THYROID SCINTIGRAPHY FINDINGS IN 2096 CATS WITH

HYPERTHYROIDISM

MARK E. PETERSON , MICHAEL R. BROOME

Thyroid scintigraphy is currently the reference standard for diagnosing and staging cats with hyperthyroidism,
but few studies describing the scintigraphic characteristics in a large number of cats have been reported. The
objective of this study was to better characterize thyroid scintigraphy findings by evaluating 2096 consecutive
cats with hyperthyroidism that were referred over a 3.5-year period. Of these cats, 2068 (98.7%) had a high
thyroid-to-salivary ratio (>1.5), whereas 2014 (96.1%) were found to have a high thyroid-to-background ratio
(>6.1). When the patterns of the cats’ thyroid disease were recorded, 665 (31.7%) had unilateral disease,
1060 (50.6%) had bilateral-asymmetric disease (two thyroid lobes unequal in size), 257 (12.3%) had bilateral-
symmetric disease (both lobes similar in size), and 81 (3.9%) had multifocal disease (3 areas of increased
radionuclide uptake). The number of areas of 99m TcO− 4 uptake in the 2096 cats ranged from 1 to 6 (median,
2), located in the cervical area in 2057 (98.1%), thoracic inlet in 282 (13.5%), and in the thoracic cavity in 115
(5.5%). Ectopic thyroid tissue (e.g. lingual or mediastinal) was diagnosed in 81 (3.9%) cats, whereas thyroid
carcinoma was suspected in 35 (1.7%) of the cats. The results of this study support conclusions that most
hyperthyroid cats have unilateral or bilateral thyroid nodules, but that multifocal disease will develop in a few
cats that have ectopic thyroid disease or thyroid carcinoma. Both ectopic thyroid disease and thyroid carcinoma
are relatively uncommon in hyperthyroid cats, with a respective prevalence of 4% and 2% in this study.

C 2014 American College of Veterinary Radiology.

Key words: cat, feline, hyperthyroidism, scintigraphy, thyroid.

Introduction hyperthyroidism, very few series have been reported, with

the largest being only 135 cats.1,2,6 In the most recent study
T HYROID SCINTIGRAPHY PROVIDES valuable information
regarding both thyroid anatomy and physiology and
plays an integral role in the diagnosis, staging, and man-
of 120 hyperthyroid cats, Harvey et al.6 reported that nearly
one of five hyperthyroid cats had multifocal disease, with
multiple areas of increased radionuclide uptake visible on
agement of feline thyroid disease.1–5 For hyperthyroid cats,
thyroid imaging; over 90% of these cats had hyperfunc-
scintigraphy is generally considered to be the thyroid imag-
tional thyroid tissue within the thorax that could not be
ing technique of choice for detecting and delineating all hy-
palpated. Many of those cats had already been treated with
perfunctioning, adenomatous thyroid tissue. Advantages of
surgical thyroidectomy, however, and were referred to the
nuclear scintigraphy include its ability to differentiate bilat-
University of Bristol for persistent or recurrent hyperthy-
eral versus unilateral thyroid disease, assess thyroid size and
roidism. Therefore, this high prevalence of intrathoracic
activity, and identify ectopic or metastatic thyroid tissue.
thyroid masses in this group of hyperthyroid cats may not
Despite the fact that thyroid scintigraphy is commonly
represent what is seen in general practice or in cats that have
recommended for diagnosis and management of cats with
not undergone a failed thyroidectomy procedure.
From the Animal Endocrine Clinic, New York, New York The purpose of this study was to better characterize thy-
(Peterson) and Advanced Veterinary Medical Imaging, Tustin, Cali- roid scan findings in 2096 consecutive hyperthyroid cats
fornia (Broome). that were referred for “routine” radioiodine (131 I) treatment
Funding sources: This research received no grant from any funding
agency in the public, commercial, or not-for-profit sectors. over a 3.5-year period. Thyroidectomy is not a commonly
Previous presentations and abstracts: This study was presented as a used treatment modality by our referring veterinarians, so
research abstract at the 32rd Annual Veterinary Medical Forum of the almost none of these cats were referred for persistent or
American College of Veterinary Internal Medicine, New Orleans, LA in
2012. recurrent hyperthyroidism following surgery. We routinely
Address correspondence and reprint requests to Mark E. Peterson, perform scintigraphic imaging in all hyperthyroid cats re-
DVM, Dip ACVIM, Animal Endocrine Clinic, 220 Manhattan Avenue, ferred to our clinics, in order to assist with staging, treat-
New York, NY 10025. E-mail: drpeterson@animalendocrine.com
ment planning, and 131 I dose estimation.4,7 The specific
Received September 23, 2013; accepted for publication March 6,
2014.
doi: 10.1111/vru.12165 Vet Radiol Ultrasound, Vol. 56, No. 1, 2015, pp 84–95.

