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Introduction: Considering the inherent vulnerability of immunoassays for heterophilic interference and the potential of Rheumatoid Factor (RF) to act as a heterophile-like antibody, we conducted this study to investigate if RF leads to any such heterophilic interference in seropositive rheumatoid arthritis (RA) patients. The study was done on the TSH assay as it is a noncompetitive, double antibody sandwich assay, which is known to be vulnerable to heterophilic interference. Methods: In this cross-sectional observational study, eighty-four consecutive newly diagnosed RF-positive RA patients underwent TSH, Free T4, and anti-TPO estimation using the chemiluminescence technique (CLIA) on Siemens Immulite 1000 platform. The samples were screened for TSH interference using four methods: 1) analysis on a different platform, 2) assessment of linearity using doubling dilutions, 3) polyethylene glycol (PEG) precipitation, and 4) addition of a commercial blocker. Results: Ten samples had a loss of linearity on serial dilution, indicating potential interference. After heterophile blocker treatment, five cases exhibited interference. One patient had diagnostic interpretation discordance on the second platform. No sample on PEG precipitation suggested the influence of antibodies. It is worth noting that even in cases where interference was suspected, the clinical interpretation was largely unaffected by the correction of TSH values based on mean dilution or measurement after heterophile blocker treatment. Conclusion: RF can cause heterophilic interference in TSH immunoassays used commercially. However, in most cases, this interference does not affect clinical decision-making.

Introduction: Considering the inherent vulnerability of immunoassays for heterophilic interference and the potential of Rheumatoid Factor (RF) to act as a heterophile-like antibody, we conducted this study to investigate if RF leads to any such heterophilic interference in seropositive rheumatoid arthritis (RA) patients. The study was done on the TSH assay as it is a noncompetitive, double antibody sandwich assay, which is known to be vulnerable to heterophilic interference. Methods: In this cross-sectional observational study, eighty-four consecutive newly diagnosed RF-positive RA patients underwent TSH, Free T4, and anti-TPO estimation using the chemiluminescence technique (CLIA) on Siemens Immulite 1000 platform. The samples were screened for TSH interference using four methods: 1) analysis on a different platform, 2) assessment of linearity using doubling dilutions, 3) polyethylene glycol (PEG) precipitation, and 4) addition of a commercial blocker. Results: Ten samples had a loss of linearity on serial dilution, indicating potential interference. After heterophile blocker treatment, five cases exhibited interference. One patient had diagnostic interpretation discordance on the second platform. No sample on PEG precipitation suggested the influence of antibodies. It is worth noting that even in cases where interference was suspected, the clinical interpretation was largely unaffected by the correction of TSH values based on mean dilution or measurement after heterophile blocker treatment. Conclusion: RF can cause heterophilic interference in TSH immunoassays used commercially. However, in most cases, this interference does not affect clinical decision-making. [ABSTRACT FROM AUTHOR]

This letter reports a case of a 63-year-old woman who had an increase in C-reactive protein (CRP) levels, a marker of inflammation, despite not having any signs of infection or inflammation. After months of investigation, it was determined that the high CRP levels were due to an analytical interference caused by the presence of human anti-animal antibodies in the patient's blood. This interference led to unnecessary surgeries, investigations, and antibiotic treatments. The study highlights the importance of considering analytical interferences when interpreting laboratory results. [Extracted from the article]

Background: This study aimed to demonstrate potential measures to discern interference and establish an algorithm for identifying interference in an hs-cTnT assay with a clinical discrepancy. Methods: Laboratory error and disease factors were first excluded. Then, a serial dilution test, polyethylene glycol (PEG) precipitation, and heterophile antibody blocking reagents (HBRs) were performed to confirm the interference substance. In addition, high-speed centrifugation and western blot were tried. Results: The sample diluted linearly (R2 = 0.9966). However, there was a dramatic reduction in the concentration of hs-cTnT concentration to a normal level after both PEG precipitation and HBR1 treatment. The results were inconclusive in high-speed centrifugation and western blot assay. Conclusions: This study elucidated a heterophile antibody interference in measurement of hs-cTnT alone on a Roche analyzer. [ABSTRACT FROM AUTHOR]

Serum thyroglobulin (Tg) is a biochemical marker used in the follow-up of patients with differentiated thyroid cancer (DTC), but heterophile antibody interference may limit the clinical use of Tg.

