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CASE REPORT
THYROTOXICOSIS FACTITIA: A DIDACTIC EXAMPLE OF WRONG INTERPRETATION OF RESULTS LEADING TO SEVERAL UNNECESSARY PROCEDURES
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G.E. Krassas
Department of Endocrinology & Metabolism "Panagia" Thessaloniki ,Greece
,
email:
krassas@the.forthnet.gr
Maria Bougoulia
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece
Stefanos Spartsis
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece
Tania Zeleva
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece
Nikolaos Pontikides
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece
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Editorial 2009
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Reviewing Editors: Eric Fliers & Luca Persani
The Authors have nothing to disclose.
Correspondence to:
Prof. G.E. Krassas, MD, PhD, FRCP (Lond)
Chairman, Department of Endocrinology, Diabetes and Metabolism
Panagia General Hospital
N.Plastira 22, N. Krini
Thessaloniki, Greece 55132
Tel & Fax: 0030-2310-479633; Fax: 0030-2310-282476
e-mail: krassas@the.forthnet.gr
ABSTRACT
Objective: to present an unusual and didactic case of thyrotoxicosis factitia (TF).
Case report: we present a patient suffering from TF who received unnecessary large doses of
antithyroid drugs and steroids, and underwent two useless surgical procedures, i.e. total
thyroidectomy and thymectomy in an attempt to treat her thyrotoxic state. We underscore that in such
cases it is important to perform radioiodine uptake and serum thyroglobulin (Tg) measurements,
which can be of help to establish the diagnosis. In addition, the estimation of urinary iodine, which in
such cases is very high, and color-flow Doppler sonography may also be helpful for the correct
diagnosis. Fecal thyroxine is also an important estimation which, however, has gradually being
abandoned.
Conclusions: this case illustrates that in most - if not all - suspected cases of TF, serum Tg and
urinary iodide will be sufficiently informative as additional investigations. The case report further
illustrates that magnetic resonance imaging (MRI) and rhTSH stimulated radioiodine uptake are not
useful and may even lead to unnecessary therapeutic (surgery, 131I treatment) procedures because
of radioiodine uptake in the thymus.
Introduction
The term Thyrotoxicosis Factitia (TF) is used to describe thyrotoxicosis produced by ingestion
of excessive amounts of exogenous thyroid hormone (1). It is also known by a variety of other names,
including alimentary thyrotoxicosis, exogenous thyrotoxicosis, occult factitial thyrotoxicosis or
thyrotoxicosis medicamentosa (2).
It is most frequently iatrogenic, when thyroxine is prescribed to suppress tumor growth in
thyroid cancer, to decrease goiter size or for therapy of hypothyroidism.
TF can also be caused by unintentional ingestion of thyroid hormone (accidental overdose in
children, “hamburger thyrotoxicosis”, cosmetic creams containing iodine and thyroid hormones,
veterinary T4 preparations).
Finally, TF is the result of surreptitious use of thyroid hormones by psychiatrically disturbed
patients or for unconventional indications such as obesity, depression, menstrual disorders and
infertility (3). In the first cases it is hard to make the diagnosis because patients usually do not admit
the misuse of thyroid hormones (4).
In the present communication we report a patient who was unsuccessfully treated for
thyrotoxicosis during 3 years with various therapies [antithyroid drugs, radioactive iodine (RAI) and
two surgical procedures], and the diagnosis of TF was indicated by different endocrine tests, although
the patient strongly denied exogenous thyroid hormone ingestion.
Case Report
A 29-year old woman presented initially to the outpatient endocrine clinic of Panagia Hospital,
Thessaloniki in May 2008 suffering from persistent thyrotoxicosis for the last 30 months.
She reported that her symptoms started in January 2006, six months after the birth of her
second child, consisting of weight loss (from 150kg to 100kg), tachycardia, tremor of the extremities
and irritability. Prior to the onset of symptoms the patient was extremely obese [body mass index
(BMI)=52]. Regarding her social history, no occupational factors were discovered that might have
predisposed her to take excess thyroid hormones or be willing to undergo inappropriate surgery. It is
of note, that the patient financially is fully dependent from her mother.
Initial investigations (January 2006) were compatible with thyrotoxicosis [free thyroxine (FT4)
= 21.85 ng/dl (NR = 0.8-2.0), thyrotropin (TSH)<0.005 μIU/ml (NR=0.3-4.0), thyroid receptor
antibodies (TRAb) =0.8 IU/ml, (NR <1.8)]. Thyroid ultrasonography revealed normal thyroid volume
with homogeneous pattern and a solid, hyperechoic nodule of 10.5 mm diameter in the right lobe. No
isotopic scanning of the thyroid gland was performed at that time.
