The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
WCIM 2014 SEOUL KOREA 17
Slide Session
OS-END-29 Endocrinology
High Diagnostic Performance of Tshrab Assays in Graves’ Disease with Different Cut-Off Values in Early GD
Sena HWANG1, Dong Yeob SHIN1, Eun Jig LEE1 Yonsei University College of Medicine, Korea1
Background: Graves’ disease (GD) is caused by autoantibodies stimulated to thy- roid-stimulating hormone receptor (TSHR). Two frequent assays were compared in relations to the diagnostic accuracy for GD. One is an inhibition assay using the mon- oclonal antibody (M22) closely mimicking the binding to TSH (M22-TRAb), and one is a bioreporter assay using the chimera transfected cell (Mc4-TSAb) and measuring stimulation of cAMP production.
Methods: This cross-sectional study examined 216 sera from thyrotoxicosis patients (including 67 subclinical thyrotoxicosis); 94 sera from GD diagnosed within one month and 120 sera from transient thyrotoxicosis (TT). We compared the diagnostic perfor- mance of two TSHRAb assays.
Results: The M22-TRAb assay and Mc4-TSAb assay were positive in 96.1 and 92.2%
of the GD patients, whereas they were negative in 92.5% and 91.7% of the TT pa- tients. We found the cut-off values of the two tests for GD diagnosis were 2.00 IU/
L and 158.0 %. However, 7 of 94 GD (7.4%) showed discordant results and 2 of them were treated with antithyroid drug that could have effects on the TSHRAb titer. In GD patients with subclinical thyrotoxicosis, the specifi cities for GD diagnosis of both assays were decreased to 82.1% and the proper cut-off levels of M22-TRAb and of Mc4- TSAb were 2.56 IU/L and 217%. M22-TRAb showed stronger correlations with T3 level (P=0.026) and thyroid I-131 uptake (P=0.025) than that of Mc4-TSAb in untreated GD.
Conclusion: Similar and high diagnostic accuracy was shown for Mc4-TSAb and M22-TRAb in GD patients. However, considering a 7.4% discordance rate between two tests, we suggest a combination of both assays can reduce the presence of TSHR- Ab-seronegative GD, especially for those under the therapy. Higher cut-off values of both assays should be considered for diagnosis of early GD.
OS-END-30 Endocrinology
Pattern of Thyroid Dysfunction and Evaluation of Atherosclerotic Cardiovascular Disease Estimator in Patients with Metabolic Syndrome
Prabin GYAWALI1, Jyoti S TAKANCHE1, Bijay Krishna PRAJAPATI2, Rajendra KOJU2 Dhulikhel Hospital-Kathmandu University Hosptial, Nepal1, Dhulikhel Hospital-Kathmandu University Hosptial, Nepal2
Background: Thyroid dysfunction (TD) and metabolic syndrome (Met S) are known risk factors for atherosclerotic cardiovascular disease (ASCVD). TD is risk factor for ASCVD mediated by the effects of thyroid hormones on lipid metabolism and blood pressure hence the components of Met S. Although traditional lipid profi le parameters are used to manage ASCVD in patients with Met S, there are no reliable biochemical parameters that can be used in early prediction, diagnosis and primary prevention. Nevertheless, recent studies have recognized serum lipid ratios, atherogenic index of plasma (AIP) and non- HDL Cholesterol (non-HDL-C) as a stronger predictive marker of coronary atherosclerosis and ASCVD events than isolated parameters used independently. Thus, the purpose of this study was to evaluate -the pattern of TD in patients with Met S and - serum lipid ratios, non-HDL cholesterol, and AIP as a predictor of ASCVD in patients with Met S.
Methods: Between, October 2012 and March 2014, total of 358 previously diagnosed patients with Met S and 341 healthy controls, who visited diabetes and endocrine clinic at Dhulikhel Hospital, Dhulikhel, Nepal were recruited in the study. The thyroid function test parameters were measured to classify TD and the serum lipid concentra- tions were measured to calculate the lipid ratios, non-HDL-C and AIP.
Results: The overall prevalence of TD in patients with Met S was 31.84 % with high prevalence of subclinical hypothyroidism. Patients with Met S had signifi cantly higher signifi cantly higher lipid ratio’s, non-HDL-C (165.78±48.66 vs 135.21±47.88), and AIP levels (0.810±0.023 vs 0.546±0.014) compared to healthy controls (P < 0.05).
Conclusions: Patients with Met S develop sub-clinical hypothyroidism greatly. The measurements of serum lipid ratios, non HDL-C, and AIP level predicts high risk of de- veloping ASCVD in patients with Met S.
