Full text of DOI:10.1007/BF03345108

J. Endocrinol. Invest. 25: 727-729, 2002
CASE REPORT
Erdheim-Chester syndrome, presenting as
hypogonadotropic hypogonadism and diabetes insipidus
M.E. Khamseh, S. Mollanai, F. Hashemi, A. Rezaizadeh, and F. Azizi
Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, I.R. Iran
ABSTRACT. Erdheim-Chester syndrome is a rare
multisystem disease in which progressive xan-
thogranulomatous infiltration of several tissues are
seen. Knee and leg pain are the most common
symptoms and bilateral symmetric sclerosis of
metaphyseal region of long bones of the lower ex-
tremity is typical. Histologically, it resembles
Langerhans cell histiocytosis (LCH). However, it is
still a matter of discussion whether Erdheim-
Chester syndrome is a distinct entity or a type of
LCH. The present case is a 46-yr-old man, that pre-
sented with signs and symptoms of diabetes in-
sipidus and hypogonadotropic hypogonadism si-
multaneously. X-rays and bone scintigraphy
showed typical and pathogonomic findings of
Erdheim-Chester syndrome. Bone biopsy and im-
munohistochemical staining strongly support the
diagnosis of non- Langerhans cell histiocytosis.
(J. Endocrinol. Invest. 25: 727-729, 2002)
©2002, Editrice Kurtis
INTRODUCTION
nuria, mild normocytic normochromic anemia, ele-
vated erythrocite sedimentation rate (ESR) (125
mm/hr), and normoglycemia were detected. Lipid
profiles were normal. Water deprivation test proved
central DI. Thyroid function tests were normal
(T4=6.1 μg/dl, T3=183 ng/dl, TSH=0.97 mU/l,
RT3U=28.5%) and PRL level was 14.7 ng/ml. T, FSH
and LH levels were 0.3 ng/ml, 0.9 and 4.4 IU/l re-
spectively. Fasting serum F was 18.6 μg/dl and
basal GH level was 1.3 ng/ml. We did not perform
TRH and GnRH tests. Results of endocrine profile
is shown in Table 1. MRI of pituitary and hypotha-
lamic area were reported normal.
Diabetes insipidus (DI) and gonadotropin insuffi-
ciency are 2 of the clinical manifestations in
Erdheim-Chester syndrome (EC). Other compo-
nents of this rare multisystem syndrome include
arthralgia, symmetric sclerosis of long bones, peri-
ocular xanthogranuloma, nephrotic syndrome, and
pulmonary fibrosis (1, 2).
The purpose of this study is to describe the first case
of Erdheim–Chester syndrome diagnosed in Tehran,
presenting with central DI, hypogonadotropic hy-
pogonadism in the presence of normal PRL level and
intact thyroid and adrenal axes.
Marked symptomatic improvement in respect of
polyuria, nocturia and polydypsia occurred after
desmopressin (DDAVP) was prescribed. During fol-
low-up the patient developed vague generalized
bone pain and easy fatigability. Calcium, phospho-
rus, ALP, Ig electrophoresis and skull X-ray were nor-
mal but ESR remained elevated and mild anemia
persisted. Serum iron and total iron binding capaci-
ty (TIBC) were normal. Bone-marrow aspiration and
biopsy revealed no pathologic changes.
CASE DESCRIPTION
On April 1999, a 46-yr-old man was referred to the
Endocrine clinic because of polyuria, nocturia and
polydypsia. There was also a history of significant
weight loss, decreased libido and impotence.
Physical examination revealed bilateral xanthelas-
ma, mild gynecomastia, normal size testicles and
normal secondary sexual characteristics. Hyposthe-
During the following 8 months, progressive weight
loss and fatigability continued and bone pain was
more pronounced especially in the lower extremi-
ties and hips. Bilateral flank pain developed some-
what later. X-rays showed a thickening of diaphy-
ses and metaphyses of both femural bones in dis-
tal portions and both proximal parts of tibias, plus
Key words: Diabetes insipidus, Erdheim-Chester syndrome, histiocytosis,
hypogonadism, hypothalamus, pituitary.
Correspondence: Prof. Fereidoun Azizi, PO Box 19395-4763, Tehran I.R. Iran.
E-mail: Azizi@ERC-IRAN.com
Accepted February 26, 2002.
727

