Upper Limit Of Reference Range Research Articles

Abstract #1407741: Pegaspargase-Induced Severe Hyptriglyceridemia

Pegaspargase (PEG) a critical medication for acute lymphoblastic leukemia (ALL). As a long-acting formulation of L-asparaginase, it leads to degradation and depletion of the amino acid asparagine and selective leukemic cell apoptosis. Despite significantly improving treatment response rates, its use can be challenging due to a complex toxicity profile, including thrombosis, hepatotoxicity, hyperglycemia, pancreatitis, and hypertriglyceridemia (HTG). We report a case of a young man who developed severe hypertriglyceridemia secondary to PEG. A 26-year-old man with no significant past medical history presented with refractory upper respiratory symptoms and cervical lymphadenopathy. He was subsequently found to have severe leukocytosis with 70% blasts and 7cm mediastinal mass with superior vena cava compression. Flow cytometry and bone marrow biopsy diagnosed T-cell ALL and he was started on chemotherapy via the GIMEMA LAL1913 protocol (a chemotherapy regimen that includes prephase cyclophosphamide and induction phase with vincristine, idarubicin, dexamethasone, and PEG). About 12 days after having received PEG, the patient developed unexplained acute hyponatremia to 123 mmol/L and other lab tests such as potassium and hepatic function tests were not able to be processed. Further workup revealed pseudohyponatremia and that lab interference was occurring from lipemia. A triglyceride (TG) level was found to be >4425 mg/dL. LDL direct was measured to be 95 mg/dL, and lipid analysis showed absent chylomicrons. Clinically, he had stable mild abdominal tenderness and a serum lipase level resulted marginally above the upper limit of reference range. At this point, he was transitioned to a low-fat diet (<20g per day). Omega-3-acid ethyl esters (EPA/DHA) and fenofibrate were started. In the next 2 weeks his TG steadily decreased to 163 mg/dL. His mild abdominal pain resolved and lipase normalized. The patient is currently undergoing cycle 2 of his chemotherapy and remains on low fat diet, EPA/DHA, and fenofibrate therapy. After 1 week of receiving his second dose of PEG, his triglycerides were 105 mg/dL. Apo E genotyping was performed and revealed normal E3/E3 genotype. He denies any family history of lipid disorders. The incidence of PEG-induced HTG is poorly described in the adult population, and recent studies have shown the condition is becoming more frequently recognized. Its underlying mechanism is not fully understood, but TG levels often rise dramatically and can lead to severe pancreatitis. Clinicians should be aware of this adverse effect and consider baseline lipid analysis prior to induction chemotherapy and TG surveillance, in addition to clinical monitoring for pancreatitis.

Elevated insulin-like growth factor-1 in patients without clinical evidence of acromegaly.

To 1) identify the frequency of IGF-1 elevation in a cohort of patients without clinically suspected GH excess, in a state-based reference laboratory over a 24-month period, and 2) to examine potential differences in comorbidities and relevant medications between people with an elevated IGF-1 compared to a matched control group. All IGF-1 measurements at Pathology Queensland between 1/12/2018 - 1/12/2020 were identified. The medical records of those with IGF-1 ≥1.1x the upper limit of the reference range were appraised to determine: 1) documentation of acromegalic features, 2) relevant comorbidities and medication use, and 3) further investigations to exclude pathological GH excess. There were 2759 IGF-1 samples measured in 1963 people ≥18 years, over the specified period. Of these, 204 had IGF-1 ≥1.1x the upper limit of the age-matched reference range; 102 cases (61M, 41F) met inclusion criteria, and were matched to 102 controls with a normal IGF-1 based on age, sex, gonadal status and pituitary anatomy on MRI. There were significant differences in the frequency of dopamine agonist use (19/102 cases vs 6/102 controls, OR=3.66, 95%CI: 1.45-9.29, P=0.009) and chronic kidney disease (CKD) (14/102 cases vs 4/102 controls, OR = 3.90, 95%CI: 1.28-11.14, P=0.024). Out of 1963 patients having IGF-1 measured, 102 (5.2%) had an elevated IGF-1 where there was no known acromegaly, GH replacement or endogenous glucocorticoid excess. Intra-individual biological variability, assay imprecision and physiological factors are known contributors to falsely elevated IGF-1, dopamine agonist therapy and CKD should also be considered. This article is protected by copyright. All rights reserved.

Reference Ranges of Selenium in Plasma and Whole Blood for Child-Bearing-Aged Women in China.

