JOURNAL OF MILITARY PHARMACO MEDICINE N 0 4 2022 203 SERUM CONCENTRATIONS OF NT PROBNP IN BASEDOW’S PATIENTS WITH THYROTOXICOSIS Ton That Kha 1 , Hoang Trung Vinh 2 Summary Objectives To assess of ser[.]
JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 SERUM CONCENTRATIONS OF NT-PROBNP IN BASEDOW’S PATIENTS WITH THYROTOXICOSIS Ton That Kha1, Hoang Trung Vinh2 Summary Objectives: To assess of serum NT-proBNP levels in patients with Basedow’s disease and its relationship with body mass index, age, and gender Subjects and methods: Serum NT-proBNP levels were measured by electrochemiluminescence immunoassay (ECLIA) with a sandwich immunoassay in 258 patients with Basedow’s disease was compared with 84 age-matched subjects in the control group [37.0 (27.0 - 52.0) vs 39.0 (30.0 - 50.5) years, p = 0.67] Results: NTproBNP concentration in patients was significantly higher than in controls [250.7 (120.4 - 511.8) vs 26.8 (10.6 - 45.8) pmol/L; p < 0.001] NT-proBNP concentration in the control group 50-75 years old was higher than that in < 50 years old [ 37.8 (19.9 - 52.0) pmol/L vs 21 ,9 (10.0 - 41.2) p < 0.001] The concentration of NT-proBNP in the 50 - 75 years old patient was higher than that of under 50 years old patient [456.0 (241.4 - 979.0) pmol/L vs 194.0 (109.0 414.3) p < 0.001] NT-proBNP concentrations in patients of all age groups were higher as compared with the control group The majority of patients (67.8%) had an NT-proBNP concentration of 125-2000 pmol/L The concentration of NTproBNP in patients and control groups was not related to gender No significant gender relationship NT-proBNP levels in patients with new onset, BMI ≥ 23 kg/m2 higher than patients with relapse or BMI < 23 kg/m2 Conclusion: Basedow's patients with thyroid hormone toxicity have increased serum NTproBNP levels The majority of increased NT-proBNP patients is in the concentration of 125 - 2000 pmol/L * Keywords: Basedow’s disease; Hyperthyroidism; Thyrotoxicosis; serum concentrations of NT-proBNP National Hospital of Endocrinology Military Medical University Corresponding author: Ton That Kha (kha13_13@yahoo.com) Date received: 28/4/2022 Date accepted: 23/5/2022 203 JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 INTRODUCTION N-terminal proBrain Natriuretic peptide (NT-proBNP) is a biomarker associated with cardiovascular damage, especially changes in heart function, in many diseases, including Basedow disease NT-proBNP is found in high concentrations in the myocardium When there is an increase in hemodynamic pressure in the heart, such as the hyperactive heart in Basedow' patients, it will cause an increase in the release into the blood, especially in the presence of heart failure The authors suggest that NT-proBNP is a novel biomarker that is recognized as a gold standard in the diagnosis of thyroid function-induced cardiac function In patients with Basedow, the stage of thyroid hormone toxicity will have elevated NT-proBNP levels associated with many different manifestations, especially changes in cardiovascular indicators, thyroid hormone, TSH, TRAb The purpose of this study was to investigate serum NT-proBNP levels in Basedow`s patients in the stage of thyroid hormone toxicity SUBJECTS AND METHODS Subjects This study included 258 patients with Basedow’s disease and 84 healthy persons in the control group 204 * Inclusion criteria: - Patient group + Basedow’s patients with thyrotoxicosis + Age > 18, both male and female - Control group + Healthy people based on health history, examination and tests + Age-matched with the patient group + Both male and female * Exclusion criteria: - Patient group + Hyperthyroidism is not caused by Basedow's disease + Who have acute illnesses + Having severe chronic diseases such as heart failure not caused by Basedow' disease, kidney failure, cirrhosis, and malignancy + Red blood cells break down when a blood sample is taken - Control group + History of thyroid disease + History of cardiovascular disease + Who have acute illnesses + Red blood cells break down when a blood sample is taken Methods * Study design: A