Krishna M. Saxena, M.D., and John D. Crawford, M.D. The Department of Pediatrics, Harvard Medical School and the Children’s Service,
Massachusetts General Hospital, Boston
(Submitted February 9,1962; accepted for publication May 21, 1962.)
This work was supported by grants HTS-5139 and H-1529 from the United States Public health
Service. The second author holds a United States Public Health Service Senior Fellowship appointment. ADDRESS: (J.D.C.) Massachusetts General Hospital, Fruit Street, Boston 14, Massachusetts.
PEDIATRICS, December 1962
JUVENILE
LYMPHOCYTIC
THYROIDITIS
917
G
REAT advances have taken place in ourknowledge and understanding of
lym-phocytic thyroiditis since its first
descrip-tion by Hashimoto1 in 1912. The fact that
it is by no means uncommon in childhood
has only recently been appreciated.
Gri-betz et al.,2 in reviewing the literature in
1954, found only 11 cases reported at that
time. They added six cases of their own
and commented on the manifestations of
the disease in this age group. Several
fur-ther reports have appeared since.37
This communication concerns 32 patients,
of whom 23 were classified as having
“lym-phocytic thyroiditis” on the basis of
his-tology as well as clinical and biochemical
evidence. In the remaining nine patients the
diagnosis was presumptive. The group
corn-prises about 20% of all cases of goiter and
about 40% of all nontoxic goiters presenting
to our Pediatric Endocrine Clinic. Only
those cases have been included in which
the onset of goiter was at or before the age
of 15 years, and where the diagnosis has
been reasonably well established by
histo-logical or other criteria. The criteria for
diagnosis was the presence of a firm, diffuse
goiter of insidious onset which did not
re-spond promptly (within a period of 2 to 4
weeks) by a significant reduction in size to
the administration of thyroid extract. Other
supportive evidences were the presence of
agglutinating antibodies to thyroglobulin
as shown by a positive result of a tanned
erythrocyte test, positive flocculation tests,
and a large discrepancy between the
pro-tein-bound iodine and butanol extractable
iodine.
CLINICAL FINDINGS
The age at onset of the goiter ranged
from 2 to 15 years, with a mean of 10.3
years. There was an overwhelming
prepon-derance of females with only three males
having been encountered in this experience
(Table I).
The patients could be categorized into
two groups on the basis of presentation. In
12 patients the appearance of the goiter
was the first indication of the disease. They
had no other symptoms whatever for a
var-iable period of time after the goiter had
been discovered by the parents or friends.
The second group consisted of patients who
had some symptoms either coincident with
or proceeding first notice of the goiter.
Symptoms
Table II depicts the symptoms most
com-monly noted. Nervousness, anxiety,
emo-tional instability, fidgetiness, and irritability formed important components of the
clini-cal manifestations. Other symptoms were
either referrable to hypothyroidism or to
pressure from the enlarged gland. Pain in
the neck was present in two patients.
Signs
The physical examination usually
re-vealed a rather nervous looking child with
a visible goiter (Table III). The thyroid was
diffusely enlarged in the vast majority of
the patients, being judged two to four
times normal in size, firm, and having a
smooth or more usually finely granular or
lobulated surface. It was characteristically
TABLE II
SYMPTOMS OF PATIENTS WITH JUVENILE LYMPHO-CYTIC THYR0IDITIs
Symptoms
Patients
-__________
No. %
Nervousness 1 1 34
Irritability 6 19
Fatigue, dullness 7 22 Hoarseness, dysphagia 6 19
Cough 5 15.6
Diminished hearing S 9.4 Headache and dizziness 3 9.4
Pain in neck 2 6.2
Constipation 2 6.2
TABLE I
CLINICAL FINDINGS IN PATIENTS WITH JUVENILE LYMPHOCYTIC THYROIDITIS
t;z: Ageof
(vi)
Sex
. . P131 (jig/lOO ml)
BEJ (g/lOO
ml)
Radio-.
TRCt Biopsy Reaponae Remarks
1 15 F Hypo Pos .. . . . . - 14 . . +1 . . Subtotal thyroidectomy
S 1 F N Nag . . . . . + +1 . . Partial resection
S 13 F N Neg 7.8 . . . . .. .. + 10 mo ..