Selenium (Se) is a “dual-surface” element. Both Se-deficiency and Se-overload have bad effects on humans. The amount of Se in the blood is a good indicator of Se intake, and there are considerable differences in the reference ranges among different regions and populations. The purpose of this study was to establish the age-specific reference interval of blood Se in healthy child-bearing-aged women in China. A total of 187 healthy women aged 18–45 years old were enrolled with strict inclusion criteria from the China Adult Chronic Disease and Nutrition Surveillance (2015 CACDNS) database to establish the reference interval of Se. Plasma and whole-blood Se were detected by inductively coupled plasma mass spectrometry (ICP-MS). The reference range (RR) estimated as P2.5–P97.5 percentiles (geometric mean) was 73.81–140.75 (100.94) μg/L and P2.5–P97.5 percentiles (median) 81.06–164.75 (121.05) μg/L for plasma and whole-blood Se, respectively. The proposed RR of plasma Se in this study was used to evaluate the Se nutritional status of a representative sample of 1950 women of child-bearing age who were randomly selected from 2015 CACDNS. The proportion of Se level lower than P2.5 cut-off value was 24.05%, and there were 5.08% child-bearing-aged women with plasma Se higher than the upper limit of RR. Women in the western and rural areas tend to have lower Se levels.

Changes in Serum Liver Function for Patients with COVID-19: A 1-Year Follow-Up Study.

ObjectiveAbnormal liver function and liver injury related to COVID-19 during hospitalization has received widespread attention. However, the long-term observation of patients’ liver functions after discharge has not been investigated. This study intends to analyze the abnormal liver function in patients one year after they are discharged.MethodsSerum liver function tests were analyzed for the first time immediately after hospitalization (T1), before discharge (T2), a median of 14.0 (14.0, 15.0) days after discharge (T3) and 1 year (356.0 (347.8, 367.0) days) after discharge (T4). Patients with at least one serum parameter (ALT, AST, ALP, GGT and TB) exceeding the upper limit of reference range were defined as having abnormal liver function.ResultsFor the 118 COVID-19 patients with a median follow-up time of 376.0 (71.5, 385.3) days from onset to the end of the follow-up after discharge, the proportion with abnormal liver function in T1, T2, T3 and T4 were 32.2%, 45.8%, 54.8% and 28.8%, respectively. The proportion of patients with at least once abnormal liver function detected from T1 to T2, T1 to T3, T1 to T4 was 60.2%, 77.4% and 88.9%, respectively. From T1 to T4, the ALT, AST, GGT and BMI at admission were significantly higher in the patients with persistently abnormal liver function than in the patients with persistently normal liver function. Abnormal liver function was mainly manifested in the elevation of GGT and TB levels. Multivariate logistics regression analysis showed that age and gender-adjusted ALT (odds ratio [OR]=2.041, 95% confidence interval [CI]: 1.170–3.561, P=0.012) at admission was a risk factor for abnormal liver function in the T4 stage.ConclusionAbnormal liver function in patients with COVID-19 can persist from admission to one year after discharge, and therefore, the long-term dynamic monitoring of liver function in patients with COVID-19 is necessary.

Comparison of the difference in serum insulin growth factor-1 levels between chronological age and bone age among children

ObjectiveBy measuring serum insulin-like growth factor-1 (IGF-1) levels in children aged 2–16, we aimed to analyze the changes in IGF-1 levels in different sex and age groups, and compare the consistency of IGF-1 results evaluated by chronological age (CA) and bone age (BA) in children. MethodsA cross-sectional study was conducted between January 2017 and December 2020 among 2979 relatively healthy children who attended the Department of Growth and Development outpatient clinic and health care center of the Affiliated Children’s Hospital of the Capital Institute of Pediatrics and underwent health examination and development assessment. Height, weight, and Tanner pubertal stage were measured by pediatricians. The CHN method was used to estimate BA. Venous blood samples were collected from the children, and IGF-1 levels were determined via chemiluminescence. ResultsIGF-1 levels in childhood increased slowly with age, dramatically during puberty,and continuously withgrowth until to 15 years for boys and reached a peak value at 13 years for girls based on CA. IGF-1 levels reached peak values at 14 and 13 years for boys and girls, respectively, based on BA. There were differences in IGF-1 values between the CA and BA groups at the age of 10–11 years for boys and 7–11 years for girls. A total of 103 boys (7.7%) and 17 girls (1.0%) had IGF-1 levels below the lower limit of the reference range based on CA; evaluating based on BA, there were 82 boys (6.1%) and 15 girls (0.9%) still had IGF-1 values less than the lower limit of the reference range. Eighteen boys (1.3%) and 173 girls (10.5%) had IGF-1 levels above the upper limit of the reference range based on CA; evaluating based on BA, these numbers reduced to 5 (0.4%) among boys and 41 (2.5%) among girls. ConclusionsThere is a significant difference between BA and CA in evaluating IGF-1 levels in children, which can significantly reduce the proportion of IGF-1 values above the upper limit of the kit reference range in children. This suggests that children with BA advanced in pubertal period, the evaluating results of IGF-1 should be corrected by using BA.

