Pituitary Metastasis of Pulmonary Adenocarcinoma
Presenting with Polyuria Masked by Poor Glycemic Control: A
case report
Chih-Yen Hsiao, Peir-Haur Hung, Pei-Chun Chiang, Ing-Chin Jong,
Ming-Cheng Wang*
Division of Nephrology, Department of Internal Medicine, Chia-yi Christian Hospital,
Chia-yi, Taiwan; Division of Nephrology, Department of Internal Medicine, National
Cheng Kung University Hospital, Tainan, Taiwan*
Correspondence author: Dr. Ming-Cheng Wang, Division of Nephrology Internal
Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan,
Taiwan.
Tel: 886-6-2353535 ext. 2594
Fax: 886-6-3028036
E-mail: wangmc@mail.ncku.edu.tw
Abstract
Hyperglycemia may present with polyuria and polydipsia, which are also the main
clinical features of diabetes insipidus (DI). Diabetic patients with polyuria and
polydipsia may be mistaken as poor glycemic control, which will delay the diagnosis
and treatment of DI and related underlying disease. Herein, we present a 54-year-old
man who had had polyuria and polydipsia for three months. Initial laboratory data
showed HbA1C 7.9%, and urine glucose 1000 mg/dl. Diabetes mellitus was the initial
diagnosis and treated with metformin. However, the polyuria and polydipsia persisted
even though hyperglycemia had been kept under control. The low urine osmolality and
high urine output led to the diagnosis of DI. A desmopressin test confirmed the presence
of central DI. After a series of study, pituitary metastasis of lung cancer
(adenocarcinoma) was the final diagnosis. His polyuria and polydipsia improved after
treatment with intranasal desmopressin; multiple brain metastases were treated with
CyberKnife® radiosurgery. In conclusion, development of DI with polyuria and
polydipsia in diabetic patients with poor glycemic control could be overlooked, which
will delay the diagnosis and treatment of underlying disease such as malignancy. A
screening urine osmolality or specific gravity for diabetic patients with significant
polyuria and polydipsia is helpful.
Key words: Central diabetes insipidus, Pulmonary adenocarcinoma, Pituitary
metastasis, Polyuria
INTRODUCTION
Although diabetes mellitus (DM) is widely known as the commonest cause of
polyuria and polydipsia, the possibility of diabetes insipidus (DI) should be considered
by physicians. DI is a clinical syndrome with hypotonic polyuria and polydipsia and
classified in four types as: (i) primary polydipsic DI, (ii) nephrogenic DI, (iii) central DI,
and (iv) gestagenic DI. Water deprivation test and/or vasopressin challenge test is useful
in differentiation among the major forms of DI. Central DI is a rare
hypothalamus-pituitary disease. It occurs in both genders equally, and affects all ages
with the most frequent age of onset between 10 and 20 years.1 Most cases of central DI
are acquired,2 and pituitary metastasis is found in 10% to 20% of patients with DI.3
Various type of neoplasms have been reported 4,5 and the most common lesions that
metastasize to the pituitary gland are secondary to pulmonary carcinoma in men and
breast carcinoma in women. Generally, pituitary metastasis involves patients with the
most frequent age being between 50 and 60 years without clear sex predominance. 6,7
The important principal finding in diagnosing metastatic disease to the pituitary is
DI.3,8,9 Herein, we report a diabetic patient with poor glycemic control presenting with
polyuria finally related to central DI caused by pituitary metastasis from pulmonary
adenocarcinoma. His symptoms resolved after treatment with intranasal desmopressin.
Because of the rarity of this manifestation in patient with pulmonary adenocarcinoma,
we report this case along with a brief review of the relevant literature.
CASE REPORT
A 54-year-old man had suffered from polydipsia and polyuria without weight loss
for three months. Initial laboratory data showed postprandial plasma glucose 274 mg/dl,
HbA1C 7.9%, and urine glucose 1000 mg/dl. DM was the initial diagnosis and was
treated with metformin 500 mg twice daily. However, polyuria and polydipsia persisted
even though hyperglycemia had been kept under control. He was admitted due to a low
urine osmolality of 94 mOsm/kg with serum sodium 149 mmol/l and osmolality 306
mOsm/kg, the other electrolytes and creatinine were all within normal range. His urine
amount was approximately 12 liters per day. Physical examination showed
unremarkable. Vasopressin test was performed with a baseline serum osmolality of 295
mOsm/kg, urine osmolality and urine specific gravity were 112 mOsm/kg and <1.005,
respectively. Central DI was confirmed considering the urine osmolality increasing to
503 mOsm/kg following vasopressin 2.5 U subcutaneously. Pituitary function including
serum follicle stimulating hormone, luteinizing hormone, adrenocorticotropic hormone,
growth hormone and prolactin levels were all within normal range.
Brain magnetic resonance imaging (MRI) showed multiple brain tumors at left
cerebellum, right thalamus, and right frontal and left temporal lobes. Moreover, absence
of hyperintensity at posterior lobe of pituitary gland suggested pituitary metastasis
(Figure 1). Chest X-ray and computed tomography (Figure 2) revealed left upper lung
tumor with multiple lung and bone metastases, and mediastinal lymphadenopathy.
