AJR:170, March 1998 621
Sonographic Detection of
Xanthomas in Normal-Sized
Achilles’ Tendons of Individuals
with Heterozygous Familial
Hypercholesterolemia
Ronald 0. Bude1
Shawna 0. Nesbitt2
Ronald S. Adler1
Melvyn Rubenfire2
OBJECTIVE.The objective ofthis study was to evaluate how well high-frequency linear array
sonography reveals xanthomas in the Achilles’ tendons of individuals with heterozygous familial
hypercholesterolemia before the xanthomas enlarge the tendons enough to become palpable.
SUBJECTS AND METHODS. Both Achilles’ tendons of 23 individuals (I8 female and
five male; age range, 16-69 years old) who had heterozygous familial hypercholesterolemia but
no clinically apparent Achilles’ tendon xanthomas were studied with high-frequency linear ar-
ray sonography. Hypoechoic areas, consistent with xanthomas, were noted.
RESULTS. Xanthomas were revealed in 36 (78%) of46 tendons and 19 (83%) of23 individuals.
CONCLUSION. Sonography reveals Achilles’ tendon xanthomas in many individuals with
heterozygous familial hypercholesterolemia before the xanthomas are clinically apparent. Because
tendon xanthomas in a hypercholesterolemic individual are essentially pathognomonic of hetero-
zygous familial hypercholesterolemia and are a mainstay in its diagnosis, our study suggests that
sonography is useful in the early diagnosis of heterozygous familial hypercholesterolemia.
Received July 3, 1997; accepted after revision
September 17, 1997.
Supported in part by a grant from the American Heart
Association.
1Department of Radiology, university of Michigan Medical
School, Taubman Center 2910K, 1500 E. Medical Center Dr.,
Ann Arbor, Ml 48109-0326. Address correspondence to
RD. Bude.
2Department of Internal Medicine, University of Michigan
Medical School, Ann Arbor, Ml 48109.
AJR 1998;170:621-625
0361-803X/98/1703-621
© American Roentgen Ray Society
D ifferentiating heterozygous famil-
ial hypercholesterolemia from the
other severe forms of hypercholes-
terolemia-familial combined hyperlipidemia
and polygenic hypercholesterolemia-has
both clinical and therapeutic implications. Not
only is the hypercholesterolemia of heterozy-
gous familial hypercholesterolemia harder to
treat than that of familial combined hyperlipi-
demia and polygenic hypercholesterolemia,
but also family members need to be screened
for this inherited disorder. Distinguishing het-
erozygous familial hypercholesterolemia from
familial combined hyperlipidemia and poly-
genic hypercholesterolemia is often not possi-
ble by standard clinical criteria.
Heterozygous familial hypercholesterolemia
is an autosomal dominant disorder with a
prevalence of approximately one in 500 [ I , 21.
Abnormal or absent low-density lipoprotein
receptors cause the accumulation of choles-
terol-rich low-density lipoprotein particles.
Total cholesterol levels range from 270 to
550 mg/dl (6.98-14.22 mmolll), with corre-
sponding elevations of low-density lipopro-
tein cholesterol [3]. Cholesterol levels in
heterozygous familial hypercholesterolemia
overlap considerably with those in polygenic
hypercholesterolemia and familial combined
hyperlipidemia, which together are approxi-
mately 20 times more common than heterozy-
gous familial hypercholesterolemia [41.
Heterozygous familial hypercholesterolemia
is characterized by an autosomal dominant in-
heritance pattern and the formation of exten-
sor tendon xanthomas, and the presence of
one of these characteristics in addition to hy-
percholesterolemia is usually needed to estab-
lish the diagnosis. In fact. the presence of
Achilles’ tendon xanthomas is essentially pa-
thognomonic of heterozygous familial hyper-
cholesterolemia [ I I. However. family histories
are often unreliable and cannot be used to
document the autosomal dominant inheritance
pattern. Furthermore. xanthomas are not pal-
pable in approximately 257c ofadults 131. Es-
tablishing the diagnosis of heterozygous
familial hypercholesterolemia is therefore cx-
tremely difficult in many affected individuals
whose tendons feel normal on palpation.
The ideal tool for detecting heterozygous
familial hypercholesterolemia in persons
without easily palpable tendon xanthomas
would be sensitive. highly specific (i.e., a
very low false-positive rate), reproducible,
widely available, and relatively inexpensive.
The only tests currently available with high
sensitivity and specificity for heterozygous
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