27 minute read
SE：Symposium-Endocrine (1-8
from 109年年會論文摘要集
by Endo 電子書上傳區
SE1-1 PARATHYROID HORMONE NEW ASSAYS
JIN-YING LU
Department Internal Medicine, National Taiwan University Hospital, Taipei , Taiwan
Parathyroid hormone (PTH) is a peptide molecule containing 84 amino acids with a molecular weight of 9,500 Daltons and is secreted by the four parathyroid glands located behind the thyroid. PTH plays a major role in the regulation of calcium and phosphate metabolism. Many disorders resulted from dysregulation of PTH secretion. Primary hyperparathyroidism due to parathyroid hyperplasia or adenoma causes increased bone resorption, hypercalcemia, and hypophosphatemia. Hypoparathyroidism as a complication of thyroid surgery results in adynamic bone disease, hypocalcemia, and hyperphosphatemia. Chronic kidney disease often hampers the excretion of phosphate and thus causes secondary hyperparathyroidism and renal osteodystrophy. The correct measurement of PTH is especially important for the diagnosis and evaluation of therapeutic effects for these disorders.
The biological activity of PTH derives from the interaction between its N-terminal 34 amino acids 1-34 (PTH 1-34) and the PTH receptor. The C-terminal amino acids 7-84 (PTH 7-84) even suppresses the receptor and exerts an opposite effect to those of whole PTH. There are several different PTH N- and C-terminal fragments in normal circulation. How to measure exactly the whole length PTH and avoid the inactive fragments is the major concern of clinical laboratory. Correct measurements of different PTH fragments is crucial for the diagnosis, treatment, and prognosis of many different disorders. In clinical laboratories, the conditions of blood collection and storage, and different assay methods all affect the measurements of PTH. The first-generation immunoassay is radioimmunoassay (RIA) uses an antibody against the C-terminal PTH (c-PTH), which might detect the inactive fragments of PTH and thus has already been abandoned from clinical use. Excluding the first- generation immunoassay, in current laboratories we have two kinds of assays for the examination of PTH, the second-generation immunoassay detects the intact PTH (i-PTH) and has been thought to detect only the active form of PTH. However, it is later noted to also detect the inactive N-terminal PTH 7-84. The third-generation PTH immunoassay detects only the whole PTH (w-PTH) containing the N-terminal amino acids. However, almost all clinical laboratories still use the second-generation immunoassays to detect i-PTH, thus might lead to falsely elevated results when measuring the concentration of serum PTH levels in patients with chronic kidney disease.
SE1-2
原發性副甲狀腺高能症
邱偉益
臺大醫院內科部代謝內分泌科
原發性副甲狀腺高能症一種常見的內分泌疾病，其特徵在於高鈣血症和血清副甲狀腺素濃度 升高或過高，現今主要是由生化檢驗數據異常而診斷。在過去的 50 年中，原發性副甲狀腺高能 症最常見的臨床表現，如尿路結石，骨病變等症狀已不如以往明顯，演變為幾乎無症狀的疾病。 原發性副甲狀腺高能症的臨床表現變異進一步擴大，一個新的特異型態已逐漸被注意，那就 是血鈣正常的原發性副甲狀腺高能症。在排除造成副甲狀腺高能症的繼發原因後，可診斷為血鈣 正常的原發性副甲狀腺高能症。但是相關自然史、手術的適應症和術後成效的研究數據有限，將 從此病的定義、流行病學、診斷、臨床表徵及其治療做一個扼要的整理。
SHU-YI WANG
Department of Endocrinology & Metabolism, Changhua Christian Hospital, Taiwan
Secondary hyperparathyroidism (SHPT) is characterized by an increase in parathyroid hormone (PTH) that is appropriate and in response to a stimulus low serum calcium.
The most common causes of secondary hyperparathyroidism are chronic kidney failure but can also be seen in a variety of bone and metabolic conditions (e.g. malnutrition, malabsorption, vitamin D deficiency, lithium use, thiazide use and chronic cholestasis). The recent increase in bariatric surgery has created an emerging population of patients with malabsorptive syndromes.
SHPT is a common complication in chronic kidney disease. Hypophosphatemia, decreased 1,25-dihydroxyvitamin D, and the resultant slight decrease in serum calcium, fibroblast growth factor 23 (FGF23) have been considered to the main contributors to the pathogenesis of SHPT.
Elevated PTH levels are associated with an increased risk of mortality and cardiovascular outcome. High-turnover bone disease has been the most widely recognized consequence of SHPT.
