iodide Deficiency) 2 TG (Coresponds to Increase in Thyroid Size) 3 TBG : - Reduced Hepatic Clearance - Synthesis due to Stimulation by Estrogen Concentration : Plateaus at 20 weeks of Gestation; Falls again Post Partally 4 Total T4 and T3 ( rise in TBG) 5 Small Rise in FT4 and FT3 in T-1 (hCG Stim, and then into Normal Range)
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Amiodarone in Clinical Practice

Turner et al 2003, Becker 2004, Greenspan et al 2004 (Summarized : Tjokroprawiro 2005)

1 It contains 39% Iodine by Weight 2 On a Dose of 200-600 mg/daily 7.21 mg Iodine is made available The Optimal Daily Iodine Intake : 150-200 g 3 Half-Life of Amiodarone : 52.6 Days, SD : 23.7 Days 4 Abnormalities of Thyroid Function : Up to 50% USA and UK : - 2% AIT (Amiodarone - induced Thyrotoxicosis) - 13% AIH (Amiodarone - induced Hypothyroidism) 5 AIT may present several months after discontinuing the drug
Continued
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Amiodarone in Clinical Practice

Turner et al 2003, Becker 2004, Greenspan et al 2004 (Summarized : Tjokroprawiro 2005)

6 Thyroid Function Tests : Should be monitored every 6 months 7 The High Iodine Content of Amiodarone may : a Inhibit Synthesis and Release of TH AIH b or Loading to Iodine-induced Thyrotoxicosis 8 Direct Toxic Effect of Amiodarone AIT Type-II

AIT Type-I

Amiodarone-induced Destructive Tyroiditis Leakage of TH from Damaged Follicles into the Circulation Can be Followed by a Transient Hypothyroid State before Euthyroidism is Restored
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Amiodarone induced Thyrotoxicosis

AIT Type-I and AIT Type-II
(Summarized : 2005)

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AIT Type-I Aetiology Iodine Toxicity

AIT Type-II Thyroiditis

Signs of Clinical Thyroid Disease

Goiter Thyroid Antibodies Radioiodine Uptake Thyroglobulin Serum IL-6 Late Hypothyroidism

Yes
Frequent Positive Normal Normal No

No
Infrequent Negative Decreased Very Elevated Possible

Normal or Slightly Elevated Very Elevated

Vascularity (Doppler)
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Increased / Normal

Reduced

V A Diagnostic Criteria for Thyroid Storm

(Burch - Wartofsky 1993)
1 Thermoregulatory Dysfunction : 5-30 Temperature : 37.2 - 37.7 5 37.8 - 38.3 10 38.4 - 38.8 15 38.9 - 39.4 20 39.5 - 39.9 25 30 > 40 2 Cardiovascular Dysfunction : 0-25 Tachycardia : 99 - 109 5 110 - 119 10 120 - 129 15 130 - 139 20 > 140 25 Congestive Heart Failure Absent : 0 Mild : Pedal Edema 5 Moderate : Bibasilar Rales 10 Severe : Pulmonary Edema 15 Atrial Fibrillation Absent : 0 Present : 10
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3 Central Nervous System Effects : 0-30 Absent : Mild : Agitation Moderate : Delirium Psychosis Extreme Lethargy Severe : Seizure Coma

0 10 20

30

4 Gastrointestinal-Hepatic Dysfunction : 0-20 Absent : 0 Moderate : Diarrhea 10 Nausea/Vomiting Abdominal Pain Severe : Unexplained Jaundice 20 5 Precipitant History : 0-10 Negative : Positive : Below 25 is Unlikely TS 25-44 is Impending TS 45-Greater is Highly Suggestive TS 0 10

V B BW-Score for Dx of Thyroid Storm: 1993

(Burch et al 1993, Summarized : Tjokroprawiro 2005)

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Burch - Wartofsky Point Scale : BWPS

Total Scoring
Below 25 Unlikely TS
1 Thermoregulatory (5 - 30)
Temperature (0C) 37.2 - 37.7 : 5 37.8 - 38.3 : 10 38.4 - 38.8 : 15 38.9 - 39.4 : 20 39.5 - 39.9 : 25 > 40 : 30
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25 - 44 Impending TS
2 Cardiovascular 3 CNS (5 - 25) (0 - 30) Tachycardia :5-25 Absent CHF AF :0-15 Mild