CT-guided biopsy of lung tumor was performed and the pathological diagnosis was
adenocarcinoma. According to the above findings, pulmonary adenocarcinoma with
multiple metastases including pituitary gland complicated with central DI was
diagnosed.
CyberKnife ® radiosurgery for pituitary metastasis and intranasal desmopressin for
central DI were administered. The patient’s urine volume returned to normal range
without polydipsia.
DISCUSSION
Patients with poor glycemic control would suffer from polyuria and polydipsia if
glucosuria occurs. However, polyuria in diabetic patient could be contributed by other
causes and must be distinguished from hypotonic disorders associated with water
diuresis. In patients with water diuresis, the clinician must verify whether DI exists or
not. In our patient, urinary analysis and urine osmolality revealed water diuresis, and
central DI was confirmed by vasopressin test. We investigated the cause of central DI by
imaging study and lung biopsy confirmed the diagnosis of pituitary metastasis of
pulmonary adenocarcinoma.
The incidence of pituitary metastasis in patients with systemic cancer varies from
1% to 27% and is higher in autopsy series.3,4,5 Breast and lung cancers account for
65%-75% of pituitary metastasis.10 Pituitary metastasis of pulmonary adenocarcinoma is
very rare, and only sparse cases have been reported. Most pituitary metastases are
asymptomatic and are found accidentally or at autopsy.3,6,10 Only 6.8 % were
symptomatic.8 The most common symptom of pituitary metastases is DI. Other
symptoms include visual loss, oculomotor palsies and hypopituitarism.11 The clinical
symptoms in patients with pituitary metastasis of pulmonary adenocarcinoma are the
same as those of other neoplasms12,13,14,15The clinical features what our patient presented
were related to DI only, no other symptom or sign was found.
There are two possible reasons why symptomatic pituitary metastasis is so rare:
most patients died of multiple systemic metastasis before DI was diagnosed,16 and
invasion of massive cancer to the pituitary gland is necessary to cause pituitary
dysfunction. Metastatic neoplasms may influence the pituitary gland via direct local
invasion, spread through the cerebrospinal fluid, or hematogenously. More than half of
pituitary metastases primarily involve the posterior lobe, only 10% to 20% primarily
affect the anterior lobe.3 The predominant pituitary metastasis to the posterior lobe can
be explained by the fact that arterial blood enters the posterior lobe, in contrast to the
lack of direct arterial blood supply to the anterior lobe, and a larger contact area with the
adjacent dura for the posterior lobe.4
The most important principal finding in diagnosis of metastatic disease to the
pituitary gland is DI. Schubiger and Haller suggested that DI is the most important
criterion for distinguishing tumor metastasis from pituitary adenoma.17,18 In an image
study by Koshimoto et al suggested that posterior pituitary is identified on MRI by the
hyperintensity, and lack of this hyperintensity on the sagittal T1-weighted images could
be the hallmark of hypothalamic-posterior pituitary disorders.19 Differentiation between
pituitary adenoma and pituitary metastasis from radiological evaluation is difficult.
Because DI is reported in only 1% of patients with adenoma20, distinguishing metastasis
from adenoma including DI as the presenting feature, age more than 50 years, cranial
nerve palsy or abnormality, rapid onset or progression of symptoms and history of
malignancy are helpful in distinguishing pituitary metastasis from pituitary adenoma.7, 21
As noted in our case, pituitary metastasis was highly suspected on the basis of the
concurrent metastasis to other areas in brain parenchyma, age of more than 50 years, and
presence of DI.
In patients of tumor with pituitary metastasis, age over 65 years at presentation,
metastasis from small-cell lung carcinoma, and short period ( <1 year) between initial
diagnosis of cancer and pituitary invasion have been related to a poorer outcome.22
Mean life span is 6-7 months and most patients died in a few months after initial
diagnosis. 5, 9, 23 Local radiation and chemotherapy are recommended for tumors with
pituitary metastasis at the present time.22 Our patient received CyberKnife ® for his
pituitary metastasis and still survived for more than another ten months.
In conclusion, although DM is the commonest cause of polyuria and polydipsia,
development of DI with polyuria and polydipsia in diabetic patients with poor glycemic
control could be overlooked, which will delay the diagnosis and treatment of underlying
diseases such as malignancy. A screening urine osmolality or specific gravity for
diabetic patients with significant polyuria and polydipsia would be helpful. In addition,
DI may occur in the course of systemic cancer even without any other clinical symptoms.
Clinicians should be aware of the possibility of pituitary metastasis to provide the
patient with early and appropriate management, especially in patients with lung cancer
who develop polyuria and polydipsia.
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Figure 1.
Absence of hyperintensity (arrowhead) at posterior lobe of pituitary gland on
T1-weighted MRI
Figure 2.
A lung tumor (arrowhead) at left upper lobe on chest CT scan
Figure 1 原圖
Figure 2 原圖