4 5 F Hyper Neg 4.4 . . 4. I +18 . . +1 . . Subtotal thyroidectomy
5 15 F Ilypo Pos 8.0 . . 5 -18 .. + 4 mo ..
6 13 F N Neg 8.8 5.1 .. .. .. .. lyr ..
7 15 F N Pos 7.5 .. .. .. .. + >Smo ..
8 1 11 N Neg 7.8 . . .. . . . . . . None Thymol turbidity, 1.5
units; C. flocc., neg 9 .5 F N Pos 7.8 . . . . . . .. + > I yr Goiter disappeared
10 13 F N Neg 8.5 . . 6 .. ++ . . None in 1 yr ..
11 7 M Ilypo Neg S. 1 . . . . -15 ++ .. 6 mo Goiter disappeared
1 9 F Ilypo Neg . . . . . . . . . . . . 1 yr ..
13 7 F Hypo Pos 7.0 3.3 .. -15 ++ + None ..
14 15 F N Neg 6.5 . . . . . . . 5 mo C. flocc., 3+
15 5 F N Pos 6.6 1.1 68 . . Neg. + None ..
16 13 F N Pos 5.8 . . 53.5 . . + . . 1 yr C. flocc. 5+
17 15 F N Po 7.4 4.0 45 .. ++ +1 None ..
18 11 F N Pos 4.9 5.6 35.9 .. + +1 >lyr ..
19 9 F N Neg 10.5 4.9 .. .. + + I4mo
50 14 F N Pos 10.0 . . . +++ + 1 yr C. flocc., 3+; T.
tur-bidity, 9.3 units
51 7 F N Pos 5.9 .. .. .. ++ >6mo ..
55 8 F N Pos 6.0 . . . ++ + 6mo ..
53 14 F N Neg 9.5 4.8 .. .. ++ + >Smo ..
24 14 F Hypo Neg .. .. .. -10 .. .. NoneinSyr ..
55 10 F N Neg 6.7 3.5 .. -8 ++ + >lyr ..
56 9 F Hyper Neg 8.8 3.7 55.8 .. ++ + lyr ..
27 9 F N Pos 4.5 . . 39 -15 ++ +1 6 mo ..
58 6 F Hypo Pos 6.5 3.7 83.5 -55 . . +1 . . Thyroidectoiny
59 4 F N Neg 5.0 . . 56.3 . . . . +1 None ..
30 10 M N Neg 5.6 5.0 70 -13 +++ +1 None ..
31 F N Neg 6.7 . . . . +17 . . + 1 yr C. fiocc., neg
35 8 F Hypo Pos 2.0 . . 30 . . . . +1 >15 nio .
SClinical thyroid status at onset. N =normal.
tTRC =Tanned erythrocyte test for antibodies to thyroglobulin.
Response as reflected by significant reduction in size of gland on 120 mg/rn’/day of thyroid extract.
I Open biopsy or operation
bruit. In eight cases one or more nodules
could be palpated in a diffusely enlarged
gland. In four other patients nodules first
became evident after administration of
thy-roid. It is noteworthy that in all eight
pa-tients in whom a nodule was palpated
be-fore
treatment,
the
diagnosis
washistolog-ically proved. The Delphian node was
palpable at the initial examination in 13
patients and became prominent in others
during follow-up. An enlarged pyramidal
lobe was noted in 16 (50%) cases. A normal
anatomic
feature,
this
finger-like
extension
of the
gland
extending
upward
along
the
left side of the trachea is usually not
Condition of Thyroid Associated Findings
TABLE III
PHYSICAL FiNDINGS IN PATIENTS WITH JUVENILE LYMPHOCYTIC THYROIDITIS
1)iffusely enlarged Firm
Soft
Delphian node Pyramidal lobe Nodules
Patients
No. %
29 90.6
26 81
6 19
13 40.6
16 50
12 37
Excessive nervousness
Allergic manifestations
Pressure symptoms Tremors
Hirsutism and/or acne
Prominent eyes
PatienLs
No. %
16 50
15 47
10 31
6 19
5 15.6
3 9
the enlargement of the gland but the
dif-fuseness of the disease process.