84
VOL. 56, NO. 1 THYROID SCINTIGRAPHY IN HYPERTHYROID CATS
goals of this study were to determine the usefulness of the
thyroid-to-salivary ratio and thyroid-to-background ratio
as diagnostic tests for hyperthyroidism; to determine the
proportion of cats with unilateral, bilateral, and multifo-
cal disease; to determine the number and location of areas
(i.e., thyroid nodules) with increased radionuclide uptake
in each cat; and finally, to determine the prevalence of in-
trathoracic, ectopic, or suspected malignant thyroid tissue
in this series of hyperthyroid cats. We hypothesized that thy-
roid scintigraphy could be used as a sensitive diagnostic test
for hyperthyroidism and that most hyperthyroid cats would
have unilateral or bilateral cervical disease, with only a few
cats having multifocal or ectopic mediastinal disease.
Materials and methods
Cats
The study was conducted prospectively from January
2009 to June 2012. Inclusion criteria included cats with
a confirmed diagnosis of hyperthyroidism, established on
the basis of consistent clinical signs (e.g., weight loss despite
a good appetite), a palpable thyroid nodule on physical ex-
amination, and the finding of high serum concentrations of
thyroxine (T4 ) and/or free T4 .8–10 If methimazole had been
administered, the drug had to be discontinued for at least
1 week prior to admission. A total of 2096 client-owned
adult cats, all referred to our clinics for thyroid scintig-
raphy and subsequent radioiodine therapy, matched these
criteria.
Clinically normal, client-owned cats were also prospec-
tively recruited for thyroid scintigraphy, in order to estab-
lish reference range values for the thyroid-to-salivary gland
ratio (T/S ratio) and thyroid-to-background ratio (T/B ra-
tio). To be included in this control group, these cats had to
be 7 years of age, and all were determined to be healthy
on the basis of the client history, physical examination find-
ings, and results of complete blood count, serum chemistry
profile, and serum T4 concentrations.
Protocol for Thyroid Scintigraphy
To perform thyroid scintigraphy, 111–148 MBq (3–4
mCi) of sodium pertechnetate (99m TcO− 4 ) was injected in-
travenously or subcutaneously.4,11 If given intravenously,
the medial femoral vein was used; if given subcutaneously,
the injection was given either over the right or left hip to
avoid interference with the thyroid scan. After a period of
20–60 min, cats were placed directly on top of the low en-
ergy, all-purpose (LEAP) collimator and held in ventral
recumbency for imaging. No sedation was given to any of
the cats to obtain the thyroid image.
Thyroid images were obtained with a large-field-of-
view scintillation camera (MaxiCamera 400 Nuclear
85
Gamma Camera, GE Medical Systems, Pittsburgh, PA;
Pho/Gamma LFOV Scintillation Camera, Searle Radio-
graphics, Des Plaines, IL) fitted with a LEAP collimator,
integrated to a dedicated imaging computer running dedi-
cated nuclear medicine software (NucLear Mac; Scientific
Imaging, Inc. Crested Butte, CO). For imaging, a 20% win-
dow was centered at a photopeak of 140 KeV. A 256 ×
256 × 16 matrix was used, and each image was acquired
for a total of 250,000 counts. Images were analyzed using
DICOM image-processing software (OsiriX Imaging Soft-
ware, Pixmeo, Geneva, Switzerland12 ).
Calculation of the Thyroid-to-Salivary Gland and Thyroid-
to-Background Ratios
In the clinically normal cats, thyroid images were ana-
lyzed to determine the amount of 99m TcO− 4 activity in three
regions of interest: (1) thyroid lobes; (2) zygomatic/molar
salivary gland; and (3) a background area. Thyroid and
salivary gland regions of interest were drawn to outline the
entire circumference of each lobe of the thyroid gland and
each zygomatic/molar salivary gland.3,5,13,14 The axillary
region was chosen for background determinations, using
a region of interest approximately equal to each thyroid
lobe, as previously described.13,15 Ventral thyroid images
were used for this analysis because it provided better delin-
eation of thyroid lobe and salivary gland uptake. Because
the size of the three regions of interest could influence their
count density values, all of these regions were drawn by one
person (M.E.P.) to reduce interoperator variability.
For each normal cat, the average thyroid-to-salivary ra-
tio (T/S ratio) was calculated by dividing the average
thyroid count density from both thyroid lobes (total thy-
roid counts/total thyroid pixels) by the average salivary
count density (total salivary counts/total salivary gland
pixels). Similarly, the average thyroid-to-background ratio
(T/B ratio) was calculated by dividing the average thyroid
count density (total thyroid counts/total thyroid pixels) by
the average background count density (total background
counts/total background gland pixels). The reference range
for the T/S ratio ranged from 0.5 to 1.5, whereas the refer-
ence range for the T/B ratio ranged from 1.6 to 6.4.
After image acquisition in the hyperthyroid cats, regions
of interest were drawn manually around each thyroid nod-
ule and compared to the ipsilateral salivary gland activ-
ity (zygomatic-molar salivary regions of interest), as pre-
viously described.3–5,13,14 A background region of interest
was placed in the axillary region, taking care not to overlap
vascular activity in the jugular veins or ectopic/metastatic
thyroid tissue. As with the normal cats, all regions of inter-
est were drawn by one person (M.E.P.). If more than one
thyroid nodule was detected (see below), the thyroid lobe
with the higher intensity (i.e., the hottest nodule) was used
to calculate the T/S and T/B ratios.