Evaluation of Sysmex Fully Automated CS Series Coagulation Analyzer at a Tertiary Care Hospital

INTRODUCTIONThe Sysmex CS coagulation series system is a high performance coagulation station that allow laboratories to perform routine and specialized testing including platelet function tests on the same platform. The CS is equipped with an optical fiber that supplies light at five wavelengths (multiwavelength detection) that simultaneously measure multiple parameters using clotting, chromogenic, immunoassay and aggregation methods. It has clot curve analysis feature.AIMS & OBJECTIVES : The aim of the present study was to evaluate the performance of the instrument as per the lab's current & future needs. The tests performed were routine coagulation (PT, APT, TT, fibrinogen, factor VIII, Lupus Anticoagulant), chromogenic (Innovance antithrombin III and Berichrom Protein C) and immunologic assays (Innovance Free Protien S). Additionally, the operational performance of the Sysmex CS- 2000i System was compared with the existing automated coagulation analyzer Sysmex CA-530.MATERIALS & METHODS :Sample collection and Preparation Blood collected in 3.2% sodium citrate vacutainers (BD) were centrifuged for 10 min at 3000g to prepare platelet poor plasma (PPP). Multiple coagulation assays were done on a total of 642 patient samples to evaluate the system. The number of tests done for different routine and specialized assays are as follows: PT (597);APTT-FS (555);APTT-FSL (545);TT (297);Fibrinogen (165);Factor VIII (23);Bethesda assay (2); Protein C (65); Free Protein S Ag(60);ATIII (76); LA1(23); LA2 (14). All assays were performed according to the manufacturers' specifications and standard laboratory methods. RESULTS1.Precision for PT,APTT was found to be <1% whereas for fibrinogen it was within 5%.(Table 1)2.Accuracy for PT,fibrinogen,AT III and factor VIII was performed and found close to the target values. (Table 2)3.Biological reference intervals were established for PT,APTT(FS,FSL),TT,LA1 and LA2. (Table 3)4.Mixing Study was carried out for a sample when a patient's PT, APTT, TT and LA were prolonged and outside the upper limit of reference range. This was done to determine the cause of prolongation in correlation with the clinical history. The mixing studies results helped clinicians to make decision regarding factor deficiencies and circulating inhibitors.5.Linearity: 21mg/dl for fibrinogen and 0.9% for factor VIII lowest limit of detection (LOD) was obtained.(Figures 1 & 2). The CS analyzer can save upto 10 calibration curves for each of the parameters viz fibrinogen,factor VIII, free protein S, Protein C, ATIII.6.Free Protein S, Protein C activity and ATIII assays were performed on CS-2000i to investigate the possibility of thrombotic disorders. The calibrators and controls were found to be within acceptable limits.7. We assessed the ability of CS-2000i to perform the platelet aggregation and examine the effect of agonist ADP at different concentrations (Figure 3). We intend to perform Plt Agg with the other agonists to enable diagnosis of platelet function defects.8. The results of the study between the CS-2000i and CA- 530 were correlated and the results are shown for PT, APTT, and Fibrinogen in Figures 4, 5 & 6. CONCLUSIONS1. The analytical performance for routine and specialized assays on CS-2000i was compared to that of Sysmex CA-530 using the same Siemens reagents on both systems. The agreement between the two systems was excellent.2.It has cap-piercing technology which supports clinical and workflow excellence by helping to prevent sample contamination and deliver accurate results.3.Platelet aggregation can be performed on CS-2000i along with routine and other specialized coagulation assays thus avoiding the requirement of procuring a separate platelet aggregometer.4.Sysmex CS analyzer showed good precision, accuracy, linearity and provided faster turn around time. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Elevated carcinoembryonic antigen in patients with COVID-19 pneumonia

