CT AND MRI EVALUATION OF SKULL BONES AND SOFT TISSUES IN SIX

CATS WITH PRESUMED ACROMEGALY VERSUS 12 UNAFFECTED CATS

ANTHONY J. FISCHETTI, KELLY GISSELMAN, MARK E. PETERSON

Feline acromegaly is predominantly caused by an adenoma of the pituitary gland, resulting in excessive growth
hormone and insulin-like growth factor (IGF-1) secretion. In advanced cases, cats will display prominent facial
features and upper airway congestion secondary to bony and soft tissue proliferation. The purpose of this
study was to describe CT and MRI characteristics of soft tissues and skull bones in six cats with presumed
acromegaly and to compare findings with those observed in 12 unaffected cats. In the five acromegalic cats with
CT or MRI evidence of a pituitary tumor, frontal bone thickness was greater than age-matched controls with
and without a history of upper airway disease. These five cats also had evidence of soft tissue accumulation in
the nasal cavity, sinuses, and pharynx. One cat with insulin-resistant diabetes mellitus, elevated IGF-1, and
a normal pituitary size did not have evidence of frontal bone thickening or upper airway congestion.  C 2012

Veterinary Radiology & Ultrasound.

Key words: CT, growth hormone, hyperostosis, insulin-like growth factor, MR, sinonasal disease.

Introduction pertrophy, tongue enlargement, and collapse of the lateral

walls of the larynx. This soft tissue thickening is the most

F ELINE ACROMEGALY IS CAUSED by chronic excess of

growth hormone (GH) and insulin-like growth factor-
1 (IGF-1), most commonly due to a functional adenoma
of the pituitary gland.1–3 Oversecretion of GH (hypersoma-
totropism) and IGF-1 leads to the syndrome of acromegaly,
which in cats includes insulin-resistant diabetes mellitus,
bony remodeling, and excessive soft tissue growth.3–5 In
advanced cases, these cats may exhibit prominent facial
features, generalized bone/soft tissue enlargement, and
prognathia.4 Respiratory stridor is also reported in up to
53% of acromegalic cats and may be due to the enlargement
of the tongue and oropharyngeal tissues.3, 6, 7 The insulin-
resistant diabetes is caused by GH-induced expression of
proteins that inhibit insulin receptor signaling by target
tissue.6 The bone and soft tissue augmentation is due to
GH/IGF-1-induced anabolic effects on bone, expansion
of total body water, and upregulation of adipogenesis.5
In people, chronic excess in GH and IGF-1 results in
maxillofacial deformities, including nasal bone hypertro-
phy, mandibular overgrowth, maxillary widening, frontal
bossing, and temporomandibular remodeling.8, 9 Soft tissue
abnormalities of the head include sinonasal mucosal hy-
From the Department of Diagnostic Imaging, Animal Medical
Center, New York, NY 10065
Dr. Gisselman’s current address is The Hope Center for Advanced
Veterinary Medicine, 140 Park Street SE Vienna, VA 22180. Dr. Pe-
terson’s current address is the Animal Endocrine Clinic, 21 west 100th
Street, New York, NY 10025.
Address correspondence and reprint requests to Anthony Fischetti
at the above address. E-mail: anthony.fischetti@amcny.org.
Received March 14, 2012; accepted for publication May 3, 2012.
doi: 10.1111/j.1740-8261.2012.01957.x
life-threatening because of chronic upper airway obstruc-
tion and associated complications, including cardiovascu-
lar disease and endotracheal intubation difficulties.8, 10 The
soft tissue changes tend to respond to treatment. However,
the bony remodeling tends to persist, even in well-regulated
human acromegalics, and has surgical implications in the
transsphenidal approach to hypophysectomy.8, 9, 11
Computed tomography (CT) or magnetic resonance
(MR) imaging of the head is recommended to confirm
the presence of a pituitary tumor in insulin-resistant di-
abetic cats with elevated IGF-1.2, 3, 11, 12 Characteristics of
pituitary enlargement in these cats have been previously
described. However, little descriptive information could be
found on the CT and MRI characteristics of soft tissues and
skull bones surrounding the brain in affected cats.1, 2, 11, 13
The purpose of our this retrospective study was to com-
pare CT and MRI characteristics of the soft tissues and
skull bones of the head in six insulin-resistant diabetic cats
with elevated serum IGF-1 (presumed acromegaly) versus
age-matched controls. We hypothesize that the frontal bone
thickness (FBT), parietal bone thickness (PBT), and upper
airway soft tissue accumulation of the acromegalic cats will
be significantly greater than the control population.
Materials and Methods
The Animal Medical Center’s clinical pathology
database was searched for feline IGF-1 submissions
Vet Radiol Ultrasound, Vol. 00, No. 0, 2012, pp 1–5.