86 PETERSON AND BROOME
Scintigraphic Classification of Hyperthyroid Disease
Abnormal scintigraphic findings indicative of thyroid
gland disease were classified into the following four ma-
jor patterns: unilateral disease, bilateral-symmetric in size,
bilateral-asymmetric in size, and multifocal disease (more
than two thyroid nodules). When extracervical thyroid dis-
ease was detected, this classification was extended to in-
clude ectopic thyroid nodules as well as suspected thyroid
carcinoma.
Unilateral thyroid disease was defined as single thyroid
lobe involvement, which is typically located in the cervical
region. This unilateral thyroid lobe has greater intensity
than the ipsilateral salivary glands (i.e., higher thyroid-to-
salivary ratio). The contralateral thyroid lobe in these cats
is completely suppressed and cannot be easily visualized.
Bilateral thyroid disease was defined as involvement of
both thyroid lobes, with one or both having greater intensity
compared with the salivary glands (i.e., higher thyroid-to-
salivary ratio). With bilateral symmetric disease, both lobes
were of similar size, whereas in bilateral asymmetric disease,
the two thyroid lobes were dissimilar in size. Again, both
of the involved thyroid lobes are typically located in the
cervical region but can fall into the thoracic inlet or thoracic
cavity if very large.
Multifocal disease was defined as areas of radionuclide
uptake involving more than just the two normal thyroid
lobes (i.e., >2 discrete, well-defined areas of radionuclide
uptake). In these cats with multifocal disease, multiple areas
of increased 99m TcO− 4 uptake were found, generally in the
thoracic as well as the cervical regions (see below).
Adenomatous ectopic thyroid disease was defined as hy-
perfunctional thyroid tissue that was not in its normal mid-
ventral cervical location. The presence of ectopic thyroid
tissue on the ventral midline from the base of the tongue
to the heart, along the tract where the thyroglossal duct
descended, can be explained by incomplete descent or by
excessive migration of thyroid tissue.16,17 Ectopic thyroid
tissue is most commonly found in the lingual and cranial
thoracic locations.18,19
Suspected thyroid carcinoma was defined as a massive
volume of hyperfunctional thyroid tissue, with multiple, ex-
tensive areas of increased radionuclide uptake, extension of
tumor through the thoracic inlet into the thorax, and/or
metastasis to regional lymph nodes or lung.4,5,20,21 The pat-
tern of thyroid radionuclide uptake in thyroid carcinoma is
commonly heterogeneous, with irregular, spiculated tumor
margins, suggesting extension beyond the thyroid capsule
and possible soft tissue invasion by the tumor tissue.
Evaluation of the Distribution of 99m
TcO− 4 Uptake into
Thyroid Lobes
In each hyperthyroid cat’s thyroid image, the distribution
of 99m TcO− 4 uptake into the thyroid mass was characterized
2015
as being either homogeneous or heterogeneous in appear-
ance. Since both window width (WW) and window level
(WL) can affect the intensity and contrast of the image,22
all of the ventral thyroid images were consistently rescaled
in the DICOM image-processing software12 to “full dy-
namic range,” that is, widening the WW to its maximum
setting (0–100% full range of pixel values), with the WL at
50% of WW. All of these evaluations were made by a single
observer (M.E.P.) to reduce interoperator variability and
ensure reproducibility across a large number of cases.
Determination of the Number and Location of Areas of
Increased 99m TcO− 4 Uptake
In each hyperthyroid cat’s thyroid image, the number and
location of each area of increased 99m TcO− 4 uptake were
recorded. For cases of unilateral, bilateral symmetric, or
unifocal ectopic disease, increased radionuclide uptake was
defined as a T/S ratio of >1.5. For cases of bilateral asym-
metric or multifocal disease, any additional areas of simul-
taneous radionuclide uptake was also considered to be ab-
normal, even if these nodules had a T/S uptake <1.5; such
radionuclide uptake was considered inappropriate since it
indicates a lack of normal feedback suppression in the face
of hyperfunctional tissue causing thyrotoxicosis. Hence, in
a cat with a bilateral asymmetric or multifocal disease and
one or more nodules with a T/S uptake ratio of >1.5, ad-
ditional foci of 99m TcO− 4 uptake with a T/S uptake ratio
of <1.5 were still considered to have an abnormal radionu-
clide uptake.
To facilitate defining the location of each nodule, a
straight line was drawn between the points of the shoul-
ders, as previously described.6 Areas of 99m TcO− 4 uptake
above this line were classified as the cervical (neck) loca-
tion, areas, or nodules touching this line were classified as
the thoracic inlet location, and areas below this line clas-
sified as an intrathoracic (mediastinal) location. When a
large area of increased 99m TcO− 4 uptake was present ex-
tending from the cervical area to within the thorax, this
was classified as involvement of the cervical, thoracic inlet,
and intrathoracic locations.
Data and Statistical Analysis
The reference ranges for T/S and T/B ratios were es-
tablished by use of the nonparametric method of percentile
estimates with confidence intervals to determine the central
95th percentile interval (i.e., 2.5 through 97.5th percentile
range) for results from the 70 clinically normal cats.23 When
determined by this method, the reference range for the T/S
ratio ranged from 0.48 to 1.50, and the reference range for
the T/B ratio ranged from 1.6 to 6.4.
VOL. 56, NO. 1 THYROID SCINTIGRAPHY IN HYPERTHYROID CATS 87

