Elevated Cardiac Troponin in the Setting of Periodic Symptomatology: A Case Report

Introduction/Objective Serial cardiac troponin measurement is a sensitive method to identify recent cardiac injury and is a necessary function of the clinical chemistry laboratory. We present a case of out-of-range cardiac troponin I (cTnI) elevation which remained spuriously elevated for at least 30 days. Methods Cardiac troponins were measured on a DxI (Beckman Coulter), Vitros 5600 (Ortho Clinical Diagnostics), iSTAT (Abbott), and Cobas e602 (Roche) according to the manufacturers’ instructions with appropriate controls. Heterophile antibody blocking (Scantibodies Laboratories) was performed according to the package insert. Results A 58-year-old male with a medical history significant for chronic non-ischemic cardiomyopathy with open valvular repair (ejection fraction 15-20%), chronic atrial fibrillation, and Hodgkin’s lymphoma in remission presented to a rural clinic with chest pain and a cTnI of 0.8 ng/mL (reference <0.04 ng/mL). He was transferred to our tertiary center for open revision. The patient’s cTnI (measured on a Beckman Coulter DxI) was above linearity threshold (>71.00 ng/mL) starting day 1 after surgery. The patient self-discharged against medical advice on day 16. On day 21 he experienced new chest pain and dyspnea and was readmitted with a cardiac troponin T (cTnT) of >35 ng/mL (iSTAT; reference <0.08 ng/mL) and cTnI again above threshold. This value remained elevated for the next five days despite abated symptoms. To address the discordant laboratory and physical findings, dilutional cTnI measurements on serum from day 30 demonstrated linearity. Heterophile antibody testing was negative. cTnI on the DxI machine remained >71.00 ng/mL but was separately measured as 3.4 ng/mL (Vitros 5600, reference <0.08 ng/mL). cTnT was found to be 1.05 ng/mL (Cobas e602; reference 0.00 ng/mL). Comparative examination of all methodologies was unrevealing. Conclusion This case demonstrates a spurious elevation of cardiac troponins which remarkably demonstrated linearity on serial dilution. Multiple testing methodologies were necessary to prove fallacy. The cause of the result remains unclear. The clinical pathologist should be aware of possible false positives and investigate unlikely continuous cardiac troponin elevations.

Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation

Background: Epstein–Barr virus (EBV) infection is associated with significant morbidity and mortality in renal transplant (RT) recipients. The spectrum of illness ranges from infectious mononucleosis (IM) to post-transplant lymphoproliferative disorder (PTLD). In association with clinical signs and symptoms, virus-specific serology and heterophile antibody tests are widely used in confirming the diagnosis of IM in the general population. However, these tests may have a limited role in immunosuppressed RT recipients from seropositive donor, especially in children who were EBV-seronegative prior to the transplant. The aim of this study is to evaluate the utility of these tests in the early diagnosis of IM in this subset of patients. Methods: This is a case study with a review of literature. Results: Here, we present a 14-year-old male with hemophilia B who presented with fever, fatigue, sore throat, palatal petechial rash, exudative tonsillitis and cervical lymphadenopathy 3 months post-RT. He was EBV seronegative prior to RT and received a deceased donor kidney transplant from a seropositive donor. Induction was done with Thymoglobulin and maintenance immunosuppression consisted of tacrolimus and mycophenolate. Initial heterophile antibody test (monospot) was negative, but became positive at 5 months and remained positive at 9 months follow-up post-RT. EBV viral capsid antigens (VCA) IgM and IgG, early antigen (EA) and nuclear antigen (EBNA) were all negative at the time of presentation. VCA IgM and IgG both became positive at 5 months and peaked at 9 months follow-up, however the EA and EBNA remained negative. EBV viral load as measured by polymerase chain reaction (PCR) was negative for the first 3 months post-RT but became positive at presentation, peaked at 6 months and started declining thereafter. Peripheral blood smear examination showed no absolute and atypical lymphocytosis. Cytomegalovirus PCR in the blood and throat culture for streptococcus were negative. There was no splenomegaly. He was managed conservatively with intravenous fluids, bed rest, antipyretics and reduction of immunosuppression. Conclusions: EBV serological markers have a limited role in the early diagnosis of EBV-IM following RT in prior seronegative children. Initial heterophile antibody test may also be negative, and hence a repeat test may be necessary. Once becoming positive, the VCA IgM may remain persistently elevated for prolonged duration. In addition to the suppressed cellular immunity secondary to immunosuppression, humoral response to viral infections is also delayed in transplant recipients, especially in the early transplant period. Hence, routine monitoring with PCR is superior to serology in diagnosing IM early and monitoring the EBV infection post-RT for timely evaluation and management.