Among other associated findings was
ex-cessive nervousness which was remarked
upon during initial examination in 50% of
the patients. There was a high incidence of
pressure symptoms including hoarseness of
voice and dysphagia. Hirsutism and acne
were noted in five patients and prominence
of eyes in three. About half the children had
allergic manifestations, such as hay fever,
eczema, and urticarial reactions.
Endocrine Status
A clinical
assessment
of the
metabolic
status of the patients at the first
examina-tion showed that despite the prevalence of
nervousness, only two were hyperthyroid at
that stage. The vast majority were
euthy-roid (Table IV). Only four had marked
hy-pothyroidism, though four more were
slightly hypothyroid. Apart from this the
endocrine status of the patients was normal.
The mean age of menarche was 13 years, a
figure not significantly different from the
TABLE IV
THYROID STATUS ON CLINICAL EXAMINATION
Duration
of Goiter
in Years
When FirstSeen Final Follow-up
Euthy- Hypo-
Ilyper-roid thyroid thyroid
Euthy- Ilypo-
Ilyper-roid thyroid thyroid
<1 1-S
5-I
1-10 >10
Total
17 9 5
1 1 ..
1
1 1
1 5 -.
55 8 5
3 1 .
3 3
5 2
6 4 -.
1 7
15 17
mean age of 13 years, 8 months ±
10
months found in a survey of
endocrinologi-cally normal girls in our general medical
pediatric clinic. The goiter often showed
cyclic change in size, being largest just
be-fore the onset of menstrual periods.
Detailed height and weight records of 22
children were available. They showed the
majority to fall within the normal
range.
Weight for age showed a normal
distribu-tion pattern, but in examining the
correla-tion of weight with height one found that
many patients were slightly overweight, this
deviation from the normal relationship
tending to become more marked with the
passage of time after appearance of goiter
and when
hypothyroidism
was present.
Family History
Almost half the patients provided a
fam-ily history of thyroid disorders, and in two
families several members had Hashimoto’s
disease. Five children of these two
families
are included in this presentation.
Thyrotoxi-cosis was present in one or more members
of six of the families. It is to be noted that
a family history of allergic disorders was
elicited in one third of all patients.
Investigations
PR0rnN-B0uND IoDn’E : The protein-bound
iodine
(
PBI), as seen in Table I, was initiallyhigh or high normal in most children (mean
:= 6.8 ,.g/100 ml; range 2.0 to 10.0 tg/
100
ml).
The
high
PBI
values
tended
to
return
to
normal with thyroid medication orsome clinically hypothyroid children, values
were paradoxically elevated.
BASAL METABOLIC RATE: Basal metabolic
rate was determined in 11 children and
found to be low in 2, normal in 7, and high
in 2 (normal range ± 15sf).
RADIOACTIVE IODINE UPTAKE : Radioactive
iodine studies were carried out in 13
pa-tients. The mean uptake was 45 (range 24
to 83.5%). The uptake was usually high at
the onset of disease but tended to fall with
time. Thyroid therapy rapidly lowered the
uptake in some patients in whom the test
was repeated, suggesting that the thyroid
gland is thyroid-stimulating-hormone (TSH)
dependent and not autonomous as in
thyro-toxicosis.
PROTEIN-BOUND IODINE AND
BUTANOL-EX-TRACTABLE IODINE DISCREPANCY:
A
diagnos-tically important finding proved to be the
large discrepancy found between the
pro-tein-bound iodine (PB!) and
butanol-extrac-table iodine (BEI). Normally the BEI is 0.5
to 1.0 ig less than the PB!. Gribetz et al.2
showed that there was an unusually large
difference between the PBI and BEI values
in lymphocytic thyroiditis. Ten of 11
pa-tients in this series in whom both tests were
performed showed differences greater than
2.0 .g/100 ml. No such discrepancy was
noted in patients with other thyroid
dis-orders attending our clinic. With thyroid
medication, PB! gradually diminished and
the discrepancy narrowed. The cause of the
high PBI is the presence of a calorigenically
inactive iodinated protein. In the serum this
moves electrophoretically with albumin. It
is probably the result of a defect in organic
iodine-binding in the thyroid or a
break-down product of thyroglobulin but not
thy-roglobulin itself.8
FLOCCULATION TESTS9: Thymol turbidity
and flocculation and cephalin-cholesterol
flocculation tests were done in five patients.
In three cases the results were positive.