cross-sectional, prospective, case-control study * Place and time of study: From 2017 to March 2022, at the National Hospital of Endocrinology JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 * Study protocol: - Patient group + Asking for medical history and clinical symptoms + Physical examination, including measuring height and weight to calculate body mass index (BMI) + Diagnostic tests include: T3 or FT3, FT4, TSH, TRAb levels + After the examination, the serum NT-proBNP concentration is quantified according to electrochemiluminescence immunoassay (ECLIA) with a sandwich immunoassay on the Cobas E411 Unit: pmol/L - Control group + Asking for medical history + Physical examination + The serum NT-proBNP levels were similar to those in the patient group * Diagnosis criteria and classification: - Diagnosis of Basedow's disease is based on symptoms of the thyrotoxicosis syndrome and the specific diagnostic test, including increased TRAb, FT4, FT3 (or T3), and decreased TSH - Classification of BMI based on Asia - Pacific standards - Grade classification of heart failure based on NT-proBNP concentration: < 125 pmol/L - definitely without chronic heart failure; 125-2000 pmol/L - possible heart failure; > 2000 pmol/L - definitely heart failure - Normal range of thyroid hormones and TRAb T3: 1,3 - 3,1 nmol/L; FT3: 3,1-6,8 pmol/L; FT4: 12-22 pmol/L; TSH: 0,27-4,2 mUI/mL; TRAb: 1-1,58 UI/L * Statistic evaluation and ethics in research: - Data processing methods + Using software SPSS 16.0 + Test for normal distribution by Kolmogorov - Smirnov test + If the variable is continuous, it will determine the mean and standard deviation with 95% confidence + If the variable is not normally distributed, it will determine the median along with the upper and lower quartiles - interquartile range (IQR) + Compare values of two groups with non-normally distributed variables by the Mann - Whitney test + Compare values of groups with non-normally distributed variables by the Kruskal - Wallis test - Medical ethics in research: Research does not violate medical ethics Subjects agreed to participate in the study The study protocol was approved and authorized by the Hospital Ethics Committee 205 JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 RESULTS Table 1: Comparison of age, gender between the two groups, and the characteristics of the patient group Characteristic Patient group (n = 258) Control group (n = 84) p Age (years) Median (IQR) 37.0 (27.0 - 52.0) 39.0 (30.0 - 50.5) < 50 187 (72.5%) 59 (70.2%) 50 - 75 71 (27.5%) 25 (29.8%) 0.67 0.69 Gender Female 213 (82.6%) 49 (58.3%) Male 45 (17.4%) 35 (41.7%) New onset 197 (76.4%) Relapse 61 (23.6%) < 0.001 + The differences in the age of the patient and the proportion of subjects according to age subgroups between the two groups was not significant + The proportion of female subjects in both groups was significantly higher than male subjects Table 2: Proportion of patients based on BMI BMI (kg/m2) Subjects (n) Proportion (%) < 18.5 - underweight 105 40.7 18.5 - 22.9: normal range 139 53.9 23 - 24.9: overweight 10 3.9 ≥ 25 - obese 1.6 + Patients with BMI in the normal range accounted for the highest percentage, followed by the underweight + Overweight and obesity accounted for a very low rate 206 JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 Table 3: Comparison of NT-proBNP concentrations between patient and control groups NT-proBNP (pmol/L) Patient group (n = 258) Control group (n = 84) p Median (IQR) 250.7 (120.4 - 511.8) 26.8 (10.6 - 45.8) < 0.001 < 125 68 (26.4%) 83 (98.8%) 125 - 2000 175 (67.8%) (1.2%) > 2000 15 (5.8%) < 0.001 + The concentration of NT-proBNP in patients was higher than in the control group + The proportion of subjects based on levels of NT-proBNP concentration in the patient group had a difference, in which the highest concentration belonged to the concentration of 125 - 2000 pmol/L + Almost all subjects in the control group had NT-proBNP levels < 125 pmol/L Table 4: Correlation of NT-proBNP concentration according to age subgroups between patient and control group Subjects < 50 years 50 - 75 years Control