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\begin{document}

\title{Factitial Hyperthyroidism: A Diagnostic Challenge}



\author[1]{Riyadh Hammamy}%
\author[1]{Dr Khalid Farooqui}%
\author[1]{Mohamed Shariff}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
Thyrotoxicosis factitia is not very uncommon. There is a high likelihood
of it being missed in our day-to-day clinical practice which can lead
not only to significant patient morbidity but also put burden on
health-care resources. We report a case masquerading as refractory
thyrotoxicosis diagnosed to have uncontrolled hyperthyroidism.%
\end{abstract}%



\sloppy


\textbf{Introduction:}

Thyrotoxicosis factitia is most often caused by excessive ingestion of
thyroid hormones which could be intentional or inadvertent
(contamination of dietary supplements). Possible causes of
hyperthyroidism are Graves disease, toxic thyroid adenoma, multinodular
goiter, some forms of subacute or chronic thyroiditis and rare pituitary
thyroid-stimulating hormone (TSH) producing tumors, other causes can be
extra thyroid in origin, may occur in ovaric strumma and thyrotoxicosis
factitia, due to intentional or accidental excessive intake of
pharmaceutical thyroid hormone preparations or thyroxin-contaminated
ground beef {[}1{]}.

The possibility of thyrotoxicosis factitia should be considered in
patients who have features of hyperthyroidism and psychiatric
disturbance without any evidence of goitre or proptosis and the results
of thyroid function are conflicting {[}2{]}.

This case report draws attention to one such instance wherein there was
an apparent thyrotoxicosis due to secretive ingestion of levothyroxine
{[}2{]}. Our patient attended to outpatient clinic during the last five
year period with clinical features suggestive of hyperthyroidism, and a
combination of thyroid function tests indicating that she was taking
exogenous thyroxine.

\textbf{Case report:}

A 43-year-old female patient referred from gynecology department to
control her hyperthyroidism as she was scheduled for hysterectomy due to
large multiple uterine fibroids, she reported to have type 2 diabetes
mellitus over the last six years and has been on metformin 1 gm twice
daily and liraglutide 1.8 mg once daily, she was also diagnosed to have
hyperthyroidism over the last five years and was on carbimazole 80 mg
daily. Clinically she looks very thin and emaciated with BMI of 17, no
exophthalmos and no goiter, with unremarkable systemic examination.
After reviewing her file we found that she underwent multiple plastic
surgeries of her breast and abdomen (mammoplasty, abdominoplasty and
liposuction), and she has also undergone gastric balloon followed by
sleeve gastrectomy to reduce her weight as she was obese six years back
with a BMI of 31, we have found that her TSH was suppressed all the
times over the last five years although she claimed taking her
carbimazole regularly, Thyroid radioactive iodine uptake (RAIU) scan
done twice showed low uptake favoring a diagnosis of thyroiditis, in
addition to this her diabetes history was inconsistent with her
investigations, serial glucose and HB A1c results all were normal even
before starting the anti-diabetic medications. we have also noticed that
some vital imaging and tests were missing like thyroid ultrasound, serum
thyroglobulin and thyroid receptor antibody. After thorough
investigations {[}Table1{]} and imaging, we excluded diabetes and
hyperthyroidism and a diagnosis of thyrotoxicosis factitia was
considered and the patient was confronted and eventually confessed that
she is taking dietary supplement containing levothyroxine and
liraglutide since long time to reduce weight and she is still not happy
with her weight and was eager to lose more.

Ultrasound Thyroid: was normal and no significant pathology. Repeated
blood investigation after two months showed significant improvement
{[}Table 2{]}.

