Lin-Hai Yan1, Xian-Wei Mo1, Yu-Zhou Qin1, Cheng Wang2, Zhi-Ning Chen3, Yuan Lin1, Jian-Si Chen1. 1. Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China. 2. Department of Nutriology, Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China. 3. Department of Pathology, Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Abstract
CONTEXT: Gastrointestinal stromal tumors (GISTs) are responsive to sunitinib (the tyrosine kinase inhibitor), this agent is widely used in prevention relapse of GISTs and neo-adjuvant chemotherapy in GIST patients without operation opportunity. The use of these agents has both advantages and disadvantages. On the one hand, it can improve the outcome for patient. On the other hand, it may lead to consumptive hypothyroidism, a rare syndrome caused by increased catabolism of T4 and T3 by increased type 3 iodothyronine deiodinase (D3) activity. D3 is the major physiologic inactivator of thyroid hormone, this selenoenzyme catalyzes the inner-ring deiodination of T(4) to reverse T(3) and T(3) to 3, 3;-diiodothyronine, both of which are biologically inactive [1]. Increased monitoring and supernormal thyroid hormone supplementation are required for affected patient. OBJECTIVE: The aim of the study was to report the first case of consumptive hypothyroidism in an athyreotic patient after surgical resection of gastrointestinal stromal tumor. DESIGN, SETTING, AND PATIENT: A 60-year-old athyreotic male was presented and he was euthyroid when receiving a stable therapeutic dose of thyroid hormone which was used to treat consumptive hypothyroidism resulting from the side effects of sunitinib, which is used for treatment of neo-adjuvant chemotherapy in gastrointestinal stromal tumor. With a discovery of large D3-expressing gastrointestinal stromal tumor, this patient suffered from marked Hyperthyrotropinemia, which instantly worsened after surgical resection of the gastrointestinal stromal tumor and then continued for 12 weeks after the surgical resection, in spite of further increases in levothyroxine therapy. The patient also had low serum T3 and elevated serum reverse T3 (rT3). INTERVENTION: The patient's consumptive hypothyroidism caused by marked overexpression of the thyroid hormone-inactivating D3 within the gastrointestinal stromal tumor and adjacent normal gastrointestinal tissue. MAIN OUTCOME MEASURES AND RESULTS: D3 immunostaining of the patient's gastrointestinal stromal tumor was positive, with no significant immunoreactivity in adjacent normal gastrointestinal tissue. The expression levels of CD34, CD117, and DOG1 in peri-tumor tissue samples was lower than that in tumor tissue. The mRNA expression level of KIT exon17 in peri-tumor tissue was higher than that in tumor tissue. CONCLUSIONS: This is the first case report of consumptive hypothyroidism in an adult after surgical partial resection of the gastrointestinal stromal tumor. This case demonstrates that hyperthyrotropinemia may worsen after surgical resection of the gastrointestinal stromal tumor.
CONTEXT: Gastrointestinal stromal tumors (GISTs) are responsive to sunitinib (the tyrosine kinase inhibitor), this agent is widely used in prevention relapse of GISTs and neo-adjuvant chemotherapy in GISTpatients without operation opportunity. The use of these agents has both advantages and disadvantages. On the one hand, it can improve the outcome for patient. On the other hand, it may lead to consumptive hypothyroidism, a rare syndrome caused by increased catabolism of T4 and T3 by increased type 3 iodothyronine deiodinase (D3) activity. D3 is the major physiologic inactivator of thyroid hormone, this selenoenzyme catalyzes the inner-ring deiodination of T(4) to reverse T(3) and T(3) to 3, 3;-diiodothyronine, both of which are biologically inactive [1]. Increased monitoring and supernormal thyroid hormone supplementation are required for affected patient. OBJECTIVE: The aim of the study was to report the first case of consumptive hypothyroidism in an athyreoticpatient after surgical resection of gastrointestinal stromal tumor. DESIGN, SETTING, AND PATIENT: A 60-year-old athyreotic male was presented and he was euthyroid when receiving a stable therapeutic dose of thyroid hormone which was used to treat consumptive hypothyroidism resulting from the side effects of sunitinib, which is used for treatment of neo-adjuvant chemotherapy in gastrointestinal stromal tumor. With a discovery of large D3-expressing gastrointestinal stromal tumor, this patient suffered from marked Hyperthyrotropinemia, which instantly worsened after surgical resection of the gastrointestinal stromal tumor and then continued for 12 weeks after the surgical resection, in spite of further increases in levothyroxine therapy. The patient also had low serum T3 and elevated serum reverse T3 (rT3). INTERVENTION: The patient's consumptive hypothyroidism caused by marked overexpression of the thyroid hormone-inactivating D3 within the gastrointestinal stromal tumor and adjacent normal gastrointestinal tissue. MAIN OUTCOME MEASURES AND RESULTS: D3 immunostaining of the patient's gastrointestinal stromal tumor was positive, with no significant immunoreactivity in adjacent normal gastrointestinal tissue. The expression levels of CD34, CD117, and DOG1 in peri-tumor tissue samples was lower than that in tumor tissue. The mRNA expression level of KIT exon17 in peri-tumor tissue was higher than that in tumor tissue. CONCLUSIONS: This is the first case report of consumptive hypothyroidism in an adult after surgical partial resection of the gastrointestinal stromal tumor. This case demonstrates that hyperthyrotropinemia may worsen after surgical resection of the gastrointestinal stromal tumor.
Entities:
Keywords:
Gastrointestinal stromal tumors; hyperthyrotropinemia; sunitinib; type 3 iodothyronine deiodinase
Authors: David Howard; Francisco G La Rosa; Stephen Huang; Domenico Salvatore; Michelle Mulcahey; Jennifer Sang-Lee; Michael Wachs; Joshua P Klopper Journal: J Clin Endocrinol Metab Date: 2011-04-20 Impact factor: 5.958
Authors: Sifrance Tran; Michael Dingeldein; Sarah C Mengshol; Saundra Kay; Anthony C Chin Journal: Pediatr Surg Int Date: 2013-11-30 Impact factor: 1.827
Authors: Stephen A Huang; Stephanie A Fish; David M Dorfman; Domenico Salvatore; Harry P W Kozakewich; Susan J Mandel; P Reed Larsen Journal: J Clin Endocrinol Metab Date: 2002-10 Impact factor: 5.958