- Email: [email protected]
Polyuria and Polydipsia in a Patient with Non–Small-Cell Lung Cancer
case repor t Polyuria and Polydipsia in a Patient with Non–Small-Cell Lung Cancer Jae Wook Jung,1 Geum Youb Noh,1 Tae Hyeon Lee,2 Yun Yong Lee,1 Ka Hee Yi,1 Cheol Hyeon Kim,1 Jae Cheol Lee1 Abstract Tumor metastasis to the pituitary gland has been infrequently reported, and this is probably because only a small proportion of these patients are symptomatic. Most of the symptoms of this malady are related to diabetes insipidus. A 78-year-old man was diagnosed 2 years previously with stage IIIA adenocarcinoma of the lung and treated with sequential chemoradiation therapy and later with whole-brain radiation therapy because of newly developed brain metastasis; he was then admitted to our hospital with symptoms of polydipsia and polyuria. He was confirmed to have central diabetes insipidus that was caused by the pituitary metastasis from lung cancer. His symptoms resolved after treatment with desmopressin. Because of the rarity of this manifestation in lung cancer patients, we report on this case along with a brief review of the relevant literature. Clinical Lung Cancer, Vol. 8, No. 9, 565-567, 2007
Key words: Desmopressin, Diabetes insipidus, Pituitary gland metastasis
Introduction
this was confirmed by mediastinoscopic biopsy. Sequential chemotherapy with 4 cycles of gemcitabine (1000 mg/m2 on days 1 and 8, every 3 weeks), carboplatin (area under the curve 6 on day 1, every 3 weeks) and radiation therapy (RT) of 6300 cGy was given to him because he refused to undergo surgery. The size of the lung mass was reduced on the follow-up computed tomography scan; thus, the patient exhibited a partial response. He presented with dizziness and intermittent headache 6 months after treatment. A 19-mm mass with ring enhancement in the left cerebellum was found upon brain magnetic resonance imaging (MRI). Radiation therapy (3000 cGy) was given to control the brain metastasis. Thereafter, he received only intermittent symptomatic management while his lung disease slowly progressed. After admission, brain MRI and water deprivation and vasopressin challenge tests were done to confirm that the central diabetes insipidus was caused by the pituitary metastasis. Brain MRI showed that small, enhancing nodules had newly appeared in both cerebra, the right cerebellum and the pons, whereas the previous metastatic lesion in the cerebellum was much improved (Figure 1). On T1-weighted MRI, the signal intensity of the posterior pituitary gland was markedly decreased, suggesting the pituitary metastasis (Figure 2). The initial serum osmolarity was 292 mOsm/kg, whereas the urine osmolarity and urine specific gravity were 102 mOsm/kg and < 1.005, respectively. During the 5-hour water deprivation testing, the urine osmolarity was not increased above 200 mOsm/kg though almost 3 kg of weight loss occured. However, it increased to 272 mOsm/kg (a 75% increase) 30 minutes after the subcutaneous injection
According to postmortem studies, pituitary gland metastasis has been found in 1%-27% of patients with systemic cancer.1-2 Lung and breast cancers represent more than half of the primary cancer sites. Pituitary metastasis from lung cancer is a later event, along with multiple metastases to other organs. Central diabetes insipidus with polyuria and polydipsia are the most common clinical manifestations,2 whereas symptoms from metastatic tumors are relatively rare.3 Herein, we report a case of diabetes insipidus that was caused by pituitary metastasis from non–small-cell lung cancer (NSCLC).
Case Report Two years ago, a 78-year-old man was admitted to our hospital with symptoms of polydipsia and polyuria; he had suffered with these symptoms for 2 weeks. His urine volume was approximately 5 L per day. He was diagnosed as having NSCLC (adenocarcinoma, stage IIIA) with the involvement of a mediastinal lymph node; 1Department 2Department
of Internal Medicine of Radiology Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul, 139-706 Submitted: Jun 28, 2007; Revised: Sep 11, 2007; Accepted: Sep 17, 2007 Address for correspondence: Jae Cheol Lee, MD, Department of Internal Medicine, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul 139-706, Korea Fax: 82-2-970-2426; e-mail: [email protected]
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1525-7304, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
Clinical Lung Cancer November 2007
565
Polyuria and Polydipsia in a Patient with NSCLC Figure 1 Axial View of Brain Magnetic Resonance Imaging
Figure 2 T1-Weighted Brain Magnetic Resonance Imaging
The markedly decreased signal intensity of the posterior pituitary gland was noted, suggesting the pituitary pathology.
