Evaluation of the Diagnostic Value of Cell Population Data in Sepsis in Comparison to Localized Infection, Chronic Inflammation, and Noninfectious Inflammation Cases.

INTRODUCTION: Sepsis, defined as an increase of 2 points or more in the sequential organ failure assessment score, is a life-threatening organ dysfunction caused by the dysregulated host response to infection. Volume-conductivity-scatter (VCS) parameters of cell counters which are known as cell population data (CPD) have been suggested to be beneficial in diagnosing sepsis. We aimed to evaluate the diagnostic value of CPD parameters in sepsis in comparison to nonsystemic infection cases (NSI) and non-infectious acute and chronic inflammatory conditions. MATERIALS AND METHODS: We prospectively included four groups of patients" data: sepsis (n = 66), localized infection (pneumonia, n = 59), chronic inflammation (rheumatoid arthritis, n = 92) and noninfectious inflammation (coronary artery bypass graft operation, n = 56) groups, according to their clinical status and laboratory results. Samples for cell counting and serum markers were collected on the same day of culture collection. VCS parameters were measured by Unicel DxH800 Coulter Cellular Analyzer (Beckman Coulter, USA). RESULTS: Mean neutrophil volume (MN-V-NE), was highest in the sepsis group [155(149-168)] compared to the localized infection [148(140-158)], chronic inflammation [144.5(142-149)] and noninfectious inflammation [149(145.2-153.7)] (P = 0.001, P < 0.001, P < 0.001, respectively). Neutrophil volume SD (SD-V-NE) was higher in the sepsis [21(18.8-23.7)], significantly differentiating sepsis from other groups. The area under curves of procalcitonin and hs-C-reactive protein were 0.846 and 0.837, respectively, in the receiver-operating characteristic curves (ROC) . CPD combinations, (SD-V NE + SD-V LY + SD-V MO), (SD-V NE + SD-V MO), and (MN-V NE + SD-V NE + SD-C LY + SD-V MO) had greater AUC values than procalcitonin's. CONCLUSION: VCS parameters might be promising for differentiating sepsis and non-sepsis cases. Additionally, obtaining these data routinely makes their prospects promising without any additional cost and time.

Determination of Complete Blood Count Reference Intervals by an Indirect Method for Newborns, Adults, and Geriatric Ages.

BACKGROUND: The availability of a reliable reference interval is crucial for clinical decision-making. Correctly defined reference intervals for different age groups are currently unavailable for many parameters. Our study aimed to determine the complete blood count reference intervals in our region from newborn to geriatric ages with an indirect method. METHODS: The study was carried out at Marmara University Pendik E&R Hospital Biochemistry Laboratory between January 2018 and May 2019 using the laboratory information system data. The complete blood count (CBC) measurements were performed by Unicel DxH 800 Coulter Cellular Analysis System (Beckman Coulter, FL, USA). A total of 14,014,912 test results belonging to infants, children, adolescents, adults, and geriatric ages were collected. We analyzed 22 CBC parameters, and an indirect method was used for reference interval determination. Data were analyzed according to the Clinical and Laboratory Standards Institute (CLSI) C28-A3 guideline for defining, establishing, and verifying reference intervals in the clinical laboratory. RESULTS: We have established reference intervals from newborn to geriatric ages for 22 hematology parameters [hemoglobin (Hb), hematocrit (Hct), red blood cell (RBC), mean red cell volume (MCV), mean red cell hemoglobin (MCH), mean red cell hemoglobin concentration (MCHC), red cell distribution width (RDW), white blood cell (WBC) count, WBC differentials, including percentages and absolute counts, platelet count, platelet distribution width (PDW), mean platelet volume (MPV) and plateletcrit (PCT)]. CONCLUSIONS: Our study showed that reference intervals established with data obtained from clinical laboratory databases are comparable to those created using direct methods.

Accurate interpretation of thyroid dysfunction during pregnancy: should we continue to use published guidelines instead of population-based gestation-specific reference intervals for the thyroid-stimulating hormone (TSH)?