The best treatment for SHPT is fixing the cause. For patients with kidney failure, the main treatments include phosphate binders, vitamin D supplements, and calcimimetics. The main reasons for a parathyroidectomy include: worsening bone density, severe pruritus, calciphylaxis, PTH levels that are consistently higher than 800 pg/ml, and inability to control calcium and phosphorus levels by dialysis.
SE1-4 RECENT ADVANCES IN SURGICAL TREATMENT FOR PRIMARY HYPERPARATHYROIDISM
SI-YUAN WU, MING-LANG SHIH
Division of General Surgery, Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan
Parathyroidectomy is the sure treatment for primary hyperparathyroidism. The hypercalcemia, bone density loss, and urolithiasis could be cured by surgery. Minimally invasive parathyroidectomy, which uses a small incision and minimal dissection, has become the preferred surgical procedure since 2000. However, it requires more dedicated preoperative planning and intraoperative decision making than a traditional standard bilateral neck exploration. Several new technologies, including 4DCT scans, intraoperative PTH analysis, or even autofluorescence, have been introduced to optimize preoperative planning and intraoperative decision. The clinician needs to recognize the advantages and limitations of each tool. A successful parathyroid surgery involves multidisciplinary teamwork. We will cover the surgical indication, proper use of the localization tests, parathyroid exploration procedure, and intraoperative verification of disease gland removal.
YEN-HSIANG CHANG
Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan.
The vast majority of thyroid cancers of follicular origin have a very favorable outcome, but 5–10% of cases will develop metastatic disease. Around 60–70% of this subset, hence less than 5% of all patients with differentiated thyroid cancer (DTC), will become radioiodine refractory (RAI-R), with a significant negative impact on prognosis and a mean life expectancy of 3–5 years. We will present consensus or guidance currently available for this challenging condition. Criteria for advanced RAI-R DTC will be proposed, and the most appropriate diagnostic tools and the local, systemic and palliative treatments will be described.
Systemic therapy with multikinase inhibitors will be fully discussed, including recommendations on how to start it and at which dosage, on the duration of treatment, and on the management of side effects. The appropriate relationship between the specialist and the patient/family as well as ethical issues will be covered. Based on the available studies and on personal experience, we will provide recommendations aimed to improve the management of advanced RAI-R TCs. Above all of them is the indication to treat and follow these patients in a specialized setting which allows the interaction between several specialists in a multidisciplinary team.
SE2-2 TYROSINE KINASE INHIBITORS FOR RADIOACTIVE IODINE – REFRACTORY DIFFERENTIATED THYROID CARCINOMA
WAN-CHEN WU
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Differentiated thyroid carcinoma (DTC) typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation and thyrotropin hormone-suppressive levothyroxine. DTCs that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. Tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of these advanced radioactive iodine refractory differentiated carcinoma (rr-DTC), and sorafenib and lenvatinib have been approved for use in clinical practice. Previous studies have reported significant improvement regarding the progression-free survival rates of these patients. However, TKIs cause various severe adverse events that damage patients’ quality of life and can even be life-threatening. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present speech will present the molecular basis of these drugs, and how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs.
SE2-3 ADVERSE EVENTS OF TYROSINE KINASE INHIBITORS AND MANAGEMENT
YI FANG CHANG
Cancer Center, MacKay Memorial Hospital, Taipei, Taiwan
The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized cancer therapy and has contributed to a steady decline in cancer related mortality since the early 2000s. The trend to treat cancer with so-called target drugs of TKIs ranging from BCR/ABL, EGFR, VEGFR to multi-target agents is on the rise. And ushered in a new era of personalized medicine for cancer.
However, with the accumulation of experience in the use of TKIs, including gastrointestinal symptoms, fatigue, hypertension, and skin or mucosa, renal dysfunction, and other related adverse reactions also caused clinical care problems. We clinically need to establish close monitoring to actively manage possible adverse reactions to the use of TKIs.
I’ll give a brief overview of the possible mechanisms of adverse toxicities, and clinical treatment for adverse reactions from TKIs. It is hoped that it will help to improve the patient’s compliance of treatment by TKIs and reduce the adverse reactions that lead to dose reduction, short-term interruption of use, and even discontinuation of the drugs. Finally, we could maximize the effectiveness of helping patients to receive the treatment of TKIs and improve the quality of life of patients.