Sensitivity of both the T/S and T/B ratios as diagnos-

tic tests for hyperthyroidism were calculated, as previously
reported.24
All statistical tests were selected and performed by the
first author (M.E.P.). Statistical analyses were performed by
nonparametric statistics25,26 using GraphPad Prism (Ver-
sion 6, La Jolla, CA). Results are given as the median and
25th to 75th percentile ranges and are represented graphi-
cally as box plots.27 The binomial and sign test was used to
compare observed and expected proportions.28 Differences
in summary data between the hyperthyroid and clinically
normal cats were analyzed using the Mann–Whitney test.
Correlations between T/S ratio, T/B ratio, and serum total
T4 concentration were tested using Spearman’s coefficient.
The Chi-square test was used to determine whether differ-
ences existed in the proportion of the cats with different
patterns of thyroid disease and the distribution of radionu-
clide uptake. For all statistical analyses, values of P < 0.05
were considered significant.

Results
Cats
Thyroid scintigraphy was performed in 2096 hyperthy-
roid cats in this study. These cats ranged in age from 2 to
23 years (median, 13.0 years; 25th and 75th percentile, 11
and 15 years, respectively). Only 108 (5.1%) of the cats were
less than 9 years of age. Of the 2096 cats, 1883 (89.8%) were
of mixed breeding (domestic short-haired, median-haired,
and long-haired); other breeds included Siamese (75 cats;
3.5%); Maine Coon (36 cats; 1.7%); Russian Blue (19 cats;
0.9%); Himalayan (12 cats); Ragdoll (10 cats); Burmese
(nine cats); Tonkinese (eight cats); Manx (seven cats);
Norwegian Forest Cat (seven cats); Abyssinian (six cats);
Bengal (six cats); Persian (six cats); Egyptian Mau (three
cats); American short-hair (two cats); Bombay (two cats);
and American Curl, Japanese Bobtail, Rex, Showshoe,
Turkish Angora (one cat each). For sex distribution, 1138 FIG. 1. (A) Box plots of thyroid-to-salivary ratios (T/S) in 70 clinically
normal cats, 2096 cats with untreated hyperthyroidism. (B) Box plots of
(54%) of the cats were female and 958 were (46%) male (P thyroid-to-background ratios (T/B) in 70 clinically normal cats, 2096 cats
< 0.001); all were castrated or spayed. with untreated hyperthyroidism.
In the 2096 cats, the median time from diagnosis to time In each graph, the box represents the interquartile range (i.e., 25–75th
percentile range or the middle half of the data). The horizontal bar in the
of thyroid scintigraphy and 131 I treatment was 1.2 months; box represents the median value. For each box plot, the T-bars represent the
1773 (84.6%) cats had been diagnosed within a year of 1–99 percentile range. Outlying data points are represented by open circles.
admission. Of the cats, 996 (47.5%) had been treated with
methimazole, but the drug was discontinued at least 1 week
haired). Thirty-eight of the cats were female and 32 were
prior to thyroid scintigraphy and 131 I treatment in all of
male; all were castrated or spayed.
these cats. Only 4 (0.2%) of the 2096 cats were referred for
131
I treatment because of recurrent hyperthyroidism 12–30
Calculation of the Thyroid-to-Salivary Gland and Thyroid-
months following thyroidectomy; none of the 2092 other
to-Background Ratios
cats had been treated with surgery.
Thyroid scintigraphy was also performed in 70 clinically In the 2096 hyperthyroid cats, the median value for the
normal (control) cats. These cats ranged in age from 7 to T/S ratio (6.2) was significantly higher (P < 0.0001) than
16 years (median, 10 years). All of these cats were of mixed the median T/S ratio (0.9) in the 70 clinically normal cats
breeding (domestic short-haired, median-haired, and long- (Fig. 1A). Similarly, the median value for the T/B ratio
88 PETERSON AND BROOME
(25.1) in the hyperthyroid cats was significantly higher
(P < 0.0001) than the median T/B ratio (3.0) in the clini-
cally normal cats (Fig. 1B). In the hyperthyroid cats, there
was a significant correlation (P < 0.0001) between the pre-
treatment serum T4 concentration and both the T/S (R =
0.60) and T/B (R = 0.54) ratios.
Of the 2096 cats with hyperthyroidism, only 28 (1.3%)
had a calculated T/S ratio (1.5) within reference range
limits; of these, seven cats had a T/S ratio <1.2, and only
four had a T/S ratio <1.0 (0.87–0.93). Using a value of 1.5
as the upper limit of the reference range, the sensitivity of
the T/S as a diagnostic test for hyperthyroidism in these
cats was 0.987. Of the 2096 cats, 119 (5.7%) were found to
have only slightly high T/S ratios (>1.5–2.0), whereas the
remaining 1977 cats had T/S ratios that were >2.0.
For the T/B ratio, 82 (3.9%) of the 2096 cats had ref-
erence range values (6.4). The calculated sensitivity of
the T/B as a diagnostic test for hyperthyroidism was 0.961.
Both T/S and T/B ratios were within reference range limits
in only 14 cats (0.67%); thus, the calculated sensitivity of
a high T/S or T/B ratio as a diagnostic test for hyperthy-
roidism was 0.993.
Of the 2096 cats with hyperthyroidism, 191 (9.1%) cats
had serum T4 concentrations within reference range limits
(0.8–4.0 µg/dl), ranging from 2.5 to 4.0 µg/dl (median,
3.4 µg/dl; 25th and 75th percentile, 3.1 and 3.7 µg/dl, re-
spectively); these cats were diagnosed on the basis of their
clinical features, physical examination findings (e.g., pal-
pable thyroid nodule), and the finding of high serum-free
T4 concentrations. As a diagnostic test for hyperthyroidism,
the sensitivity of both T/S and T/B ratios were significantly
higher (P < 0.0001) than the basal T4 concentrations in our
cats.
Of the 191 hyperthyroid cats that had reference range
serum T4 concentrations, 15 (7.8%) had a calculated T/S
ratio within reference range limits (1.5) and 38 (19.9%)
had only slightly high T/S ratios (1.5–2.0). Only three of
these cats had T/S ratios of <1.2, and only one had a
T/S ratio of <1.0. Of the 191 cats, 36 (18.9%) had normal
T/B ratios (6.4). Both T/S and T/B ratios were within
reference range limits in only 9 (4.7%) of these 191 cats.
Scintigraphic Classification of Hyperthyroid Disease
When the scintigraphic findings in the 2096 hyperthyroid
cats were subclassified into four major patterns of thyroid
disease, 665 (31.7%) of the cats had unilateral disease, 1060
(50.6%) cats had bilateral-asymmetric disease (two thyroid
lobes unequal in size), 257 (12.3%) had bilateral-symmetric
disease (both lobes similar in size), and 81 (3.9%) had mul-
tifocal disease ( 3 areas of increased 99m TcO− 4 uptake)
(Fig. 2). All of the cats with multifocal disease were con-
sidered to either have ectopic thyroid nodules (n = 51) or
thyroid carcinoma (n = 30).
2015
The remaining 33 (1.6%) cats had one or two areas of in-
creased radionuclide uptake that did not fit into any of our
four major patterns for classification. These cats did not fit
our classification for multifocal disease (defined as >2 well-
defined areas of radionuclide uptake) because they only had
one or two thyroid nodules. In addition, these 33 cats could
not be categorized as having unilateral or bilateral disease
because they either had a single ectopic nodule in the me-
diastinum (10 cats), had unilateral cervical disease with an
additional ectopic nodule in the mediastinum (17 cats) or
tongue (one cat), or had suspected thyroid carcinoma with
only one or two nodules (five cats).
All 81 of the cats with multifocal disease, as well as the
33 cats that could not be categorized into one of the four
patterns of thyroid disease, had areas of radionuclide up-
take that were outside of the confines of the normal cervical
location of the thyroid gland (i.e., tongue or mediastinum).
Of the 665 cats with unilateral disease, 372 (55.9%) had
a left-sided thyroid nodule, whereas 293 cats (44.1%) had
a right-sided thyroid uptake. This difference in prevalence
between right- and left-sided thyroid masses was significant
(P = 0.0025).
Of the 996 cats that had been treated with methimazole,
310 (31.1%) had unilateral disease, 622 (62.4%) had bilat-
eral disease, and 39 (3.9%) had multifocal disease. This was
similar to the prevalence in the cats not treated with me-
thimazole, in which 355 (32.5%) had unilateral disease, 695
(63.2%) had bilateral disease, and 42 (3.8%) had multifocal
disease. There was no significant difference in the propor-
tion of unilateral, bilateral, or multifocal disease between
these two groups of cats.
The distribution of 99m TcO− 4 uptake into the thyroid
lobe(s) differed among the five groups of cats (Table 1;
Fig. 2). Most cats with unilateral disease showed a homo-
geneous distribution of radionuclide uptake into the thy-
roid mass. In contrast, cats with bilateral-symmetric disease
showed a more equivalent incidence of homogeneous versus
heterogeneous distribution of radionuclide uptake into the
two lobes, whereas most cats with bilateral-asymmetric and
multifocal disease had a heterogeneous distribution of the
radionuclide into their thyroid masses (Fig. 2). The differ-
ence in prevalence of homogeneous versus heterogeneous
distribution of radionuclide uptake among the cats with
unilateral, bilateral-asymmetric, bilateral-symmetric, and
multifocal disease was statistically significant (P < 0.0001).
Determination of the Number and Location of Areas of
Increased 99m TcO− 4 Uptake
The number of areas of increased 99m TcO− 4 uptake in
the 2096 cats ranged from 1 to 6 (median 2), with 81 (3.9%)
cats having 3 (Table 2; Fig. 3). These areas or nodules
of increased 99m TcO− 4 uptake were located in the cervical
region in 2057 (98.1%), thoracic inlet in 282 (13.5%), and in
VOL. 56, NO. 1 THYROID SCINTIGRAPHY IN HYPERTHYROID CATS 89