1
2 FISCHETTI, GISSELMAN, AND PETERSON 2012

between 2006 and 2012, and for cats that also had CT∗
or MR† of the head. Cats were defined as acromegalic if
they had insulin-resistant diabetes mellitus (>6 U/dose)14
and elevated serum IGF-1 (normal = 5–70 nmol/l). Cats
that had skull CT scans performed for reasons other than
pituitary disease and had a history of chronic upper air-
way disease (stridor, congestion, or nasal discharge), cats
with suspected pituitary disease other than acromegaly, and
cats without history of pituitary or upper respiratory dis-
ease were included as controls. Controls were age matched
and chosen by randomized selection from our imaging and
medical record database, limiting our search by species, age,
modality, and diagnosis.
The following information was recorded from medical
records of acromegalic cats: age, sex, breed, history of nasal
discharge or stridor, physical exam evidence of facial defor-
mity and prognathia, duration of diabetes mellitus, and
IGF-1 value. FIG. 1. Example of frontal bone thickness measurements made from a
transverse CT image of a control cat without history of upper respiratory
Skull CT studies included the tip of the nose to mid-C2, disease (group B). Measurements were made at the level of the olfactory
with 3-mm-thick slices, standard and bone algorithm re- lobes, midway between the rostral and caudal-most extent of the frontal
constructions, and pre- versus postintravenous contrast.‡ sinus. The black line represents frontal bone thickening (FBT). The white
line represents the height from the dorsal margin of the frontal bone to the
Brain MR studies included transverse, pre- and postcon- ventral margin of the cranial vault (HFBCV).
trast§ T1-weighted images, and transverse and sagittal T2-
weighted images. Sagittal MR images included the nasal
cavity, but transverse images did not. All transverse CT
and MRI images were obtained perpendicular to the hard
palate.
From the bone algorithm transverse CT images win-
dowed for bone, measurements of FBT and PBT were made.
All measurements were made by a single author (A.J.F.)
blinded to group assignment. An average of three values
was obtained for each measurement. Frontal bone thick-
ness and height from the dorsal margin of the frontal bone
to the ventral margin of the cranial vault (HFBCV) were
measured at the level of the rostral olfactory bulbs (Fig.
1). Frontal bone thickness was made 0.2 cm from midline,
and HFBCV was made 0.4 cm from midline. Parietal bone
thickness and height from the dorsal margin of the parietal
bone to the ventral margin of the cranial vault (HPBCV) FIG. 2. Example of parietal bone thickness (PBT) measurements made
were measured at the level of the orbital fissure (Fig. 2). from a transverse CT image of a control cat without history of upper respira-
Parietal bone thickness was measured 0.2 cm from midline, tory disease (group B). Measurements were made at the rostral aspect of the
parietal bone, at the level of the oribital fissure entrance into the skull. The
and HPBCV was made 0.4 cm from midline. The maxi- black line represents PBT. The white line represents the height of the parietal
mum height of the pituitary gland was measured on the bone to the ventral margin of the cranial vault (HPBCV).
transverse postcontrast CT images (standard algorithm,
soft tissue window), acquired 30–40 s after bolus injection. Statistical Analyses
Subjective findings also recorded were soft tissue thicken-
ing in the nasal passages, frontal sinus, sphenoid sinus, and Cats were divided into three groups for statistical com-
oropharynx; and remodeling of the temporomandibular parisons. Categorical data were described in percentages.
joint and mandible. Statistical analyses were performed using commercially
available software.∗∗ Data are described as median ± in-