\textbf{Table 1:}

\textbf{Initial laboratory results;}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Labs} & \textbf{Results} & \textbf{Normal range}\tabularnewline
\midrule
\endhead
WBC & 6700 & 4000-10000\tabularnewline
HB\% & 11.4 gm/dl & 12.0-15.0 gm/dl\tabularnewline
Platelets & 362,000 & 150,000-400,000\tabularnewline
Urea & 6.2 mmol/L & 2.5-7.8 mmol/L\tabularnewline
Creatinine & 72 umol/L & 44-80 umol/L\tabularnewline
Sodium & 138 mmol/L & 133-146 mmol/L\tabularnewline
Potassium & 2.5 mmol/l & 3.5-5.3 mmol/L\tabularnewline
Magnesium & 0.76 mmol/l & 0.7-1.0 mmol/L\tabularnewline
Total Protien & 71 gm/L & 60-80 gm/L\tabularnewline
Albumin & 33 gm/L & 35-50 gm/L\tabularnewline
ALT & 9 U/L & 0.0-33 U/L\tabularnewline
AST & 12 U/L & 0.0-32 U/L\tabularnewline
TSH & \textless{}0.01 mIU/l & 0.3-4.2 mIU/l\tabularnewline
FT4 & 35.5 pmol/l & 11.6-21 pmol/l\tabularnewline
FT3 & 18.6 pmol/l & 3.7-6.4 pmol/l\tabularnewline
TPO Antibodies & Negative &\tabularnewline
TRAB Antibodies & Negative &\tabularnewline
Thyroglobulin & Negative &\tabularnewline
\bottomrule
\end{longtable}

Table 2: Follow up laboratory results two months after stopping her
herbal medicine that contain thyroxine;\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Labs} & \textbf{Results} & \textbf{Normal Range}\tabularnewline
\midrule
\endhead
TSH & 0.2 mIU/l & 0.3-4.2 mIU/l\tabularnewline
FT3 & 6.0 pmol/l & 3.7-6.4 pmol/l\tabularnewline
FT4 & 14.0 pmol/l & 11.6-21 pmol/l\tabularnewline
K+ & 3.8 mmol/L & 3.5-5.3 mmol/L\tabularnewline
\bottomrule
\end{longtable}

\textbf{Discussion:}

Thyrotoxicosis factitia is the term used to describe hyperthyroidism due
to excessive intake of exogenous thyroxine, it can be intentional for
therapeutic suppression of TSH in cases of thyroid malignancy and in
some cases to treat obesity {[}3{]}, or inadvertent due to contamination
of supplements Like weight reducing supplements which claimed to be
herbal but contained an appreciable amount of both T3 and T4 or animal
thyroid tissue {[}4{]}.

It is also seen in individuals with a background of underlying
psychiatric disease, for cosmetic reasons or accidental ingestion of
high quantity of thyroid hormones, most often seen in paramedical
personnel who have access to thyroid hormone or in patients for whom
thyroid hormone medication has been prescribed in the past {[}5{]}.

The diagnosis of factitial hyperthyroidism in the absence of preexisting
disease of the thyroid is certain when there are typical thyrotoxic
manifestations like abdominal cramps, diarrhea, weight loss, heat
intolerance, together with thyroid atrophy and hypofunction which is
evidenced by the subnormal values of RAIU. Infiltrative ophthalmopathy
is never a feature but the eye signs are obvious. Serum TSH levels are
suppressed and serum T4 is high in most of the cases unless the patient
is taking T3, in such situation the T4 might be subnormal. Serum T3
concentrations is high in either case. Unlike true thyrotoxicosis the
presence of low, rather than elevated, values of serum thyroglobulin
(Tg) is a clear indication that the thyrotoxicosis results from
exogenous hormone and not from thyroid hyperfunction.

Other clinical complications commonly include skeleton system
(osteoporosis) and the cardiovascular system (tachyarrhythmias mainly
atrial fibrillation) which are the major target tissues adversely
affected by chronic use of exogenous thyroxine, however, abnormalities
in other systems have been reported.

A patient taking excessive amounts of levothyroxine and concealing this
from her doctors can pose a difficult diagnostic problem.

In terms of published literature, Braustein et al reported five cases of
unintentional thyrotoxicosis factitia where all of them ingested
levothyroxine pills as they believed that this hormone is non-toxic
substance that would help them to lose weight {[}6{]}.