TANNID ERYTHROCYTE ANTIBODY TEST10’2:
The tanned erythrocyte antibody test was
performed according to the technique of
Boyden.bo Of 17 patients in whom this test
was performed, 16 gave a positive result,
but the titers in general were not high.
Numbers 1, 2, 3, 4, etc., were assigned to
correspond to the the usual dilutions of
serum, 1 : 10, 1 : 20, 1 : 40, 1 : 80, etc., at which
agglutination is tested. The numbers
cor-responding to the highest dilutions at which
agglutination was seen in these children
ex-eluding the two negatives yielded a mean
and standard error of 3.60 ± 0.55. A series
of 24 adults with lymphocytic thyroiditis,
tested, as were the children, during
admin-istration of thyroid, showed a mean of 6.96
± 0.79 (t = 3.07; p < 0.005). Of
addi-tional interest is the fact that among
sib-lings and parents of patients where
agglu-tination tests were positive but there was no
clinical evidence of thyroid disease, the
chil-dren showed similarly lower values than
did their parents.
PATHOLOGY: Material for histological
ex-amination was obtained by needle biopsy
in 16 patients and by open biopsy or
thy-roidectomy in 10. In some patients repeated
biopsies were done. Thus in a total of 23
patients, the diagnosis was proven
histolog-ically. In those children in whom surgical
exploration was undertaken to rule out
car-cinoma of the thyroid an opportunity for
direct examination of the thyroid was
af-forded. The glands were diffusely enlarged,
with or without nodules, and had a pale
greyish color. The surface was irregular or
slightly granular, the consistency firm, and
the vascularity diminished. Lymph glands
around the thyroid were usually enlarged.
The characteristic histological picture was
that of a gland showing diffuse
interfollicu-lar infiltration with plasma cells and
lym-phocytes, atrophy of the follicles, and
vary-ing degrees of epithelial degeneration.
Cel-lular hyperplasia was often noted in the
early stages. Hyperplasia of the thyroid was
the only change noted at first in a gland
where serial biopsies over a course of 6
years showed transition to the appearance
typical of lymphocytic thyroiditis.’3 Fibrosis
of the thyroid was not a prominent feature
ARTICLES
921TREATMENT: Nineteen of our patients
were treated with desiccated thyroid alone,
10 were treated with subtotal
thyroidect-omy or isthmectomy plus thyroid, and 3
re-ceived no treatment at all. The dose of
thyroid routinely given was 120 mg/rn2!
day, a dose which we considered to be
suf-ficient to suppress TSH production.14 In
only 4 of 19 patients treated with thyroid
alone did the goiter disappear entirely; in
most it decreased in size after months of
therapy, but some enlargement persisted
indefinitely, and in a few cases there was
no change in size. As seen in Table IV,
hy-pothyroidism had developed in 17 of the
patients at the final follow-up, whereas 15
were euthyroid.
COMMENT
The observations on this relatively large
group of children seem sufficiently
homo-geneous as to require little comment.
Be-fore discussion of certain contrasts between
the adult type of lymphocytic thyroiditis
and that seen in children and of results of
treatment, a consideration of data relative
to the etiology of the disease seems
perti-nent.
Etiology
Knowledge about the etiology of
thy-roiditis has advanced rapidly in the last
decade. The observation of Fromm et al.15
that these patients exhibit elevated
gamma-globulin values, and the demonstration by
Luxton and Cook9 that they show abnormal
flocculation tests results, led Roitt et al.16,17
to postulate that the disease might be due
to an immune process directed against the
thyroid gland. They supported this
hypoth-esis by demonstrating that patients’ sera
re-acted specifically with extract of human
thyroid gland to give precipitate formation,
indicating the presence of antibodies.18 At
the same time Rose and WitebskylO20
showed that pathological changes
resem-bling human Hashimoto’s thyroiditis could
be produced in the remainder of a donor
animal’s thyroid by injection of
thyro-globulin extracted from a portion of the
gland previously removed. The concept of
auto-immunity as the etiological factor of
the disease thus came into being. It was
proposed that the thyroid contains antigenic
substances which normally are kept inside
the thyroid follicles away from the immune
mechanisms by the follicular basement
membrane. When there is damage to the
follicles, the continuity of the basement
membrane is disrupted2l 22 and the antigenic
substances, one of which is thyroglobulin, are
liberated in the extrafolliciilar interstices and
thence into the circulation. When this
hap-pens, antibody-producing lymphocytes and
plasma cells infiltrate the gland. The
pres-ence of antibodies in the blood appears to be
due to simple spillover from the large
amounts produced locally by the infiltrating
cells.23 One of the antibodies has a cytotoxic
effect on the follicular epithelium at least in
vitro, and if this happens in vivo, it may
re-suit in further release of antigens.