BACKGROUND: Considering the changes in thyroid physiology associated with pregnancy and poor outcomes related to abnormal maternal thyroid function, international guidelines recommend using population-based trimester-specific reference intervals (RIs) for thyroid testing. If these RIs are not available in the laboratory, implementing recommended fixed cut-off values globally is still controversial. To address this issue, we aimed to establish appropriate RI of thyroid-stimulating hormone (TSH) in pregnant Turkish women for our laboratory and compare the prevalence of thyroid dysfunction based on the established and recommended criteria. METHODS: Of 2638 pregnant women, 1777 women followed in the obstetric outpatient were enrolled in the reference interval study after applying exclusion criteria related to medical and prenatal history. A retrospective study was conducted by collecting data from July 2016 to March 2019. Serum TSH was measured by UniCel DxI 800 Immunoassay System (Beckman Coulter Inc., Brea, CA, USA). The study design relied on two approaches in order to classify pregnant women: trimester-specific and subgroup-specific; the latter involved dividing each trimester into two subgroups: T1a, T1b, T2a, T2b, T3a, T3b. The lower and upper limits of the RIs were derived by the parametric method after normalizing the data distribution using the modified Box-Cox power transformation method. RESULTS: The lowest TSH value was detected at 8-12 weeks in early pregnancy, and the median value of TSH in the T1b subgroup was significantly lower than the T1a subgroup (P < 0.05). TSH levels showed a gradual trend of increase along with the pregnancy and increased significantly in the T2a, T2b, and T3b subgroups compared to the preceding subgroups (P < 0.05). Compared to the diagnostic criteria recommended by American Thyroid Association (ATA), the prevalence of thyroid dysfunction was significantly different from the established trimester- and subgroup-specific RIs throughout the pregnancy (P < 0.001). CONCLUSIONS: We conclude that establishing gestation- and laboratory-specific RIs, especially for TSH, is essential for diagnosing thyroid disorders in pregnancy, and the recommended universal cut-off values, which may contribute to the risk of a misdiagnosis or a missed diagnosis, should be taken with caution in the clinical setting. However, regarding the fluctuation of thyroid function tests throughout pregnancy, trimester-specific RIs are insufficient, and implementing split phases is required.

VDBP, VDR Mutations and Other Factors Related With Vitamin D Metabolism May Be Associated With Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is an insulin dependent autoimmune disorder resulting the progressive destruction of pancreatic beta cells. Another possible factor considered to be related with T1DM is vitamin D deficiency. Therefore in this study it was aimed to investigate the associations between T1DM, vitamin D binding protein (VDBP) and vitamin D receptor (VDR) gene mutations which are related with vitamin D metabolism. Fifty five T1DM paitents and 40 healthy volunteers were recruited to the study. FokI (rs2228570), BsmI (rs1544410) mutations in VDR; rs4588 and rs7041 polymorphisms in VDBP were investigated with real-time polymerase chain reaction (RT-PCR). Other risk factors related with T1DM were also investigated. Results were evaluated statistically. Statistically significant relations were found in glucose, HbA1c, TSH, higher 25[OH]D, free vitamin D, calcium, albumin, log25[OH]D, retinopathy, higher than 30 mg/day microalbuminuria in T1DM patients. Also statistically significant association was found between C allele in Fok1 and T1DM in patients. When the relation between the risk factors and mutations were investigated, it was found that VDBP, free vitamin D and bioactive vitamin D were significantly associated with rs7041 mutation in VDBP whereas HDL was significantly associated with rs2228570 mutation in VDR. Other studies with larger data sets may demonstrate more reliable statistical results to rule out genotype-phenotype correlations of the disease.

The diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and procalcitonin (PCT) in children with systemic inflammatory response syndrome (SIRS).

BACKGROUND: The aim of the present study was to determine the diagnostic and prognostic values of suPAR and to compare them to CRP and PCT in pediatric patients with systemic inflammatory response syndrome (SIRS). MATERIAL-METHODS: A prospective case-control study was performed.The study was performed in a tertiary university hospital which has a 649-bed capacity. Patients included 27 children with SIRS and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4-7th days of the hospital stay. RESULTS: The median (min-max) serum levels of suPAR obtained on the first day of the admission were 10.06 (2.7-57.46) and 2.22 (1.08-5.13) ng/Ml for the SIRS group and control group, respectively. The median serum levels of suPAR in the SIRS group was significantly higher than that in the control group (p < 0.05). The serum suPAR levels was significantly higher in nonsurvivors than in survivors in SIRS group (p < 0.05). In the SIRS group, the area under the receiver operating characteristics curve (AUCROC) for suPAR revealed an optimum cut-off value, sensitivity, specificity, NPV and PPV of 0.978, 3.8 ng/mL, 96%, 96%, 96%, and 96%, respectively. CONCLUSIONS: We conclude that suPAR does have diagnostic value in children with SIRS. Additionally, persistent high serum suPAR level predicts mortality in SIRS in children.

The effect of different protease inhibitors on stability of parathyroid hormone, insulin, and prolactin levels under different lag times and storage conditions until analysis.

