PEDIATRICS Vol. 108 No. 5
November 2001,
p. e96
ELECTRONIC ARTICLE:
Unmasking of Childhood Hypothyroidism by Disseminated Xanthomas*
Jörg Dötsch, MD,
Kristina Zepf, MD,
Stefan Schellmoser, MD,
Wolfgang Rascher, MD, and
Helmuth G. Dörr, MD
From the Universitätsklinik für Kinder und
Jugendliche, Erlangen, Erlagen, Germany.
 |
ABSTRACT |
Secondary hyperlipidemia is a common laboratory
finding in children with nephrotic syndrome, diabetes mellitus, and
hypothyroidism. However, clinical signs of hyperlipidemia are extremely
rare in childhood.
We report on an 11-year-old girl who presented with a disseminated
yellow papulomatous rash on the lower limbs and yellow skin creases on
the palms of her hands. Blood tests yielded an opaque serum with a
triglyceride concentration of 820 mg/dL and cholesterol of 1050 mg/dL.
Skin biopsy of one of the papules confirmed the diagnosis of xanthomas.
Additional examinations revealed clinical (weight gain, diminished
growth rate) and biochemical primary hypothyroidism (free T4: 0.4 ng/L
[normal 8-22 ng/L]; thyroid-stimulating hormone: >200 mU/L) as a
consequence of Hashimoto thyroiditis (thyroid peroxidase and
thyroglobulin: 4400 U/mL and >2000 U/mL, respectively; normal <60
U/mL). The patient was started on L-thyroxine, which led to
a gradual decline of cholesterol and triglycerides to normal concentrations and a complete remission from the xanthomatous rash.
For the first time, this case depicts disseminated xanthomas of the
skin as the presenting complaint of severe hypothyroidism. hyperlipidemia, hypothyroidism, xanthoma.
With an incidence of 1 in 500, hyperlipidemia is one of the
commonest congenital disorders of metabolism.1
Heterozygous type III hyperlipoproteinemia is clinically relevant, as
it is frequently associated with the presence of xanthomas in
adulthood.2 However, although nonspecific skin lesions may
occur in childhood type III hyperbetalipoproteinemia, xanthomas are
extremely uncommon.
Apart from inborn hyperlipidemia, secondary causes of elevated serum
lipids have to be excluded. These diseases include the nephrotic
syndrome,3 diabetes mellitus, and
hypothyroidism.1 Particularly in childhood, however,
secondary hyperlipidemia is rarely associated with clinical signs
or symptoms.4
We present a child with disseminated xanthomas and massively elevated
serum lipid concentrations as a consequence of severe hypothyroidism.
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CASE REPORT |
An 11-year-old girl presented to the pediatric endocrine
outpatient department of the University of Erlangen with a disseminated yellow papulomatous rash on her lower limbs and yellow skin creases of
the palms of her hands (Fig 1). The rash
had been developing gradually over the past 2 years. On presentation,
the patient was 137.5 cm tall (standard deviation score [SDS]: 
2.4; Fig 2) and had a weight of 37 kg (50th
percentile). Body mass index was 19.6 (SDS + 1.8 according to 5). When
the patient was 4 years old, her height had been at the 50th percentile
(102 cm; SDS: 0), decreasing to SDS 2.1 (136 cm) at age 10.25 years. The patient had dry skin and a resting heart rate of 52 beats per minute. Her blood pressure and physical examination were normal. She showed no signs of puberty.
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Fig. 1.
Abdominal wall (A) and palm of the hand (B) of an 11-year-old girl with
hypothyroidism after Hashimoto thyroiditis and
hyperbetalipoproteinemia. The diagnosis of xanthoma was confirmed by
skin biopsy.
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Fig. 2.
Growth curve of an 11-year-old girl with hypothyroidism after Hashimoto
thyroiditis and hyperbetalipoproteinemia. Bone age is represented by
squares. PC indicates percentile.
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Six months before, the patient was found to have slightly elevated
serum concentrations of the hepatic enzymes aspartate aminotransferase (56 U/L; normal <22 U/L) and alanine aminotransferase (36 U/L; normal
<21 U/L). There was no history of jaundice and no biochemical signs of
cholestasis nor of an abnormal synthesis of hepatic proteins. Serologic
tests for hepatitis B and C were normal. The girl did not complain of
fatigue, deterioration of mental or physical function, constipation, or
any other symptoms of hypothyroidsm.