Abstract Background The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities. Case A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto’s thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance. Conclusions Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.

Background: The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities.Case: A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto's thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance.Conclusions: Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering. [ABSTRACT FROM AUTHOR]

Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein‐Barr virus. Seven commercially available assays currently widely utilized in clinical laboratories were compared in this study. Variable performance characteristics and assay times are observed, and these pieces of data may assist clinical laboratories in assay selection and result interpretation. [ABSTRACT FROM AUTHOR]

We present the case of an 83-year-old man with metastatic prostate cancer who had testosterone levels reading above castration range despite appropriate medical and surgical castration. Mass spectrometry was performed to confirm presence of testosterone, but no testosterone was detected. The elevated testosterone as measured by standard immunoassay was postulated to be secondary to heterophile antibodies in the patient's serum. This report highlights the need for a high index of suspicion for interference in testosterone immunoassays when levels remain mildly elevated. Mass spectrometry may provide a more reliable method by which to detect testosterone concentration prior to escalation of care.

Abstract In this case report, we describe a young athletic male with a family history of early sudden cardiac death who presented with atypical chest pain and was found to have a positive serum troponin. Although his symptoms resolved without intervention, workup revealed hypertension, hyperlipidemia, mild left ventricular hypertrophy, non-obstructive coronary artery disease, and the presence of serum heterophile antibodies. Ultimately, it was concluded that his rigorous exercise regimen as well as the presence of heterophile antibodies may have contributed to his positive serum troponin. This case serves as a reminder of the nonspecific diagnostic value of modern troponin assays, and that the results of these tests should always be incorporated into the clinical context.

Detectable serum levels of beta subunit of human chorionic gonadotropin (βhCG) in nonpregnant, perimenopausal women bring confusion in both clinician and patient and could lead to unnecessary diagnostic and therapeutic procedures. A 45‐year‐old woman with the continuous elevation of βhCG underwent hysteroscopy, two laparoscopic surgeries, two explorative uterine cavity curettages and three cycles of cytostatic therapy. No ultrasonographic, macroscopic or histological signs of pregnancy, both uterine and ectopic or gestational trophoblastic disease were found. Both radiographic and computed tomography reports ruled out the presence of a nongynecological neoplasm. All recommended steps were taken for confirmation or ruling out the possibility of heterophile antibodies interference, but the results were not absolute. Finally, the referent laboratory confirmed the presence of the antibodies, but their exact type remains unknown. This case underlines the importance of the universally accepted protocol in the cases of persistent βhCG elevation in nonpregnant, perimenopausal women. [ABSTRACT FROM AUTHOR]

Analysis of many clinically important analytes is dependent on antibody-based assays. However, depending on the design, these assays are vulnerable to interference from endogenous molecules including circulating antibodies and free biotin. In this case report, we describe a patient whose laboratory findings from immunoassay based methodologies, are inconsistent with the clinical presentation. A 14-year-old male was referred to Pediatric Endocrinology for suspected hyperthyroidism based on critically elevated free thyroxine (fT4) levels although clinical assessment was inconsistent with hyperthyroidism. Because repeat testing was discrepant, Endocrinology questioned the validity of the results prompting consultation with the laboratory to investigate the source of the inconsistent findings. Review of discordant results revealed that fT4 levels measured in laboratories utilizing Roche instrumentation were critically high, while results from laboratories using alternative platforms (i.e. Siemens Centaur) were within normal limits. After a comprehensive evaluation which included testing of paired specimens on multiple platforms, measurement of serially diluted specimens and a formal evaluation for the presence of heterophile antibodies, it was determined that a heterophile antibody interference was the most likely cause of the aberrant results in this patient. [ABSTRACT FROM AUTHOR]