INTRODUCTION: Proteolytic cleavage through proteases affects peptide hormone levels, which is of particular significance when the time interval between sampling and analysis is prolonged. We evaluated the stability of parathyroid hormone, insulin, and prolactin molecules (i) with different protease inhibitors such as K2 EDTA, aprotinin, and protease inhibitor cocktail (PIC), (ii) with different lag times (6-72 hours), and (iii) under different storage temperatures (4°C vs room temperature [RT]) until analysis. MATERIALS AND METHODS: Blood samples were collected into 2 sets of 5 Vacutainer® tubes (Becton Dickinson) from 10 healthy adults. Tubes 1 and 2 were plain gel separator tubes. Tubes 3, 4, and 5 contained PIC (1%), aprotinin (500 KIU/mL), and K2 EDTA, respectively. After centrifugation at 1300 g for 10 minutes, PIC added to tube 2 of each set. Samples were analyzed and then one set was stored at 4°C, whereas the other at RT until analysis at 6, 24, 48, and 72 hours. Hormone levels were determined with electrochemiluminescence immunoassay (ModularE170; Roche Diagnostics). The results were compared with desirable bias limits (DBL) from Westgard QC database. RESULTS: Insulin at RT decreases exceeding the DBL starting from 24 hours and K2 EDTA preserved insulin. PTH exceeded the DBL at RT for 48 hours or longer and PIC addition after centrifugation inhibited its degradation. Prolactin remained stable in all tested conditions. All parameters in the plain gel separator tubes remained within DBL when stored at 4°C until 72 hours. CONCLUSIONS: Different proteases may degrade peptide hormones and measures should be taken to counteract these effects especially if there is a delay before analysis.

The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia.

The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

Free and Bioavailable Vitamin D Levels of Patients with Type 1 Diabetes Mellitus and Association with Bone Metabolism.

Aim: Vitamin D deficiency is known to be associated with metabolic bone diseases. The aim of this study is to evaluate vitamin D and calculated free and bioactive vitamin D levels of type 1 diabetic patients and to evaluate the association with bone turnover markers. Method: This cross-sectional study includes 60 patients admitted to endocrinology outpatient clinic with diagnosis of type 1 diabetes mellitus and 60 controls. Weight, height and waist circumference were recorded and blood samples were taken for measurement of 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP), osteocalcin, bone alkaline phosphatase (bone-ALP), c-telopeptide. Free and bioavailable vitamin D levels were calculated with formula. Results: Vitamin D levels of type 1 diabetic patients were significantly higher (p = 0.01). Parathormone levels of the group with vitamin D level under 20 ng/ml was significantly higher (p = 0.029). VDBP levels were similar in both groups. Correlation analysis of free and bioavailable vitamin D level with osteocalcin, c-telopeptide, bone alkaline phosphatase revealed only a weak significant correlation between free vitamin D and osteocalcin (r = -0.201; p = 0.028). A negative correlation was determined between 25(OH)D and parathormone levels (r = -0.294; p < 0.005). Serum osteocalcin, bone alkaline phosphatase and c-telopeptide levels of control group were significantly higher. Conclusion: 25(OH)D levels of the study population was extremely low. The measurement of VDBP and calculated free and bioactive vitamin D levels did not show a better correlation with bone turnover markers according to 25(OH)D levels.

The effect of immunization with inactivated SARS-CoV-2 vaccine (CoronaVac) and/or SARS-CoV-2 infection on antibody levels, plasmablasts, long-lived-plasma-cells, and IFN-γ release by natural killer cells.

OBJECTIVES: We evaluated the antibody response, natural killer cell response and B cell phenotypes in healthcare workers (HCW) who are vaccinated with two doses of CoronaVac with or without documented SARS-CoV-2 infection and unvaccinated HCWs with SARS-CoV-2 infection. METHODS: HCWs were divided into four groups: vaccine only (VO), vaccine after SARS-CoV-2 infection (VAI), SARS-CoV-2 infection only (IO), and SARS-CoV-2 infection after vaccine (IAV). Anti-SARS-CoV-2 spike protein (Anti-S) antibodies were measured by Elecsys Anti-SARS-CoV-2 S ELISA kit. Memory B cells (CD19+CD27+), plasmablast B cells (CD19+CD138+) and long-lived plasma cells (LLPC; CD138+CD19-) were measured by flow cytometry in 74 patients. Interferon gamma (IFN-γ) release by natural killer (NK) cells were measured by NKVue Test (NKMAX, Republic of Korea) in 76 patients. RT-PCR was performed with Bio-speedy® COVID-19 qPCR detection kit, Version 2 (Bioexen LTD, Istanbul, Turkey). RESULTS: The Anti-S antibodies were detectable in all HCWs (n: 224). The median Anti-S titers (BAU/mL) was significantly higher in VAI (620 25-75% 373-1341) compared to VO (136, 25-75% 85-283) and IO (111, 25-75% 54-413, p < 0.01). VAI group had significantly lower percentage of plasmablasts (2.9; 0-8.7) compared to VO (6.8; 3.5-12.0) and IO (9.9; 4.7-47.5, p < 0.01) (n:74). Percentage of LLPCs in groups VO, VAI and IO was similar. There was no difference of IFN-γ levels between the study groups (n: 76). CONCLUSION: The antibody response was similar between uninfected vaccinated HCWs and unvaccinated HCWs who had natural infection. HCWs who had two doses of CoronaVac either before or after the natural SARS-CoV-2 infection elicited significantly higher antibody responses compared to uninfected vaccinated HCWs. The lower percentages of plasmablasts in the VAI group may indicate their migration to lymph nodes and initiation of the germinal center reaction phase. IFN-γ response did not differ among the groups.