45 - Greater Highly Suggestive TS

4 GI-Hepatic 5 Precipitant (0 - 20) (0 - 10) :0 Absent :10 :0 Negative : 0 Moderate :10 Positive : 10 :20

Moderate :20

:0-10 Severe

:30 Severe

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V C Cardinal Signs of Thyroid Storm

(Burch - Wartofsky 1993, Summarized : 2005)
Thermoregulatory Dysfunction

Cardiovascular Dysfunction
Tachycardia/min CHF AF

Temperature 0C

37.2 - 37.7 : 5 37.8 - 38.3 : 10

99 - 109 : 5 Absent : 0 Absent : 0 110 - 119 : 10 Mild

38.4 - 38.8 : 15
38.9 - 39.4 : 20 39.5 - 39.9 : 25 > 40
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: 5 Present : 10 (Pedal Edema)

(Bibasilar Rales)

120 - 129 : 15 Moderate: 10 130 - 139 : 20 > 140 : 25

Severe : 15

: 30

(Pulmonary Edema)

Summarized Burch-Wartofsky Score 1993

(BW-Score 1993, Summarized : Tjokroprawiro 2005)

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1 Thermoregulatory Dysfunction (Temp. 37.2 > 40 0C) : 5-30

2 Cardiovascular Dysfunction (5-25) a Tachycardia (90 more than 140/min) : 5 - 25 b Congestive Heart Failure : 0 - 15 c Atrial Fibrillation : 0 - 10
3 Central Nervous System Effects (0 30) 4 Gastrointestinal-Hepatic Dysfunction (0 20) 5 Precipitant History (0 10)

Diagnostic Score
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- Below 25 is Unlikely Thyroid Storm (TS) - 25 - 44 is Impending TS - 45 - Greater is Highly Suggestive TS

Tetralogy of Thyroid Storm-Score : TTS-Score

(Based on BW-Score 1993)

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Goiter-Temperatur-Tachycardia-Precipitant

Go - T - TP

TTS-Score
(Clinical Experiences : 2002-2005) 1 Two of the Following : a Goiter, b Orbital Signs, c And/Or : TSHs, FT3, FT4 2 Temperature > 39.5 0C : Score > 25 3 Tachycardia > 120/min : Score > 15

4 Precipitant (+) : Score 10, or CNS Effects (+) : Score 10-30

Should this Tetralogy is Met, the SCORE will be > 50

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Diagnostic Criteria for Thyroid Storm in Daily Practice

BW-Score (> 45)
(Burch-Wartofsky 1993) (Clinical Experiences : Tjokroprawiro 2005)

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TTS-Score (> 50)

Go - T - TP

Tetralogy of Thyroid Storm-Score : TTS-Score

(Clinical Experiences : Tjokroprawiro 2005 )
1 Two of the Following : a Goiter, b Orbital Signs, c And/Or : TSHs, FT3, FT4) 2 Temperature >39.5 oC 3 Tachycardia >120/min (> 25) (> 15) 4 Precipitant(+) or CNS Effects(+) (> 10)

If Such is Not the Case : Back to BW-Score

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VI Treatment of Thyroid Storm

(Clinical Experiences : Tjokroprawiro 2002-2005)

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I Supportive Care : A Must or If Needed

1 IV Fluids : Dextrose and Electrolytes are preferred for the Hypermetabolic Demand 2 Hyperpyrexia : Cooling Blanket/Ice Packs Acetaminophen 15 mg/kg, q 4 h; or Chlorpromazine 25-100 mg I.M 3 Chlorpromazine is needed to treat Agitation and Hyperpyrexia (Its Effect in Inhibiting Central Thermoregulation)

4 NG Tube (if needed) : many drugs are given orally

5 Supplemental Oxygen, if needed : Ventilatory Support

II Specific Measures : FORMULA TS 41668-24-6

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FORMULA TS 41668 - 24 - 6
Practical Guidelines for the Treatment of Thyroid Storm
(Clinical Experiences : Tjokroprawiro 2002-2005)