PurposeCoronavirus disease 2019 (COVID-19) tends to affect multiple organs and induce abnormal laboratory parameters. We designed this study to investigate the association between carcinoembryonic antigen (CEA) elevation and SARS-CoV-2 infection.MethodsWe retrospectively analyzed 177 patients with confirmed SARS-CoV-2 infection who received plasma CEA assays during hospitalization. Patients with other causes of CEA elevation were excluded. Data regarding epidemiological and demographical characteristics, clinical symptoms, laboratory tests, and outcomes were analyzed. Linear regression analysis was used to evaluate the correlation between CEA levels and inflammation severity.Results171 patients were included in the final study and 32 patients (18.7%) had raised serum of CEA (> 5 ng/ml), with a median (range) age of 66 (53–86). The median [interquartile range (IQR)] CEA level was 11.4 ng/ml (8.1–21.6), which was significantly higher than the upper limit of reference range. CEA level between 5–10 ng/ml was in 11 patients, 10–15 ng/ml in 10 patients, and > 15 ng/ml in 11 patients. No correlation was found between CEA levels and lymphocyte (R2 = 0.055; P = 0.10) nor CRP (R2 = 0.026; P = 0.38). The median levels of CEA were 20.0 ng/ml (IQR, 14.7–23.0) in non-survivors and 10.9 ng/ml (IQR 7.5–16.1) in survivors, and the difference between two groups was statistically significant (P = 0.048).ConclusionSARS-CoV-2 infection might be another cause of CEA elevation, with nearly 20% of patients experienced transient and marked CEA increment during COVID-19 pneumonia. The false-positive results of CEA elevation might have clinical significance for patients with colorectal cancer.

Age- and Sex-Specific TSH Upper-Limit Reference Intervals in the General French Population: There Is a Need to Adjust Our Actual Practices.

It is well known that thyroid dysfunction increases with age. This study is aimed to determine reference intervals, in males and females, suitable for thyroid disease exploration during adult life using routinely collected serum thyrotropin (TSH) data in a tertiary center from 2007 to 2018. Over 11 years, 295,775 TSH levels were measured in a single lab. Among the 156,025 TSH results available for analysis, 90,538 values were from female subjects, 82,019 were from patients aged >60 years and 26,825 were from patients aged >80 years. By using an indirect approach, we determined reference values of TSH adapted to age and sex, and we then evaluated the proportion of patients who would have been reclassified with these reference values. The median TSH ranged from 1.2–1.4 mUI/L during the study period. The upper limit of reference range of TSH increased with age; in females the median to 97.5th percentile values increased continuously from the age of 30 years to the oldest age group. Using new calculated reference values in patients with TSH above the conventional upper-limit reference value (4 mUI/L), the proportion of results reclassified as within the reference interval among patients aged >60 years ranged, according to age group, from 50.5% to 65.1% of females and from 33.0% to 37.7% of males. The use of TSH age-specific and sex-specific upper-limit reference values led to the reclassification of a great number of samples, notably among women. This suggests that age-specific TSH upper-limit reference intervals in daily practice should be used in order to avoid misclassification.

OR19-2 Big Data Strategy Used to Draw TSH Reference Values for Elderly Population

Introduction: Determination of reference ranges for thyroid function tests, such as TSH, are not a simple task. There are several biological and individual aspects to be considered, one of the most important is age, particularly for the extremes, children and the elderly population. Several studies demonstrated a progressive increase in age-related TSH in older adults. Therefore, the aim of this study is to establish specific reference values for Brazilian population over 60 years old using Big Data strategy. Methods: Data from 10.43 million TSH tests performed in the same method were retrospectively analyzed. All the samples are from the same clinical laboratory, with samples from several regions of Brazil. The samples were selected using the following filters: free T4 concentration within the reference values (RV), absence of anti-thyroid antibodies and of medication use. Groups were divided by age from 18 to 59 years old (under-60), and over 60 up to 107 years old (over-60). Statistical analyzes were performed using R software and EP Evaluator. Both R package ‘boot’ and EP Evaluator nonparametric (CLSI C28-A) were used to estimate the 97.5% confidence interval (IC). Results: After filtering the samples, 306,289 were selected. Mean TSH was similar in both sex. However, there were differences between the two age-groups, in under-60 group, the lower RV was 0.59 mUI/L (95% IC = 0.57, 0.59) and the upper RV was 6.00 mUI/L (95% IC = 5.94, 6.08). Interestingly, in over-60 group the lower RV was 0.36 mUI/L (95% IC = 0.34, 0.38) and the upper RV was 9.38 mUI/L (95% IC = 8.86, 9.44). Furthermore, this upper limit of reference range increases within the older group with TSH of 7.4 mUI/L from 60 to 69, 9.60 mUI/L from 70 to 79 and 12.30 mUI/L above 80 years old. Conclusion: Big data strategy could be a useful tool to reach agreeable population reference values. In particular, for TSH, the higher upper reference limits for adults over 60 years old would be important to avoid overdiagnosis and over-treatment of subclinical hypothyroidism in this population.