Hamburger Thyrotoxicosis was a rare form of exogenous thyrotoxicosis
which resulted when the grounded beef contained thyroid tissue. This
condition disappeared when there was a change in slaughtering practices.
The possibility of such a condition needs to be considered in the event
of an epidemic exogenous thyrotoxicosis {[}7{]}.

In general thyrotoxicosis factitia is thought to be caused by the secret
ingestion of excessive amount of thyroxine by neuropsychiatric patients
{[}2{]}. The diagnosis of thyrotoxicosis factitia depends on careful
history to determine the use of exogenous thyroxine or dietary
supplements, a detailed examination to exclude goiter and exophthalmos,
thyroid image with normal ultra-sound and low thyroid iodine uptake and
laboratory findings with suppressed TSH, high FT4 and FT3, with negative
thyroid receptor antibody and low thyroglobulin {[}8{]}.

In our case since the patient was referred for control of
hyperthyroidism from gynecology unit as patient was supposed to go for
elective resection of multiple uterine fibroids. With detailed history,
careful reviewing of patient previous files and labs along with focused
clinical examination, there was a high index of clinical suspicion about
the exogenous use of levothyroxine and there were missing investigations
like ultrasound thyroid and thyroglobulin levels. Since the patient was
diagnosed as hyperthyroidism five years ago with suppressed TSH on
carbimazole maximum dose at present and still her TSH was suppressed
along with missing investigations. Given the patients inclination
towards cosmetic looks, leading question were put to the patient about
the use of any weight reducing medications, and to our surprise she was
taking herbal medications for weight loss with levothyroxine as one of
its content. We report this case as it was misdiagnosed as
thyrotoxicosis for five years and initiated on carbimazole, This

case highlights the importance of detailed history taking \& medication
reconciliation which is vital in such a diagnostic dilemma.

\textbf{References:}

\begin{enumerate}
\tightlist
\item
  Meurisse M, Gollogly L, Degauque C, et al. Iatrogenic thyrotoxicosis:
  causal circumstances, pathophysiology, and principles of
  treatment-review of the literature. World J Surg 2000; 24: 1377--85.
  ~doi: 10.1007/s002680010228.
\item
  Harvey RF. Thyroxine ``addicts''. Br Med J 1973; 2: 35--6. doi:
  10.1136/\textbf{bmj} .2.5857.\textbf{35} .
\item
  Cohen JH 3rd, Ingbar SH, Braverman LE. Thyrotoxicosis due to ingestion
  of excess thyroid hormone. Endocr Rev. 1989;10(2):113. doi:
  10.1210/edrv-\textbf{10} -2-113.
\item
  Kang GY, Parks JR, Fileta B, et al. Thyroxine and triiodothyronine
  content in commercially available thyroid health supplements. Thyroid.
  2013 Oct;23(10):1233-7. Epub 2013 Sep 14. DOI: 10.1089/thy.2013.0101.
\item
  Williams text book of endocrinology 14\textsuperscript{th} Edition
  2020,section III, Page no.402. http://ISBN: 9780323555968.
\item
  Braunstein GD, Koblin R, Sugawara M, et al. Unintentional
  thyrotoxicosis factitial due to a diet pill. West J Med
  1986;145:388-91. PMC1306951.
\item
  Hedberg CW, Fishbein DB, Janssen RS, et al. An outbreak of
  thyrotoxicosis caused by the consumption of bovine thyroid gland in
  ground beef. N Engl J Med. 1987;316(16):993--998. doi:
  10.1056/NEJM198704163161605.
\item
  Mariotti S, Martino E, Cupini C, et al. Low serum thyroglobulin as a
  clue to the diagnosis of thyrotoxicosis factitia. N Engl J Med.
  1982;307(7):410. DOI: 10.1056/NEJM198208123070705.
\end{enumerate}

\textbf{Acknowledgment:} None

\textbf{Conflict of Interest:} The authors declare no conflict of
Interest

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