SHYANG-RONG SHIH
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Sorafenib and lenvatinib are approved by FDA to be used in the treatment of radioiodine refractory differentiated thyroid cancer (rrDTC). Mitogen-activated protein kinase (MAPK) pathway involves in the main pathogenesis of papillary thyroid cancer. BRAFV600E mutation and RAS are the two main initiators. Other mutations such as genes in the phosphatidylinositol 3’ -kinase (PI3K) pathway or fusion gene variants are reported. Sorafenib and lenvatinib are multi-kinase inhibitors to block MAPK pathway, but tumor escape effect exists. Therefore, other medications are urged to be developed.
Lapatinib (HER2 inhibitor) and neratinib (pan-ErbB inhibitor) target on HER2/3 receptor to block MAPK and PI3K pathways. ALK translocation, especially STRN-ALK fusion, occurs in thyroid cancer. It will stimulate MEK and activate MAPK pathway. Crizotinib is an ALK inhibitor. Temsirolimus and everolimus are mTOR inhibitors, which block PI3K pathway. BRAF inhibitors and MEK inhibitors block MAPK pathway, and can be used in combination to treat thyroid cancers with BRAFV600E mutation.
Down-regulation of sodium-iodide symporter (NIS) gene results in disability of iodine absorption in thyroid cancer and thus radioiodine refractories. Several medications, such as retinoids, rosiglitazone, selumetinib, and dabrafenib, were shown to be able to improve NIS gene expression and thus radioiodine sensitivity.
Immunotherapies are under investigation for the treatment of rrDTC. The most commonly used immunotherapy currently are CTLA-4 antagonist (such as ipilimumab and tremelimunab), PD-1 antagonist (such as pembrolizumab and nivolumab), and PD-L1 antagonis (such as atezolizumab and durvalumab). Combination of immunotherapy and multi-kinase inhibitors are also used to treat rrDTC in several studies.
Other emerging medications for the treatment of rrDTC include histone deacetylase inhibitors, miR-335-5p, miR-205, 177Lu-DOTA-RGD2, miRNA-497, MDM2-p53 antagonist, HSP90 inhibitor, miRNA-146b, and etc. They also shed lights on the improvement of survival and life-quality in patients with rrDTC.
SE3-1 MANAGEMENT OF RECURRENT CUSHING DISEASE
LIANG-YU LIN
Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan
Cushing disease is caused by pituitary adenomas, most common form of endogenous Cushing syndrome, that secrete adrenocorticotrophic hormone (ACTH). Transsphenoidal surgery is the treatment of choice in patients with these tumors because of reported remission rates of 69–93%. A therapeutic challenging for neurosurgeons and endocrinologists, however, is management of the remaining patients whose Cushing disease is refractory to initial transsphenoidal surgery or recurs after initial remission. Findings in recent published reports on the treatment of recurrent ACTH–secreting tumors suggest that repeat resection, radiation-based therapies such as Gamma Knife surgery and proton-beam radiosurgery, pharmacotherapy, and bilateral adrenalectomy all have important roles in the treatment of recurrent CD. Each of these interventions has inherent risks and benefits that should be presented to the patient during counseling on retreatment options. Radiation-based therapies increasingly appear to have efficacies similar to those of repeat resection in achieving biochemical remission and tumor control. In addition, an expanding retinue of medication-based therapies, several of which are currently being evaluated in clinical trials, has shown some promise as tertiary adjunctive therapies. Lastly, bilateral adrenalectomy may offer durable control of refractory recurrent CD. An increasing number of published studies with long-term patient outcomes highlight the evolving treatment patterns in the management of recurrent CD.
SE3-2 HYPOGONADOTROPIC HYPOGONADISM : CLINICAL PRESENTATION, PATHOGENESIS AND TREATMENT FOR ADULT PATIENT
WEI-TSEN LIAO
Division of Endocrinology & Metabolism, Department of Internal Medicine, Mackay Memorial hospital, Taiwan
Idiopathic hypogonatropic hypogonadism is a rare reproductive disorder. It was defined as deficient hypothalamic gonadotrophinreleasing hormone (GnRH) or pituitary gonadotrophin secretion. We will discuss its clinical presentation, genetics, pathogenesis, and management. and share experience of fertility treatment in adult cases.
SE3-3 THYROID-STIMULATING HORMONE-SECRETING PITUITARY ADENOMA (TSHoma)
YAN-RONG LI
Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taiwan
TSHoma is rare, accounting for only 2% of all secretory pituitary tumors, and <1% of all causes of hyperthyroidism. TSHoma is usually diagnosed in the fifth-sixth decades of life, and affects males and females equally. Most patients have the typical symptoms and signs of hyperthyroidism, but a few patients have mild or even no hyperthyroid symptoms; instead, with symptoms related to the expanding tumor mass.
