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Early View Article: Online published version of an accepted article before publication in the

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Journal Name: Journal of Case Reports and Images in Medicine

Type of Article: Case Report

Title: Case Report of Hyperthyroidism associated with an increased risk for infection

Authors: Andrew Dookhan, Hiren Patel, Mihir Patel, Kaival Patel, James Bass, Abhinav

Sinha

doi: To be assigned

Early view version published: June 4, 2016

How to cite the article: Dookhan A, Patel H, Patel M, Patel K, Bass J, Sinha A. Case

Report of Hyperthyroidism associated with an increased risk for infection. Journal of Case

Reports and Images in Medicine. Forthcoming 2016.

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TYPE OF ARTICLE: Case Report 1

2

TITLE: Case Report of Hyperthyroidism associated with an increased risk for 3

infection 4

5

AUTHORS: 6

Andrew Dookhan1, 7

Hiren Patel2, 8

Mihir Patel3, 9

Kaival Patel4, 10

James Bass5, 11

Abhinav Sinha6 12

13

AFFILIATIONS: 14

1MS-IV at Spartan Health Sciences University - [email protected] 15



4MS-III at Spartan Health Sciences University - [email protected] 18

5MS-III at Spartan Health Sciences University - [email protected] 19

6MD – Chief Director of Medicine at North Vista Hospital - [email protected] 20

21

CORRESPONDING AUTHOR DETAILS 22

Andrew Dookhan 23

197 Tysen Street, Staten Island, NY 10301, 718-501-5568 24

Email: [email protected] 25

26

Short Running Title: Hyperthyroidism and its association for an increased infection 27

risk 28

29

Guarantor of Submission : The corresponding author is the guarantor of 30

submission. 31

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TITLE: Case Report of Hyperthyroidism associated with an increased risk for 33

infection 34

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ABSTRACT 36

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Introduction 38

Infection risk associated with hyperthyroidism although not uncommon, may present 39

with increased mortality if left untreated. 40

The role of hyperthyroidism and its risk for infection is primarily due to the 41

hypermetabolic effect on the body. Modification to the sympathetic nervous system 42

produces a downregulation of the neutrophil response towards the sites of 43

inflammation and/or infection. Consequently, remarkably increasing the risk for 44

complications of infections to occur i.e.: bacterial pneumonia. 45

46

Case Report 47

A 34-year-old Caucasian female presented to the ER complaining of tachycardia, 48

isolated systolic hypertension, tremors, dyspnea, fever, chills, and productive cough 49

with yellow-brown sputum for 5 days. 50

She reported several similar episodes have occurred in the past. A clinical diagnosis 51

of Hyperthyroidism with thyroid storm induced pneumonia was made by the 52

physician and the patient was admitted to the ICU for treatment and close 53

monitoring. 54

Urinary antigen testing detected a positive result for Streptococcus pneumoniae or 55

pneumococcal pneumonia to confirm the pneumonia and treatment was initiated. 56

57

Conclusion 58

The role of hyperthyroidism and its risk for infection causes devastating infectious 59

complications, such as pneumonia, an example that this patient experienced along 60

with having similar episodes in the past but without causality to account for why they 61

are recurrent. Clinical suspicion for diagnosing hyperthyroidism will vastly aid in the 62

management of patient’s more effectively and hopefully avoid any infectious 63

complication that may result. It is entirely important that these patients should be 64


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closely monitored to help prevent any further complications that may present upon 65

admission. 66

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Keywords: Hyperthyroidism, Infection, Pneumonia, Thyroid storm 68

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TITLE: Case Report of Hyperthyroidism associated with increased risk for infection 97

