CLINICAL EXPERIENCES

Massive Levothyroxine Ingestion

Conservative Management
Scott H. Mandel, MD, A. Roy Magnusson, MD, Brent T. Burton, MD, J. Robert Swanson, PhD,
Stephen H. LaFranchi, MD

The clinical course of a 29-month-old girl who was referred for evaluation
after ingesting ninety 0.2-mg tablets of levothyroxine is reported. Despite an
initial thyroxine (T
) level of 282 μg/dl and a triiodothyronine (T
4 ) level of 1,837
3
ng/dl at 48 hours postingestion, her symptoms were mild and included irritabil-
ity, vomiting, tremor, and tachycardia. Treatment was limited to activated char-
coal and propranolol. Thyroid hormone levels fell to normal by 13 days postin-
gestion. The child’s clinical course was benign.
Even after massive acute ingestions of levothyroxine, children’s symptoms are
usually mild and may be controlled with propranolol. This conservative ap-
proach should be considered before expensive and potentially dangerous thera-
pies are undertaken.

THYROID HORMONE is a commonly pre-

scribed medication in the United States. More than
18 million prescriptions are filled annually. The
American Association of Poison Control Centers
documented more than 2,200 poisonings with thy-
roid preparations in 1986.1
Although children commonly have a benign clini-
cal course after an acute ingestion of thyroid hor-
mone, previous reports give disparate opinions re-
garding appropriate management of massive inges-
tions. Several authors have advocated a conservative
approach limited to gastrointestinal decontamination
for significant ingestions and beta-blocker adminis-
tration for patients with symptoms.2.3 However,
more aggressive therapies including cholestyramine,
steroids, propylthiouracil, iopinoic acid, plasmapher-
esis, charcoal hemoperfusion, and exchange transfu-
sion have also been advocated. 1-7
We report of massive thyroxine ingestion in
a case
a 29-month-old child. Despite thyroid hormone
From the Doernbecher Memorial Hospital for Children,
Oregon Health Sciences University, Portland, Oregon.
Correspondence to: Scott H. Mandel, MD, Oregon
Health Sciences University, 3181 S.W. Sam Jackson Park
Road, Portland, OR 97201.
Received for publication January 1989 and
March 1989.
levels greater than in any
tient, this child was treated
previously reported pa-
conservatively and had a
benign clinical course.
Case
Report
A healthy 29-month-old girl was thought to have
ingested ninety 0.2-mg tablets of levothyroxine
(Synthroid). Twenty-four hours later her parents
contacted the regional poison center and were imme-
diately referred to the local emergency department.
On arrival, the child was asymptomatic. She had a
pulse rate of 130 beats/minute, axillary temperature
of 37.2°C, respiratory rate of 24 breaths/minute,
and blood pressure of 102/72 mm Hg. Because of
the delay from ingestion to presentation, treatment
was limited to a single dose of activated charcoal.
Initial laboratory evaluation revealed a total thyrox-
ine (T4) of 282 pg/dl (normal, 7.3-15.0 ~,g/dl) and
Ts resin uptake of 42% (normal, 30-40%). She was
hospitalized for observation, and over the next 3
days she remained asymptomatic except for irritabil-
ity and mild tachycardia (120-160 beats/minute).
Four days after ingestion, the patient was referred
to Doernbecher Memorial Hospital for Children be-
cause of increased tachycardia (165 beats/minute)
accepted and two episodes of vomiting. Physical examination
at that time revealed a mild tremor and a grade 1/6