MON-462 Rebel Nodule or Reluctant Gland? the Challenge Presented by Heterophile Antibodies

Introduction: Interpretation of thyroid function tests (TFTs) in background of non-specific symptoms concerning for hypothyroidism, has become challenging with assay interference. Heterophile antibody interferences are both test and laboratory platform dependent. We present a case of a toxic nodule erroneously diagnosed as isolated central hypothyroidism due to heterophile antibody interference. Case: A 38 year old lady was referred to Endocrinology for possible central hypothyroidism with symptoms of progressive fatigue, 40lb unintentional weight loss, poor appetite, nausea, intermittent diarrhea/constipation, occasional cold intolerance and intermittent lightheadedness. TFTs suggested low TSH 0.175 mcIU/ml (N 0.35-3.8 mcIU/ml) and low FT4 0.74 ng/dl (N 0.8-1.8 ng/dl). Pituitary hormone evaluation revealed normal ACTH, AM cortisol, IGF-1, prolactin and FSH. A pituitary MRI was normal. Two months later, she had worsening fatigue, anxiety with palpitations and tremors, and 14lb weight gain. TFTs again confirmed low TSH (0.575 mcIU/ml) and lower FT4 (0.70 ng/dl). Empirical weight-based levothyroxine (LT4) supplementation was initiated for central hypothyroidism. Six weeks later, TFTs showed hyperthyroidism (TSH <0.005 mcIU/ml, FT4 1.57 ng/dl). The patient endorsed worsening lightheadedness and palpitations on LT4, which resolved on LT4 discontinuation. One month later, TFTs were abnormal again (TSH 0.047 mcIU/ml, FT4 0.74 ng/dl). Due to persistent discordance in symptoms and biochemical tests, TFTs were evaluated for heterophile antibody interference. While HAMA-treated TSH remained low (0.04 mIU/l), FT4 by equilibrium dialysis (FT4 ED) was normal (1.1 ng/dl, regular assay 0.74 ng/dl), suggesting subclinical hyperthyroidism. A thyroid uptake scan confirmed an autonomous toxic right thyroid nodule with suppressed remaining gland. Patient ultimately underwent 15 mCi RAI ablation of the nodule. TFTs done 1 month post-RAI suggested normal TSH (1.2 mcIU/ml) and normal FT4 ED (1 ng/dl). Previous symptoms have since resolved. Conclusion: Current methods of TFTs are generally reliable in diagnosing and monitoring thyroid disease. Rarely, medications, supplements, and endogenous antibodies can bind to TSH, T4 or lab reagent, resulting in inaccurate values. This has become increasingly common with use of high dose biotin. TSH with HAMA/heterophile antibodies and FT4 ED are more accurate forms of diagnostic testing. When approaching patients with symptoms not consistent with typical hypo- or hyperthyroidism and are not responding as expected to therapy, it is important to consider more accurate testing to rule out assay errors. References: 1. Soh SB, Aw TC. Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. Ann Lab Med. 2019;39(1):3-14. doi:10.3343/alm.2019.39.1.3 2. Spencer C., PhD. Assay of Thyroid Hormones and Related Substances