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INTRODUCTION 99

Hyperthyroidism can be defined as an overactive thyroid, a condition in which your 100

thyroid gland produces too much of the hormone thyroxine (T4). An overactive 101

thyroid increases the basal metabolic rate and increased sympathetic nervous 102

system activity in the human body. Changes in the sympathetic nervous system 103

cause a downstream of effects, an example being a rare complication of thyroid 104

storm with increased infection risk. It manifests itself as a state of exaggerated 105

hyperthyroidism accompanied by systemic organ decompensation. The etiology of 106

thyroid storm can range from poorly controlled to precipitant such as infection, 107

surgery, diabetic ketoacidosis, etc. Increased infection risk is a serious complication 108

these patients face because they are at a higher risk than the normal average 109

person due to the lapse of neutrophil attraction towards sites of inflammation and/or 110

infection. This occurs because hyperthyroidism causes a hypermetabolic effect 111

causing a downregulation of neutrophil response to sites of infection, resulting in 112

complications such as bacterial pneumonia. 113

114

CASE REPORT 115

A 34-year-old Caucasian female presented to the ER complaining of tachycardia, 116

isolated systolic hypertension (148/82), tremors, dyspnea (respiratory rate of 28), 117

fever (102.4), chills, and productive cough with yellow-brown sputum for 5 days. She 118

reported several similar episodes have occurred in the past. Also, the patient stated 119

that she had persistent symptoms of anxiety and myalgia as well, especially for the 120

past 2 weeks. Nothing alleviated or persisted the patient’s symptoms. She denied 121

any medication use, recent travel, contact with those whom are sick, rhinorrhea, 122

nausea, rash, urinary/bowel changes, sleep disturbance, recent infection, and 123

dizziness. Physical exam revealed bilateral expiratory wheezing along with a normal 124

S1/S2, no murmur, rub, and gallop present on arrival. 125

Chest radiograph and echocardiogram were ordered initially. The results revealed 126

left lower lobe opacification with pleural effusions consistent of a lobar pneumonia 127

and revealed a mild systolic ejection murmur, respectively. 128


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A clinical diagnosis of Hyperthyroidism with thyroid storm induced pneumonia was 129

made and the patient was admitted to the ICU for treatment and close monitoring. 130

131

Treatment regimen consisted of: 132

• Rocephin – 1g IM once every 24 hours 133

• Zithromax – 500mg by mouth once then 250mg by mouth once a day for 4 134

days. 135

• Tamiflu – 75mg by mouth once a day for 10 days (ICU prophylaxis due to 136

another patient whom acquired H1N1 influenza) 137

• Methimazole – 15mg by mouth three times a day 138

• Propranolol - 5mg IV 139

• Atrovent HFA – 2 puffs by mouth every six hours or as needed. 140

• IV steroids – 125mg IV for three days 141

142

Day 1 to day 3 of hospitalization, following the results of radiology and the 143

echocardiogram, the patient experienced a change in consciousness and was 144

placed on mechanical ventilation due to high risk of aspiration potentially worsening 145

the pneumonia. Additional tests were ordered to confirm the physician’s clinical 146

diagnostic suspicion: CBC with diff. (complete blood count with differential), CMP 147

(comprehensive metabolic panel), TFTs (thyroid functioning tests), sputum gram 148

stain, urinalysis, and blood cultures. 149

Result findings proved to have a decreased TSH (<0.07 µU/mL; Normal: 0.5-5.0 150

µU/mL) and an increased T3 (490 ng/dL; Normal: 115-190 ng/dL) and free T4 level 151

(33.5 µg/dL; Normal: 5-12 µg/dL). It is also noted that within the CBC differential, the 152

absolute neutrophil count was 1.13 (ANC normal range: 1.5-8.0 or 1,500- 153

8,000/mm3). 154

Sputum gram stain was inconclusive due to lack of specimen gathered from patient. 155

Urinary antigen testing detected a positive for Streptococcus pneumoniae and 156

treatment remained the same but route of administration changed from by mouth to 157

either IV or IM. 158

Day 2 of hospitalization, the patient’s vitals were unstable exhibiting hyperpyrexia 159

(101.6) but blood pressure was managed within normal limits. The patient was 160


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closely monitored and remained on mechanical ventilation as she was in and out of 161

consciousness. Medication regimen remained the same. 162

Day 3 of hospitalization, the patient’s body temperature fell slightly above normal 163

limits. Blood pressure was still controlled and was within normal limits. Mechanical 164

ventilation was still in place but ordered for extubation the following day pending 165

patient stability and new radiographs and labs were to be drawn. 166

Day 4 of hospitalization. Patient’s vitals were within normal limits and new 167

radiographs and labs were taken. Extubation was unremarkable. Physical exam 168

revealed decreased bilateral expiratory wheezing. Result findings of chest 169

radiographs proved to show diminished right lower lobe opacification and no pleural 170

effusions present. Lab results improved but the patient to still had a decreased TSH 171