FIG. 2. Thyroid scintigrams illustrating the four major patterns of thyroid disease in the 2096 hyperthyroid cats. (A) Unilateral disease in 665 (31.7%) cats.
(B) Bilateral-asymmetric disease in 1060 (50.6%) cats. (C) Bilateral-symmetric disease in 257 (12.3%) cats. (D) Multifocal disease in 81 (3.9%) cats.

TABLE 1. Distribution of Radionuclide Uptake by the Thyroid Tumor(s) TABLE 2. Number and Locations of Areas of Increased 99m TcO− 4
in the 2096 Hyperthyroid Cats, Subdivided Into the Four Major Patterns Uptake in the 2096 Hyperthyroid Cats
Thyroid Disease
Number of areas of increased 99m TcO− 4 uptake 1 2 3 4 5 6
Homogeneous Heterogeneous
Classification of No. of distribution of distribution of Total number of cats 679 1334 57 14 8 2
thyroid disease cats radionuclide uptake radionuclide uptake Cats with area(s) of uptake in neck 655 1321 56 13 8 2
Cats with area(s) of uptake in thoracic inlet 60 179 19 12 7 2
Unilateral 665 606 (91%) 59 (8.9%) Cats with area(s) of uptake in thorax 15 41 37 12 8 2
Bilateral-symmetric 257 107 (41.6%) 150 (58.4%)
Bilateral-asymmetric 1,060 107 (10.1%) 953 (89.9%)
Multifocal 81 2 (2.5%) 79 (97.5%)
Unclassified 33 12 (36.4%) 21 (63.56%) Of the four cats that had been previously treated with
unilateral thyroidectomy, all were found to have a single
thyroid nodule in the cervical area; none of these cats had
the thoracic cavity in 115 (5.5%); 59 cats (2.8%) had uptake areas of 99m TcO− 4 uptake in either the thoracic inlet or in
in all three locations (cervical, thoracic inlet, thorax). All of the thoracic cavity.
the cats with multifocal disease (3 areas of 99m TcO− 4 up- Twenty-eight (1.2%) of the 2096 cats had no 99m TcO− 4
take) were considered to have either ectopic thyroid disease uptake in the “expected” cervical location. Of these 28 cats,
(54 cats) or thyroid carcinoma (30 cats). 12 had a single area of increased 99m TcO− 4 uptake only in
90 PETERSON AND BROOME 2015