terquartile range (IQR). Normality of data was tested us-
∗ GE CTi single-detector CT, GE Healthcare, Milwaukee, WI.
† Philips
ing the Shapiro–Wilk test. One-way analysis of variance
Achieva, 1.5T MR, Andover, MA.
‡ Iohexol-240, Omnipaque, GE Healthcare, Wakesha, WI.
§ Magnevist, Bayer Healthcare Pharmaceuticals, Inc, Wayne, NJ. ∗∗ SigmaPlot
R
11 Systat Software, Inc, San Jose, CA 95110.
VOL. 00, NO. 0 BONE AND SOFT TISSUE PROLIFERATION IN FELINE ACROMEGALY
(ANOVA) was used to test for differences among the three
groups of cats (presumed acromegalics, controls without
upper respiratory disease, and controls with respiratory dis-
ease) for recorded variables. When data were not normally
distributed, differences among the three groups were tested
using the Kruskal–Wallis one-way ANOVA on ranks. When
a test showed significance, posthoc tests were performed us-
ing the Student-Newman-Keuls method. Proportions were
compared using Fisher exact test. For all tests, P < 0.05
was considered significant.
Results
Three cohorts consisting of six cats each were included in
the study: group A = cats with presumed acromegaly (n =
6); group B = cats without upper respiratory disease (n = 6);
and group C = cats with upper airway disease (n = 6). Five
cats included in group B had no CT evidence of a pituitary
tumor. One cat included in group B had a pituitary tumor
and hyperadrenocorticism. None of the cats in group C had
CT evidence of a pituitary tumor.
There was no significant difference in gender or age
among groups (P = 0.333, 0.350). Age similarities are
consistent with previous reports. However, a previously re-
ported male predilection to acromegaly was not observed
in our cats (50% male).1, 3, 7 For the acromegalic cats (group
A), two of six had physical exam findings that included
enlargement of the head and body. Three of six had physi-
cal exam findings of stridor and/or nasal discharge. These
findings are consistent with previous reports of the preva-
lence of upper airway disease in acromegalic cats.7 Five of
six had a greater than two-year history of diabetes mellitus.
All cats had a CT performed either as the primary diag-
nostic test or following MR for radiation treatment plan-
ning. Two cats also had MR because of presenting clinical
signs of obtundation and clinician preference.
Frontal bone thickness was significantly greater (me-
dian;IQR) in group A (2.95 mm; 2.8, 4 mm) than group
B (1.05 mm; 1.0, 1.2 mm) and group C (1.15 mm; 1.0,
1.2 mm) (P = 0.029). On pairwise comparison, group A
was significantly different (P < 0.05) than group B and C.
Frontal bone thickness for group B and C were not signifi-
cantly different (P > 0.05). Height from the dorsal margin
of the frontal bone to the ventral margin of the cranial
vault was significantly greater in group A (2.5 mm; 2.3,
2.6 mm) than group B (2.2 mm; 2.2, 2.2 mm) and group
C (2.3 mm; 2.2, 2.3 mm) (P = 0.013) (Fig. 3). On pairwise
comparison, group A was significantly different (P <0.5)
than group B and C. Height from the dorsal margin of the
frontal bone to the ventral margin of the cranial vault for
group B and C were not significantly different (P > 0.05).
Parietal bone thickness was significantly different among
the three groups (P = 0.023). On pairwise comparison,
3
FIG. 3. Acromegalic cat from group A (left) compared with a control cat
with chronic upper airway disease and no history suggestive of acromegaly
(group C) (right). Global frontal bone thickening and sclerosis is greater in
the acromegalic cat. The control cat has a focus of frontal bone thickening as
well as air-fluid interfaces consistent with chronic sinusitis. Focal thickenings
such as this were not included in measurements.
FIG. 4. Transverse CT image of an acromegalic cat from group A
(left) with clinical signs of chronic upper airway disease compared with a