She was treated with antithyroid drugs for one year but euthyroidism was never achieved. Due
to apparent failure of drug treatment and concern about her continuing thyrotoxicosis, a total
thyroidectomy was performed on February 2007 in a hospital in Athens. Histology showed a normal
thyroid gland with a single hyperplastic 6 mm nodule in the right lobe.
Immediately after thyroidectomy the patient commenced replacement therapy with Lthyroxine.
About a month later she reported symptoms of thyrotoxicosis, which persisted despite the
suggested discontinuation of thyroxine therapy. Neck ultrasonography and computer tomography
(CT) were performed to exclude residual thyroid tissue, and both showed no evidence of thyroid
remnant. A few enlarged cervical lymph nodes were noted. A fine needle aspiration of one cervical
lymph node revealed reactive changes only, without any evidence of malignancy.
Three months after total thyroidectomy (May 2007), the patient presented to another hospital
in Athens with severe thyrotoxic symptoms including tachyarrythmia non responsive to medication,
hypertension, irritability, hyperhidrosis, and tremor of the extremities. Her body weight was 61 kg with
BMI 22. Endocrine investigation showed TSH<0.005 μIU/ml, free triiodothyronine (FT3=16.7 pg/ml
(NR=2.0-4.4), FT4=25.85 ng/dl. Her TRAb were normal = 0.9 IU/ml (NR<1.8), while her Tg levels
were 7.5 ng/ml (NR = 0.0-5.0 after thyroidectomy). Moreover, thyroid peroxidase (TPO) antibodies
and Tg antibodies were 37.0 IU/ml and 21.0 IU/ml, respectively (NR <50 and <60, respectively). Her
symptoms remained unchanged, despite the administration of high doses of propylthiuracil and
corticosteroids for a week. She was advised to continue taking antithyroid drugs.
She was investigated for the first time in our clinic in May 2008. After confirming that she was
thyrotoxic [FT4 = 32 pg/ml (NR=7-18), FT3 = 7.2 pg/ml (NR=2.2-5.5), TSH=0.05 μIU/ml (NR=0.3-4.0)],
with normal TRAb and low Tg levels (<0.1 ng/ml), a chest MRI was performed, to exclude ectopic
hyperfunctional thyroid tissue, which however revealed a 4x2 cm soft tissue mass in the anterior
mediastinum. An ultrasound of her uterus and ovaries was normal. 131I whole body scan after
stimulation with rhTSH [(Thyrogen®, Genzyme, USA) (2 amp x 0.9 mg)] demonstrated significant
radioiodine uptake in the mediastinum. A therapeutic dose of 40mCi 131I after stimulation with rhTSH
(2 amp x 0.9 mg) was administered, but without any clinical improvement, at least in the first two
months after treatment. No post-therapy scan was performed after the 40 mCi 131I dose. Three
months after 131I treatment, and while the patient was waiting for her follow-up appointment in our
clinic, she underwent surgical excision of the anterior mediastinal mass in a private hospital in Athens
despite being severely thyrotoxic. On histological examination the mass was proved to be a
hyperplastic thymus without signs of malignancy or presence of thyroid tissue.
The patient presented to our department again in December 2008, four months after her last
surgery, complaining of tachycardia, diarrhea, hyperhidrosis, irritability and menstrual disorders. She
denied taking any drug or supplements for the last 6 months. Her body weight was 71 kg and her BMI
24.5.
On physical examination she had a fine tremor, hyperhidrosis and lid lag. She had tachycardia
110 beats per minute and her blood pressure was 150/90 mmHg. Respiratory, gastrointestinal and
urinary systems were unremarkable. Laboratory tests revealed: elevated FT4 (6.1 ng/dl, NR = 0.8-
2.0), elevated FT3 (2.2ng/ml, NR = 0.7-2.0) and suppressed TSH (0.065 μIU/ml). A whole-body scan
with 131I after stimulation with rhTSH (2 amp x 0.9 mg) was performed and no pathological uptake was
found. In addition, serum Tg was low (0.2 ng/ml), and did not rise after stimulation with rhTSH. Anti
Tg, anti TPO and TRAb antibodies were within normal range. Finally, very high levels of urine iodine
(1150 μg/24h, NR<150) were found. All the above tests were indicative of a case of excess thyroid
hormone ingestion, which the patient strongly denied.
Discussion
The term of TF has been used in several ways. One is any situation where thyrotoxicosis is
induced by self administration of thyroid hormones, even in cases where the patient is unaware of it
(i.e. hamburger thyrotoxicosis) and the other is when the patient is surreptitiously ingesting enough
thyroid hormone to make himself thyrotoxic (5). The diagnosis of TF should be considered in any
patient with apparent hyperthyroidism, but lacking any thyroid enlargement. It becomes more likely if
the patient has a low thyroid radioiodine or pertechnetate uptake and a low serum Tg concentration
(6). Usually, patients on thyroid hormone for the unconventional indications such as obesity,
depression, menstrual disorders and infertility are as likely to admit the use of thyroxine as those
receiving the same medication for hypothyroidism.