Background: Heterophile antibody (HAb) interferences in immunoassays can cause falsely elevated hCG concentrations leading to incorrect diagnosis and treatments options. When results are not consistent with the clinical findings, hCG HAb interference investigation may be requested by the physician. A retrospective evaluation of the frequency of HAb interference was performed among cases of physician-requested investigations and the effectiveness of commercially available blocking reagents to detect HAb interference in two immunoassay systems was evaluated. Methods: One hundred and thirteen physician requests for hCG HAb investigation from 2008 to 2017 were reviewed. The primary method used to measure hCG was the Beckman Coulter Access Total βhCG (2008–2010) and the Roche Elecsys HCG+β (2014–2017). HAb investigation included measurement by two immunoassays before and after treatment of samples with heterophile blocking reagents and serial dilution studies. Results: Five cases of HAb and HAb-like interference were identified. The interference frequency was 6.7% for the Beckman assay and 2.9% for the Roche assay. The presence of HAb was detected using heterophile blocking reagents and an alternative method in three cases. The other two cases were detected due to discrepant results with an alternative method and non-linear serial dilutions (HAb-like). Conclusions: HAb interference was observed in the Beckman and the Roche assays. The heterophile blocking reagents failed to detect 40% of interference cases. Blocking reagents should not solely be used for these investigations. Multiple strategies including the use of serial dilutions and using an alternative platform are critical when troubleshooting interferences in hCG immunoassays. [ABSTRACT FROM AUTHOR]

In this case report, we describe a young athletic male with a family history of early sudden cardiac death who presented with atypical chest pain and was found to have a positive serum troponin. Although his symptoms resolved without intervention, workup revealed hypertension, hyperlipidemia, mild left ventricular hypertrophy, non-obstructive coronary artery disease, and the presence of serum heterophile antibodies. Ultimately, it was concluded that his rigorous exercise regimen as well as the presence of heterophile antibodies may have contributed to his positive serum troponin. This case serves as a reminder of the nonspecific diagnostic value of modern troponin assays, and that the results of these tests should always be incorporated into the clinical context. [ABSTRACT FROM AUTHOR]

The practice of medicine depends on the accuracy of biochemical assays. The high prevalence of incidental masses on imaging necessitates a correct biochemical diagnosis before proceeding to radiological studies. Hormonal assays, tumour markers, and markers of cardiac injury are particularly susceptible to heterophile antibody interference which may lead to inaccurate and misleading results, inappropriate investigation and/or treatment, patient concern and potential harm. A case of heterophile antibody interference in the measurement of ACTH in a patient with Cushing's syndrome resulting in unnecessary invasive investigation is presented. Close collaboration and communication between laboratory and clinical staff is essential where laboratory results and the clinical picture are not congruent. [ABSTRACT FROM AUTHOR]

Cardiac troponin I and T are particularly sensitive and specific markers for cardiomyocyte damage. Myocardial injury can occur due to a discrepancy between oxygen supply and demand (eg coronary artery occlusion and arrhythmias), other cardiac causes (eg pericarditis, myocarditis, cardiac surgery, cardioversion etc) or systemic conditions (eg sepsis, stroke and chronic renal disease). The latest European Society of Cardiology guidelines help to guide clinicians through these different causes. Occasionally troponin concentrations may not fit the clinical presentation and, therefore, other aetiologies should be considered. An under-appreciated basis of a high troponin concentration is a false positive result, which can be attributable to analytical interference from components in the patient's blood. Uncovering this interference can be pivotal to avoid unnecessary and potentially harmful investigations or treatment for patients. We present two cases of false positive troponin results caused by analytical interference. The normal reference range for the assay (Access; Beckman Coulter, High Wycombe, UK) used at our organisation is 0--18 ng/L. [ABSTRACT FROM AUTHOR]