nonacromegalic control from group C (right) at the level of the parietal bone.
Subjectively, the bones appear more sclerotic in acromegalic cats even though
thickening was not statistically significant for all quantitative measurements
of parietal bone thickening. Additionally, the cat on the left also has temporo-
mandibular joint remodeling and soft tissue thickening in the nasopharynx
and ventral mandible.
PBT was not significantly greater in group A (5.5 mm; 5.4,
7 mm) compared with group B (3.75 mm; 3.5, 5 mm) (P >
0.05), but did show significance when compared to group C
(2.95 mm; 2.5, 4.3 mm) (P < 0.05). Height from the dorsal
margin of the parietal bone to the ventral margin of the cra-
nial vault was not significantly different in the three groups
(P = 0.094) (Fig. 4).
The height of the pituitary was significantly greater (me-
dian;IQR) in group A (7.5 mm; 4.25, 9.25 mm) compared
with group B (2.0 mm; 1.0 mm, 4.0 mm) and group C
(1.5 mm; 1.0, 2.0 mm) (P = 0.005). One cat in group A did
not have evidence of pituitary enlargement.15 This cat was
also the only cat in group A without bony or soft tissue
proliferation. The other five cats all had varying degrees
of soft tissue proliferation in the nasal cavity, paranasal
sinuses, pharynx, or subcutaneous tissues (Fig. 5 and
Fig. 6). Serum IGF-1 at the time of imaging was not asso-
ciated with severity of bony or soft tissue thickening in any
cats in group A.
Discussion
Imaging findings were consistent with a pituitary tu-
mor and diffuse frontal bone thickening in five presumed
4 FISCHETTI, GISSELMAN, AND PETERSON
FIG. 5. Transverse CT image at the level of the frontal sinuses in a cat from
group A with progressive mandibular swelling. In addition to thickening and
sclerosis of the frontal bone, the mandibular rami appear sclerotic and there
is a increase in soft tissue thickening of the muscles and subcutaneous tissues
ventral and lateral to the mandible.
FIG. 6. CT (left) versus MR (right) comparison of the frontal bone in
an acromegalic cat. Mucosal soft tissue accumulation is present in both
frontal bones but the right-sided mucosal thickening is more obvious on
the MR. The bony sclerosis and thickening is perhaps more obvious on the
CT. Asymmetric fluid accumulation is also present in the nasopharynx and
sphenoidal sinuses.
acromegalic cats. Similar findings have been identified in
people with acromegaly.7, 9, 16 A brief radiographic descrip-
tion of hyperostosis of the bony calvarium has been previ-
ously described in acromegalic cats.1 Although prominent
facial features have been previously reported in physical ex-
ams of severely affected cats,4 only one of the acromegalic
cats in our study had physical exam findings consistent with
a thickened frontal bone (Fig. 3). This indicates that thick-
ening of the frontal bone may go unnoticed on physical
examination in some cats with acromegaly.
Although the parietal bone and other bones of the cau-
dal skull appeared sclerotic and subjectively thickened for
group A cats on CT (Fig. 4), quantitative values were not
statistically significant for all measurements. Likely rea-
2012
sons for this include low statistical power due to small
sample sizes and observer-induced variations in the mea-
surement. The presence of the dorsal sagittal crest made
measurement of the parietal bone particularly difficult rel-
ative to the frontal bone measurements. Bony proliferation
of the caudal aspect of the skull has been described as a
common characteristic in people with acromegaly, often
leading to hearing impairment and pain on opening the
mouth.8, 9, 16, 17 One of our cats had severe remodeling of
the temporomandibular joint, but no associated clinical
signs (Fig. 4).
Two quantitative measures of bony thickening were eval-
uated in our study, one measuring the thickness of the dor-