In TF exogenous thyroid hormone suppresses TSH secretion by negative feedback on the
pituitary thyrotroph cells and this leads to suppression of endogenous thyroid function. As a result, the
thyroid radioiodine or pertechnetate uptake is very low to undetectable (4). Serum Tg measurement
can distinguish TF from other causes of thyrotoxicosis with low thyroid radioiodine uptake, since
serum Tg levels are low or undetectable in cases of excess thyroid hormone ingestion, but normal or
elevated in most other cases of thyrotoxicosis. In order to increase the uptake of eventual thyroid
remnant, rhTSH was administered in our case on an empirical basis. It is of note, that the presence
of anti-Tg antibodies in serum, can interfere with the serum Tg assay, yielding in most cases false
negative results (7-9). In our case, Tg antibodies were elevated in May 2007 and low in May 2008.
In our patient, the diagnosis was further complicated by the pathological radioiodine uptake in
the anterior mediastinum on whole body iodine scanning, leading to the erroneous diagnosis of
ectopic thyroid tissue, which proved to be thymus on the histology. Radioiodine uptake by the thymus
is a well-recognized phenomenon. Wilson et al. described uptake in the thymus in 10 of 38 patients
undergoing post radioiodine therapy scans (10). Also, Veronikis et al. confirmed the same
phenomenon (11) with reported frequencies between of 3.5-25% (10, 12). Radioiodine uptake in the
thymus can occur in the absence of ectopic thyroid tissue or thyroid metastases (13) and reflects
expression of human sodium-iodide symporter (14). Serum Tg determination should be performed in
such cases to differentiate between ectopic or metastatic thyroid tissue and physiological uptake in
thymus. It is noteworthy that rhTSH stimulation test is not useful in the diagnosis of TF per se and is
not recommended in the investigation of such cases. In our case, it was used to evaluate if the uptake
of the anterior mediastinum mass could be increased and in a positive case to administer a
therapeutic dose of RAI. After demonstrating significant uptake of the mass, we proceeded to the
administration of 40 mCi RAI after rhTSH administration. In our case rhTSH was used on an empirical
basis before the administration of the diagnostic dose of RAI to check if the mass in the anterior
mediastinum was trapping radioiodine. After demonstrating significant uptake of the mass, rhTSH
stimulation was also used immediately before the administration of the therapeutic dose of 40 mCi
131I, to augment the uptake and to achieve the best therapeutic results. However, the whole
procedure was proved unsuccessful the reason being that the mass was not an ectopic thyroid but an
enlarged thymus.
Another helpful diagnostic tool in the evaluation of our patient was the measurement of urine
iodine, which was extremely raised. Since most of the dietary iodine is excreted in the urine, a 24-
hour urinary iodine concentration is an accurate index of dietary intake (15). Our patient, who was
thyrotoxic, had a very low serum Tg concentration, had no evidence of thyroid tissue on imaging and
had not received radiographic contrast. On these grounds iodine induced thyrotoxicosis was
excluded. The only remaining diagnosis consistent with thyrotoxicosis associated with low serum Tg
and high urine iodine is exogenous thyroxine ingestion. One reliable measurement, which is very
useful to establish the diagnosis of the latter, is the measurement of thyroxine in the feces. Fecal T4
measurements are approximately 1 nmol/g in normal healthy subjects, are mildly increased in Graves’
disease (about 2 nmol/g), and are markedly elevated in individuals with Tg (over 12 nmol/g) (16).
However, this diagnostic procedure has progressively been abandoned in such cases. Finally, colorflow
Doppler sonography has been used to distinguish Graves’ disease or toxic nodular goiter, in
which the thyroid is hypervascular, from TF, in which thyroid hypervascularity is absent (17). In our
case, this procedure could not be used as the patient had previously undergone total thyroidectomy.
We believe that the incentive for the patient may have been to address her morbid obesity. Also, as
the T4/T3 ratio was not as high as it would have expected if she was taking thyroxine, the combination
of T4 and T3 or thyroid extract should be the most possible thyroid compound. However, no specific
data on this issue can be provided. Finally, it should be mentioned that according to the law in
Greece, thyroxine should be provided by the chemists only by official prescription. However, it is not
unusual in some cases to be supplied over the counter.