Here we reported 3 cases (2 men an 1 woman, aged from 35 to 53 years-old) of TSHoma initially presenting with typical hyperthyroidism and treated with anti-thyroid drugs, all of them received transsphenoid surgery 1 to 3.5 years after the diagnosis. The clinical presentation, differential diagnosis, pathogenesis, treatment modalities, and prognosis of TSHoma will be reviewed and discussed.
SE4-1 CLINICAL FEATURES AND BIOMARKERS OF NET
HAO-CHANG HUNG
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital,Tainan, Taiwan
Neuroendocrine tumor (NET), or neuroendocrine neoplasm (NEN), represent a heterogenous group of rare neoplasms, which are derived from the neuroendocrine cell throughout the whole body. The incidence and prevalence of neuroendocrine tumor (NET) are steadily rising. In the USA, the ageadjusted incidence rate increased from 1.09 per 100000 in 1973 to 6.98 per 100000 in 2012. In Taiwan, the age-standardized incidence rate increased from 0.3 per 100000 in 1996 to 1.51 per 100000 in 2008. The most common sites of NETs were gastroenteropancreatic site and lung. NETs are classified as being functional and nonfunctional based on the ability to secret hormones. The clinical presentation depends on the location of the tumor and its secreted hormones. The WHO classification of NETs includes criteria for determining malignant potential, tumor histopathology (well or poorly differentiated), and proliferative activity (grade 1,2 or 3). Most NET have an indolent clinical course, whereas some grow rapidly with distal metastasis.
Due to its heterogeneity, the diagnosis of NET should be confirmed based on the presence of clinical symptoms and associated syndrome, measurement of hormone as biomarkers of disease, radiological and nuclear imaging, and histological confirmation. Additionally, genetic testing for multiple endocrine neoplasia-1 mutation or von Hipple-Lindau disease should be considered for patients with suspected familial syndrome.
SE4-2 ENDOSCOPIC APPLICATIONS ON NET
TSU-YAO CHENG
Department Laboratory Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
Neuroendocrine tumor (NET) is a relatively rare cancer arising from most organs of the body, especially in lung and gastrointestinal (GI) tract. NETs have attracted more attention in recent years because there is a five-fold increase of the incidence rates of NETs in Taiwan from 1996 to 2008.
Among all NETs, gastroenteropancreatic (GEP)-NETs account for 54% in one nation-wide study of NETs in Taiwan. Traditional white light endoscopy along with biopsy is the most common tool for detection of intra-luminal GI NETs. Endoscopic ultrasound (EUS), an excellent imaging tool for both intra-luminal assessment of layer differentiation and extra-luminal evaluation of surrounding tissues of the GI tract, has played a pivotal role in these GEP-NETs in spite of advances in radiological and metabolic imaging studies. EUS can offer information about both the depth of tumor invasion and regional nodal status (T and N staging) in intra-luminal GI NETs. Endoscopic resection of rectal NETs with modified endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) has become an alternative treatment choice to traditional surgical resection. Currently, EUS along with fine needle aspiration/biopsy (FNA/FNB) is the modality of choice for diagnosing pancreatic NETs and for locoregional staging of all GEP-NETs. EUS is also helpful in treatment planning, such as parenchymapreserving resection/ enucleation for small pancreatic NETs.
Newer diagnostic techniques such as contrast enhanced harmonic EUS (CEH-EUS) have been shown to be helpful in detecting small pancreatic NETs. Therapeutic applications including EUSguided tumor injection and radiofrequency ablation (RFA) of small pancreatic NETs have also been under investigation. The future endoscopic applications on GEP-NETs are exciting and worthy of more enthusiastic studies.
SE4-3 UPDATE OF NET TREATMENT
MING-HUANG CHEN
Department Medical Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
Neuroendocrine tumors are a group of heterogeneous malignancies arising from neuroendocrine cells throughout the body. Data from population-based registries indicate that 51% of neuroendocrine tumors arise from the gastrointestinal (GI) tract, 27% from the lungs, and 6% from the pancreas. Clinically, neuroendocrine tumors are regarded as functional if they are associated with symptoms of hormonal hypersecretion, or non-functional if they are not associated with these symptoms. Although carcinoid syndrome is classically associated with metastatic, well-differentiated neuroendocrine tumors of the small intestine, an analysis of National Comprehensive Cancer Centre database showed that most (74%) neuroendocrine tumors are nonfunctional.
