\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,greek,english]{babel}



\usepackage{float}








\begin{document}

\title{Ruptured appendicitis with undiagnosed Graves' disease: contrast-induced
impending thyroid storm}



\author[1]{Chutida Sungworawongpana}%
\author[1]{Wongsakorn Chaochankit}%
\affil[1]{Prince of Songkla University - Hat Yai Campus}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Thyrotoxicosis is a relatively common endocrine disorder. The diagnosis
of thyrotoxicosis is upon clinical examination, laboratory, and further
investigation. To prevent the thyroid storm is the goal of treatment of
patients with thyrotoxicosis especially patients undergoing surgery.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Thyrotoxicosis is a relatively common endocrine disorder. The prevalence
of hyperthyroidism in the US is 1.3\% {[}1{]}. Hyperthyroidism and
thyrotoxicosis are different. Hyperthyroidism is characterised by
increased thyroid hormone synthesis and secretion from the thyroid
gland, but thyrotoxicosis refers to the clinical symptoms of excess
circulating thyroid hormones such as thyroiditis, and iodine-induced or
drug-induced thyroid dysfunction. The most common cause of
hyperthyroidism is Graves' disease {[}2{]}. Diagnosis of thyrotoxicosis
is upon clinical examination, laboratory tests, and further
investigation to assist with diagnosing the specific cause and to
arrange necessary treatment. The important issue among patients with
thyrotoxicosis needing an operation is perioperative management and
multidisciplinary care to prevent the thyroid storm that increases
morbidity and mortality {[}1{]}.

\textbf{Case report}

A 19-year-old female presented with abdominal pain for three days. She
had colicky pain around the umbilicus with low grade fever and then
migratory pain for one day. She denied history of past illness or drug
allergy. Her physical examination showed normal appearance, and her
lungs and heart were normal. Her abdomen revealed no distension,
hypoactive bowel sound, soft, moderate tenderness at right lower
quadrant area with localized guarding without mass. Completed blood clot
showed leukocytosis with shift to the left (white blood cell 18350, PMN
81\%), no anemia and normal platelet count. The urinalysis was normal
and urine pregnancy test showed negative. Her computed tomography of the
abdomen revealed retrocecal type acute appendicitis with focal
nonenhanced wall at the appendiceal tip. She received a diagnosis of
gangrenous appendicitis and was sent to operating theater for emergency
laparoscopic appendectomy. The baseline vital signs included a blood
pressure of 125/75 mmHg, a regular sinus rhythm heart rate of 120
beats/min, and peripheral oxygen saturation of 99\%. Propofol (120 mg),
succinylcholine (100 mg) and fentanyl (100mcg) were administered
intravenously, and the trachea was intubated using a 7.0 mm cuffed
endotracheal tube. Anesthesia was maintained using 1 L/min
O\textsubscript{2}, 1 L/min Air, and 2.5-3.0 vol\% sevoflurane. During
procedure, she presented persistent sinus tachycardia (heart rate
130-140 beats/min) and fever (body temperature 39\selectlanguage{ngerman}°C). Fever was treated
using intravenous paracetamol 1000 mg and cool pack. However, the
E\textsubscript{T}CO\textsubscript{2},~maintained between 30-35 mmHg,
had no signs of inadequate anesthesia and malignant hyperthermia. The
anesthetist and surgeon discussed her tachycardia after treatment of
dehydration and pyrexia. We suspected thyrotoxicosis and remained
cautious regarding complications from this issue, e.g., the thyroid
storm. The operation took approximately 1 hour and proceeded
unremarkably. The neuromuscular blocker was then reversed using 2.5 mg
neostigmine and 0.4 mg glycopyrrolate. Extubation was performed without
complication. When the patient completely recovered from anesthesia, she
was transferred to the PACU. At the ward, the patient presented BP of
140/100 mmHg, 100\% SpO\textsubscript{2}, and the ECG showed sinus
tachycardia with a HR of 140 beats/min. Complete physical exam found
mild thyroid gland enlargement with thyroid built positive. She did not
have palpitation or syncope. She had history of unintentional weight
loss for 17 kg over 4 months. Her thyroid function test revealed FT4
\textgreater{}7.77 ng/dL (0.93-1.7), FT3 13.1 pg/mL (2-4.4) and TSH
\textless{}0.005 mIU/L (0.27-4.2). The endocrinologist was consulted to
co-evaluate and found the cause of severe thyrotoxicosis suspected from
post iodine-contrast injection. The Burch Warsofsky point was 45
(impending storm) and thyroglobulin antibody (TgAb) was 16.1 IU/L
(0-1.75). Her medications were PTU loading then switched to methimazole,
intravenous hydrocortisone total 1 day and propranolol. Her clinical
conditions had been observed for two days then she was discharge without
complications. Her appendectomy wounds were completely healed, and the
pathological report was ruptured appendix. The written informed consent
of publication for the case details in this report has been obtained. At
6 months, her clinical conditions improved. Her weight was regained, and
her thyroid function test showed FT4 5.02 ng/dL, FT3 13.3 pg/mL and TSH
\textless{}0.005 mIU/L. Her current medications were methimazole (5) 3
tabs per oral bid and propranolol (40) 1-tab po bid. She was followed up
at endocrine clinic regularly every 3 months.