Three thyroidal auto-antigens have been
clearly demonstrated, and the possibility
exists that more may be present.24 One, thyroglobulinio 25, 26 is normally present in
the thyroid follicles. Another, the
comple-ment-fixing antigen272#{176} is present more
commonly in thyrotoxic glands and is
lo-cated in the microsomal fraction of the
cytoplasm of thyroid epithelium. The third,
CA2,
5 also a colloid antigen but is distinctfrom thyroglobulin.5#{176}
Antibodies to one or more of these
antigens are demonstrable in the serum of
patients with lymphocytic thyroiditis. Many
different techniques have been employed
for their demonstration. The most reliable
and sensitive test for antibodies against
thyroglobulin is the tanned erythrocyte
agglutination.10’30’3’ In untreated, active
Hashimoto’s disease, high titers are seen in
about 80% of patients. In our series, 16 of
17 (94%) gave a positive result, even though
all were under thyroid therapy. The titer’s
decrease after partial thyroidectomy or
sus-tained thyroid therapy but still remain
JUVENILE THYROIDITIS
in the
present
series. When both tannederythrocyte agglutination and
complement-fixation tests were employed, Roitt and
Doniach12
found
that
97% of their
patients
gave positive results.
The
presence
of antibodies
is not init-self evidence that they are the cause of
thyroiditis, and there is some evidence, in
fact, which casts doubt on the causative
role
of
the
antithyroglobulin
antibodies.
Passive transfer to monkeys and dogs of
serum
containing
antibodies
did
notpro-duce
changes
in
the
thyroid
of
the
re-32 Observations in cases of
thy-roiditis
occurring
in association
with mumps
showed
that
the
process
was self-limiteddespite the appearance of this antibody in
the
3 Antibodies were foundin a large number of other thyroid
dis-34, 35, 36 Finally, no very close
cor-relation
between
thyroglobulin
antibody
titers
and
the
extent
of experimental
thy-roid
lesions
or the clinical
course
in
Hashi-moto’s disease has been 23 38
The cytotoxic factor, almost always
pres-ent in association with the microsomal
com-plement fixing antibodies in the sera of
patients with lymphocytic thyroiditis, has
been most extensively explored by
Pulver-taft et al.8
and
by Irvine.39’
This
factor
is cytotoxic to human thyroid cells growing
in tissue
culture.
According
to Irvine39
the
cytotoxic effect may be related to an antigen
antibody reaction, but it is quite
independ-ent of autoimmunity to thyroglobulin.41 Its
role in causing lymphocytic thyroiditis is
again not definitely proved. Passive transfer
in a human subject produced no effect on
the thyroid tissue, but this does not
elimi-nate its consideration in the pathogenesis
of thyroiditis.9
Several hypotheses have been forwarded
as to the initial cause of thyroid
auto-immunity:
Virus Infection. Mumps virus, as has
al-ready been mentioned, can cause follicular
damage with release of thyroglobulin and
consequent formation of antibodies.18,42
However,
the
process
is self-limited andhas not led to progressive thyroid
dam-age or chronic thyroiditis.hi 31 It is of
inter-est in this connection that upper respiratory
infections were often associated with the
initial
appearance
and
later
exacerbations
of goiters in our patients. However, no
clear-cut etiologic relationship between virus
infection and thyroiditis has been shown.43
Excessive TSH Stimulation. There is
evi-dence that a defect of organic iodine
bind-ing exists in patients with lymphocytic
thyroiditis57 The possibility exists, therefore,
that excessive TSH stimulation secondary to
this defect is the initiating factor in
lympho-cytic thyroiditis. This would require
devel-opment of a hyperplastic response which
somehow overtaxed the follicular basement
membrane barrier to permit escape of
thyro-globulin. The antigen-antibody complex
re-sulting from the production of antibodies
could then modify the hyperplastic response
to give chronic thyroiditis. It is significant
in this connection that susceptibility of cells
in tissue culture to cytotoxic factor is
pres-ent only in the first 36 hours when they are
rapidly dividing and that cultured cells
from hyperplastic glands are much more
amenable to
The strong family history of
“thyrotoxi-cosis” in our patients, the hyperthyroid
clinical status of some patients at onset, the
elevated radioactive iodine uptake, and the
hyperplasia found in some thyroid glands
in the early phase of the disease all give
support to the view that excessive TSH
stimulation initiates thyroditis. Furthermore,
autoantibodies are often present in
thyro-toxicosis,31 and about 10% of thyrotoxic
pa-tients without treatment eventually become
rnyxedematous. However, it has to be
pointed out that in thyroiditis the normal
pituitary-thyroid relationship is still
main-tained and in this respect it differs from
true thyrotoxicosis.