THE MEASUREMENTS OF BLOOD CLOTTING IN CARDIORENAL SYNDROME IN ELDERLY

Aim. To assess the changes in hemocoagulation parameters according to the grade of renal dysfunction in elderly patients with cardiorenal syndrome types II and IV.Material and methods. In 56 patients of the elderly age group (mean age 78±10 y.o.), with coronary heart disease and chronic heart failure, the parameters of blood clotting were assessed and the relations with kidney dysfunction grade measured by the level of glomerular filtration rate (GFR). Patients were selected to 3 groups. In 47 (83,9%) there was decline of GFR &lt;60 mL/min/1,73 m2, of those in 8 (17,3%) &lt;30 mL/min/1,73 m2; in 9 GFR &gt;60 mL/min/1,73 m2, with no signs of proteinuria (16,1%). All patients underwent coagulological assessment of the blood with measurement of the activated partial thromboplastin time, thrombin time and prothrombin time, international normalized ratio and fibrinogen concentration, as the complete blood count with platelet number, mean platelet volume, thrombocyte distribution width, and thrombocrit.Results. The number of platelets did differ significantly in groups 1 and 3 (p=0,040), as 2 and 3 (p=0,007). Thrombocrit values did differ significantly only in 2 and 3 (p=0,029). In the group 3 the rate of the mentioned values was below the respective reference values. Fibrinogen levels did differ significantly in groups 1 and 3 (p=0,042), and 2 and 3 (p=0,037). In the group 3 the parameter was higher than upper limit of reference range. Correlation found for GFR and fibrinogen level (r=-0,425; p=0,004), for GFR and platelet number (r=0,271; p=0,049). The platelet number correlated with creatinine level (ρ=-0,392; p=0,004). Creatinine level also correlated with fibrinogen level (ρ=0,375; p=0,012).Conclusion. In the elderly, with the decline of GFR there is decline of thrombocyte number and increase of fibrinogen concentration together with an increase of the severity of kidney dysfunction. The pathological changes that were found might probably serve as additional factor influencing the risk of adverse events related to disorder of blood clotting. The importance of the revealed relations, as the aimfulness for clinical application, should be evaluated in controlled studies.

Effect of Low Dose Oral Contraceptive Pill on Coagulation Status in Women with Normal and Low Body Mass Index

Background: Oral contraceptive pill (OCP) is widely used by millions of women of various socioeconomic conditions.Use of low dose oestrogen and newer progesterone in OCP now associated with less thromboembolic and cardiovascular risk. The safety aspects of these pills had not been investigated in details in malnourished women of developing countries. In the present study the effects of the pillson coagulation status have been studied.Objective: To explore the effect of the most widely used low dose OCP (Shukhi) on coagulation status of Bangladeshi women with normal and low BMI(Body Mass Index). Materials and Methods: The study population group (n=29) comprised of women with normal BMI and the underweight group (n=11,BMI&lt;18.5). Both groups use low dose OCP(30?g ethinyl estradiol and 150?g levonorgestrel) for 6-60 months. The coagulation status were assessed as follows: Plasma Fibrinogen, Prothrombin time and Platlete aggregation and Anticoagulation statuseg: AntithrombinIII (ATIII).Result:Coagulation status showed no significant difference in platelet aggregation between the groups. Plasma fibrinogen median value (450mg/dl) just exceeded the upper limit of reference range (normal range: 200-400mg/dl) in normal BMI. In contrast, the corresponding value in the low BMI (318mg/ dl) group was almost at the middle of the reference range. A significantly prolonged prothrombin time (13.80 seconds) was found in the low BMI group (p=0.058); values were still within the reference range (10-14 seconds). No significant correlation existed between plasma fibrinogen, prothrombin time and platelet aggregation in normal BMI or low BMI groups. Antithrombin IIIactivity in normal BMI group was 108% and in low BMI group it was 105%. Atendency of positive correlation existed between antithrombin III activity and BMI in low BMI pill users (r=0.591,p=0.072).Conclusion:The study suggested that a) Reported risk of procoagulant or thromboembolic changes in pill users is lower in low BMI &amp;normal BMI and b) Low BMI users showed significantly longer prothrombin time due to the effect of malnutrition itself or due to the effect of pills in this nutritional background.J Bangladesh Coll Phys Surg 2017; 35(1): 3-8

Using Hashimoto thyroiditis as gold standard to determine the upper limit value of thyroid stimulating hormone in a Chinese cohort.