\textbf{Discussion}

Thyrotoxicosis is a common problem of endocrine disorder {[}2{]}. The
common cause of hyperthyroidism is Graves' disease that commonly occurs
among female, aged 20-40 years. Prevalence of hyperthyroidism is 0.8\%
in Europe, and 1.3\% in the USA. Thyrotoxicosis has many different
causes both endogenous and exogenous {[}1{]}. Exogenous thyrotoxicosis
is factitious or iatrogenic, develops after ingestion of excessive
amounts of thyroid hormone, and is associated with low serum
thyroglobulin concentrations. In this case report, she had many clinical
conditions of thyrotoxicosis {[}1{]}. She received a diagnosis of
Graves' disease due to high TgAb level. It could explain that she had
subclinical Graves' disease. When she underwent CT of the abdomen with
contrast-injection that excessed contrast-induced thyrotoxicosis, she
showed clinical conditions of hyperthyroidism. It revealed that this
event was very dangerous because it might lead to the thyroid storm at
any moment since the preoperative until the postoperative period.
Clinical features are similar to hyperthyroid symptoms such as
palpitations, dyspnea, and weight loss {[}3{]}.

The mechanism of iodine- or contrast-induced thyrotoxicosis can be
explained in massive iodine exposure to the thyroid gland. Patients
suspected of iodine-induced thyrotoxicosis need to receive
iodine-contrast injection not exceeding 24 hours {[}4{]}. Iodine is used
to synthesize thyroid hormones using sodium-iodine symporters at the
thyroid follicles {[}5{]}. Large amounts of iodine can affect thyroid
dysfunction. Diet, medications, or radiographic iodine-contrast media
(ICM) are iodine excess sources {[}6{]}. Iodine-induced hyperthyroidism
has been reported with as little as 300--500 \selectlanguage{greek}μ\selectlanguage{english}g of iodide. A typical
dose of iodinated contrast medium contains about 13500 \selectlanguage{greek}μ\selectlanguage{english}g of free iodide
and 15--60 g of bound iodine that may be liberated as free iodide in the
body {[}4{]}. Exogenous iodine decreases thyroidal radio-iodine uptake
both by dilution of the total body iodine pool, and by inhibiting the
thyroid hormone synthesis via the Wolff- Chaikoff effect. Among patients
with euthyroidism, exogenous iodine in large doses inhibits
organification of iodide and thyroid hormone synthesis and may lead to
hypersecretion of thyroid hormones, a phenomenon known as the
Jod--Basedow effect {[}7,8{]}.

