0021-7557/00/76-05/383 Jornal de Pediatria - Vol.

76, Nº5, 2000 383

Jornal de Pediatria
Copyright © 2000 by Sociedade Brasileira de Pediatria

CASE REPORT

Diabetes insipidus as an early clinical manifestation

of pineal tumor
José S.S. Diniz1, Eduardo A. Oliveira2, Marina M. Servilha3

Abstract
Objective: to present a pineal tumor diagnosed after long clinical course of diabetes insipidus.
Case Report: a ten years old male patient, with symptoms of polyuria, polydipsia and nocturia for 18
months was admitted at the Nephrology Unit with the diagnosis of nephrogenic diabetes insipidus. Six
months prior to his admission, he had been submitted to a computed tomography scan, which was
considered inconclusive. The diagnosis of central diabetes insipidus was confirmed by a water deprivation
test. A head magnetic resonance imaging demonstrated two masses suggesting germinoma.
Conclusions: our observations show that patients with central diabetes insipidus need close clinical,
laboratory and neuroradiological follow-up in order to detect the intracranially tumors in an early stage.
J Pediatr (Rio J) 2000; 76(5): 383-6: diabetes insipidus, germinoma.

Introduction
Central diabetes insipidus is a disorder characterized by
polyuria and polydipsia due to vasopressin (antidiuretic
hormone) deficiency caused by a lesion at the hypothalamo-
hypophyseal axis. It may be secondary to infections, trauma,
tumors, and other pathologic processes that damage this
axis.1 Frequently, central diabetes insipidus is wrongly
considered idiopathic if not associated with other
neurological signs and symptoms.2 On the other hand,
tumors in the pineal region are rare, being responsible for
0.4-1% of all intracranial masses in childhood.3 The clinical
presentation of these tumors is highly variable, ranging
1. Emeritus Professor, Department of Pediatrics, School of Medicine,
Universidade Federal de Minas Gerais (UFMG).
2. Associate Professor, Department of Pediatrics, School of Medicine,
Universidade Federal de Minas Gerais (UFMG).
3. Undergraduate Student, Nephrology Unit, School of Medicine,
Universidade Federal de Minas Gerais (UFMG).
from disorders of the pubertal development to neurological
symptoms of intracranial masses. Yet, central diabetes
insipidus may be an isolated initial manifestation of pineal
tumors, and an adequate clinical approach may contribute
to an earlier diagnosis of these tumors. In this study, we
present the report of a case that illustrates the difficulties in
the diagnosis and the frequent delay in the approach of this
neurological condition.
Case report
A 10 year-6-month old, male child was referred to the
Pediatric Nephrology Unit at Hospital de Clínicas,
Universidade Federal de Minas Gerais, with history of
polydipsia, polyuria, and nocturia for 18 months. He had
performed encephalic computed tomography 6 months
before, which showed the thickening of the hypothalamo-
hypophyseal infundibulum; this finding was not considered
significant (Figure 1A).

383
384 Jornal de Pediatria - Vol. 76, Nº5, 2000 Diabetes insipidus as an early clinical manifestation... - Diniz JSS et alii

Figure 1 - Neuroradiological evaluation. A) Computed tomography of

the encephalon (March 1997) shows thickening of the
hypothalamo-hypophyseal infundibulum. B) Magnetic
resonance imaging (October 1997), axial section, shows an
isodense lesion at the floor of the third ventricle (arrow). C)
Similar lesion located posteriorly (arrow). D) On the same
examination, sagittal section, the two homogeneous masses
can be observed

