Volume 15, Number 10, 2005
© Mary Ann Liebert, Inc.
Atypical Subacute Thyroiditis Caused by Epstein-Barr Virus
Infection in a Three-Year-Old Girl
Cecilia Volta, Nicola Carano, Maria Elisabeth Street, and Sergio Bernasconi
Subacute thyroiditis is a rare disease in childhood and is considered postviral in origin. Epstein-Barr virus (EBV)
involvement has been suspected, but just once demonstrated in an adult female. We report a case of subacute
thyroiditis during infectious mononucleosis in a 3-year-old girl. The diagnosis of infectious mononucleosis was
supported, in addition to the typical clinical symptoms, by presence of EBV DNA both in plasma and leuko-
cytes. Subacute thyroiditis was diagnosed based on elevated thyroid hormone levels with thyrotropin (TSH)
suppression, high inflammation markers and almost absent 99TC uptake by thyroid. Moreover after 3 months
from diagnosis thyroid function went back to normal as well as the 99TC uptake.
It is an autolimiting inflammatory condition of the thyroid
gland that can last from few weeks to some months. The
main clinical characteristics are pain in the thyroid region,
goiter, and eventually symptoms of thyrotoxicosis. Fatigue,
malaise, and fever can also be present. Thyroid hormones
are typically increased and thyrotropin (TSH) suppressed,
markers of inflammation such as erythrocyte sedimentation
rate (ESR) and C-reactive protein (CRP) are markedly ele-
vated and, because of disruption of thyroid follicles, ra-
dioiodine or 99-technetium (99Tc) uptake by the thyroid is
very low or absent. Treatment, if necessary, consists in a
short course anti-inflammatory or steroids drugs.
Subacute thyroiditis is considered postviral in origin even
if a genetic predisposition is probably necessary. The etiol-
ogy is, however, is difficult to identify, depending both on
serum antibodies or thyroid tissue cultures. Epstein-Barr
virus (EBV) is among the suspected viruses, but positive anti-
EBV antibodies during subacute thyroiditis have been re-
ported in the literature only in an adult female (4).
We here report a similar case of a 3-year-old girl with sub-
acute thyroiditis having infectious mononucleosis.
UBACUTE THYROIDITIS (or of de Quervain) is an uncommon
disease in adult age (1,2) and very rare in childhood (3).
A 3-year-old Caucasian female was transferred to our de-
partment from another hospital where she was admitted 5
days before for a fever of unknown origin resistant to anti-
biotics. The relevant clinical and laboratory data reported
were cervical lymphoadenopathy, elevated white blood
count (WBC) and markers of inflammation; anti-EBV im-
munoglobulin G (IgG) and immunoglobulin M (IgM) were
negative. During the admission in our department the re-
mitting fever continued to be present, spleen and liver en-
largement were present both clinically and at ultrasound.
Main biochemical data are reported in Table 1. In particular,
the presence of EBV DNA, both in plasma and leucocytes,
shown by polymerase chain reaction (PCR), together with
the high titer of anti-EBV IgM, previously negative, con-
firmed the clinical suspicion of infectious mononucleosis.
Thyroid function was investigated because of unexplained
tachycardia with unexpected results: thyroid-stimulating
hormone (TSH) level was suppressed with high levels of free
triiodothyronine (FT3) and free thyroxine (FT4). Antiperoxi-
dase and antithyroglobulin antibodies as well anti-TSH re-
ceptor antibodies were negative. A thyroid gland ultrasound
showed a slight enlargement of the gland with normal thy-
roid tissue and the 99Tc scintigram (Fig. 1, left) did not show
any uptake of the tracer neither in the normal or ectopic po-
sition. Considering these findings and the high values of ESR
and CRP (115 mm/h and 26100 ?g/L (26.1 mg/L), respec-
tively) the diagnosis of subacute thyroiditis caused by EBV
This patient was treated with a 10 day course of steroids
(deflazacort, 1.5 mg/kg per day, orally, once daily) with pro-
gressive resolution of fever, liver and spleen enlargement,
Department of Paediatrics, University of Parma, Parma, Italy.
and of lymphoadenopathy. Inflammation markers returned
within the normal range as well as thyroid function 3 months
later (Table 1). A thyroid scintigram performed 3 months af-
ter diagnosis showed an almost complete recovery of the
tracer uptake of the thyroid (Fig. 1, right).