FIG. 3. Thyroid scintigrams illustrating the 1–6 areas of 99m TcO− 4 uptake in the 2096 cats. (A) One nodule (unilateral disease). (B) Two nodules (bilateral
cervical disease). (C) Three nodules (bilateral disease with third ectopic midline nodule in thorax). (D–F) Four–six nodules (cats with multifocal disease
resulting from suspected thyroid carcinoma).

the thoracic inlet, eight had a single area of uptake only in

the chest, and eight cats had one to four areas of increased
radionuclide uptake located in both thoracic inlet and chest
regions. Seven of the eight cats with a solitary area of in-
creased 99m TcO− 4 uptake located only in the thorax were
considered to be ectopic tumors; similarly, five of the eight
with areas of uptake located in both the thoracic inlet and
chest were considered as ectopic tumors.
Thirty-one of the 35 cats with suspected thyroid carci-
noma also had areas of increased 99m TcO− 4 uptake within
the thoracic cavity, but these carcinomas generally extended
from the cervical area though the thoracic inlet and into
the chest. All cats with suspected carcinoma had areas
of increased 99m TcO− 4 uptake in the “expected” cervical
location.

Ectopic Thyroid Disease

Of the 2096 cats, 79 (3.8%) had ectopic disease. These
79 cats had one to four areas of increased 99m TcO− 4 uptake
(median, three areas). Of these cats, 64 (81%) of the ectopic
masses were in the mediastinal location (Fig. 3C and 4), 8
FIG. 4. Thyroid scintigram of a hyperthyroid cat ectopic disease resulting
from a single midline nodule in the intrathoracic (mediastinal) location.
Notice that neither of the thyroid lobes in the normal cervical location is
visible on this scintiscan.
VOL. 56, NO. 1 THYROID SCINTIGRAPHY IN HYPERTHYROID CATS
FIG. 5. Thyroid scintigram of a hyperthyroid cat with multifocal disease (i.e., bilateral cervical disease with a third ectopic sublingual nodule). Notice that
the ectopic tissue is on the ventral midline in the sublingual location.
(10.1%) were in the sublingual location (Fig. 5), and one cat
had ectopic masses in both mediastinal and sublingual lo-
cations. The remaining six cats had three areas of 99m TcO− 4
uptake in the cervical region; these cats were considered to
have bilateral disease, with an ectopic cervical nodule. Of
the 79 cats, the ectopic nodules were small to moderate in
size in 60 cats (75.9%) and large in size in only 19.
Suspected Thyroid Carcinoma
Thyroid carcinoma was suspected in 35 (1.7%) cats
(Fig. 3 D–F and 6). These 35 cats had 2–6 areas of in-
creased 99m TcO− 4 uptake (median, four areas) that spread
beyond the margins of the thyroid nodule(s). These tumors
were very large, with extension of the tumor from the cervi-
cal region through the thoracic inlet (four cats) or into the
thorax (31 cats). Evidence for metastasis to the retropha-
ryngeal lymph nodes was found in two of these 35 cats.
Discussion
The results of this study indicate that most hyperthyroid
cats will have unilateral or bilateral disease, with only a few
cats having multifocal disease ( 3 areas of radionuclide
uptake). Almost all cats have thyroid disease in the normal
cervical location, but many of the larger masses can fall
ventrally into the thoracic inlet. Such intrathoracic thyroid
masses can generally be distinguished from ectopic medi-
astinal masses on the basis of their left- or right-lateral loca-
tion; in contrast, ectopic thyroid tissue is characteristically
found medially on the ventral midline, along the tract where
the thyroglossal duct descended.17,18 A subset of hyperthy-
roid cats will have extracervical thyroid disease within the
thoracic cavity, but this is relatively rare, accounting for
only about 5% of our cases.
When we divided the scintigraphic findings in our 2096
hyperthyroid cats into the four major patterns of thyroid
91
disease, almost a third of the cats had unilateral disease, half
of the cats had bilateral-asymmetric disease, about 10% had
bilateral-symmetric disease, and less than 5% had multifo-
cal disease. This breakdown of the different scintigraphic
patterns of 99m TcO− 4 uptake in our cats agrees quite closely
to what has previously been reported in another series of
165 hyperthyroid cats.29 Only a few of our cats (1.6%) had
one or two areas of increased 99m TcO− 4 uptake that did
not fit into any of our four major scintigraphic patterns for
classification; of those, almost all had an ectopic thyroid
nodule in the lingual or mediastinal region (Fig. 4 and 5),
but a few cats had suspected thyroid carcinoma.
In a recent series of 120 hyperthyroid cats,6 nearly one
of five hyperthyroid cats were found to have multifocal dis-
ease, with multiple areas of increased radionuclide uptake
visible on thyroid imaging; over 90% of these cats had hy-
perfunctional thyroid tissue within the thorax that could
not be palpated. Those results obviously differ greatly with
the findings reported in the present study. One explanation
for this difference in prevalence of intrathoracic disease is
that almost one in four of the cats in the previous study6
had been initially treated with surgical thyroidectomy, and
many of those cats had been referred for persistent or recur-
rent hyperthyroidism. In contrast, thyroidectomy does not
appear to be a commonly used treatment modality by our
referring veterinarians, since only 0.2% of our 2096 cats had
ever been treated with surgery. Therefore, we believe that
the much lower prevalence of intrathoracic thyroid masses
reported in this present study better represents what can be
expected in general practice, especially in cats that have not
undergone a failed thyroidectomy procedure.
The finding of a high thyroid-to-salivary ratio (T/S) on
99m
TcO− 4 imaging, calculated by dividing the thyroid count