A 27-year-old male was admitted with diabetic ketoacidosis and altered sensorium with slurring of speech and ataxia. He was managed with intravenous insulin and fluids and later shifted to basal bolus insulin regimen and during further evaluation was diagnosed to be suffering from primary hypothyroidism and adrenal insufficiency. He was started on thyroxin replacement and steroids only during stress. After three months of follow up he was clinically euthyroid. His glycemic control was adequate on oral anti-hyperglycemic drugs and adrenal insufficiency recovered. However, his thyrotropin levels were persistently elevated on adequate replacement doses of thyroxin. His repeat TSH was estimated after precipitating serum with polyethylene glycol which revealed normal TSH. Here we report reversible adrenal insufficiency with hypothyroidism with falsely raised TSH because of presence of heterophile antibodies in a case of poly glandular endocrinopathy syndrome.

Abstract: Background: A variety of immunoassays including multiplex suspension bead array have been developed for tumor marker detections; however, these assays could be compromised in their sensitivity and specificity by well-known heterophile antibody interference and hook effect. Methods: Using Luminex® multiplex suspension bead arrays, we modified protocols with two newly-developed solutions that can identify heterophile antibody interference and AFP hook effect. Effectiveness of the two solutions was assessed in serum samples from patients. Results: Concentrations of 9 tumor markers in heterophile antibody positive samples assayed with Solution A, containing murine monoclonal antibodies and mouse serum, were significantly reduced when compared with those false high signals assayed without Solution A (all p<0.01). With incorporation of Solution H (fluorescent beads linked with AFP antigen), a new strategy for identification of AFP hook effect was established, and with this strategy AFP hook effect was identified effectively in serum samples with very high levels of AFP. Conclusions: Two proprietary solutions improve the identification of heterophile antibody interference and AFP hook effect. With these solutions, multiplex suspension bead arrays provide more reliable testing results in tumor marker detection where complex clinical serum samples are used. [Copyright &y& Elsevier]

Immunometric assays are inherently vulnerable to interference from heterophilic antibodies, endogenous antibodies that bind assay antibodies. The consequences of such interference can be devastating. In this review, we discuss strategies that reduce the damage caused by heterophilic antibodies. Clinicians should only order blood tests that are indicated for the patient and clinical setting at hand, and have the confidence to question laboratory results discordant with the clinical picture. Laboratorians should familiarize themselves with the vulnerability of the assays they offer, and be able to perform and interpret adequate confirmatory measures correctly. When designing immunoassays, the immunoassay industry should invest the necessary resources in specific protective measures against heterophilic antibody interference. Examples include using antibody fragments and the addition of effective blockers to assay reagents. The increasing use of modified monoclonal mouse antibodies both in therapy and diagnostics could present a particular challenge in the future. [Copyright &y& Elsevier]

The potential for interfering substances to cause inaccurate laboratory results that may cause significant adverse effects on patient care is well known. Immunoassays are subject to interferences that are not readily detectable prior to analysis, but may cause erroneous results. Learning Objectives After reading this article, readers should understand potential causes of interference that are specific to immunoassays, methods used to detect interference, and approaches used to resolve discrepancies between laboratory results and the clinical picture. [ABSTRACT FROM AUTHOR]

Background: Heterophilic antibodies are still an important source of interference in immunoassays. We have conducted a screening study for interference in a panel of commercially available assays using two sera known to contain high titer Fc-reactive heterophilic antibodies. Methods: The sera were distributed to laboratories participating in the Nordic External Quality Assessment cooperation (EQANord). Duplicate samples pre-blocked with aggregated murine monoclonal MAK33 were also supplied. Discrepancies (>50%) between the results for native and blocked samples were used to classify the tested assays as susceptible to interference. A total of 170 different assay kits covering 91 analytes were tested. Results: We found that 21 assays, covering 19 different analytes, were susceptible to interference from the heterophilic antibodies in the two sera. Many of these are clinically and commercially important assays. Some of the false results were grossly elevated and could have been detrimental to patient care in a clinical setting. Conclusions: Heterophilic antibodies with Fc-reactivity remain a threat. A more widespread use of antibody fragments and aggregated immunoglobulin could potentially improve the heterophilic antibody resistance of assays intended for clinical use. [ABSTRACT FROM AUTHOR]