20

Based on BW-Score > 45 (1993) and/or TTS-Score > 50 (2005)

Description
4-1-6-6-824-6 : Each shows Time of Treatment Period
4 1 6 6 8 24 6 Every 4 Hours of PTU-administration 1 Hour Interval between PTU (first) and Lugol (later) Administrations Every 6 Hours of Lugol-Administration Every 6 Hours of Propranolol-Administration Every 8 Hours of Hydrocortisone/Dexamethasone Treatment Clinical Improvement should occur within 24 Hours Adequate Therapy should Resolve the Crisis within 6 Days
Continued
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FORMULA TS 41668 - 24 - 6
Practical Guidelines of Thyroid Storm Treatment
(Clinical Experiences : Tjokroprawiro 2002-2005)

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This Formula should be given by a SEQUENTIAL MANNER 4 Loading Dose 400 mg PTU or 40 mg Methimazole Orally Maintenance : 100-200 mg PTU or 10-20 mg Methimazole Every 4 Hours Minimally, 1 Hour after PTU or Methimazole, and then Lugol can be given Lugol's Sol. can be given 6 gtt / 6 h (6 drops Every 6 Hours) Or, Sodium Iodide 0.25 g IV Every 6 Hours Oral Propranolol (Empty Stomach) can be given 10-40 mg Every 6 Hours Or, 1-3 mg/dose slow IV Propranolol, not to exceed 1 mg/min, and Repeat in 2 min, if needed Hydrocortisone 100 mg IV Every 8 Hours Formula 6.30 - 12.30 - 16.30 Or, Dexamethasone 2 mg Orally, Every 8 Hours Continued
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1 6
6

FORMULA TS 41668 - 24 - 6
Therapeutical Guidelines of Thyroid Storm Treatment
(Clinical Experiences : Tjokroprawiro 2002-2005)

22

This Formula should be given by a SEQUENTIAL MANNER 24 Clinical Improvement should occur within 24 Hours 6 The Crisis should be Resolved within 6 Days Special Attention : 1 Adequate Therapy has reduced Mortality from 90% (in the past) to 20% 2 The Precipitant is often the Cause of Death 3 Sympathomimetic Drugs fe. Pseudoephedrine and Amiodarone are : Daily Used Precipitants 4 Lugol's Sol. should be given After Meal , whereas Propranolol is better be given in Empty Stomach 5 Plasmapheresis, Peritoneal Dialysis, Cholestyramine or Colestipol 20-30 g/day, Chlorpromazine 25-100 mg I.M can be attempted if Patient is Seriously Ill. 6 ASA should be Avoided (!!)
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Diagnostic Criteria for Thyroid Storm in Daily Practice

BW-Score (> 45)
(Burch-Wartofsky 1993) (Clinical Experiences : Tjokroprawiro 2005)

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TTS-Score (> 50)

Go - T - TP

Tetralogy of Thyroid Storm-Score : TTS-Score

(Clinical Experiences : Tjokroprawiro 2005)
1 Two of the Following : a Goiter, b Orbital Signs, c And/Or : TSHs, FT3, FT4) 2 Temperature >39.5 oC 3 Tachycardia >120/min (> 25) (> 15) 4 Precipitant(+) or CNS Effects(+) (> 10)

If Such is Not the Case : Back to BW-Score

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FORMULA TS 41668 - 24 - 6
Therapeutical Guidelines for the Treatment of Thyroid Storm
(Clinical Experiences : Tjokroprawiro 2002-2005)

24

Based on BW-Score > 45 (1993) and/or TTS-Score > 50 (2005)

Description
4-1-6-6-824-6 : Each shows Time of Treatment Period
4 1 6 6 8 24 6 Every 4 Hours of PTU-administration 1 Hour Interval between PTU (first) and Lugol (later) Administrations Every 6 Hours of Lugol-Administration Every 6 Hours of Propranolol-Administration Every 8 Hours of Hydrocortisone/Dexamethasone Treatment Clinical Improvement should occur within 24 Hours Adequate Therapy should Resolve the Crisis within 6 Days

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Bosporus-Bridge (1.1 km)

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Penang Bridge (13.8 km) Malaysia

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