- Email: [email protected]
Impending myxedema coma as the initial presentation of lung cancer
+
MODEL
Journal of the Formosan Medical Association (2016) xx, 1e2
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.jfma-online.com
CORRESPONDENCE
Impending myxedema coma as the initial presentation of lung cancer Chia-I Shen a, Hsu-Ching Huang b, Yi-Chen Yeh c,d,e, Chao-Hua Chiu b,d,e,* a
Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan c Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan d Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan e Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan b
Received 26 July 2016; received in revised form 22 September 2016; accepted 27 September 2016
Myxedema coma is an endocrine crisis,1 and metastatic malignancy induced thyroid dysfunction is uncommon but receiving increased attention. Progressive destruction of the thyroid gland caused by metastatic malignancy can contribute to hypothyroidism and potentially eventual myxedema coma.2 Here, we report a patient with impending myxedema coma diagnosed as lung cancer with thyroid-gland metastasis in conclusion. A 72-year-old man presented to our Emergency Department with altered consciousness, progressive dyspnea, and general edema over 2 weeks. Chest radiograph revealed bilateral pleural effusion and pericardial effusion, which were lymphocyte-predominant exudate. Laboratory investigations showed that sodium levels had dropped to 110 mmol/L (normal range: w135e147 mmol/L). Serum free-T4 levels were also below the detectable level (<0.4 ng/dL) and thyroid-stimulating hormone levels had increased to 71.0 uIU/mL (normal range: w0.400e4.000 uIU/mL). Both anti-thyroglobulin antibody
Conflicts of interest: The authors have no conflicts of interest relevant to this article. * Corresponding author. Department of Chest Medicine, Taipei Veterans General Hospital 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan. E-mail address: [email protected] (C.-H. Chiu).
and anti-thyroid peroxidase antibody were negative. On thyroid sonography, 3.6- and 3.5-cm diameter heterogeneous hypoechoic masses with diffuse microcalcification were observed in the right and left lobes of the thyroid gland, respectively. Fine-needle aspiration revealed malignant cells. Following thyroxine and glucocorticoid replacement, the patient underwent total thyroidectomy. Pathology demonstrated that the normal thyroid gland had been almost completely replaced by metastatic carcinoma cells that were positive for TTF-1, CK7, and napsin A, but negative for thyroglobulin and PAX-8 (Figure 1). A metastatic tumor of pulmonary origin was favored. Chest computed tomography confirmed a 5.5-cm diameter mass in the right middle lobe of the lung, with multiple enlarged mediastinal lymph nodes. The final diagnosis was stage IV lung adenocarcinoma with thyroid-gland metastasis, causing secondary hypothyroidism and impending myxedema coma. Erlotinib was prescribed due to the presence of the EGFR L858R mutation in the biopsied tumor cells. The patient responded well, and the level of consciousness returned to normal status within 2 months. However, the disease progressed with pleural seeding, pericardial effusion, and massive pleural effusion after 10 months of treatment. Myxedema coma constitutes an emergency situation, with high mortality rates ranging from w25% to 60%.1 Most
http://dx.doi.org/10.1016/j.jfma.2016.09.009 0929-6646/Copyright ª 2016, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Shen C-I, et al., Impending myxedema coma as the initial presentation of lung cancer, Journal of the Formosan Medical Association (2016), http://dx.doi.org/10.1016/j.jfma.2016.09.009
+
MODEL
2
C.-I. Shen et al.