Advanced neuroendocrine tumors are incurable in nearly all cases. The somatostatin analogue, approved for control of hormonal syndrome, has been shown to delay disease progression in patients with neuroendocrine tumors. Targeted therapies such as everolimus and sunitinib are approved for advanced pancreatic neuroendocrine tumors.
In addition, everolimus showed robust anti-tumor activity with acceptable tolerability across a broad range of neuroendocrine tumors, including those arising from the GI tract and lung (RADIANT 4 study). Other treatment strategies, including chemotherapy (E2211 trial) and peptide receptor radiotherapy (NETTLER study) are also approved for advanced well differentiated NETs. Furthermore, several potential targeted therapies were developed in well differentiated NETs and showed promising results in phase 2 clinical trials. NETs have emerged due to an improved understanding of the molecular mechanisms responsible for tumor development and progression.
SE4-4 UPDATE OF NET TREATMENT
MING-HUANG CHEN
Department Medical Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
Neuroendocrine tumors are a group of heterogeneous malignancies arising from neuroendocrine cells throughout the body. Data from population-based registries indicate that 51% of neuroendocrine tumors arise from the gastrointestinal (GI) tract, 27% from the lungs, and 6% from the pancreas. Clinically, neuroendocrine tumors are regarded as functional if they are associated with symptoms of hormonal hypersecretion, or non-functional if they are not associated with these symptoms. Although carcinoid syndrome is classically associated with metastatic, well-differentiated neuroendocrine tumors of the small intestine, an analysis of National Comprehensive Cancer Centre database showed that most (74%) neuroendocrine tumors are nonfunctional.
Advanced neuroendocrine tumors are incurable in nearly all cases. The somatostatin analogue, approved for control of hormonal syndrome, has been shown to delay disease progression in patients with neuroendocrine tumors. Targeted therapies such as everolimus and sunitinib are approved for advanced pancreatic neuroendocrine tumors.
In addition, everolimus showed robust anti-tumor activity with acceptable tolerability across a broad range of neuroendocrine tumors, including those arising from the GI tract and lung (RADIANT 4 study). Other treatment strategies, including chemotherapy (E2211 trial) and peptide receptor radiotherapy (NETTLER study) are also approved for advanced well differentiated NETs. Furthermore, several potential targeted therapies were developed in well differentiated NETs and showed promising results in phase 2 clinical trials. NETs have emerged due to an improved understanding of the molecular mechanisms responsible for tumor development and progression.
SE5-1 THE TANGLE BETWEEN DIABETES AND CANCER RELATED TREATMENT
JUNG-FU CHEN
Kaohsiung Chang Gung Memorial Hospital, Taiwan
Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality. People with malignancies and diabetes had significantly more emergency department presentations, more inpatient admissions, longer length of hospital stay and higher rates of all-cause mortality compared to people with a malignancy without diabetes. Diabetes and cancer commonly co-exist, and outcomes in people with both conditions are poorer than in those who have cancer but no diabetes. There is no randomized trial evidence that treating hyperglycemia in people with cancer improves outcomes, and a personalized approach to managing hyperglycemia in people with cancer is needed. Notwithstanding massive efforts and investment in improving cancer therapy, the limited progress made in reducing overall mortality has mostly been achieved through early diagnosis. As cancer therapeutics continues to improve and progress, the adverse side effects associated with anticancer treatments have also attracted more attention and have become extensively explored. Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints(ICPi) cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) and programmed death 1 (PD-1) with inhibitory antibodies has demonstrated effective and durable antitumor activity in subgroups of patients with cancer. ICPirelated hypophysitis and thyroid dysfunction are relatively common irAEs(Immunotherapy related adverse effects) and Pip-related insulin deficient DM and PAI(Adrenal insufficiency) may occur as well. This rare form of iatrogenic diabetes is a result of an accelerated, fulminant islet autoimmunity induced by immune checkpoint inhibitors. Further studies are eagerly awaited and it would be prudent at least for now to instruct diabetic patients to follow healthy lifestyles and to encourage them to have evidence-based cancer screening.