(<0.33 µU/mL; Normal: 0.5-5.0 µU/mL) and an increased T3 (244 ng/dL; Normal: 172

115-190 ng/dL) and free T4 level (18 µg/dL; Normal: 5-12 µg/dL). CBC differential 173

was unremarkable. The patient was scheduled for discharge within the next 24 hours 174

along with a management plan for the hyperthyroidism. 175

Day 5 of hospitalization, the patient was discharged and discharge plan consisted of: 176

• Cefuroxime sodium – 250mg by mouth twice a day for ten days 177

• Salbutamol – 2mg by mouth four times a day for 14 days 178

• Methimazole – 15mg by mouth three times a day for 14 days 179

• Tamiflu – 75mg by mouth once a day for 5 days 180

• Rest and hydration 181

182

The patient chose to arrange follow-up appointments with the attending physician 183

within the next two weeks at their outpatient office and adjust treatment regimen as 184

needed to manage the hyperthyroidism. 185

186

DISCUSSION 187

Hyperthyroidism with thyroid storm is a rare clinical case and may present with 188

overwhelming complications. This should be overseen as mortality rates from thyroid 189

storm alone ranges from 20-50% and complications such as infections i.e.: 190

pneumonia, increases the risk furthermore. Due of the potentially high mortality rate, 191

early diagnosis and treatment of thyroid storm is of the utmost importance [1]. 192


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Patients experiencing a thyroid storm are at a higher infection risk due to the fact that 193

an overactive metabolic state acts as a catalyst to delay the neutrophil response 194

towards sites of infection. Consequences of this physiologic process may lead to 195

neutropenia (low white blood cell count in blood) where the body lacks its defense 196

mechanism to fight infection. In a similar prospective and observational study 197

conducted, all patients enrolled had an absolute neutrophil count (ANC) below 198

2 × 109/L, documented in at least 3 consecutive occasions within the last 3 months 199

[2]. This process increases susceptibility to infections i.e.: bacterial pneumonia, 200

especially seen in this patient with a noted lower than normal absolute neutrophil 201

count (ANC). The incidence of absolute neutropenia in hyperthyroid patients varied 202

from less than 5% to 18% [3]. 203

It should also be stated that the patient experienced similar episodes in the past. It 204

cannot be coincidental but only fortifying the support a correlation between 205

hyperthyroidism and infection risk does indeed exist. Several reported documents 206

continue to prove a relationship between severe hyperthyroid states and infection 207

acquisition whether it is either bacterial or viral [4,5,6]. Severe complications, fatal if 208

not treated, may arise if a patient presents with symptoms of a thyroid storm and 209

should be a diagnostic clue to expeditiously admit them to the ICU where they will be 210

under close observation, as it is the standard of care in an acute intervention setting 211

[7]. 212

The role of hyperthyroidism and its risk for infection is primarily due to the 213

hypermetabolic effect on the body. The increased sympathetic response causes a 214

downward regulation of neutrophil response to areas of inflammation and/or 215

infection. Devastating infectious complications such as pneumonia is an example 216

that this patient experienced along with having similar episodes in the past but 217

without causality to account for why were are recurrent. A comparable analysis by 218

Rosenthal et al, exhibited similar findings [8]. 219

Through the metabolic process of hyperthyroidism, it can be noted that it indeed 220

does play a part to increase infection risk particularly since the patient had recurrent 221

bouts of pneumonia. A similar case report by Lum et al, had related findings where 222

streptococcus pneumoniae was diagnosed in a patient with characteristics of 223

hyperthyroidism via sputum gram stain [9]. Clinical diagnosis can either be confirmed 224