In conclusion, we present a patient suffering from TF who received large doses of antithyroid
drugs and steroids, and underwent two major surgical procedures in an attempt to treat her thyrotoxicosis,
all of which failed. We suggest that in such cases it is important to perform radioiodin
uptake and serum Tg measurements, which will help to establish the diagnosis. In addition, an
important investigation in suspected TF, is the estimation of urinary iodine, which in such cases is
very high. Fecal thyroxine, which is also a reliable method to establish the diagnosis, is being
gradually abandoned. Usually, the patient denies the exogenous use of thyroid hormones and
confirmation of the diagnosis is often very difficult.
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1. Cohen JH, Ingbar SH, Braverman LE. Thyrotoxicosis due to ingestion of excess thyroid
hormone. Endocr Rev 10: 113-124, 1989.
2. Yoon SJ, Kim DM, Kim JU, Kim KW, Ahn CW, Cha BS, Lim SK, Kim KR, Lee HC, Huh KB. A
case of thyroid storm due to thyrotoxicosis factitia. Yonsei Med J 44: 351-354, 2003.
3. Pearce EN. Thyrotoxicosis of extrathyroid origin. In: Braverman LE, Utiger RD (eds)
Werner&Ingbar’s The Thyroid A Fundamental and Clinical text, Lippincott Williams & Wilkins,
Philadelphia, 2005, 9th edn, pp 548-551.
4. Greer MA. Thyrotoxicosis of extrathyroid origin. In: Braverman LE, Utiger RD (eds)
Werner&Ingbar’s The Thyroid A Fundamental and Clinical text, Lippincott Williams & Wilkins, Philadelphia, 7th edn 7, pp 592-594.
5. Bogazzi F, Bartalena L, Scarcello G, Campomori A, Rossi G, Martino E. The age of patients with
thyrotoxicosis factitia in Italy from 1973 to 1996. J Endocrinol Invest 22: 128-133, 1999.
6. Ross DC. Exogenous and ectopic hyperthyroidism. UptoDate, The Endocrine Society, Wolters
Kluwer Health, www.uptodate.com.
7. Mariotti S, Martino E, Cupini C Low serum thyroglobulin as a clue to the diagnosis of
thyrotoxicosis factitia. N Engl J Med 307: 410-412, 1982.
8. Pacini F, Pinchera A. Serum and tissue thyroglobulin measurement: clinical applications in
thyroid disease. Biochimie 81: 463-467, 1999.
9. Jahagirdar VR, Strouhal P, Holder G, Gama R, Singh BM. Thyrotoxicosis factitia masquerading
as recurrent Graves’ disease: endogenous antibody immunoassay interference, a pitfall for the
unwary. Ann Clin Biochem 45(Pt 3): 325-327, 2008.
10. Wilson LM, Barrington SF, Morrison ID, Kettle AG, O’Doherty MJ & Coakley AJ. Therapeutic
implications of thymic uptake of radioiodine in thyroid carcinoma. Eur J Nucl Med 25: 622-628,
1998.
11. Veronikis IE, Simkin P, Braverman LE. Thymic uptake of iodine-131 in the anterior mediastinum.
J Nucl Med 37: 991-992, 1996.
12. Davidson J, McDougall IR. How frequently is the thymus seen on whole-body iodine-131
diagnostic and posttreatment scans? Eur J Nucl Med 27: 425-430, 2000.
13. Connolly LP & Connolly SA. Thymic uptake of radiopharmaceuticals. Clin Nucl Med 28: 648-651,
2003.
14. Meller J, Becker W. The human sodium-iodine symporter (NIS) as a key for specific thymic
iodine-131 uptake [editorial]. Eur J Nucl Med 27: 473-474, 2000.
15. Greenspan FS, Gardner DG. Basic & Clinical Endocrinology. In: Greenspan FS, Gardner DG
(eds). Lange Medical Books/McGraw-Hill Medical Publishing Division, New York, 2001, 6th edn, p
205.
16. Bouillon R, Verresen L, Staels F, Bex M, De Vos P, De Roo M. The measurement of fecal
thyroxine in the diagnosis of thyrotoxicosis factitia. Thyroid 3: 101-103, 1993.
17. Bogazzi F, Bartalena L, Vitti P, Rago T, Brogioni S, Martino E. Color flow Doppler sonography in
thyrotoxicosis factitia. J Endocrinol Invest 19: 603-606, 1996.
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Address:
CASE REPORT
THYROTOXICOSIS FACTITIA: A DIDACTIC EXAMPLE OF WRONG INTERPRETATION OF RESULTS LEADING TO SEVERAL UNNECESSARY PROCEDURES |
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Title: Hot Thyroidology; Abbreviated key title: Hot Thyroidol.; Online ISSN: 2075-2202
Legal Note: © All rights reserved European Thyroid Association 2009
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