Figure 1 Normal thyroid gland architecture was destroyed and largely replaced by cancer cells [A, 40; B, 200 (hematoxylin and eosin stain)]. Both thyroid follicular cells (arrow) and cancer cells (arrow head) were positive for TTF-1 (C, 200), but only thyroid follicular cells were positive for thyroglobulin (D, 200).
cases are related to thyroidectomy or with a previous history of radioiodine therapy.1 There are increasing case reports of hypothyroidism caused by treatment with a tyrosine kinase inhibitor, most notably sunitinib.3 The clinical presentation is systemic failure, including respiratory failure and altered mental status. The treatment consists of supportive care and emergent thyroid-hormone replacement.1 Tumor metastasis as the cause of hypothyroidism is rare, with autopsy studies reporting the incidence of thyroid metastasis in patients with known malignancy ranging from 1.9% to 24%.4 The most common origins are kidney, breast, gastrointestinal tract, and lung.4 Pathology with an ancillary panel of immune-histochemical staining is needed to make a final diagnosis.4 In our case, the presence of a classical EGFR mutation supported the diagnosis. Surgical resection provides evidence for both diagnosis and treatment; however, the benefits and disadvantages remain controversial.5 There is increased awareness of thyroid dysfunction caused by metastatic cancer-cell infiltration. In most cases, thyroid function remains normal; however, both thyrotoxicosis and hypothyroidism have been reported.2 To clinical
physicians, it is important to note that thyroid metastasis is among the differential diagnoses of hypothyroidism, especially in patients with thyroid nodules.
References 1. Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res 2011;2011:493462. 2. Youn JC, Rhee Y, Park SY, Kim WH, Kim SJ, Chung HC, et al. Severe hypothyroidism induced by thyroid metastasis of colon adenocarcinoma: a case report and review of the literature. Endocr J 2006;53:339e43. 3. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012;18:988e1028. 4. Chung AY, Tran TB, Brumund KT, Weisman RA, Bouvet M. Metastases to the thyroid: a review of the literature from the last decade. Thyroid 2012;22:258e68. 5. Moghaddam PA, Cornejo KM, Khan A. Metastatic carcinoma to the thyroid gland: a single institution 20-year experience and review of the literature. Endocr Pathol 2013;24:116e24.
Please cite this article in press as: Shen C-I, et al., Impending myxedema coma as the initial presentation of lung cancer, Journal of the Formosan Medical Association (2016), http://dx.doi.org/10.1016/j.jfma.2016.09.009
MODEL
Journal of the Formosan Medical Association (2016) xx, 1e2
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.jfma-online.com
CORRESPONDENCE
Impending myxedema coma as the initial presentation of lung cancer Chia-I Shen a, Hsu-Ching Huang b, Yi-Chen Yeh c,d,e, Chao-Hua Chiu b,d,e,* a
Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan c Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan d Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan e Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan b
Received 26 July 2016; received in revised form 22 September 2016; accepted 27 September 2016
Myxedema coma is an endocrine crisis,1 and metastatic malignancy induced thyroid dysfunction is uncommon but receiving increased attention. Progressive destruction of the thyroid gland caused by metastatic malignancy can contribute to hypothyroidism and potentially eventual myxedema coma.2 Here, we report a patient with impending myxedema coma diagnosed as lung cancer with thyroid-gland metastasis in conclusion. A 72-year-old man presented to our Emergency Department with altered consciousness, progressive dyspnea, and general edema over 2 weeks. Chest radiograph revealed bilateral pleural effusion and pericardial effusion, which were lymphocyte-predominant exudate. Laboratory investigations showed that sodium levels had dropped to 110 mmol/L (normal range: w135e147 mmol/L). Serum free-T4 levels were also below the detectable level (<0.4 ng/dL) and thyroid-stimulating hormone levels had increased to 71.0 uIU/mL (normal range: w0.400e4.000 uIU/mL). Both anti-thyroglobulin antibody
Conflicts of interest: The authors have no conflicts of interest relevant to this article. * Corresponding author. Department of Chest Medicine, Taipei Veterans General Hospital 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan. E-mail address: [email protected] (C.-H. Chiu).