sal aspects of the bones (FBT and PBT) and another in-
cluding the outer margins to the bony limits of the skull
(HFBCV and HPBCV). The additional measurements of
including the outer margins of the skull were made to de-
termine if bony thickening occurred inwardly or outwardly.
Height from the dorsal margin of the frontal bone to the
ventral margin of the cranial vault was significantly greater
in acromegalic cats than the controls, consistent with an
outward bony thickening to the frontal bone. This is simi-
lar to the process in acromegalic people where hyperostosis
and frontal bossing occurs outwardly rather than inwardly
within the sinus cavity. Inward thickening occurs as an age-
related variant and is not associated with acromegaly in
people.9, 16
Soft tissue changes of the nose and paranasal sinuses
in acromegalic people were first described by surgeons
performing approaches for hypophysectomy. Surgeons ob-
served macroscopic proliferation of the mucosal lining
in the nasal cavity and paranasal sinuses.10 Since then,
the imaging features of soft tissue and bony prolifera-
tion have been extensively documented for people with
acromegaly.8, 9, 17, 18 In our series, all acromegalic cats with
imaging evidence of a pituitary tumor also had evidence of
soft tissue proliferation. However, some of these cats had no
clinical signs of upper airway disease. Thickening of the soft
palate in acromegalic cats has been briefly described.11, 12
Findings were illustrated on preoperative CT evaluation of
a surgically treated acromegalic cat. The influence this soft
tissue thickening had on surgery was not mentioned.11
Imaging findings of mandibular enlargement and prog-
nathism were mild in most of our cases. Assessing mandibu-
lar enlargement from transverse and sagittal CT or MR
images was difficult in that images provided incomplete in-
formation on the rostral-to-caudal position of the mandible
relative to the maxilla. More objective assessments of these
relationships and evaluation of subtle changes could be
made using plaster models. In experimental studies of
acromegalic-like rats, mandibular growth was greater in the
lateral direction than in the anterior–posterior direction.19
Two of our cats in group A had evidence of subcutaneous
soft tissue accumulation ventral and lateral to the mandible
VOL. 00, NO. 0 BONE AND SOFT TISSUE PROLIFERATION IN FELINE ACROMEGALY
(Figs. 4 and 5). One of these cats (Fig. 5) also had physical
exam evidence of mandibular enlargement (Fig. 5).
One cat in group A (insulin-resistant diabetes mellitus
and elevated serum IGF-1) did not have evidence of bony or
soft tissue proliferation. This cat also did not have imaging
evidence of a pituitary tumor. Acromegaly in cats without
imaging features of a pituitary mass has been previously
reported and determined to be secondary to pituitary hy-
perplasia on necropsy.2, 3 Additionally, elevations in serum
IGF-1 have been reported in well-regulated diabetic cats
without acromegaly.3, 7 These scenarios make the definitive
diagnosis of acromegaly challenging. Having other pheno-
typic changes can support the diagnosis.
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In conclusion, cats with suspected acromegaly that un-
dergo CT or MR imaging of the head for pituitary tumors
may also show evidence of frontal bone thickening and soft
tissue proliferation of the upper airway, paranasal sinuses,
and ventral mandible. These findings may be present in af-
fected cats with no clinical signs of facial enlargement or
upper respiratory disease and may provide further support
for a diagnosis of acromegaly.
ACKNOWLEDEMENTS
The authors would like to thank Dr. Philip R. Fox, DVM, MS,
DACVIM/ECVIM (Cardiology), DACVECC for his assistance with
statistical testing and analysis.
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