Objectives This case report investigates the origin of a false positive result on a serum qualitative human chorionic gonadotropin (hCG) device. Patient and methods A 46-year-old woman diagnosed with chronic myeloid leukemia presented with nausea and vomiting. A qualitative serum hCG test was interpreted as positive; however, a quantitative serum hCG test was negative (< 5 IU/L). To further investigate this discrepancy, the sample was pretreated with heterophilic blocking reagent (HBR). Additionally, the sample was tested on other qualitative hCG devices composed of antibodies from different animal sources. Blocking reagent from an automated quantitative immunoassay was also tested for its ability to inhibit the heterophile antibody interference. Results The qualitative test result was negative after pretreatment with heterophilic blocking reagent. Other devices composed of antibodies from different animal sources also demonstrated mixed results with the patient's sample. Blocking reagent obtained from the automated quantitative assay inhibited the heterophile antibody interference in the patient's sample. Conclusion This case demonstrates that positive serum point-of-care hCG results should be interpreted with caution and confirmed with a quantitative serum hCG immunoassay when clinical suspicion is raised. [ABSTRACT FROM AUTHOR]

Abstract: The present study describes positive and negative interference of human cytokine measurement in multiplexed bead-based immunoassays. Significant differences in measured IL-6 and TNF-α values in 30 normal human plasma samples were apparent depending on whether measurements were with a 2-plex assay or embedded in a multiplex of 8-or more cytokine antibody pairs, as well as among the kits of 3-different vendors. Sample diluents containing proprietary blocking ingredients were shown to greatly affect the outcome of measured cytokine values. Additionally, recovery of IL-6 and TNF-α from spiked samples suggests significant negative interference from either endogenous antibodies, soluble receptors or anti-cytokine antibodies in 10% and 26% of samples, respectively. While it is evident that multiplexed immunoassays hold great promise for cytokine profiling, there are still important issues needing further study. Especially needed are universally optimized sample diluents, uniformly calibrated standards with mass values, and internal assay controls, which should greatly facilitate intralaboratory accuracy and precision and interlaboratory comparisons of cytokine measurements. Possible causes of interference and remedies are discussed. [Copyright &y& Elsevier]

A patient with IgA deficiency had a series of positive serum pregnancy tests which led to medical and surgical procedures for suspected molar pregnancy. These tests were found to be falsely positive due to heterophile antibody. The aim of this study was to determine the frequency of false positive βhCG assays in sera of IgA deficient patients. Sera from a panel of IgA deficient (IgA < 7 mg/dl) patients were tested for the presence of βHCG using three different assays, and also for IgG anti-goat and anti-mouse antibodies. Patients were seen at Mount Sinai Medical Center and included 54 patients (ages 1–80 years, 32 females, 22 males) with IgA deficiency. Thirty percent of 54 IgA deficient patient sera yielded positive pregnancy tests by one or more of the three βhCG assays, however, none of the patients were pregnant. In comparison to sera of normal controls, 39% of the patient sera contained significant amounts of anti-goat antibody and 18% contained significant amounts of anti-mouse antibody. While heterophile antibodies are common in IgA deficient serum, false positive assays for βhCG in IgA deficient serum have not been previously reported. The possibility of false positive test results should be considered prior to invasive procedures in IgA deficient patients. [ABSTRACT FROM AUTHOR]