and anti-thyroid peroxidase antibody were negative. On thyroid sonography, 3.6- and 3.5-cm diameter heterogeneous hypoechoic masses with diffuse microcalcification were observed in the right and left lobes of the thyroid gland, respectively. Fine-needle aspiration revealed malignant cells. Following thyroxine and glucocorticoid replacement, the patient underwent total thyroidectomy. Pathology demonstrated that the normal thyroid gland had been almost completely replaced by metastatic carcinoma cells that were positive for TTF-1, CK7, and napsin A, but negative for thyroglobulin and PAX-8 (Figure 1). A metastatic tumor of pulmonary origin was favored. Chest computed tomography confirmed a 5.5-cm diameter mass in the right middle lobe of the lung, with multiple enlarged mediastinal lymph nodes. The final diagnosis was stage IV lung adenocarcinoma with thyroid-gland metastasis, causing secondary hypothyroidism and impending myxedema coma. Erlotinib was prescribed due to the presence of the EGFR L858R mutation in the biopsied tumor cells. The patient responded well, and the level of consciousness returned to normal status within 2 months. However, the disease progressed with pleural seeding, pericardial effusion, and massive pleural effusion after 10 months of treatment. Myxedema coma constitutes an emergency situation, with high mortality rates ranging from w25% to 60%.1 Most
http://dx.doi.org/10.1016/j.jfma.2016.09.009 0929-6646/Copyright ª 2016, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Shen C-I, et al., Impending myxedema coma as the initial presentation of lung cancer, Journal of the Formosan Medical Association (2016), http://dx.doi.org/10.1016/j.jfma.2016.09.009
+
MODEL
2
C.-I. Shen et al.
Figure 1 Normal thyroid gland architecture was destroyed and largely replaced by cancer cells [A, 40; B, 200 (hematoxylin and eosin stain)]. Both thyroid follicular cells (arrow) and cancer cells (arrow head) were positive for TTF-1 (C, 200), but only thyroid follicular cells were positive for thyroglobulin (D, 200).
cases are related to thyroidectomy or with a previous history of radioiodine therapy.1 There are increasing case reports of hypothyroidism caused by treatment with a tyrosine kinase inhibitor, most notably sunitinib.3 The clinical presentation is systemic failure, including respiratory failure and altered mental status. The treatment consists of supportive care and emergent thyroid-hormone replacement.1 Tumor metastasis as the cause of hypothyroidism is rare, with autopsy studies reporting the incidence of thyroid metastasis in patients with known malignancy ranging from 1.9% to 24%.4 The most common origins are kidney, breast, gastrointestinal tract, and lung.4 Pathology with an ancillary panel of immune-histochemical staining is needed to make a final diagnosis.4 In our case, the presence of a classical EGFR mutation supported the diagnosis. Surgical resection provides evidence for both diagnosis and treatment; however, the benefits and disadvantages remain controversial.5 There is increased awareness of thyroid dysfunction caused by metastatic cancer-cell infiltration. In most cases, thyroid function remains normal; however, both thyrotoxicosis and hypothyroidism have been reported.2 To clinical
physicians, it is important to note that thyroid metastasis is among the differential diagnoses of hypothyroidism, especially in patients with thyroid nodules.
References 1. Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res 2011;2011:493462. 2. Youn JC, Rhee Y, Park SY, Kim WH, Kim SJ, Chung HC, et al. Severe hypothyroidism induced by thyroid metastasis of colon adenocarcinoma: a case report and review of the literature. Endocr J 2006;53:339e43. 3. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012;18:988e1028. 4. Chung AY, Tran TB, Brumund KT, Weisman RA, Bouvet M. Metastases to the thyroid: a review of the literature from the last decade. Thyroid 2012;22:258e68. 5. Moghaddam PA, Cornejo KM, Khan A. Metastatic carcinoma to the thyroid gland: a single institution 20-year experience and review of the literature. Endocr Pathol 2013;24:116e24.
Please cite this article in press as: Shen C-I, et al., Impending myxedema coma as the initial presentation of lung cancer, Journal of the Formosan Medical Association (2016), http://dx.doi.org/10.1016/j.jfma.2016.09.009