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 TABLE 1. Results of Thyroid Function Tests
*
T4 measurement on day 1 was done by Abbott TDx
automated immunoassay analyzer and may have been arti-
ficially elevated (see text).
systolic ejection murmur. Although she had increas-
ing symptoms and signs of thyrotoxicosis, serum thy-
roxine (T4) and triiodothyronine (T3) levels (103
Agldl and 1,200 ng/dl, respectively) were both de-
creasing. She was started on propranolol, which was
titrated to a maximum dose of 5 mg orally every 6
hours. Tremor and tachycardia improved (pulse,
110 to 145 beats/minute), and she was discharged 7
days postingestion. She remained clinically stable,
and propranolol was discontinued 12 days postinges-
tion. Thirteen days postingestion she had no clinical
features of thyrotoxicosis.
T4 and Ts levels were serially measured and are
shown in the Table 1. The T4 level at 27 hours post-
ingestion of 282 wg/dl was measured using the Ab-
bott TDx automated immunoassay analyzer after di-
lution with Abbot TDx buffer. Subsequent levels
were all measured in duplicate at the referral hospital
by radioimmunoassay. The T~ and Ts levels at 48
hours postingestion were 139 wg/dl and 1,837
ng/dl, respectively. Thyroid hormone levels were in
the normal range by 13 days postingestion. There
was no apparent relationship between thyroid hor-
mone levels and the severity of symptoms.
Discussion
The outcome of ingestion of excessive thyroid
hormone depends on the duration of exposure and
the age of the patient. Several case reports describe
thyroid storm in adults after ingestion of large doses
of thyroid preparations.’ Chronic ingestions in adults
may lead to sudden death.’ However, children are
most often exposed to a single ingestion and have a
higher tolerance for excessive levels of thyroid hor-
mone.
Litovitz et al.~ reviewed 78 cases of accidental thy-
roid ingestion in children under the age of 12 years.
Symptoms developed in only four patients and were
limited to fever, tachycardia, lethargy, irritability,
vomiting, and abdominal pain. T4 levels were mea-
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sured in only three patients and ranged from 26.4 to
32.8 Ag/dI. Treatment was limited to ipecac-induced
emesis and activated charcoal in all but one patient
who received propranolol despite absence of clinical
manifestations of toxicity.
Golightly et al.3 described 41 cases of thyroxine
ingestion in children 1 to 5 years of age. Eleven pa-
tients developed symptoms (tachycardia, hyperactiv-
ity, fever, vomiting, diarrhea, diaphoresis, and flush-
ing) that were categorized as mild and resolved with-
out treatment. A 2-year-old child attained a T4 level
of 54.8 Agldl at 4.5 hours after ingestion and had a
staring spell and became diaphoretic 7 days after the
ingestion.
Tenenbein and Dean’° observed nine children
with acute ingestions of levothyroxine resulting in
peak serum T4 levels of 19.9 to 84.7 Agldl and T3
levels of 113 to 742 ng/dl. Therapy was limited to
gastrointestinal decontamination, and all children
experienced benign clinical courses.
Massive ingestions of levothyroxine have been re-
centl~ reported in four single case reports. Nystrom
et al. reported a 19-year-old female who developed
fever and tachycardia after ingestion of 10 mg of
levothyroxine resulting in a peak T4 of 113 Agldl.
Roesch et a1.12 described a 22-month-old boy who
developed mild hypertension and tachycardia after
an ingestion of 5.7 mg of levothyroxine resulting in a
peak T4 level of 90 ttg/dI. Gorman et al. 13 reported a
12-month-old boy who developed fever, tachycardia,
diarrhea, and diaphoresis after an ingestion of 12 mg
of levothyroxine resulting in a peak T4 of 180 ~g/dl
and Ts of 1,031 ng/dl. All three patients had benign
clinical courses after treatment with gastrointestinal
decontamination and propranolol. Kulig et al. 14 de-
scribed a 30-month-old boy who had a T4 of 117
Agldl 6 to 8 hours after an ingestion of 18 mg of
levothyroxine. The child did well until 7 days after
the ingestion when he had a generalized seizure,
clinical signs of hyperthyroidism, and a T4 of 38
Agldl. The child had no previous history of seizures,
and extensive examination failed to suggest other
possible causes of seizure activity.
Despite the mild clinical symptoms reported after
almost all acute thyroid hormone ingestions in chil-
dren, more aggressive approaches have been taken
by other authors. Lerhner and Weir’ reviewed the
literature and reported two children, including a 3-
year-old girl with a peak T4 level of 35.1 Agldl who
was treated with propranolol, prednisone, propyl-
thiouracil, cholestyramine, and charcoal hemoperfu-
sion. LaCoutare et al.5 reported on the use of pro-
pylthiouracil and iopinoic acid to inhibit the conver-
sion of T4 to Ts in acute thyroxine ingestions in two
children. Gerard et al. used exchange transfusion to
lower T4 levels after an acute thyroid hormone in-
gestion in a 3-year-old girl. Finally, plasmapheresis
has been successfully used, mainly in adult patients
with symptoms of severe thyrotoxicosis, to remove
circulating thyroid hormone.7 These therapies have
been used in too few cases, to evaluate their effective-
375
 ness and the appropriate indications for their use, if
any, in the pediatric patient.
The clinical course of the patient we describe is
typical of children with acute thyroid ingestion in
many respects. Her symptoms were mild and con-
sisted of vomiting, irritability, tachycardia, and
tremor. Her symptoms were delayed in onset and
were most pronounced 4 days after ingestion when
T4 and Ts levels were both falling. The delay in onset
of symptoms and the lack of correlation between
serum T4 levels and symptoms have been attributed
to the time necessary to convert T4 to Ts in serum
and tissues. 14 Tissue levels of Ts might lag behind
serum concentrations. Serum Ts levels were clearly
decreasing when our patient experienced her most
severe symptoms. Alternatively, changes in cellular
nuclear receptor binding or postreceptor events
could dampen the response to an acute elevation in
thyroid hormone. The duration of exposure to high
thyroid hormone levels may be important in the de-
velopment of symptoms, as thyrotoxicosis is common
after chronic ingestions.’
The patient we describe is unique because of the
extraordinarily high thyroid hormone levels and the
serial measurements of both T4 and Tg that were
done. The initial T4 level of 282 Agldl was per-
formed with the Abbot TDx automated immunoas-
say analyzer after dilution with the provided buffer
solution rather than the zero standard (protein-con-
taining) solution. According to the manufacturer,
this may have artificially elevated this result. Even if
this level is discarded, the 48-hour T4 level of 139
jug/dl and Ts level of 1,837 ng/dl document an im-
pressive thyroid ingestion.
General recommendations for treatment of acute
levothyroxine ingestions in children include: 1) no
gastric decontamination for ingestions less than 0.5
mg, 2) ipecac-induced emesis at home for ingestions
of 0.5 to 3.0 mg, 3) ipecac-induced emesis followed
by oral activated charcoal in an emergency depart-
ment for ingestions greater than 3.0 mg with careful
follow-up for the next 5 to 7 days.2 Hospitalization is
recommended only if significant symptoms develop.
Even after massive acute ingestions of levothyrox-
ine, symptoms in children are usually mild and may
376
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be controlled with propranolol. This conservative
approach should be considered before expensive and
potentially dangerous therapies are undertaken.
References
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1986. Am J Emerg Med 1987;5:432.
2. Litovitz TL, White JD. Levothyroxine ingestions in
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1985;3:297-300.
3. Golightly LK,Smolinske SC, Kulig KW, et al. Clinical
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