M.E Khamseh, S. Mollanai, F. Hashemi, et al.
Table 1 - Results of serum concentrations of various hormones
until today. Histologically, it resembles Langerhans
cell histiocytosis (LCH), and it is still a matter of dis-
cussion whether EC syndrome is a distinct entity or
a type of LCH (3). Langerhans cells stain with S-100
protein stain, but non-Langerhans cell histiocytes
do not stain for S-100 protein (4). Some studies sug-
gest that EC syndrome is a monoclonal lesion con-
sistent with neoplastic disorder (5).
Knee and leg pain are the most common symptoms
and bilateral, symmetric sclerosis of metaphyseal
region of long bones of the lower extremity is typ-
ical (1, 6, 7). Other clinical manifestations reported
in the literature include bilateral periocular xan-
thogranuloma (8), nephrotic syndrome (9), pro-
gressive dyspnea due to extensive pulmonary fi-
brosis (10), DI (1, 11), and gonadotropin insuffi-
ciency (11). Clinical presentations and progression
are quite variable in the reported cases in the liter-
ature, ranging from isolated organ involvement to
a widely disseminated disorder.
in patient with Erdheim-Chester syndrome.
Hormone
T (ng/ml)
LH (IU/l)
Serum level
0.3
4.4
FSH (IU/l)
TSH (mU/l)
T4 (μg/dl)
T3 (ng/dl)
RT3U (%)
FT4I
0.9
0.97
6.1
183
28.5
1.74
308
IGF-I (μg/l)
GH (ng/ml)
F (μg/dl)
PRL (ng/ml)
1.3
18.6
14.7
Central DI is characterized by polyuria and poly-
dypsia due to a deficiency of arginine vasopressin.
Differential diagnosis of DI is large, and many pa-
tients with a diagnosis of DI and a normal hy-
pothalamic-pituitary CT or MRI are diagnosed as
having idiopathic DI (4). In many normal subjects,
the posterior pituitary is hyperdense on saggital T1-
weighted MRI. The absence of this finding serves
as a non-specific indicator of central DI (12, 13). The
finding of a thickened infundibulum or pituitary
stalk, suggests the presence of an infiltrative dis-
ease (13, 14). However, the pituitary may remain
hyperintense in 6% and pituitary stalk may be nor-
mal in 46% of the patients with central DI on initial
MRI (13). In patients with Langerhans-cell histiocy-
tosis and DI the risk of anterior pituitary hormone
abnormality is independent of the size of the pitu-
itary stalk even though the size of anterior pituitary
on last MRI study remains normal in 75% (13). How-
ever, loss of pituitary hyperintensity and thickening
of the stalk may be shown during follow-up MRI.
The present case presented with simultaneous
signs and symptoms of DI and hypogonadotropic
hypogonadism; some of the common etiologies of
central DI, such as head injury, brain surgery or
brain tumor can be readily excluded in our patient.
However, tuberculosis, lymphoma metastatic can-
cer, Wegener granulomatosis and histiocytosis can
also cause central DI (15). The lack of lung in-
volvement, the absence of lymphadenopathy, the
unremarkable bone marrow and normal urine sed-
iment argue against any of these processes in this
patient. During follow-up, progressive weight loss
and disabling bone pain developed. X-rays and
bone scintigraphy showed typical and pathogno-
sclerotic changes of these areas. Bone scintigraphy
showed increased uptake in the mentioned areas.
Abdominal sonography showed bilateral enlarged
kidneys with increased parenchymal thickness and
indistinct cortico-medullary junction. Bone biopsy
from distal femur showed fibro-collagenous and fat-
ty tissue infiltrated by clusters of foamy histiocytes
with central vesicular nucleus and abundant vacuo-
lated cytoplasm, some touton-shaped giant cells,
small aggregation of histiocytic like cells with eosi-
nophilic cytoplasm and ovoid-grooved nuclei.
Immunohistochemical staining of the bone biopsy
showed leukocyte common antigen (LCA) in most
mononuclear and histiocytoid cells. CD.15 was pos-
itive in 10% and C.D.3 in 30% of mononuclear cells.
S100 was negative in the histiocytic cells. Un-
fortunately CD 68 was not available. Pulmonary
function tests and echocardiography were both nor-
mal. The patient developed severe upper gastro-
intestinal bleeding on prednisolone and inedome-
thacin, so they were discontinued. Azathioprine 5
mg daily and vinblastin every 2 weeks, were started.
The patient has received 20 courses of vinblastin
ever since and there is marked symptomatic im-
provement of his bone pain and disability. He still
needs DDAVP and T enanthate injections.
DISCUSSION
Erdheim-Chester syndrome is a rare multisystem
disease in which a progressive xanthogranuloma-
tous infiltration of several tissues is seen (1, 2). Sixty-
two patients have been reported in the literature
728

Erdheim-Chester syndrome and endocrine dysfunction
6. Sisterman R., Katthagen B.D. Erdheim-Chester disease; a
rare cause of knee and leg pain. Dr. si@t-online.
nomic findings of EC syndrome including bilateral
symmetrical thickening and sclerosis of metha-
physial regions of long bones of lower extremities.
Bone biopsy and immunohistochemical staining
strongly support the diagnosis of non-Langerhans
cell histiocytosis (S-100 - negative histiocytic cells).
In conclusion, the clinical presentation, character-
istic radiological and histological findings, and the
evidence against other disorders led us to the di-
agnosis of Erdheim-Chester syndrome in this pa-
tient.
7. Park Y.K., Ryu K.N., Huh B., Kim J.D. Erdheim-Chester dis-
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periocular xanthogranuloma. Klin. Monatsbl. Augenheilkd.
1997, 211: 349-354.
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syndrome and amyloidosis in a patient with Erdheim-
Chester disease. Nephron 2000, 86: 195-196.
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pathology of Erdheim-Chester disease. Med. Pathol. 2000,
13: 747-754.
11. Tritos N.A., Weinrib S., Kaye T.B. Endocrine manifestations
of Erdheim-Chester disease. J. Intern. Med.1998, 244: 529-
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