After a 6-month follow-up, thyroid function and thyroid
ultrasound were normal and antithyroid antibodies nega-
tive. At the same time, as expected, anti-EBV IgM became
negative and IgG positive.
The diagnosis of subacute thyroiditis is supported by thy-
roid hormone and TSH serum concentrations, increased
VOLTA ET AL.1190
TABLE 1. MAIN LABORATORY DATA AT DIAGNOSIS AND AFTER TWO MONTHS
3 months after
diagnosis At diagnosisNormal values
WBC ? 109cells/L
CRP ?g/L (mg/L)
EBV DNA by PCR
0–5000 (0–5) 22,610 (26.1)
FT3 pmol/L (pg/mL)
TPO and TGAb
WBC, white blood count; ESR, erythrocyte sedimentation rate; CPR, C-reactive protein; EBV DNA by PCR: Epstein-Barr virus DNA by
polymerase chain reaction; EBV-IgM; Epstein-Barr virus immunoglobulin M; TSH, thyroid-stimulating hormone; FT4, free thyroxine; FT3,
free triiodothyronine TPO and TG-Ab, antiperoxidase and antithyroglobulin antibodies; TSHR-Ab, anti-TSH receptor antibodies.
(right) showing an almost complete recovery of 99Tc uptake.
99Tc scintigram of the thyroid at diagnosis (left) showing no uptake of the tracer and 3 months after diagnosis
markers of inflammation, absent thyroid uptake of 99Tc, re- Download full-text
sponse to corticosteroid treatment, and the evolution after a
The main causes of hyperthyroidism in childhood, namely
Graves’ disease and hyperthyroid phase of Hashimoto’s thy-
roiditis, were excluded, the former by absence of anti-TSH
receptors antibodies and of thyroid uptake, the latter by ab-
sence of thyroid antibodies and normal ultrasound and both
by subsequent evolution. Furthermore, thyrotoxicosis facti-
tia (i.e., accidental or voluntary ingestion of thyroid hor-
mones) must be considered in this age group and could have
been consistent with the laboratory and imaging data. How-
ever, this was excluded in this case because no drugs con-
taining thyroid hormones were available in the household
and increased thyroid hormone levels were found after 10
days of admission in the hospital.
Acute infectious thyroiditis has also to be considered in a
young child. In this case, however, only the elevation of in-
flammation markers were consistent with this diagnosis. In
fact, no alterations of thyroid function tests nor absent thy-
roid uptake of 99Tc are present in infectious thyroiditis. Thy-
roid pain, usually present in subacute thyroiditis, was unre-
ferred; this could be because of the young age of the child
or to the fact that she also had pain caused by severe acute
throat inflammation and symptoms could have been con-
fused. However, atypical painless subacute thyroiditis has
been reported (5). The only symptom related to hyperthy-
roidism was tachycardia, in adults however hyperthyroid
symptoms were described only in 50% of the cases (6).
The general clinical symptoms and the presence of EBV
DNA both in plasma and leucocytes together with the ele-
vated titer of anti-EBV IgM, previously negative, strongly
suggest the etiology (7).
To our knowledge this is the first reported case in the
childhood showing convincing evidence of EBV as a cause
of subacute thyroiditis. The only case reported in an adult
female (4), was less clear-cut because only the titer of anti
EBV IgG was positive indicating a past infection. Moreover,
failure of detection of EBV in thyroid tissue in some patients
with subacute thyroiditis has been reported (8).
In conclusion, this case report confirms the viral etiology
of subacute thyroiditis in children and suggest that this dis-
ease could be more frequent than reported during viral in-
fections as symptoms specific of thyroid gland involvement
can be absent.
Presented to the national meeting of the Italian Society of
Pediatric Endocrinology. Rome, September 2003.
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