OS-END-31 Endocrinology
Whole-Exome Sequencing Reveals Strong Genetic Pre- dictors of Antithyroid Drugs Induced Agranulocytosis
Sin-Gi PARK2, Jong BHAK2, Jong-Soo KIM2, Tae-Hyung KIM2, Jee Hyun AN3, Sang Youl RHEE4, Hee Kyung KIM5, Min Joo KIM6, Hyun Jeong JEON1, Taekeun OH1, Hyung Jin CHOI1 Chungbuk National University Hospital, Korea1, TheragenEtex, Korea2, Korea University Anam Hospital, Korea3, Kyung Hee University School of Medicine, Korea4, Chonnam National University Medical School, Korea5, Korea Cancer Center Hospital, Korea6
Background: Agranulocytosis is a rare but life-threatening side effect of antithyroid drugs. Several reports, including familial cases, suggested that there could be substan- tial genetic susceptibility determinants which could predict the risk of antithyroid drug induced agranulocytosis. However, no tests are currently available to predict the risk of antithyroid drug induced agranulocytosis.
Methods: In this study, we performed whole-exome sequencing to comprehensively identify the genetic variations responsible for antithyroid drug induced agranulocy- tosis. For discovery stage 1, whole-exome sequencing was performed for seven an- tithyroid drug induced agranulocytosis cases. Variant based approach and gene based approach were performed to discover candidate variants or genes for antithyroid drug induced agranulocytosis. For HLA loci, HLA-sequence-based typing was performed.
For validation stage 2, Sanger sequencing and HLA-sequence-based typing were performed for eight additional independent antithyroid drug induced agranulocytosis cases. Antithyroid drug users without agranulocytosis side effect, Korean local healthy controls and public HLA database were used as control group.
Results: Discovery stage genome-wide association study results revealed strong signals in chromosome 6 (P=2.7×10-8) and chromosome 19 (P=1.7×10-14). HLA typing of seven discovery cases and eight validation cases revealed several HLA types, which showed strong association with antithyroid drug induced agranulocytosis (odds ratio=4.6-6.3, P=3×10-3-5×10-5). Gene based approach indicated several candidate genes for antithy- roid drug induced agranulocytosis. In these genes, several loss of function variants were found, which were common among antithyroid drug induced agranulocytosis cases, but these variants were very rare among controls (P=2.0×10-3-1.8×10-4).
Conclusions: In conclusion, several strong genetic predictors of antithyroid drug induced agranulocytosis were discovered. To avoid the risk of life-threatening agranu- locytosis side effect, these pharmacogenomics markers could be tested in clinic before initiation of antithyroid drugs.
OS-END-32 Endocrinology
Challenges in the Management of A Patient with Thyrotoxicosis and Carbimazole-Induced Neutropenia:
Illustration with a Case Report
Veerendra CHADACHAN1, Yi Lin TEH1, Pritish Kumar GEHLOT1 Tan Tock Seng Hospital, Singapore1
Background: Carbimazole is the standard antithyroid drug treatment for patients with thyrotoxicosis, especially in young women of reproductive age. A serious side effect of antithyroid drug use, however, is agranulocytosis. Management of a severely thyrotox- ic patient who has antithyroid drug induced agranulocytosis is challenging.
Methods: We report here a young female who presented with fever, cough and severe neutropenia after she was started on carbimazole for thyrotoxicosis. She complainted of intermittent episodes of palpitations and diarrhoea. Physical examination revealed a diffuse goitre and multiple oral ulcers. She was tachycardic, but hemodynamically stable. Rest of the physical examination was unremarkable. Investigations revealed she had severe neutropenia, and markedly elevated free T4 and T3 hormone levels.
Results: She was started on broad spectrum antibiotics. The administration of gran- ulocyte colony stimulating factor resulted in an improvement in the white blood cell count only after seven days. With carbimazole being stopped, her thyrotoxicosis went on worsening, and she had features of high output cardiac failure. She underwent 3 cycles of plasmapheresis, with which her thyroid function tests stabilised. However, she developed hypotension and hypoxia during the fourth cycle of plasmapheresis due to cardiac failure. Once her thyroid function tests stabilised, she was transferred to receive radio-active iodine.
Conclusions: Antithyroid drug–induced agranulocytosis is a potentially lethal condi- tion but is completely reversible when recognised early and when prompt treatment is offered. Management of such a patient who is severely thyrotoxic is very diffi cult.
We will discuss here the literature review on carbimazole-induced agranulocytosis and illustrate the challenges we face in managing such situations and discuss what are the strategies in managing such patients.
WITHDRAWAL
