Etiological and clinical characteristics of central diabetes insipidus in children: a single center experience

The cohort included 21 male patients and 14 female patients whose median age at diagnosis
of CDI was 4.8 years (range, less than 1 month to 16 years). In the patients with
CDI at their initial presentation, mean duration of symptoms prior to diagnosis was
6.3 months (range, less than 1 week to 36 months). Characteristics of the cohort and
etiologies of CDI are reported in detail in Table 1. Etiologies included CNS malformations in 17 patients (48.5 %), intracranial masses
in 13 patients (37.2 %), and Langerhans cell histiocytosis (LCH) in 3 patients (8.6 %).
The underlying cause of CDI remains unclear in 2 patients (5.7 %) but both had abnormal
MRI findings. Their cases are discussed in detail later in the article. No patients
had a family history of DI. Median duration of follow-up was 5 years (range, 2 months
to 16 years).

Table 1. Patient demographics and etiologies of central diabetes insipidus

All patients underwent MRI of the brain. Thirty-three patients had neuroimaging performed
at NCCH, and reports from referring hospitals were available for the remaining 2 patients.
All but one had abnormalities on MRI of the brain including CNS malformations, intracranial
masses, pituitary gland or stalk abnormalities. The one patient with a normal MRI
of the brain was diagnosed with LCH (biopsy-proven) after presenting with a posterior
auricular mass. Of the 17 patients with CNS malformations on MRI, 9 (25.7 %) had septo-optic
dysplasia (SOD), 5 (14.2 %) had holoprosencephaly, 2 (5.7 %) had isolated pituitary
hypoplasia, and 1 (2.9 %) had a large encephalocele. MRI revealed intracranial masses
in 13 patients (37.2 %), including craniopharyngioma (6 patients, 17.1 %), astrocytoma
(3 patients, 8.6 %), germ cell tumor (3 patients, 8.6 %), and pituitary adenoma (1
patient, 2.9 %). Four patients had pituitary stalk thickening. Of these patients,
2 were diagnosed with LCH, 1 was diagnosed with a germ cell tumor, and 1 has not yet
undergone biopsy to determine a definitive diagnosis. One patient had absence of the
posterior pituitary bright spot alone, without other structural abnormalities on MRI.

Six of 35 patients required formal water deprivation testing for diagnosis of CDI.
The remaining patients already fulfilled the diagnostic criteria. All patients who
required water deprivation test had abnormal findings on MRI of the brain, and etiologies
for CDI included LCH, ectopic pituitary gland, pituitary hypoplasia, SOD, astrocytoma,
and pituitary adenoma. Two of 6 patients had ADH deficiency alone at the time of diagnosis
while the remainder had concurrent hormone deficiencies at presentation.

Twenty-one patients (60 %) had CDI at their initial presentation and 10 patients (29 %)
developed CDI as a result of neurosurgical management of intracranial masses (6 with
craniopharyngioma, 2 with astrocytoma, 1 with germinoma, and 1 with adrenocorticoptropic
hormone (ACTH) secreting pituitary adenoma). Four patients (2 with SOD and 2 with
ectopic posterior pituitary glands) did not have CDI at presentation but developed
it during the follow-up period. One of the patients with SOD was diagnosed with thyrotropin
(TSH), ACTH, and growth hormone (GH) deficiencies at birth but did not develop symptoms
of CDI until 2 months of age. The second patient was diagnosed with SOD at 4 months
of age but did not develop CDI until 12 years of age. One patient with an ectopic
pituitary gland was diagnosed with panhypopituitarism except CDI at 2 months of age
and developed CDI 1 year later. The other patient with an ectopic pituitary gland
presented with GH deficiency and delayed puberty at 12 years of age and was diagnosed
with CDI at 15 years of age.

GH deficiency was the most common concurrent hormone deficiency at presentation in
patients with CDI and occurred in 12 patients (34 %). TSH, ACTH, and gonadotropin
deficiencies were present at the time of diagnosis in 23 %, 23 %, and 6 % of patients,
respectively. TSH deficiency was subsequently diagnosed in an additional 40 % of patients
during follow-up. ACTH deficiency and gonadotropin deficiencies were later diagnosed
in 37 % and 14 % of patients, respectively (Figure 1). Eighteen patients (51 %) were prepubertal in age so that the presence of gonadotropin
deficiencies could not be assessed accurately. All 3 patients with LCH had CDI at
presentation, and 1 developed subsequent hormone deficiencies as a result of disease
progression and neurosurgery for diagnosis. Of the 5 patients with CDI as a result
of holoprosencephaly, only 1 developed an additional hormone deficiency over time.
The development of additional anterior hormone deficiencies occurred over time in
44 % of patients with SOD. Time from diagnosis of SOD to onset of subsequent hormone
deficiencies ranged from months to years, with one patient having a normal pituitary
evaluation at 4 months of age who did not develop subsequent hormone deficiencies
until 12 years of age (see Table 2).

Table 2. Timing of development of pituitary hormone deficiencies in patients with cns malformations

There were 2 patients with CDI of unclear etiology. The first patient has been followed
at NCCH for 6 years. He has undergone MRI of the brain on an annual basis which has
demonstrated a stable 4 mm focus of hypoenhancement within his right pituitary gland
which may represent a Rathke’s cleft cyst or adenoma; however, he continues to follow-up
with oncology given the possibility of LCH or germ cell tumor. He has had a total
of two osseous surveys (2 years apart) that have failed to demonstrate evidence of
LCH. He has undergone pituitary hormone screening every 6 to 12 months without development
of subsequent hormone deficiencies. The other patient with CDI of unknown etiology
is 13 year old female who presented for evaluation secondary amenorrhea, rapid weight
gain, polydipsia and polyuria. She has been followed in our clinic for nearly 1 year,
and her evaluation is significant for evidence of pituitary stalk thickening with
absence of the posterior pituitary bright spot on MRI as well as TSH, GH, and gonadotropin
deficiencies. A skeletal survey was normal. Neurosurgery has not yet agreed to obtain
a biopsy for definitive diagnosis.

CDI in 31 patients was successfully managed with DDAVP. Chlorothiazide was used in
3 patients during infancy. One patient was managed with oral free water intake alone
per the family’s preference. One patient with an astrocytoma had resolution of CDI
after four years as a result of surgical intervention and chemotherapy.