Risk factors include nontoxic diffuse or nodular goiter, latent Graves'
disease, and long-standing iodine deficiency {[}9{]}. Generally, for
patients suspected of ICM-induced thyrotoxicosis, their serum TSH
concentrations will be suppressed, and T4, FT4 and/or total T3
concentrations may be elevated. Once contrast-induced hyperthyroidism is
diagnosed, further excess iodine exposure should be avoided. In this
case, we suspected iodine-induced thyrotoxicosis with undiagnosed
Graves' disease that was confirmed by TgAb. When a patient develops
amiodarone or iodine-induced thyrotoxicosis, distinguishing between the
two forms of thyrotoxicosis would be extremely important. Type I usually
occurs when patients with an underlying euthyroid nodular goitre or
latent Graves' disease are exposed to the high iodine content of
amiodarone. This exposure leads to excess thyroid hormone synthesis and
release, similar to iodine-induced hyperthyroidism among patients
receiving excess iodine from other sources. It can be treated with
antithyroid drugs but type II constitutes a destructive thyroiditis
caused by a direct toxic effect of amiodarone on thyrocytes. This form
is usually self-limiting and, when necessary, amiodarone can be
continued {[}1{]}. However, the Contrast Media Safety Committee of the
European Society of Urogenital Radiology has concluded that routine
monitoring of thyroid function before contrast-injection among patients
with a normal thyroid is not indicated. However, high risk patients,
i.e., those with a history of Graves' disease or nodular goiter,
especially the elderly or those residing in areas of dietary iodine
deficiency, should be carefully monitored after iodinated contrast
studies {[}10{]}. This includes patients, particularly unable to
tolerate thyroid dysfunction, such as those with underlying unstable
cardiovascular disease. CT scanning is being used much more frequently
in the acute care setting. A study in one emergency department revealed
that from 2000 to 2005, CT scanning of the chest increased by 226\%, and
of the abdomen by 72\% {[}11{]}. Prompt diagnosis of thyrotoxicosis,
along with awareness of the interference of intravenous contrast with
use of radioactive iodine and the frequency with which this occurs, may
prevent unnecessary CT scans among some patients. Therefore, it might
lead to increased incidence of ICM-induced thyrotoxicosis and produce
severe thyrotoxicosis or the thyroid storm. However, thyroid storm is a
rare disorder. The incidence is 0.2 per 100,000 person-years in Japan
and occurs in 1-5\% of patients admitted to a hospital for
thyrotoxicosis. It constitutes an emergency with a high mortality rate
of 8--25\% {[}12{]}. The pathogenesis of the thyroid storm is still
poorly understood. Diagnosis is clinical and based on the presence of
hyperthyroidism in a patient with severe and life-threatening
manifestations {[}1{]}. To make the diagnosis, Burch and Wartofsky
proposed a scoring system, modified by Akamizu and colleagues {[}12{]}.
A multidisciplinary treatment approach should be used. Goals of
treatment are lowering thyroid hormone synthesis and secretion, reducing
circulating thyroid hormones, controlling peripheral effects of thyroid
hormones, and treating any precipitating illness {[}1{]}.

In conclusion, the clinical clues of thyrotoxicosis remain very crucial.
To prevent the thyroid storm is the goal of treatment of patients with
thyrotoxicosis especially patients undergoing surgery. Widespread use of
radiologic investigations and interventional procedures is important and
can increase the incidence of contrast-induced thyrotoxicosis especially
among high-risk patients. Clinicians need to prompt manage
thyrotoxicosis and prevention the thyroid storm using a
multidisciplinary team.

\textbf{Funding:} None.

\textbf{Conflicts of Interest:} All authors declare they have no
conflict of interest.

\textbf{Reference:}

\begin{enumerate}
\tightlist
\item
  De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet.
  2016;388(10047):906-18.
\item
  Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer
  CA, et al. Serum TSH, T4, and thyroid antibodies in the United States
  population (1988 to 1994): National Health and Nutrition Examination
  Survey (NHANES III). J Clin Endo Metab. 2002;87:489--99.
\item
  Devereaux D, Tewelde SZ. Hyperthyroidism and thyrotoxicosis. Emerg Med
  Clin North Am. 2014; 32:277--92.
\item
  Leung AM, Braverman LE. Iodine-induced thyroid dysfunction. Curr Opin
  Endocrinol Diabetes Obes. 2012;19(5):414-9.
\item
  Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid
  iodide transporter. Nature. 1996;379(6564):458-60.
\item
  Bizhanova A, Kopp P. Minireview: the sodium-iodide symporter NIS and
  pendrin in iodide homeostasis of the thyroid. Endocrinology.
  2009;150(3):1084-90.
\item
  Dunne P, Kaimal N, MacDonald J, Syed AA. Iodinated contrast-induced
  thyrotoxicosis. CMAJ. 2013;185(2):144-7
\item
  Zimmermann MB. Iodine deficiency. Endocr Rev. 2009;30:376--408
\item
  Lee SY, Rhee CM, Leung AM, Braverman LE, Brent GA, Pearce EN. A
  review: Radiographic iodinated contrast media-induced thyroid
  dysfunction. J Clin Endocrinol Metab. 2015;100(2):376-83.
\item
  Wu SY, Leung AM, Chambers MD, Chen CL, Khan MU, Brent GA, et al.
  Coexistent presentation of Graves' disease and an autonomous thyroid
  nodule following administration of an iodinated contrast load. Journal
  of Clinical and Translational Endocrinology: Case Reports 2018.
\item
  Phillips BD, Hennessey JV. Iodinated contrast prior to evaluation for
  thyrotoxicosis. J Hosp Med. 2009;4(5):285-8.
\item
  Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm.
  Endocrinol Metab Clin North Am. 1993;22:263--77.
\end{enumerate}

\selectlanguage{english}
\FloatBarrier
\end{document}