Compared with the previous brain MRI taken 10 months before, multiple small enhancing nodules have newly appeared on both cerebrum lobes, the right cerebellum and pons. The previous metastatic lesion on the left cerebellum, which was treated with RT, was much improved.
of 5 U of vasopressin (Figure 3). Central diabetes insipidus was diagnosed, and the patient started to take 0.2 mg of desmopressin at bedtime. His urine volume normalized, and the polydipsia ceased. Although radiosurgery was suggested, he refused further management and was discharged.
Discussion Diabetes insipidus is a clinical syndrome that is characterized by hypotonic polyuria and polydipsia, as a result of deficient antidiuretic hormone (ADH) secretion (central diabetes insipidus), inadequate renal response to ADH (nephrogenic diabetes insipidus), or primary polydipsia.4 Central diabetes insipidus is caused by a variety of diseases that affect the hypothalamicneurohypophyseal axis, and these can be classified as traumatic, inflammatory, or neoplastic. Before symptoms of diabetes insipidus develop, disruption of > 50% of the supraoptic-hypothalamic tract or near-total destruction of the posterior pituitary lobe must occur.1 This explains the relative rarity of clinically evident diabetes insipidus in patients with cancer. Most of these patients die of disseminated lesions before diabetes insipidus is noticed, and physicians are reluctant to pursue this diagnosis in severely ill patients. Metastases in the posterior pituitary lobe are more common than that in the anterior lobe, and this is probably caused by the direct blood supply of the posterior lobe from systemic circulation.3,5 However, the anterior pituitary can be involved in 15% of patients through the portal vessels or via direct extension from juxtasellar and skull base metastasis.6 The posterior pituitary is identified on MRI by the hyperintensity, which is probably caused by the phospholipids or the
566
Clinical Lung Cancer November 2007
secretory granules in the pituicytes. A lack of this hyperintensity on the sagittal T1-weighted images could be the hallmark of hypothalamic-posterior pituitary disorders, though the same change can occasionally be found in healthy persons.7 Pituitary adenoma is difficult to differentiate radiogically from metastasis to the gland.2 Because diabetes insipidus is reported in only 1% of patients with adenoma, Schubiger and Haller suggest that diabetes insipidus is the most important criterion for distinguishing metastasis from adenoma.8 In our case, the possibility of adenoma seemed to be very low considering that there was no abnormal finding in the pituitary gland on the previous MRI taken 10 months before the diagnosis of diabetes insipidus, the patient had combined metastasis to other areas of brain parenchyma, and the clinical manifestations of diabetes insipidus. Treatments are usually palliative when considering poor progFigure 3 Water Deprivation and Vasopressin Challenge Test
mOsm
Kg
350 56
300 250
55
200
54
150 53
100 Posm B. wt Uosm
50
52
0 Basal
1 hr
2 hrs 3 hrs 4 hrs 5 hrs
6 hrs
Vasopressin 5 U s.c. The plasma osmolarity did not change during the test and the urine osmolarity was increased 75% after subcutaneous injection of 5 U vasopressin. Abbreviations: B. wt = body weight; s.c. = subcutaneously
Jae Wook Jung et al nosis because of the aggressiveness of the primary disease per se. However, early treatment with RT or surgical exploration and decompression can improve the quality of life in some patients.2
Conclusion Although symptomatic diabetes insipidus from lung cancer is rare, physicians should be aware of this possibility to provide the patient with early and appropriate management.
References 1. Kimmel DW, O’Neill BP. Systemic cancer presenting as diabetes insipidus. Clinical and radiographic features of 11 patients with a review of metastatic-induced
diabetes insipidus. Cancer 1983; 52:2355-8. 2. Komninos J, Vlassopoulou V, Protopapa D, et al. Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 2004; 89:574-80. 3. Matsuda R, Chiba E, Kawana I. Central diabetes insipidus caused by pituitary metastasis of lung cancer. Internal Medicine 1995; 34:913-8. 4. Makaryus AN, McFarlane SI. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med 2006; 73:65-71. 5. Leclercq TA, Grisoli F. Arterial blood supply of the normal pituitary gland: an anatomical study. J Neurosurg 1983; 58:678-81. 6. Rajput R, Bhansali A, Dutta P, et al. Pituitary metastasis masquerading as nonfunctioning pituitary adenoma in a woman with adenocarcinoma lung. Pituitary 2006; 9:155-7. 7. Koshimoto Y, Maeda M, Naiki H, et al. MR of pituitary metastasis in a patient with diabetes insipidus. AJNR Am J Neuroradiol 1995; 16:971-4. 8. Schubiger O, Haller D. Metastases to the pituitary–hypothalamic axis. An MR study of 7 symptomatic patients. Neuroradiology 1992; 34:131-4.