Genetic Predisposition. There is recent
evidence that lymphocytic thyroiditis may
be genetically determined. Hall et al.45
found antibodies in 50% of 38 siblings of
8 patients with thyroiditis, whereas
nor-ma! control studies showed only 5%
‘5
L
I0
ARTICLES 923
0- 5 6-10 11-15 6-20 21-25
AGE GROUPS
FIG. 1. Age incidence in juvenile thyroiditis.
trait of inheritance. A similar inheritance
was seen by Van Wyk4#{176} in one of his
families.
How the genetic predisposition manifests
itself is still in the realm of conjecture. It
seems most likely that the fault lies in an
abnormal or hypersensitive immune
re-sponse. The high incidence of allergic
mani-festations in our patients (47%) and their
families (30%) is noteworthy in this regard.
The usual incidence of allergic disease in
childhood is around 10%.
Recent observations by several workers
suggest that cellular hypersensitivity may
be important in the pathogenesis of
thy-849
A
close
relationship
between
the incidence of delayed type
hypersensi-tivity to thyroglobulin and the production
of experimental thyroiditis has been found.5#{176}
Immune thyroiditis, while it has not yet
been seen in response to passage of
anti-body or cytotoxic factor, has been passively
transferred to guinea pigs by means of
lymph node cells by Felix-Davies and
Waksman’ and by Porter and Fennell.52
Juvenile and Adult Lymphocytic Thyroiditis
There are certain well-marked differences
between juvenile lymphocytic thyroditis
and adult Hashimoto’s disease. Perhaps the
most striking is the distribution of age at
onset. As seen in Figure 1, the juvenile
form has its peak of onset between 5 and
15 years, while the peak incidence of the
adult form is the fourth and fifth decades
Sept. I 961 of 54 This clearly is not a
continua-tion of the childhood condition, for history
of goiter in childhood or adolescence is
conspicuously lacking in the adult patients.
The clinical manifestations in the
juve-nile patients also differs from those in adults
accurately described by Hashimoto in 1912
and recently reviewed by Luxton53 and
Beare.54 Hashimoto described a condition
characterized by a diffuse progressive goiter
of recent onset appearing in a middle-aged
woman, with signs of hypothyroidism and
pressure symptoms. In children the onset
of the goiter is much more insidious, often
to be measured in years rather than months.
Evidence of slight hyperactivity of the
thy-roid not only is usually seen clinically but
also is reflected in a high radioactive iodine
uptake and protein-bound iodine in the
mi-tial stages. In adult thyroiditis these last
two parameters of thyroid function are
usu-ally within normal limits or low.55
Aggluti-nating antibodies to thyroglobulmn are
pres-ent in children in a much lower titer than
seen in the adult patients. In our limited
cx-perience, it would appear that
gamma-globulins are not much elevated and that
results of serum flocculation tests are often
negative, unlike the situation in the adult
patient with Hashimoto’s disease.#{176} The
his-tologic picture in juvenile lymphocytic
thy-roiditis also shows some difference from the
adult
variety in that hyperplastic changesare quite prominent, eosinophilic
degenera-tion of the epithelium is frequent, and
fibro-sis is minimal.