density from the hottest thyroid nodule by the ipsilateral
salivary count density, has long been accepted as an accu-
rate diagnostic test for feline hyperthyroidism.3–5,11,13,14,30
Some have stated that T/S ratio is more accurate than a
total T4 concentration,4 but this has not been evaluated
92
FIG. 6. Thyroid scintigram of six hyperthyroid cats with multifocal disease resulting from suspected thyroid carcinoma. Notice that all of these cats had
large multifocal disease, with extension of tumor from the cervical region through the thoracic inlet or into the thorax.
in a large population of hyperthyroid cats, especially in
cats with “occult” hyperthyroidism in which the serum T4
value may remain within the upper third to half of the ref-
erence range.8–10,31,32 Free T4 determinations, although a
more sensitive diagnostic test than total T4 alone, will pro-
vide false-positive results in many cats, especially in those
with nonthyroidal illness;9–11 therefore, caution is recom-
mended in diagnosing hyperthyroidism in cats on the basis
of a high concentration of free T4 alone, since many of
those cats will not be hyperthyroid. In this study, use of
the T/S ratio as a diagnostic test for hyperthyroidism was
found to have a much higher test sensitivity (98.7%) than
that of the total T4 concentration (90.9%); therefore, calcu-
lation of the T/S ratio is extremely useful in confirming the
diagnosis in cats with occult or mild hyperthyroid disease.
The proportion of hyperthyroid cats with a reference range
serum T4 concentration in this study (9.1%) was similar to
the proportion (8.7%) similarly reported in a series of 917
cats with hyperthyroidism.8
While the T/S ratio remains a useful diagnostic test,
our results suggest that calculation of the thyroid-to-
background (T/B) ratio may also be used as an accurate
diagnostic test in cats with hyperthyroidism. In this study,
PETERSON AND BROOME 2015
the test sensitivity of the T/B ratio sensitivity (96.1%) was
a bit lower than the results for the T/S ratio, but it was still
significantly higher than the sensitivity of the total T4 con-
centration. Because the salivary uptake of 99m TcO− 4 can
be altered by salivary gland disease, as well as the amount
of saliva being produced or swallowed, the main advantage
of the T/B ratio over the T/S ratio is that it eliminates
the measured salivary gland activity from calculation.5,15
In addition, in a few cats with very high thyroid activity,
the salivary glands may be difficult to trace.3 Overall, be-
cause the T/B ratio is not influenced by salivary disease,
it can also be helpful in the diagnosis and evaluation of
hyperthyroid disease in cats.
For our T/B ratio calculations, we chose the axillary
region for our background region of interest, as previously
described.13,15 However, the most suitable location for this
background region of interest remains to be determined,
and selecting a different area of placement could certainly
improve the accuracy of the T/B ratio. In one recent study,
placement of the background region of interest over the
heart was found to correlate best with plasma radioactivity
concentrations,33 suggesting that this heart location may
be better than the axillary region. Additional studies to
VOL. 56, NO. 1 THYROID SCINTIGRAPHY IN HYPERTHYROID CATS
investigate the use of other background placement sites for
calculation of the T/B ratio is needed to clarify the ideal
location for this background region of interest.
In this study, about half of the cats had been treated for
variable periods with methimazole, a drug shown to poten-
tially increase the T/S ratio, at least in clinically normal
cats made hypothyroid.34 In the study by Nieckarz et al.,34
this drug induced an increase in the thyroid radionuclide
uptake that persisted after discontinuing the methimazole,
leading the authors to suggest that prior administration of
the drug could affect interpretation of thyroid scintigraphy
for up to 3 weeks. Although circulating concentrations of
thyroid stimulating hormone (TSH) were not measured in
these clinically normal cats before and after induction of
hypothyroidism, it is likely that serum TSH concentrations
increased to high levels after the serum T4 fell to subnormal
levels on methimazole treatment.35 Since high circulating
TSH levels will stimulate radionuclide uptake in cats,36 the
high endogenous TSH concentration is the most likely ex-
planation for why normal cats made hypothyroid will show
increases in thyroid uptake (and T/S ratio). In this study
by Nieckarz et al.,34 the scintigraphic pattern of increased
uptake that was induced by methimazole was bilateral and
symmetric in appearance, as would be expected following
an increase in circulating TSH levels.
One potential weakness of the present study is that the
cats that had been given methimazole had not been off
the drug for more than 3 weeks at the time of scintigra-
phy; therefore, it is possible that this drug may have led to
mild increases in the values for the T/S (and T/B ratios)
in our methimazole-treated cats. However, Fischetti et al.37
reported that methimazole treatment did not increase the
T/S ratio in cats with hyperthyroidism, suggesting that the
effects of prior methimazole treatment on thyroid uptake
may be negligible in hyperthyroid cats. Therefore, we be-
lieve that it is unlikely that methimazole produced falsely
high values for the T/S or T/B ratios in our hyperthyroid
cats, especially since the drug was stopped at least 1 week
prior to thyroid imaging, and all of these cats had clearly
high serum T4 values at the time of thyroid scintigraphy.
Although serum TSH concentrations were not measured
in this study, we have since shown that virtually all hyper-