Background: Erythropoietin (EPO) is a glycoprotein hormone produced by specialized cells in the kidney that acts as the primary regulator of erythropoiesis. Serum EPO measurements are useful for diagnostic evaluations of anemia and polycythemia. Methods: The IMMULITE 2000 is an automated random access immunoassay analyzer for the central laboratory. The limit of detection (LOD), linearity, imprecision, comparison to another commercially available assay, and reference interval of a new EPO assay for this analyzer were assessed. Results: The LOD was 0.2 U/l. The assay was linear within an allowable systematic error of 10% over the range tested (2–178 U/l). The total imprecision of the new assay was <7% for concentrations from 15.8 to 68.4 U/l. Comparison with the Advantage EPO assay method showed comparable results. Deming regression analysis gave a slope of 1.13±0.02, an intercept of −1.09±0.97, and a Sy/x of 7.1 (r=0.99) over the range tested (2–200 U/l). Conclusions: The IMMULITE 2000 EPO assay shows acceptable performance and is suitable for routine clinical use. [Copyright &y& Elsevier]

Objective: The present study has been carried out to analyse the trend of heterophile antibody positive infectious mononucleosis cases.Methods: A total of 1741 cases of clinically suspected infectious mononucleosis from various age groups were investigated during the period January, 1986 to December, 2000 and were analysed for infectious mononucleosis (IM) specific heterophile antibody by Paul-Bunnel-Davidsohn (PBD) test. Forty seven heterophile antibody negative samples were also tested simultaneously for the presence of the IgG antibody to viral capsid antigen (VCA) and Epstein Barr nuclear antigen (EBNA) to detect the exposure to Epstein Barr Virus (EBV) infection.Results: The overall percentage of EBV specific heterophile (Paul-Bunnel) antibody positivity was found to be 11.1% (194/1741). The average Paul-Bunnel antibody positivity between 1986 to 1990 was 20.5% which declined drastically to 5.7% during 1991-2000. Males comprised of 55.2% of the serologically proven IM cases. Of the 47 heterophile antibody negative cases, 38 (80.9%) and 33 (70.2%) were found to be positive for anti-VCA IgG and anti-EBNA IgG antibodies respectively. Paul Bunnel antibody positivity was found to be higher in >14 year age group patients than those below 14 years.Conclusion: These findings suggest that the EBV infection still continues to be endemic in this part of the country, however, a declining trend in IM cases was observed during the last decade. [ABSTRACT FROM AUTHOR]

The scenario in which a patient tests positive for human chorionic gonadotropin (hCG) in the absence of pregnancy can pose a diagnostic dilemma for clinicians. The term "phantom hCG" refers to persistently positive hCG levels on diagnostic testing in a nonpregnant patient and such results often lead to a false diagnosis of malignancy and subsequent inappropriate treatment with chemotherapy or hysterectomy. There remains a need for a consistent and rational diagnostic approach to the "phantom hCG." This article aims to review the different etiologies of positive serum hCG testing in nonpregnant subjects and concludes with a practical, stepwise diagnostic approach to assist clinicians encountering this clinical dilemma., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

A 27-year-old male was admitted with diabetic ketoacidosis and altered sensorium with slurring of speech and ataxia. He was managed with intravenous insulin and fluids and later shifted to basal bolus insulin regimen and during further evaluation was diagnosed to be suffering from primary hypothyroidism and adrenal insufficiency. He was started on thyroxin replacement and steroids only during stress. After three months of follow up he was clinically euthyroid. His glycemic control was adequate on oral anti-hyperglycemic drugs and adrenal insufficiency recovered. However, his thyrotropin levels were persistently elevated on adequate replacement doses of thyroxin. His repeat TSH was estimated after precipitating serum with polyethylene glycol which revealed normal TSH. Here we report reversible adrenal insufficiency with hypothyroidism with falsely raised TSH because of presence of heterophile antibodies in a case of poly glandular endocrinopathy syndrome. [ABSTRACT FROM AUTHOR]