BackgroundSubclinical hypothyroidism, commonly caused by Hashimoto thyroiditis (HT), is a risk factor for cardiovascular diseases. This disorder is defined as merely having elevated serum thyroid stimulating hormone (TSH) levels. However, the upper limit of reference range for TSH is debated recently. This study was to determine the cutoff value for the upper normal limit of TSH in a cohort using the prevalence of Hashimoto thyroiditis as “gold” calibration standard.MethodsThe research population was medical staff of 2856 individuals who took part in health examination annually. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, thyroid peroxidase antibody (TPAb), thyroglobulin antibody (TGAb) and other biochemistry parameters were tested. Meanwhile, thyroid ultrasound examination was performed. The diagnosis of HT was based on presence of thyroid antibodies (TPAb and TGAb) and abnormalities of thyroid ultrasound examination. We used two different methods to estimate the cutoff point of TSH based on the prevalence of HT.ResultsJoinpoint regression showed the prevalence of HT increased significantly at the ninth decile of TSH value corresponding to 2.9 mU/L. ROC curve showed a TSH cutoff value of 2.6 mU/L with the maximized sensitivity and specificity in identifying HT. Using the newly defined cutoff value of TSH can detect patients with hyperlipidemia more efficiently, which may indicate our approach to define the upper limit of TSH can make more sense from the clinical point of view.ConclusionsA significant increase in the prevalence of HT occurred among individuals with a TSH of 2.6–2.9 mU/L made it possible to determine the cutoff value of normal upper limit of TSH.

Low DHEAS: A Sensitive and Specific Test for the Detection of Subclinical Hypercortisolism in Adrenal Incidentalomas.

Subclinical hypercortisolism (SH) occurs in 5% to 30% of adrenal incidentalomas (AIs). Common screening tests for adrenocorticotropin-independent hypercortisolism have substantial false-positive rates, mandating further time and resource-intensive investigations. To determine whether low basal dehydroepiandrosterone sulfate (DHEAS) is a sensitive and specific screening test for SH in AI. In total, 185 patients with AI were screened for adrenal medullary (plasma metanephrines) and cortical [1 mg overnight dexamethasone suppression test (ONDST), 24-hour urinary free cortisol (UFC), serum DHEAS, plasma renin, and aldosterone] hyperfunction. Positive ONDST [≥1.8 mcg/dL (≥50 nmol/L)] and/or UFC (more than the upper limit of reference range) results were further investigated. We diagnosed SH when at least 2 of the following were met: raised UFC, raised midnight serum cortisol, 48-hour dexamethasone suppression test (DST) cortisol ≥1.8 mcg/dL (≥50 nmol/L). 29 patients (16%) were diagnosed with SH. Adrenocorticotropin was <10 pg/mL (<2.2 pmol/L) in all patients with SH. We calculated age- and sex-specific DHEAS ratios (derived by dividing the DHEAS by the lower limit of the respective reference range) for all patients. Receiver operating characteristic curve analyses demonstrated that a ratio of 1.12 was sensitive (>99%) and specific (91.9%) for the diagnosis of SH. Cortisol following 1 mg ONDST of 1.9 mcg/dL (53 nmol/L) was a sensitive (>99%) screening test for SH but had lower specificity (82.9%). The 24-hour UFC lacked sensitivity (69%) and specificity (72%). A single basal measurement of DHEAS offers comparable sensitivity and greater specificity to the existing gold-standard 1 mg DST for the detection of SH in patients with AIs.