The patient was then considered to have diagnostic
suspicion of nephrogenic diabetes insipidus. The urinary
volume in 24 hours was approximately 6.5 l; the water
ingestion of liquids was 5 l. On the physical examination at
the moment of admission, he weighed 28,900 g (5-10th
percentile) and was 133 cm high (25-50th percentile), with
no other alterations (including neurological evaluation).
There were no signs of development of secondary sexual
characters. Arterial pressure was 80/50 mmHg. On the
preliminary evaluation, the examinations presented the
following results: urinalysis (density = 1,005, pH = 6,
glycosuria = 0); serum biochemistry (glycemia at fasting =
93 mg/dl, urea = 19 mg/dl, creatinine = 0.9 mg/dl, sodium
= 144 mEq/L, potassium = 3.7 mEq/L, chloride = 102 mEq/
L); venous gasometry (pH = 7.378, pCO2 = 50.3, HCO3 =
28.8, BE = +4.8); hemogram (Hb = 11.6 mg/dl, Ht = 35%,
leukocytes = 5.900 cells/mm3); vasopressin = 2.2 pg/ml,
plasmatic osmolality = 288 mOsm/kg. The ultrasonographic
study of the urinary tract revealed kidneys with normal
volume for the age, besides the absence of calculi and
nephrocalcinosis.
These results characterized the presence of diabetes
insipidus, so performance of a water deprivation test was
indicated. The results of the test may be observed in Figure
2: after a 6-hour fasting period, there was no increase in the
urinary concentration; 2 hours after the stimulus with
desmopressin (0.2 ml = intra-nasal 20 mcg), there was an
evident increase in urinary osmolality.
Thus, after the test, we verified the presence of central
diabetes insipidus, and a therapy with DDAVP was initiated,
and magnetic resonance imaging of the central nervous
system was indicated. The therapy with vasopressin (an
intra-nasal 20 mcg/day dose) resulted in the complete
regression of the symptoms and in the normalization of the
laboratory findings (urinary density and osmolality).
Diabetes insipidus as an early clinical manifestation... - Diniz JSS et alii
Figure 2 - Result of the water deprivation test, stimulus with
desmopressin. Two hours later, an important increase
in the urine osmolality occurs
Magnetic resonance imaging showed two isodense intra-
parenchymal lesions, with a homogeneous contrast
concentration: the first, placed at the anterior part of the
third ventricle, invading hypophyseal optic chiasma,
infundibulum, and hypophyseal stalk. The other lesion,
with the same characteristics, was located at the posterior
portion of the third ventricle. Cerebral ventricles presented
normal volume in anatomical position. Basal cisterns and
peripheral sulci had a normal aspect (Figure 1B-1D).
Considering the radiological and clinical findings, the
most probable diagnostic hypothesis was pineal tumor;
among these tumors, germinoma is the most common
histological type. We required preliminary complementation
with serum and liquor dosages of HCG and alpha-fetoprotein,
which presented normal results. After evaluation by the
Neurology Service at Hospital de Clínicas, Universidade
Federal de Minas Gerais, radiotherapy was indicated, and it
has been performed with a satisfactory clinical response.
Discussion
Germinomas are rare tumors originated from primordial
germinative cells. They arise in regions of the medium line,
such as gonads, retroperitoneum, mediastinum,
diencephalon, and the ocular orbit.4 Independently of the
region, they are identical, both from the optic or electronic
microscopy, and from the histochemical analysis points of
view.5,6 Friedman7 established the term germinoma, which
has a widely accepted teratoid nature and unknown etiology.3
The incidence of germinomas varies according to the
region: in Japan and Taiwan, they represent 2 to 9% 8,9 of
intracranial tumors, while in eastern countries, this
percentage is consistently lower, varying from 0.4 to 1%.10
They occur mainly among during adolescence and in young
adults, and predominate in male children.4 They are malign
Jornal de Pediatria - Vol. 76, Nº5, 2000 385
tumors, frequently multifocal and that may originate
metastases in the central nervous system or other organs.
The clinical presentation of the germinomas at the central
nervous system is highly variable, depending on the patient’s
age and on the location of the tumor. Tumors at the pineal
region usually present signs of increased intracranial pressure
and pubertal disorders. In contrast, suprasellar lesions
determine endocrine and visual disorders.11 Unfortunately,
the diagnosis of germinomas at the central nervous system,
especially of those located at the sella turcica area, is very
difficult and usually obtained late.
The present report illustrates the difficulties in diagnosing
these tumors. The only initial clinical presentation was
diabetes insipidus. The typical symptomatology lasted for
18 months and, after a simplified initial investigation, it was
considered idiopathic. Some problems called our attention
in this case: initially, the child was not submitted to the basic
investigation of diabetes insipidus, that is, water deprivation
test and stimulus with desmopressin. Later, he was submitted
to a computed tomography, and, considering the findings,
we discarded the presence of central diabetes insipidus and
referred him to a nephrology service, due to a suspicion of