Clinical Lung Cancer November 2007
567
Key words: Desmopressin, Diabetes insipidus, Pituitary gland metastasis
Introduction
this was confirmed by mediastinoscopic biopsy. Sequential chemotherapy with 4 cycles of gemcitabine (1000 mg/m2 on days 1 and 8, every 3 weeks), carboplatin (area under the curve 6 on day 1, every 3 weeks) and radiation therapy (RT) of 6300 cGy was given to him because he refused to undergo surgery. The size of the lung mass was reduced on the follow-up computed tomography scan; thus, the patient exhibited a partial response. He presented with dizziness and intermittent headache 6 months after treatment. A 19-mm mass with ring enhancement in the left cerebellum was found upon brain magnetic resonance imaging (MRI). Radiation therapy (3000 cGy) was given to control the brain metastasis. Thereafter, he received only intermittent symptomatic management while his lung disease slowly progressed. After admission, brain MRI and water deprivation and vasopressin challenge tests were done to confirm that the central diabetes insipidus was caused by the pituitary metastasis. Brain MRI showed that small, enhancing nodules had newly appeared in both cerebra, the right cerebellum and the pons, whereas the previous metastatic lesion in the cerebellum was much improved (Figure 1). On T1-weighted MRI, the signal intensity of the posterior pituitary gland was markedly decreased, suggesting the pituitary metastasis (Figure 2). The initial serum osmolarity was 292 mOsm/kg, whereas the urine osmolarity and urine specific gravity were 102 mOsm/kg and < 1.005, respectively. During the 5-hour water deprivation testing, the urine osmolarity was not increased above 200 mOsm/kg though almost 3 kg of weight loss occured. However, it increased to 272 mOsm/kg (a 75% increase) 30 minutes after the subcutaneous injection
According to postmortem studies, pituitary gland metastasis has been found in 1%-27% of patients with systemic cancer.1-2 Lung and breast cancers represent more than half of the primary cancer sites. Pituitary metastasis from lung cancer is a later event, along with multiple metastases to other organs. Central diabetes insipidus with polyuria and polydipsia are the most common clinical manifestations,2 whereas symptoms from metastatic tumors are relatively rare.3 Herein, we report a case of diabetes insipidus that was caused by pituitary metastasis from non–small-cell lung cancer (NSCLC).
Case Report Two years ago, a 78-year-old man was admitted to our hospital with symptoms of polydipsia and polyuria; he had suffered with these symptoms for 2 weeks. His urine volume was approximately 5 L per day. He was diagnosed as having NSCLC (adenocarcinoma, stage IIIA) with the involvement of a mediastinal lymph node; 1Department 2Department
of Internal Medicine of Radiology Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul, 139-706 Submitted: Jun 28, 2007; Revised: Sep 11, 2007; Accepted: Sep 17, 2007 Address for correspondence: Jae Cheol Lee, MD, Department of Internal Medicine, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul 139-706, Korea Fax: 82-2-970-2426; e-mail: [email protected]
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1525-7304, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
Clinical Lung Cancer November 2007
565
Polyuria and Polydipsia in a Patient with NSCLC Figure 1 Axial View of Brain Magnetic Resonance Imaging
Figure 2 T1-Weighted Brain Magnetic Resonance Imaging
The markedly decreased signal intensity of the posterior pituitary gland was noted, suggesting the pituitary pathology.
Compared with the previous brain MRI taken 10 months before, multiple small enhancing nodules have newly appeared on both cerebrum lobes, the right cerebellum and pons. The previous metastatic lesion on the left cerebellum, which was treated with RT, was much improved.
of 5 U of vasopressin (Figure 3). Central diabetes insipidus was diagnosed, and the patient started to take 0.2 mg of desmopressin at bedtime. His urine volume normalized, and the polydipsia ceased. Although radiosurgery was suggested, he refused further management and was discharged.