PO-CHUNG CHENG
Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Taiwan
Cancer cells evade the immune system by interacting with immunologic checkpoints to prevent T lymphocyte activation. In recent years, medications that block immune checkpoints to enhance the clearance of cancer cells have shown clinical efficacy against a variety of malignancies. However, immune checkpoint inhibitors can induce undesirable response against self-antigens to trigger the development of endocrinopathy. Commonly prescribed cancer immunotherapies, including Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors and Programmed death 1 (PD1) inhibitors, are associated with autoimmune-related endocrinopathy.
Cancer immunotherapies may trigger endocrinopathy by activating quiescent T lymphocytes that target self-antigens in the endocrine system. Both CTLA-4 and PD-1 are abundantly expressed in the pituitary, thyroid, and adrenal glands, which may become susceptible to immunotherapy related injury. Furthermore, CTLA-4 and PD-1 can trigger the expression of autoantibodies against the pancreatic islet, resulting in insulitis and overt hyperglycemia. A characteristic pattern of adverse reactions may follow the use of immune checkpoint inhibitors. After the use of CTLA-4 or PD-1 inhibitors, allergic skin reactions, gastrointestinal side effects, and liver dysfunction usually precede the onset of endocrinopathy.
Management of immunotherapy induced endocrinopathy involves periodic monitoring of endocrine hormone and plasma glucose levels after initiating immune checkpoint inhibitors. Cancer immunotherapies may be continued after adequate hormonal replacement therapy. In the case of immunotherapy induced insulitis, insulin therapy may be necessary to alleviate the subsequent hyperglycemia. In summary, clinicians should be vigilant in screening for endocrinopathies during the course of cancer immunotherapies and initiate appropriate hormonal replacement therapy to prevent complications.
SE6-1 PREGNANCY -ASSOCIATED OSTEOPOROSIS
WEN-PING YANG
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei City Hospital, Ren-Ai branch, Taipei, Taiwan
Pregnancy-associated osteoporosis (PAO), also termed pregnancy and lactation-associated osteoporosis (PLO), is a rare syndrome of fragility fractures affecting women during late pregnancy and the early postpartum period. Formation of the fetal skeleton during pregnancy requires substantial calcium transfer. Whilst this is predominantly achieved through pregnancy adaptations such as increased intestinal calcium absorption, it can also lead to maternal skeletal resorption , and comparison of BMD measurements before and after pregnancy suggests that pregnancy is associated with some degree of bone mass reduction in the mother. In mothers who go on to breastfeed, marked decreases in BMD are frequently observed. Management of these patients has a limited evidence base. Treatment with anti-resorptive therapy, whilst effective, is controversial and has the potential to cause harm to the fetus. Clinicians should be aware of PAO, a rare but recognised complication of pregnancy. The condition should be especially considered in women presenting with new onset back pain in pregnancy or the postpartum period.
SE6-2 POSTPARTUM HYPOPHYSITIS
YU-FANG CHENG
Section of Endocrinology and Metabolism, Department of Medicine, Changhua Christian Hospital, Changhua County, Taiwan
Hypophysitis is a rare inflammatory condition of the pituitary gland that has three main histologic subtypes: lymphocytic hypophysitis (LH), granulomatous hypophysitis (GH), and xanthomatous hypophysitis (XH). Among these, LH is the most common and is strongly associated with the postpartum state, while XH is the least common.
Lymphocytic hypophysitis most often occurs in women in late pregnancy or the postpartum period, but can also occur in pre-pubertal or post- menopausal women, and in men. Of the 57% of patients who develop the disorder in association with pregnanacy, most do so during the last month of pregnancy or the first 2 months after delivery.
In this section, we will discuss the subtype of hypophysitis associated with Pregnancy, include their clinical features, laboratory finding and how to management.
SE6-3 HYPERTHYROIDISM INDUCED BY EXCESS β-HCG
KUAN-HUA CHEN
Department of Endocrinology and Metabolism, E-Da Hospital, Kaohsiung City, Taiwan
Gestational trophoblastic disease includes complete and partial hydatidiform moles, choriocarcinoma, and placental-site trophoblastic tumor. All these neoplasms secrete β-hCG, free β-units, or other additional forms of these molecules. The patient may thus bear extreme high hCG levels and its subsequent reaction. β-hCG is a glycoprotein heterodimer composed of α and β subunits. Like other glycoprotein hormones, such as TSH, LH, and FSH, hCG shares common α-subunits with the rest while it carries a specific β-subunits. Despite of the unique β subunit, hCG can bind to human TSH receptor with a weak in vitro potency, and it is estimated that 1U hCG equals to only 0.7μU of human TSH. In normal pregnancies, β-hCG is first detected in maternal serum 6 to 9 days after conception, and the placenta is the major source. Its concentration rises in a logarithmic fashion and it peaks at the 8th week after last menstrual period. The average peak serum concentration is about 50 IU/mL, and this concentration rarely induced serious thyrotoxicosis. However, under conditions where hCG is severely elevated, patients suffer from β-hCG induced hyperthyroidism. The patient may be characterized by diffuse goiter, elevated free T4, and suppressed TSH. Meanwhile, thyroid auto-antibodies remained low.