thyroid cats will have suppressed TSH values, unlike the
situation in the clinically normal cats made hypothyroid
with methimazole34 in which high serum TSH values are
expected.35 Therefore, because of their suppressed circulat-
ing TSH levels, an increased thyroid uptake would not be
expected in these hyperthyroid cats. Finally, of the cats with
reference range serum T4 values (the “occult” hyperthyroid
group whose T/S and T/B ratios would most likely be af-
fected by methimazole), none of those cats had been treated
with the drug.
In this study, we recruited 70 client-owned, clinically nor-
mal cats that were of similar age and signalment to our
93
2096 hyperthyroid cats to established the reference range
limits for both T/S and T/B ratios. We did not use any
chemical restraint in any of our normal or hyperthyroid
cats, inasmuch as drugs used commonly for sedation or
anesthesia may interfere with thyroid or salivary gland
99m
TcO− 4 uptake and could lead to a false diagnosis of
hyperthyroidism.38 The upper limit of our reference range
for T/S ratio was slightly higher than that reported by many
previous studies in which smaller numbers of younger labo-
ratory cats were studied;3,13,30 however, our reference range
limits are almost identical to that reported in a group of 32
older euthyroid cats (aged 8–13 years).14
In cats, as in all higher vertebrates, the thyroid develops
from the anterior foregut (pharyngeal) endoderm, which
proliferates and migrates ventrally along the midline and
then expands laterally, forming the characteristic bilobed
structure of the normal thyroid gland.39–42 Therefore, thy-
roid gland development during embryogenesis involves its
migration from the region at the base of the tongue to its
normal pretracheal position in the neck. This process can
be arrested at any point along the line of medial descent,
resulting in ectopic thyroid tissue.16,17,41 Failure of the thy-
roid primordium (or a portion of it) to fully descend leads
to the development of lingual or sublingual ectopic thy-
roid tissue. Migration of the thyroid appears dependent on
its association with the developing aortic sac.43 Because of
this, failure of the thyroid primordium (or a portion of it)
to fully disassociate with the embryologic aortic sac leads
to the additional descent of the thyroid beyond its normal
cranial cervical location, resulting in ectopic cranial medi-
astinal or heart-base thyroid tissue.16,17,41
Ectopic thyroid tissue is subject to the same pathological
processes (i.e., inflammation, hyperplasia, and tumorigen-
esis) that can develop in eutopic thyroid tissue, and neo-
plasia of ectopic thyroid tissue has been well documented
in both humans and dogs.16,17,44–46 In cats, ectopic thyroid
tissue in both euthyroid and hyperthyroid cats has also been
reported,6,18,19,47,48 but there are no large case series to de-
termine the prevalence of neoplastic ectopic thyroid tissue
in cats.
In this series of 2096 hyperthyroid cats, ectopic thyroid
neoplasia was diagnosed in 79 cats, with an overall preva-
lence of about 4%. In most of these cats, the ectopic nod-
ules were small to moderate in size, compared to the very
large-sized masses seen in the cats with suspected thyroid
carcinoma. Of these cats with ectopic disease, the intratho-
racic (mediastinal) location was most common (over 80%),
followed by the lingual/sublingual location (10%), with
the remainder having lateral ectopic thyroid tissue in the
cervical location (7.6%). In man, as well as cats, the vast
majority of thyroid ectopias are located on the ventral mid-
line, along the tract of the descending thyroglossal duct.16,17
Rarely, however, the lack of merging of lateral thyroid cell
clusters with the main median thyroid primordial tissue can
94 PETERSON AND BROOME
lead to lateral ectopic thyroid tissue located in the cervical
location.16,17,49–52 In humans, it can sometimes be difficult
to distinguish primary neoplastic involvement of ectopic
thyroid cancer from latero-cervical lymph node metastasis,
but none of our cats with such cervical ectopic nodules were
considered to have thyroid carcinoma and all responded
completely to low doses of radioiodine.
In this series of cats, “suspected” thyroid carcinoma was
diagnosed in 35 (1.7%) cats. This prevalence of malignant
disease is similar to what has previously been reported in
other studies (i.e., 1–3.5%).20,53,54 Since none of our hy-
perthyroid cats had a thyroid biopsy for histopathological
evaluation, we cannot say with certainty that these 35 cats
did indeed have thyroid carcinoma. In addition, it is possi-
ble that a few of our other hyperthyroid cats, especially
those with bilateral or multifocal disease, were misclas-
sified and actually had thyroid carcinoma. However, our
35 cats with suspected thyroid carcinoma displayed many of
the scintigraphic features characteristic for malignant dis-
ease, including multifocal disease, heterogeneous areas of
99m
TcO− 4 uptake, and irregular, spiculated tumor margins
(suggesting extension beyond the thyroid capsule and/or
soft tissue invasion by the tumor tissue). In addition, the
tumors were large in these 35 cats, with extension of tumor
from the cervical region through the thoracic inlet (four
cats) or into the thorax (31 cats). Evidence for metastasis
to regional lymph nodes was also found in two of these
35 cats. In addition to these scintigraphy findings, the cats
also displayed clinical features that are commonly found in
cats with thyroid carcinoma, including a large palpable goi-
ter, a long history of hyperthyroidism (initially controlled
with antithyroid drugs but now unresponsive to medical
treatment), and extremely high serum T4 concentrations
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