Discussion Diabetes insipidus is a clinical syndrome that is characterized by hypotonic polyuria and polydipsia, as a result of deficient antidiuretic hormone (ADH) secretion (central diabetes insipidus), inadequate renal response to ADH (nephrogenic diabetes insipidus), or primary polydipsia.4 Central diabetes insipidus is caused by a variety of diseases that affect the hypothalamicneurohypophyseal axis, and these can be classified as traumatic, inflammatory, or neoplastic. Before symptoms of diabetes insipidus develop, disruption of > 50% of the supraoptic-hypothalamic tract or near-total destruction of the posterior pituitary lobe must occur.1 This explains the relative rarity of clinically evident diabetes insipidus in patients with cancer. Most of these patients die of disseminated lesions before diabetes insipidus is noticed, and physicians are reluctant to pursue this diagnosis in severely ill patients. Metastases in the posterior pituitary lobe are more common than that in the anterior lobe, and this is probably caused by the direct blood supply of the posterior lobe from systemic circulation.3,5 However, the anterior pituitary can be involved in 15% of patients through the portal vessels or via direct extension from juxtasellar and skull base metastasis.6 The posterior pituitary is identified on MRI by the hyperintensity, which is probably caused by the phospholipids or the
566
Clinical Lung Cancer November 2007
secretory granules in the pituicytes. A lack of this hyperintensity on the sagittal T1-weighted images could be the hallmark of hypothalamic-posterior pituitary disorders, though the same change can occasionally be found in healthy persons.7 Pituitary adenoma is difficult to differentiate radiogically from metastasis to the gland.2 Because diabetes insipidus is reported in only 1% of patients with adenoma, Schubiger and Haller suggest that diabetes insipidus is the most important criterion for distinguishing metastasis from adenoma.8 In our case, the possibility of adenoma seemed to be very low considering that there was no abnormal finding in the pituitary gland on the previous MRI taken 10 months before the diagnosis of diabetes insipidus, the patient had combined metastasis to other areas of brain parenchyma, and the clinical manifestations of diabetes insipidus. Treatments are usually palliative when considering poor progFigure 3 Water Deprivation and Vasopressin Challenge Test
mOsm
Kg
350 56
300 250
55
200
54
150 53
100 Posm B. wt Uosm
50
52
0 Basal
1 hr
2 hrs 3 hrs 4 hrs 5 hrs
6 hrs
Vasopressin 5 U s.c. The plasma osmolarity did not change during the test and the urine osmolarity was increased 75% after subcutaneous injection of 5 U vasopressin. Abbreviations: B. wt = body weight; s.c. = subcutaneously
Jae Wook Jung et al nosis because of the aggressiveness of the primary disease per se. However, early treatment with RT or surgical exploration and decompression can improve the quality of life in some patients.2
Conclusion Although symptomatic diabetes insipidus from lung cancer is rare, physicians should be aware of this possibility to provide the patient with early and appropriate management.
References 1. Kimmel DW, O’Neill BP. Systemic cancer presenting as diabetes insipidus. Clinical and radiographic features of 11 patients with a review of metastatic-induced
diabetes insipidus. Cancer 1983; 52:2355-8. 2. Komninos J, Vlassopoulou V, Protopapa D, et al. Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 2004; 89:574-80. 3. Matsuda R, Chiba E, Kawana I. Central diabetes insipidus caused by pituitary metastasis of lung cancer. Internal Medicine 1995; 34:913-8. 4. Makaryus AN, McFarlane SI. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med 2006; 73:65-71. 5. Leclercq TA, Grisoli F. Arterial blood supply of the normal pituitary gland: an anatomical study. J Neurosurg 1983; 58:678-81. 6. Rajput R, Bhansali A, Dutta P, et al. Pituitary metastasis masquerading as nonfunctioning pituitary adenoma in a woman with adenocarcinoma lung. Pituitary 2006; 9:155-7. 7. Koshimoto Y, Maeda M, Naiki H, et al. MR of pituitary metastasis in a patient with diabetes insipidus. AJNR Am J Neuroradiol 1995; 16:971-4. 8. Schubiger O, Haller D. Metastases to the pituitary–hypothalamic axis. An MR study of 7 symptomatic patients. Neuroradiology 1992; 34:131-4.
Clinical Lung Cancer November 2007
567