nephrogenic diabetes insipidus.
In our opinion, when a status of polyuria and polydipsia
is present, it is important to establish the unequivocal
diagnosis of diabetes insipidus. Initially, the status of
pathologic polyuria and polydipsia must be characterized,
in general, above 2 l/m2/day, interfering with the child’s
normal activities (the child frequently wakes up during the
night to drink water or presents nocturia). Besides that, the
pediatrician must be alert to the data about the child’s
longitudinal growth and to the signs of associated endocrine
or neurological alterations, such as precocious puberty and
visual disorders, on the physical examination. The following
examinations should be included in the preliminary
evaluation: determination of serum osmolality, sodium,
potassium, glycemia, calcium, urea, and the evaluation of
urine, osmolality, density, and glycosuria. Serum osmolality
higher than 300 mOsm/kg, with urine osmolality lower than
300 mOsm/kg, characterizes the presence of diabetes
insipidus. After the characterization of the clinical status,
the patient should be submitted to the water deprivation test,
in order to identify the origin of the problem (whether
central or nephrogenic).12 The test is performed after a
nocturne period of maximum tolerated fasting, the child
being followed with clinical and laboratory evaluations for
a period of 8 to 10 hours.13,14 During the test, the patient
must be rigorously monitored, with periodic samples of
weight and arterial pressure; the procedure should be
interrupted when signs of hypovolemia occur.
Some comments on the difficulties in the identification
of germinative cell tumors situated in the central nervous
system should be made. The initial clinical presentation of
our case was only diabetes insipidus. There are several
reports about this manifestation associated with other
findings in patients with tumors in the pineal region. Legido
386 Jornal de Pediatria - Vol. 76, Nº5, 2000
et al.15 report diabetes insipidus in 80% of their patients, but
most times associated with cephalea, vomiting, diplopia,
and other symptoms. In other studies, there are reports
varying around 30 to 50%, and they are almost always
accompanied by other manifestations.1,16,17 Yet, there are
reports of central diabetes insipidus as an initial sing for
germinomas. Ramelli et al.2 report seven cases of these
tumors; in six children, the isolated initial manifestation
was central diabetes insipidus. More recently, Dokek et
al.11 described two other cases. Some authors emphasize
the early occurrence of diabetes insipidus in the clinical
course of germinomas.18
Another important information concerns the time interval
between the beginning of the symptoms and the diagnosis.
In our case, there was an 18-month interval between the first
manifestations of diabetes insipidus and the detection of the
tumor. This fact is not rare considering germinomas of the
central nervous system. Bulger et al.19 also report an 18-
month interval between the manifestation and the diagnosis
in a 14 year-old teenager. It is interesting to comment that,
similarly to our case, this patient was initially submitted to
a computed tomography, which failed in detecting any
abnormality in the central nervous system. In the cases
reported by Ramelli et al.,2 there was a variable time
interval (between 12 and 66 months) for these cases of
isolated manifestation of central diabetes insipidus, while
for the case with manifestation associated with visual
disorders, this interval was of only 3 months. Though in
prognostic studies there are no correlations between the
time interval from the initial manifestation up to the diagnosis
of the tumor and survival, the latter is strongly associated
with the tumor extension and with the presence of
metastases.4 Thus, the early diagnosis, in the initial course
of the disease, will benefit the patients, possibly lengthening
survival.
The approach to these tumors is still controversial.
Previously, several studies recommended craniotomy and
biopsy to establish a definitive diagnosis.15 However, some
authors, according to their growing experience, have
indicated radiotherapy, based in clinical, neuroradiological,
and neuroendocrine parameters.16 In our case, the procedure
was to indicate radiotherapy based on these parameters, and
the clinical response has been satisfactory up to the present
moment.
Conclusions
Our case report emphasizes the difficulties in the
diagnosis of tumors at the pineal region. Germinomas may
have central diabetes insipidus as their isolated manifestation.
The symptoms of diabetes insipidus may precede the
alterations in the computed tomography. Whenever a clinical
status suggestive of diabetes insipidus is present, the
pediatrician should perform a complete clinical investigation
Diabetes insipidus as an early clinical manifestation... - Diniz JSS et alii
and an adequate preliminary approach, considering that the
presence of these tumors cannot be discarded, even in cases
of an initially normal neurological examination.
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Correspondence:
Eduardo A. Oliveira
Rua Patagônia, 515/701
CEP 30320-080 – Belo Horizonte, MG, Brazil
E-mail: eduolive@ medicina.ufmg.br