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via sputum gram stain, blood cultures, and/or urinary antigen testing. Urinary antigen 225

testing has been proven to be a more favorable confirmatory test due to its rapid 226

success and minimum invasiveness compared to a bronchoalveolar lavage [10]. 227

Clinical suspicion for diagnosing hyperthyroidism will vastly aid in the management 228

of patient’s more effectively and hopefully avoid any infectious complication that may 229

result. It is entirely important that these patients should be closely monitored to help 230

prevent any further complications that may present upon admission. 231

232

CONCLUSION 233

Thyroid storm is a rare and life- threatening endocrinologic emergency that may be 234

precipitated by trauma, surgery, systemic illness, particularly infection and sepsis [5]. 235

Prompt recognition and immediate treatment is vital to limit the concurrent morbidity 236

and mortality associated with this condition. 237

238

CONFLICT OF INTEREST 239

The authors declare no conflict of interest. 240

241

AUTHOR’S CONTRIBUTIONS 242

Andrew Dookhan 243

Group 1 – Substantial contributions to conception and design, acquisition and 244

analysis of data 245

Group 2 – Drafting the article, revising it critically for important intellectual content 246

Group 3 – Final approval of the version to be published 247

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Hiren Patel 249





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Mihir Patel 257





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Kaival Patel 263





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James Bass 269





Abhinav Sinha, MD 274





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REFERENCES 280

1. Refener S, Arunachalam V, Ajluni R, Sil A. Thyroid Storm Precipitated by 281

Infection: An Atypical Case Involving Multisystem Organ Dysfunction. 282

Endocrinologist: March/April 2005 - Volume 15 - Issue 2 - pp 111-114. 283

CME Review Article #9 284

2. Kyritsi EM, Yiakoumis X, Pangalis GA, Pontikoglou C, Pyrovolaki K, et al. 285

High Frequency of Thyroid Disorders in Patients Presenting With Neutropenia 286

to an Outpatient Hematology Clinic STROBE-Compliant Article. Medicine 287

(Baltimore). 2015 Jun; 94(23). doi: 10.1097/MD.0000000000000886 288


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3. Baidya A, Singha A, Bhattacharjee R, Dalal BS. Tuberculosis of the thyroid 289

gland: two case reports. Oxf Med Case Rep (2015) 2015 (4): 262-264. doi: 290

10.1093/omcr/omv028 291

4. Bahatoon SA. H1N1 infection-induced thyroid storm. Ann Thorac Med. 2010 292

Apr-Jun; 5(2): 110–112. doi: 10.4103/1817-1737.62475 293

5. Oguz A, Ersoy R, Guner R, Cakir B. Thyroid storm accompanied by H1N1 294

influenza infection. European Society of Endocrinology - Endocrine Abstracts 295

(2010) 22 P194. 296

6. Ford HC, Carter JM. The haematology of hyperthyroidism: abnormalities of 297

erythrocytes, leucocytes, thrombocytes and haemostasis. Postgraduate 298

Medical Journal (1988) – 64, 735-742. 299

7. Carroll R, Matfin G. Endocrine and metabolic emergencies: thyroid storm. 300

Ther Adv Endocrinol Metab. 2010 Jun; 1(3): 139–145. 301

doi: 10.1177/2042018810382481 302

8. Rosenthal MJ, Goodwin JS. A case of hyperthyroidism presenting as 303

recurrent pneumonia. West J Med. 1985 Apr; 142(4): 550–552. PMCID: 304

PMC1306097 305

9. Lum SA, Kaptein EM, Nicoloff JT. Influence of Nonthyroidal Illnesses on 306

Serum Thyroid Hormone Indices in Hyperthyroidism. West J Med. 1983 May; 307

138(5): 670–675. PMCID: PMC1010785 308

10. Couturier MR, Graf EH, Griffin AT. Urine antigen tests for the diagnosis of 309

respiratory infections: legionellosis, histoplasmosis, pneumococcal 310

pneumonia. Clin Lab Med. 2014 Jun;34(2):219-36. 311

doi:10.1016/j.cll.2014.02.002. Epub 2014 Apr 12. 312

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FIGURE LEGENDS 314

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Figure 1: Gross anatomy of the thyroid gland – Anteromedial view 316

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Figure 2: Gross anatomy of the thyroid gland – Anteromedial view 318

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FIGURES 321

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Figure 1: Normal gross anatomy of the thyroid gland – Anteromedial view 325

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Figure 2: Normal gross anatomy of the thyroid gland – Anteromedial view 329

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