Hydatidiform moles are initially treated with uterine dilatation and curettage with or without adjunctive chemotherapy with methotrexate or actinomycin D. β-hCG itself may also serve as a tumor marker reflecting the effect of the therapy. As β-hCG is lowered, transient hyperthyroidism may resolve, and long-term medical therapy is not necessary.
SE7-1 THE ROLE OF NUCLEAR MEDICINE IN THYROID DISEASE
YEN-HSIANG CHANG
Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan.
Nuclear medicine is directly involved in both the diagnosis and treatment of thyroid disease. The management of thyroid disease using radioisotope has changed over the last 60 years and recent work suggests “risk-adapted” approach, especially in differentiated thyroid cancer. Post-operative radioiodine ablation has been no longer used routinely in those with small tumor and low risk features. Scintigraphic characteristics also help differentiate between nodular and Graves’ disease. However, it is no longer used routinely to assess patients with normal thyroid function test. Advances in imaging especially using (18)F-fluorodeoxy-glucose PET has enabled patients with thyroid cancer to be more accurately imaged, especially if uptake of (131)I is poor. Another approach has been the idea of using radiolabeled somatostatin analogs, which are able to demonstrate uptake in the tumor and, more recently, beta-emitting isotopes have been used for therapy when other options have failed.
SE7-2
個案分享：腎上腺
胡雅惠
台北慈濟醫院新陳代謝內分泌科
腎上腺疾病這個範圍很大，臨床醫師透過抽血檢測以及 24 小時尿液的分析，判斷個案是否 罹患內分泌過量的疾病，在影像方面，常常透過電腦斷層或是核磁共振，搜尋腫瘤位置，核子醫 學影像造影協助定位功能性腫瘤的位置。 1. 原發性醛固酮增多症合併皮質類固醇分泌過量 (primary aldosteronism with cortisol excess)， 確診原發性醛固酮增多症 (primary aldosteronism) 之後，需要區分亞型，是單側還是雙側的病 灶，用來建議病患治療方針，目前臨床上用以區分亞型的黃金標準檢測是雙側腎上腺靜脈採血 (bilateral adrenal venous sampling, AVS)，但是 AVS 在原發性醛固酮增多症合併皮質類固醇分泌過量 的病人，數據會受到干擾，影響判讀，核子醫學造影 (NP59 with SPECT CT)，此時可以輔助定位 皮質功能性腫瘤的位置。 2. 庫欣氏症 雙側腎上腺增生 (Cushing’s syndrome with bilateral macronodular adrenal hyperplasia BMAH) ，倘若此疾病患者需要進行手術治療，核子醫學造影 (NP59 with SPECT CT) ，在此可提 供手術部位 ( 內分泌較強的一側 ) 指引。 3. 嗜鉻細胞瘤 副神經節瘤 (pheochromocytoma paraganglipma PPGL) 核子醫學造影 (MIBG with SPECT CT) 可以協助定位腫瘤的位置，但越是惡性度高的腫瘤或副神經節瘤，MIBG 的顯像率越 低，需要其他的核子醫學造影提供協助。
SE7-3 APPLICATION OF PET IMAGING IN NEUROENDOCRINE TUMORS
MEI-FANG CHENG
Department Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
Neuroendocrine tumors (NETs) are slow-growing malignancies, mostly occur in the respiratory and gastrointestinal tracts, and can cause significant morbidity. Symptoms and signs relate to the location and overproduction of bioactive substances or hormones in the functioning tumors. Not all NETs secrete bioactive hormones (non-functioning tumors), their diagnosis is even more difficult and often are present at an advanced stage. More than 90% of NETs express somatostatin receptors (SSTRs), especially type 2. Positron emission tomography (PET) imaging using 68Ga-DOTATOC (DOTATOC) is a radiotracer that targets SSTR2 and SSTR5. In contrast, 18F-flurodeoxyglucose (FDG) measuring the differential tissue glucose transport in tumors, can be used in aggressive NETs that do not express SSTRs. I will focus on the clinical use of SSTR PET and FDG PET/CT in the standard of care in patients with NETs.