孕中期羊水AFP水平与不良妊娠结局分析

目的：了解孕中期羊水AFP水平及其与不良妊娠的关系。方法：对孕中期妊娠25,038例羊水采用酶联免疫吸附法进行AFP检测，随访妊娠结局，建立羊水AFP参考值及2.5 MoM。结果：孕16~23 w羊水参考值上限为15,665.6~28,766.9 ng/ml，2.5 MoM为18,712.3~38,694.3 ng/ml，且其值随孕周增加而降低，开放神经管缺陷、颈部淋巴管瘤、死胎和腹部畸形妊娠羊水AFP异常比例较高，其他不良妊娠结局则较低，但其AFP值明显增加。结论：羊水AFP异常升高与神经管缺陷、颈部淋巴管瘤、死胎和腹部畸形等不良妊娠相关，但仍有一定漏诊和误诊，应结合动态超声监测以确诊和排除相关畸形。 Objective: To investigate the level of second trimester amniotic fluid alpha-fetoprotein (AFP) and the relationship between the level of AFP and adverse pregnancy outcomes. Methods: The concen-tration of AFP in amniotic fluid sample from 25,038 second trimester pregnancy women was de-tected by using enzyme linked immunosorbent assay. The outcomes were recorded. Results: The upper limit of reference range and 2.5 MoM of the AFP in different gestational weeks are from 15,665.6 to 28,766.9 ng/ml and from 18,712.3 to 38,694.3 ng/ml, and the level of AFP was high with increasing gestational age. The proportion of abnormal AFP were higher in Neural tube defects (NTDs), cystic hygroma, fetal demise and ventral wall defects (VWDs), and that were low in others, but all of them had abnormal increased AFP value significantly. Conclusion: Levels of AFP correlate with the likelihood of NTDs, cystic hygroma, fetal demise and VWDs. But some pregnancies were misdiagnosed or missed. In order to identify and eliminate related deformities, ultrasound should be needed for further diagnosis.

Effects of pyridoxal phosphate in analysis of aminotransferase activity in patients undergoing hemodialysis

Background and Aims: Factors like hemodilution, pyridoxine deficiency, hepatocyte growth factor and uremic toxins have been proposed for low aminotransferase activity in chronic kidney disease (CKD) patients undergoing haemodialysis. This may be a concerning factor in making diagnosis of liver disorders like hepatitis in patients undergoing haemodialysis. In present study we attempted to find out the cause of hypoaminotransferasemia in chronic kidney diseases and biochemical principle of analysis. Materials and Methods: Serum levels of various biochemical parameters are measured in CKD patients undergoing haemodialysis. The serum activities of Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are determined (with and without the addition of PLP) in a group of 176 patients undergoing hemodialysis Results: Serum AST and ALT activities are significantly lower in the CKD patients compared to the control group (P value 0.0003 and 0.001 respectively). Measurement of activity with pyridoxal phosphate containing reagent resulted into a significant increase in values comparison to without pyridoxal phosphate. The percentage activation is higher in patients as compared to controls. Conclusion: The upper limit of reference range for aminotransferases in CKD patients undergoing hemodialysis should be considered lower as compared to healthy subjects. Reagent containing pyridoxal phosphate is considered appropriate for aminotransferase activity measurement.

Hyperprolactinemia

Hyperprolactinemia is frequently diagnosed endocrine problem in routine clinical practice. Once hyperprolactinemia is suspected, repeat test for s prolactin can be done with appropriate precondition for sampling like rest, single prick, adequate light etc. to exclude macroprolactinemia specially in asymptomatic or unrelated symptoms. Once diagnosed as Hyper prolactinemia, secondary causes should be ruled out by history, specially drugs. Pregnancy should be excluded by history and if indicated, by test. Mild elevation of s prolactin can be also due to Polycystic Ovary Syndrome (PCOS), hypothyroidisom, CKD, CLD etc. Of course Hook Effect should be kept in mind. Contrast MRI should be done to see if there is any prolactinoma or hyperplasia. Sometimes Growth Hormone (GH) secreting tumors may be associated. Rarely extra pituitary tumors or disconnection of hypothalamus-pituitary may be seen. In symptomatic patient (hypogonadism, infertility, menstrual disturbances, sexual weakness, unexplained low bone mass and sometimes galactorrhoea etc) and specially if s prolactin is more than 2-3 times of upper limit of reference range, MRI with contrast should be done. Medical therapy with dopamine agonist is the treatment of choice for symptomatic any level of s prolactin and with prolactinoma. Cabergoline may be tried as a first line of treatment because it is more effective and better tolerated than bromocryptine. Though cabergoline is coming up with safety issues, bromocriptine has the largest safety database in pregnancy till date. All patient should be tried with medical treatment, specially cabergoline irrespective of symptoms and size of the tumor. Transsphenoidal microsurgery remains second option when medical treatment is ineffective. Radiotherapy may be the last adjuvant in the management . Rarely malignant prolactinoma may be found and have poor response to medical treatment. Birdem Med J 2013; 3(2): 99-105 DOI: http://dx.doi.org/10.3329/birdem.v3i2.17214

Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism

L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

Determination of upper reference value of urinary calcium-creatinine ratio for the paediatric population in Burdwan district

To estimate the rate of excretion of urinary calcium, a 24-hour sample of urine is required and this is not always easy to collect accurately in infant and children. So, random urine calcium to creatinine ratio (Ca/Cr ratio) has been developed. But as the ratio varies worldwide, reference values of the parameter in paediatric population are not developed. To determine reference value, the present study was conducted in healthy paediatric population in Burdwan district, West Bengal. This study was performed on 693 healthy paediatric subjects, aged between 3 months to 18 years and divided into five groups. Early morning non-fasting urine samples from all study groups were analyzed for Ca/Cr ratio. A negative correlation was observed between age and urinary Ca/Cr ratio, but there was no significant difference of urinary Ca/Cr ratio between two sexes. Considering 97.5th percentile of the underlying distribution of values as the upper limit of reference range, upper reference values of urinary Ca/Cr ratio for age groups of

Giant Cystic Pheochromocytoma Containing High Concentrations of Catecholamines and Metanephrines

A 27-yr-old woman, known with neurofibromatosis type 1 and generalized anxiety disorder, presented with headaches, episodic palpitations, and pallor. Atenolol, started for hypertension by her family doctor, triggered a hypertensive crisis (226/126 mm Hg). Twentyfour-hour urine analysis demonstrated elevated excretion of metanephrine [65.7 ( 1.52; upper limit of reference range) mol/d] and normetanephrine [59.27 ( 1.95) mol/d], and to a lesser extent norepinephrine [2806 ( 569) nmol/d] and epinephrine [1222 ( 149) nmol/d]. Abdominal computed tomography (CT) scan showed a large solid and cystic lesion involving the right adrenal gland (Fig. 1A). 131-I methyliodobenzylguanidine scan showed a right adrenal tumor with prominent peripheral uptake and large central defect (Fig. 1B). After medical preparation with 3 wk of phenoxybenzamine (up to 90 mg/d), propranolol, and preoperative saline loading, the patient appeared clinically adequately blocked. However, anesthetic induction (fentanyl, propofol, lidocaine, and rocuronium) caused a hypertensive crisis (280/170 mm Hg) and prevented surgery. Phenoxybenzamine dosage was increased to 60 mg three times a day, and nifedipine SR 30 mg was added. Intravenous phenylephrine (1 mg) did not affect intraarterial blood pressure, indicating adequate -blockade. The next day, during open adrenalectomy, brittle blood pressure was noted until completion of tumor dissection. A sample of the liquefied tumor center was obtained (Fig. 2). Compared with plasma reference values (1), the cystic fluid contained extremely high concentrations of norepinephrine [65,967 ( 3.4) nmol/liter], epinephrine [51,000 ( 0.8) nmol/liter], dopamine [791.5 ( 0.21) nmol/liter], metanephrine [1,150 ( 0.3) nmol/liter], and normeta-

Early Volume Expansion During Diarrhea and Relative Nephroprotection During Subsequent Hemolytic Uremic Syndrome

To determine if interventions during the pre-hemolytic uremic syndrome (HUS) diarrhea phase are associated with maintenance of urine output during HUS. Prospective observational cohort study. Eleven pediatric hospitals in the United States and Scotland. Children younger than 18 years with diarrhea-associated HUS (hematocrit level <30% with smear evidence of intravascular erythrocyte destruction), thrombocytopenia (platelet count <150 × 10³/mm³), and impaired renal function (serum creatinine concentration > upper limit of reference range for age). Intravenous fluid was given within the first 4 days of the onset of diarrhea. Presence or absence of oligoanuria (urine output ≤ 0.5 mL/kg/h for >1 day). The overall oligoanuric rate of the 50 participants was 68%, but was 84% among those who received no intravenous fluids in the first 4 days of illness. The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% confidence interval, 1.1-2.4; P = .02). Children with oligoanuric HUS were given less total intravenous fluid (r = -0.32; P = .02) and sodium (r = -0.27; P = .05) in the first 4 days of illness than those without oligoanuria. In multivariable analysis, the most significant covariate was volume infused, but volume and sodium strongly covaried. Intravenous volume expansion is an underused intervention that could decrease the frequency of oligoanuric renal failure in patients at risk of HUS.