The Association of Thyroid Hormone Changes with Inflammatory Status and Prognosis in COVID-19.

BACKGROUND: COVID-19 infection may have multiorgan effects in addition to effects on the lungs and immune system. Recently, studies have found thyroid function abnormalities in COVID-19 cases which were interpreted as euthyroid sick syndrome (ESS) or destructive thyroiditis. Therefore, in this study, we aimed to evaluate the thyroid function status and thyroid autoimmunity in COVID-19 patients. Material and Method. 205 patients were included. The medical history and laboratory parameters at admission were collected from medical records. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, and thyroglobulin antibody were measured, and patients were classified according to thyroid function status. RESULTS: 34.1% of the patients were euthyroid. Length of hospitalization (p < 0.001), rate of oxygen demand (p < 0.001), and intensive care unit (ICU) admission (p=0.022) were lower, and none of the euthyroid patients died. 108 (52.6%) patients were classified to have ESS, 57 were classified as mild, and 51 were moderate. The inflammatory parameters were higher in patients with moderate ESS. In cluster analysis, a high-risk group with a lower median FT3 value (median = 2.34 ng/L; IQR = 0.86), a higher median FT4 value (median = 1.04 ng/dL; IQR = 0.33), and a lower median TSH value (median = 0.62 mIU/L; IQR = 0.59) included 8 of 9 died patients and 25 of the 31 patients that were admitted to ICU. Discussion. Length of hospitalization, oxygen demand, ICU admission, and mortality were lower in euthyroid patients. Moreover, none of the euthyroid patients died. In conclusion, evaluation of thyroid function tests during COVID-19 infection may give information about the prognosis of disease.

Revisiting Classical 3ß-hydroxysteroid Dehydrogenase 2 Deficiency: Lessons from 31 Pediatric Cases.

CONTEXT: The clinical effects of classical 3ß-hydroxysteroid dehydrogenase 2 (3ßHSD2) deficiency are insufficiently defined due to a limited number of published cases. OBJECTIVE: To evaluate an integrated steroid metabolome and the short- and long-term clinical features of 3ßHSD2 deficiency. DESIGN: Multicenter, cross-sectional study. SETTING: Nine tertiary pediatric endocrinology clinics across Turkey. PATIENTS: Children with clinical diagnosis of 3ßHSD2 deficiency. MAIN OUTCOME MEASURES: Clinical manifestations, genotype-phenotype-metabolomic relations. A structured questionnaire was used to evaluate the data of patients with clinical 3ßHSD2 deficiency. Genetic analysis of HSD3B2 was performed using Sanger sequencing. Novel HSD3B2 mutations were studied in vitro. Nineteen plasma adrenal steroids were measured using LC-MS/MS. RESULTS: Eleven homozygous HSD3B2 mutations (6 novel) were identified in 31 children (19 male/12 female; mean age: 6.6 ±â€…5.1 yrs). The patients with homozygous pathogenic HSD3B2 missense variants of > 5% of wild type 3ßHSD2 activity in vitro had a non-salt-losing clinical phenotype. Ambiguous genitalia was an invariable feature of all genetic males, whereas only 1 of 12 female patients presented with virilized genitalia. Premature pubarche was observed in 78% of patients. In adolescence, menstrual irregularities and polycystic ovaries in females and adrenal rest tumors and gonadal failure in males were observed. CONCLUSIONS: Genetically-documented 3ßHSD2 deficiency includes salt-losing and non-salt-losing clinical phenotypes. Spared mineralocorticoid function and unvirilized genitalia in females may lead to misdiagnosis and underestimation of the frequency of 3ßHSD2 deficiency. High baseline 17OHPreg to cortisol ratio and low 11-oxyandrogen concentrations by LC-MS/MS unequivocally identifies patients with 3ßHSD2 deficiency.