group (n = 84) (n = 59) (n = 25) 21.9 (10.0 - 41.2) 37.8 (19.9 - 52.0) Patient group (n = 258) (n = 187) (n = 71) 194.0 (109.0 - 414.3) 456.0 (241.4 - 979.0) p < 0.001 < 0.001 p < 0.001 < 0.001 + NT-proBNP levels in the 50 - 75 age group were higher in both the control group and the patient group than those in the group aged < 50 + The concentration of NT-proBNP in each age group was higher in the patient than in the control group 207 JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 Table 5: Comparison of proportion of patients of different ages according to serum NT-proBNP level NT-proBNP (pmol/L) < 50 years (n = 187) 50 - 75 years (n = 71) < 125 59 (31.6%) (12.7%) 125 - 2000 121 (64.7%) 54 (76.1%) > 2000 (3.7%) (11.3%) p 0.002 The proportion of patients aged 50 - 75 years with high NT-proBNP levels (125-2000 pmol/L or > 2000 pmol/L) was higher than that of patients < 50 years of age Table 6: Comparison of serum NT-proBNP levels between male and female patients NT-proBNP (pmol/L) Female (n = 213) Male (n = 45) p Median (IQR) 247.3 (121.0 - 498.0) 256.0 (120.4 - 519.1) > 0.05 < 125 56 (26.3%) 12 (26.7%) 125 - 2000 146 (68.5%) 29 (64.4%) > 2000 11 (5.2%) (8.9%) > 0.05 The NT-proBNP concentration and the proportion of patients with different levels of NT-proBNP concentration in males and females were not statistically significant Table 7: Comparison of NT-proBNP levels between new-onset and relapsed patients NT-proBNP (pmol/L) New onset (n = 197) Relapse (n = 61) p Median (IQR) 257.0 (140.0 - 496.4) 184.3 (49.6 - 614.0) < 0.05 < 125 41 (20.8%) 27 (44.3%) 125 - 2000 148 (75.1%) 27 (44.3%) > 2000 (4.1%) (11.5%) < 0.001 + The concentration of NT-proBNP in patients with new onset was significantly higher than in patients with relapsed 208 JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 + New onset patients with NT-proBNP levels at 125-2000 pmol/L accounted for the highest rate and higher than relapse patients Table 8: Comparison of NT-proBNP levels in patients between levels of BMI NT-proBNP (pmol/L) BMI < 23kg/m2 (n = 244) BMI ≥ 23 kg/m2 (n = 14) p Median (IQR) 232.7 (117.1 - 486.9) 627.5 (335.0 - 829.2) 0.009 < 125 67 (27.5%) (7.1%) 125 - 2000 163 (66.8%) 12 (85.7%) > 2000 14 (5.7%) (7.1%) > 0.05 + The concentration of NT-proBNP in overweight and obese patients was higher than in underweight or normal patients + The proportion of subjects in two BMI subgroups between the three levels of NT-proBNP concentrations, the difference was not statistically significant DISCUSSION General characteristics of research subjects Patient age is a feature associated with Basedow' disease Most of the authors believe that the age range of Basedow' disease is 30 - 50, although there are still cases of the disease in children or adolescents as well as in the elderly, but at a lower rate The age of the patient will be related to disease characteristics, progression, complications, and treatment outcome The age of the patients in the study was 37.0 To have similarities with the age of the control group, the study selected subjects in this group at the age of 39 Most of the authors found that NT-proBNP concentrations were different between age groups, whereby most of the authors agreed to divide into age groups to observe NT-proBNP concentrations, including < 50; 50 - 75, and > 75 However, in the study, there were no patients aged > 75 (the oldest patient was 74) Both the age of the patients and the proportion of subjects between the age groups of the patient 209 ... concentration of NT- proBNP in patients with new onset was significantly higher than in patients with relapsed 208 JOURNAL OF MILITARY PHARMACO - MEDICINE N04 - 2022 + New onset patients with NT- proBNP. .. The NT- proBNP concentration and the proportion of patients with different levels of NT- proBNP concentration in males and females were not statistically significant Table 7: Comparison of NT- proBNP. .. concentration of NT- proBNP in patients was higher than in the control group + The proportion of subjects based on levels of NT- proBNP concentration in the patient group had a difference, in which