The height of the parents (father 176 cm; mother 168 cm) resulted in a
target height for the patient of the 50th percentile, according to
German reference data.6 There was no known family history
of Hashimoto thyroiditis or other autoimmune disease nor of
hyperlipidemia.
Blood tests revealed an opaque serum with triglycerides of 820 mg/dL
and a cholesterol concentration of 1050 mg/dL. Because of the massive
lipid elevation, lipoprotein electrophoresis was not possible. Skin
biopsy of one of the papules confirmed the diagnosis of xanthomas of
the skin. The second most striking finding was a primary hypothyroidism
with a free serum T4 concentration of 0.4 ng/L [normal 8-22 ng/L]
and a thyroid-stimulating hormone (TSH) concentration of >200 mU/L
[normal <4 mU/L]. Antibodies against thyroid peroxidase and
thyroglobulin were massively elevated (4400 U/mL (normal <60 U/mL) and
>2000 U/mL [normal <60 U/mL], respectively). Ultrasound examination
of the thyroid gland revealed a normal-sized (7 mL) thyroid gland with
reduced and inhomogenous echogeneity, confirming the diagnosis of
autoimmune thyroiditis.
The patient was started on 75 µg/d of L-thyroxine and
later raised to 100 µg/d. After 3 months the patient was clinically euthyroid, had lost 2 kg of weight, but the xanthomas persisted. Thyroid function had normalized (fT4:12 ng/L, TSH: 2.0 mU/L) while moderate fasting hypertriglyceridemia (359 mg/dL; cholesterol 169 mg/dL) was still present.
However, after 1 year of treatment, serum triglycerides and cholesterol
were almost normal (211 mg/dL, and 149 mg/dL, respectively). Free T4
was 12.2 ng/L, and TSH was 0.4 mU/L. The patient now had a growth
velocity of 9.6 cm per year (97th percentile), and her weight was 35.9 kg (reduced by 1.9 kg in 1 year). The patient's prospective height had
increased from 152 cm to 160 cm according to Bayley and Pinneau. The
xanthomas had resolved completely (Fig
3).
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Fig. 3.
In our patient with hypothyroidism after Hashimoto thyroiditis and
hyperbetalipoproteinemia, at the age of 13, the xanthomas on the palm
of the hand (and on the trunk) had completely subsided.
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In both parents fasting lipid concentration and thyroid function were
normal.
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DISCUSSION |
This case illustrates that hypothyroidism in childhood may lead to
severe hyperlipidemia with the subsequent emergence of xanthomas.
Although hypothyroidism is generally regarded to be one
potential cause of hyperlipidemia in childhood,7,8 childhood hypothyroidism usually presents with different symptoms and
signs, among which deterioration of mental or physical strength, obesity, and a drop in growth rate appear to be the most
common.9 Oligosymptomic presentation of hypothyroidism is
rare in childhood but tends to become more common in the
elderly patient. To our knowledge, xanthoma as the presenting complaint
for hypothyroidism in children has not been reported. Even in
adulthood, only 1 case of xanthoma tuberosum attributable to
hypothyroidism has been published during the last 35 years.10
In adulthood, xanthomatous lesions are commonly found in
hyperbetalipoproteinemia (type III, according to Fredericksen).
However, even in children with severe
hyperbetalipoproteinemia, typical lesions usually do not appear before
adolescence.3,11 The long period before the lesions occur
highlights the rarity of the present case.
There is no indication of a coexisting congenital hyperlipidemia in our
patient, as has been previously reported in other patients.12
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CONCLUSION |
Cutaneous xanthomas as a consequence of severe hyperlipidemia may
be an extremely rare sign of childhood hypothyroidism.
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FOOTNOTES |
*
Dedicated to Prof. Wolfgang Sippell for his 60th birthday.
Received for publication May 8, 2001; accepted Jul 5, 2001.
Reprint requests to (J.D.) Klinik für Kinder und
Jugendliche, Friedrich-Alexander-University Erlangen-Nürnberg,
Loschgestrasse 15, 91054 Erlangen, Germany. E-mail:
joergwdoetsch{at}yahoo.com
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ABBREVIATIONS |
fT4, free T4;
SDS, standard deviation score;
TSH, thyroid-stimulating hormone.
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Pediatrics (ISSN 0031 4005). Copyright ©2001 by the American Academy of Pediatrics
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Abstract
Discussion