Abnormal gel flotation in a patient with apperant pneumonia diagnosis: a case report.

INTRODUCTION: Serum blood collection tubes with separator gel are widely used by many laboratories for chemistry analyses. We describe a case of a primary blood collection tube filled with blood sample and a floating separator gel. MATERIALS AND METHODS: The blood sample was collected from a 51 years old female in intensive care unit with the diagnosis of pneumonia into a BD Vacutainer SST tube (Becton Dickinson, NJ, USA) containing serum separator gel and conveyed to the core laboratory of Marmara University Hospital within 30 minutes from collection. Sample was immediately centrifuged at room temperature at 1500 × g for 10 minutes. RESULTS: The analyses revealed a highly increased total protein concentration of 145 g/L (reference interval 64-83 g/L). The nephelometric analyses showed an elevated serum IgG concentration of 108 g/L (reference interval 6.5-16 g/L) and IgG lambda monoclonal band was determined by serum immunofixation electrophoresis. CONCLUSION: Limitation of the separator gel tubes in patients with a high plasma density and its possible effects on test results and laboratory costs should be remembered. The clinical diagnosis stated in the information system should also reveal known comorbid conditions besides the apparent admission reason. This information would avoid resampling, additional testing, and communication efforts with the clinicians.

Serum erythropoietin, insulin-like growth factor 1, and vascular endothelial growth factor in etiopathogenesis of retinopathy of prematurity.

BACKGROUND AND OBJECTIVE: The role of growth factors in the pathogenesis of retinopathy of prematurity (ROP) is known. To better understand this issue, the authors investigated vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and erythropoietin (EPO) levels in the cord blood of premature newborns. PATIENTS AND METHODS: IGF-1, VEGF, and EPO levels were measured in cord blood samples obtained from 93 infants less than 32 weeks of gestational age at birth, and their predictive value in the development of ROP was investigated. RESULTS: The mean birth age and mean birth weight were 32.2 ± 1.5 weeks and 1,678 ± 326 g, respectively, in infants without ROP and 29.6 ± 2.3 weeks and 1,384 ± 343 g, respectively, in infants with ROP. Multivariate logistic regression analysis showed that only the gestational age and the serum VEGF at birth were independently associated with the risk of developing ROP (P = .002, Exp[B] = 0.514, CI = 95%: 0.341-0.775; P = .028, Exp[B] = 0.999, CI = 95%: 0.997-1.00). CONCLUSION: Serum VEGF levels at birth were lower in infants who later developed ROP. This may have a predictive value for ROP and contribute to the pathogenesis, because affected infants may be more susceptible to extrauterine hyperoxic insult.

Serum adipokine levels in type 1 diabetic patients: association with carotid intima media thickness.

BACKGROUND: Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis. METHODS: Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography. RESULTS: Adiponectin levels in diabetics were higher (25.8±14.8 µg/mL vs. 5.5±7.3 µg/mL; P<0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine. CONCLUSIONS: Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.

Macroprolactin does not contribute to elevated levels of prolactin in patients on renal replacement therapy.

OBJECTIVE: Three molecular forms of PRL with molecular weights of 23, 50-60 and > 100 kDa have been defined. The high-molecular-weight forms are called macroprolactin. Different immunoassays produce varyingly elevated results with macroprolactin-containing sera. The kidneys are reported to clear 25% of PRL from the circulation. Hyperprolactinaemia is seen in 20-75% of patients with chronic renal failure (CRF). PRL clearance rate has been reported to be reduced in CRF and the resulting hyperprolactinaemia is due to reduced renal function. PATIENTS: To determine the contribution of macroprolactinaemia to elevated PRL levels in CRF, 91 patients receiving haemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation (RT) therapies and 72 control subjects were included in the study. MEASUREMENTS: Serum PRL levels were measured by a sandwich immunoassay with electrochemical detection. Following polyethylene glycol (PEG) precipitation, recovery ratios were calculated and samples with a recovery of < 50% were identified as having macroprolactin isoforms. RESULTS: The serum and supernatant PRL levels of CRF patients were significantly higher than those of the control group (P < 0.001). The serum PRL levels of HD and CAPD patients were significantly higher than those of the RT patients (P < 0.001). The serum PRL levels of the RT patients and the control group did not differ significantly (P > 0.05). A moderate correlation was found between PRL and creatinine levels (r = 0.609, P < 0.001). CONCLUSIONS: The hyperprolactinaemia seen in renal replacement therapy is not associated with the presence of macroprolactin isoforms but with the decline in renal function.