Diagnosis
Diagnosis is not difficult if it is kept in
mind that thyroiditis is quite common in
childhood. Suspicion should be aroused by
the finding of a diffuse, firm, smooth, or
slightly nubbly goiter in a pre-adolescent
girl in whom striking signs of thyrotoxicosis
or hypothyroidism are absent. The
diag-nosis is strongly supported by the PBI-BEI
discrepancy and the tanned erythrocyte
ag-glutination test. These tests may rarely be
924
may be resorted to for confirmation where
necessary, but it is to be recalled that
hyper-plasia may predominate early in the disease
and fibrosis is seldom prominent. The
re-sponse to administration of a thyroid active
agent is also very informative. A dose of 120
mg/m2/day of USP thyroid brought about a
very significant reduction in size within
7 to 10 days in all other types of
non-toxic goiters seen in our clinic. A lack of
similar response was characteristic of
pa-tients with lymphocytic thyroiditis.
Dessi-cated thyroid was usually given in the
pres-ent series, but there would appear to be
advantages in using triiodothyronmne
be-cause of the rapidity of its action. Ten days
administration of a TSH suppressive dose
of this compound should restore to normal
the PBI-BEI relationship.
Medical therapy essentially consists of
dessicated thyroid (about 120 mg/rn2! day)
or thyroxine in sufficient dosage to suppress
TSH production. In most patients this is
at best a long-term undertaking. One is
likely to be disheartened with the results
unless the aims are understood. If the aim
is to effect reduction in size of the goiter,
the therapy is not always satisfactory. In
only 4 of 19 patients given thyroid alone
did the goiter disappear altogether. In most
it diminished in size but persisted
indefi-nitely, and in some there was no change in
the goiter despite long-term therapy. The
second aim is to treat hypothyroidism when
it develops. When untreated the majority
of patients will eventually become
hypothy-roid. Whether we are able by any therapy
to prevent further damage to the gland is
not clear. The final follow-up in our patients
shows that despite treatment some became
hypothyroid in the course of time (Table
IV). A reduction in the antibodiy titer is
seen after thyroid medication,#{176} but its
significance in relation to the clinical
condi-tion of the patient is not definitely known.
Adrenocortical steroids have been used
by others in treatment with apparent
suc-cess.5 This form of treatment has not been
evaluated in the present group. We wish
to emphasize that surgery has no place in
the treatment of this condition apart from
relieving pressure symptoms.
SUMMARY AND CONCLUSIONS
Lymphocytic thyroiditis was the most
common cause of nontoxic goiters in
child-hood, comprising about 40% of these and 20%
of all goiters seen in our pediatric endocrine
clinic. The diagnosis should be considered
whenever a nontoxic goiter does not
dimin-ish significantly in size within about two
weeks in response to
thyroid-stimulating-hormone (TSH) suppressive doses of USP
thyroid.
Observations on 32 children with
lympho-cytic thyroiditis have been recorded. The
diagnosis was proven histologically in 23.
In nine patients the diagnosis was
presump-tive. The condition occurred mostly in
pre-adolescent girls as a slowly developing
firm, diffuse, and smooth or nubbly goiter
with or without symptoms of anxiety,
nervousness and pressure in the neck. The
majority of patients were euthyroid when
first encountered, though examples both of
mild hyperthyroidism and hypothyroidism
were also seen. A high protein-bound
iodine value, a large discrepancy between
protein-bound iodine and
butanol-extracta-ble iodine, and positive tanned erythrocyte
antibody test results provided the best
diag-nostic criteria apart from biopsy.
The pathological picture is one of
hyper-plasia with lymphocytic infiltration and
atrophy of thyroid follicles and epithelium.
Treatment consisted in giving TSH
suppres-sive doses of thyroid for a prolonged period.
The results of treatment were not entirely
satisfactory. Genetic predisposition,
prob-ably manifested in an abnormal cellular
hypersensitivity, and excessive TSH
stimu-lation of the thyroid seem for the moment
the two factors in pathogenesis best
sup-ported by laboratory evidence.
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Acknowledgment
Our thanks are due to the Adult Thyroid Clinic of the Massachusetts General Hospital, Boston, in
general, and to Drs. John B. Stanbury, Leslie
DeGroot, and Reginald Hall, in particular, for allowing us to include some of their patients and
for their suggestions in the preparation of this
manuscript. We wish also to express our gratitude