SE8-1 MEDICAL TREATMENT OF ADRENOCORTICAL CARCINOMA
I-WEN CHEN
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan
Adrenocortical carcinoma (ACC) is a rare malignancy with an annual incidence of 1 per 1 million population. The diagnosis of malignancy relies on careful investigations of clinical, biological, and imaging features before surgery and pathological examination after tumor removal.
Sixty percent of tumors are functional, most commonly secreting glucocorticoids alone (45%), glucocorticoids and androgens (45%), or androgens alone (10%). Fewer than 1% of all tumors secrete aldosterone. Patients present with features of the hormone excess state (glucocorticoid, androgen, or both) but abdominal pain, weight loss, anorexia, and fever occur in 25% of cases. Large tumors can press on other organs in the abdomen, causing pain or a feeling of fullness. An adrenal tumor larger than 5 or 6 cm is assumed to be a cancer. In one study, the average size of an adrenal cancer was about 13 cm. After the diagnosis, in order to assess the ACC prognosis and establish an adequate basis for treatment decisions different tools are proposed. Two major staging systems used for adrenal cancer are the American Joint Committee on Cancer (AJCC) TNM staging system and the ENSAT (European Network for the Study of Adrenal Tumors) staging system. Pathology reports define the Weiss score, the resection status and the proliferative index, including the mitotic count and the Ki67 index.
As far as the treatment is concerned, in case of tumor limited to the adrenal gland, the complete resection of the tumor is the first option. Most patients benefit from adjuvant mitotane treatment. In metastatic disease, mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression.
SE8-2 TARGET THERAPY AND IMMUNOTHERAPY FOR ADRENAL CORTICAL CARCINOMA
CHIA- JUI YEN
National Cheng Kung University, Tainan, Taiwan
Adrenal cortical carcinoma (ACC) is a rare disease. It is caused by a cancerous growth in the adrenal cortex, which is the outer layer of the adrenal glands. The adrenal glands lie on top of the kidneys. They play an important role in the endocrine system, which is the system that produces and regulates hormones. In metastatic disease, different parameters had to be considered: the tumoral volume, the number of metastatic organs, the progression slopes. Mitotane remains the only drug approved by the U.S food and drug Administration (FDA) and European Medicine Executive Agency (EMEA) for treatment of “metastatic ACC.” M-EDP (mitotane with etoposide-cisplatin-doxorubicine) is considered as first-line therapy for patients requiring cytotoxic treatment. Yhe sunitinib, a multiTKI, demonstrated in a cohort of 35 patients 14% of stable disease. The association of cituximab with temsirolomus, an inhibitor of mammalian targets of IGF-1R signaling, led to a stable disease in 42% of the patients. The disappointing results of a huge phase 3 trial “GALACCTIC” with a highly specific IGF-1R inhibitor linstinib (OSI-906) showed the progression-free and overall survival did not differ between the “OSI-906” and placebo groups. Immune checkpoint inhibitors can be tested in selected ACC patients, such as those with alterations in the mismatch repair (MMR) pathway that leads to high levels of microsatellite instability (MSI-H). There is an increasing interest in combining chemotherapy, radiotherapy or molecular target therapies with immunotherapy.
SHUO-MENG WANG
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
Adrenal cortical carcinoma (ACC) is also called cancer from adrenal cortex. Cancer from adrenal medulla is called pheochromocytoma. Adrenal cortical carcinoma is rare but aggressive disease. Abdomen mass is usually the first sign at nonfunctional cases. At functional (hormone-secreting) cases may present as Cushing's syndrome and/or virilization,.
There are different types of treatment for patients with adrenocortical carcinoma including surgery, radiation therapy and chemotherapy.
Surgery to remove the adrenal gland (adrenalectomy) is often used to treat adrenocortical carcinoma. Sometimes surgery is done to remove the nearby lymph nodes and other tissue where the cancer has spread.
Surgery (adrenalectomy) can be done at Stage I-III adrenocortical Carcinoma. And at stage IV Adrenocortical Carcinoma, treatment may include the following several modalities as palliative therapy to relieve symptoms and improve the quality of life, and role of srgery to remove cancer that has spread to tissues near the adrenal cortex.
Treatment Options for Recurrent Adrenocortical Carcinoma including surgery, radiation therapy and clinical trial of chemotherapy or biologic therapy.
