Falsely elevated serum oestradiol due to exemestane therapy

Mandić, Sanja; Kratzsch, Juergen; Mandić, Dario; Debeljak, Željko; Lukić, Iva; Horvat, Vesna; Gaudl, Alexander; Šerić, Vatroslav

doi:10.1177/0004563216674031

Cited by 19 publications

(12 citation statements)

References 13 publications

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“…This property should strongly discourage one to use evaluated immunoassays for establishment of diagnoses associated with gland hypofunction or its therapeutic suppression. There are number of cases described in literature showing the harmful effect of falsely elevated serum steroid concentrations on the patient treatment (21)(22)(23). Study of Mandić et al describes the impact of exemestane therapy on falsely elevated serum estradiol measurement, while Stowasser et al discuss the importance of correct aldosterone measurement in patients with hypertension, primary hyperaldosteronism and Addison disease (21,22).…”

Section: Discussionmentioning

confidence: 99%

Analytical bias of automated immunoassays for six serum steroid hormones assessed by LC-MS/MS

Debeljak

Marković

Pavela

et al. 2020

Biochem. med. (Online)

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Introduction: There is a growing amount of evidence showing the significant analytical bias of steroid hormone immunoassays, but large number of available immunoassays makes conduction of a single comprehensive study of this issue hardly feasible. Aim of this study was to assess the analytical bias of six heterogeneous immunoassays for serum aldosterone, cortisol, dehydroepiandrosterone sulphate (DHEAS), testosterone, 17-hydroxyprogesterone (OHP) and progesterone using the liquid chromatography coupled to the tandem mass spectrometry (LC-MS/MS). Materials and methods: This method comparison study included 49 serum samples. Testosterone, DHEAS, progesterone and cortisol immunoassays were performed on the Abbott Architect i2000SR or Alinity i analysers (Abbott Diagnostics, Chicago, USA). DiaSorin’s Liaison (DiaSorin, Saluggia, Italy) and DIAsource’s ETI-Max 3000 analysers (DIAsource ImmunoAssays, Louvain-La-Neuve, Belgium) were chosen for aldosterone and OHP immunoassay testing, respectively. All immunoassays were evaluated against the LC-MS/MS assay relying on the commercial kit (Chromsystems, Gräfelfing, Germany) and LCMS-8050 analyser (Shimadzu, Kyoto, Japan). Analytical biases were calculated and method comparison was conducted using weighted Deming regression analysis. Results: Depending on the analyte and specific immunoassay, mean relative biases ranged from -31 to + 137%. Except for the cortisol, immunoassays were positively biased. For none of the selected steroids slope and intercept 95% confidence intervals simultaneously contained 0 and 1, respectively. Conclusions: Evaluated immunoassays failed to satisfy requirements for methods’ comparability and produced significant analytical biases in respect to the LC-MS/MS assay, especially at low concentrations.

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Section: Discussionmentioning

confidence: 99%

Analytical bias of automated immunoassays for six serum steroid hormones assessed by LC-MS/MS

Debeljak

Marković

Pavela

et al. 2020

Biochem. med. (Online)

Self Cite

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“…This patient was taking letrozole for her AI therapy, which excluded potential interactions that have been reported between immunoassay and a steroidal AI such as exemestane (Mandic et al. ).…”

Section: Resultsmentioning

confidence: 99%

“…It is known that exemestane can interact with the ELISA reagents on some kits, resulting in a spuriously high estradiol value (Mandic et al. ). Thus, her estradiol levels may have varied from 14.6 to 21.3 because of a cross‐reaction with exemestane.…”

Section: Discussionmentioning

confidence: 99%

Challenges of measuring accurate estradiol levels in aromatase inhibitor‐treated postmenopausal breast cancer patients on vaginal estrogen therapy

Niravath

Bhat

Al-Ameri

et al. 2017

Pharmacology Res & Perspec

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Breast cancer patients who are taking adjuvant Aromatase Inhibitor (AI) therapy typically have extremely low estradiol levels, which are undetectable by routine clinical laboratories. Thus, it becomes difficult to assess the safety of interventions such as low‐dose vaginal estrogen, which may increase estradiol levels. In this study, we aimed to assess the utility of enzyme‐linked immunosorbent assay (ELISA) to measure low estradiol concentrations in breast cancer survivors on AI therapy treated with either vaginal estrogen or lubricant for atrophic vaginitis as a part of clinical trial. The samples were tested using two independent ELISA kits. Some of the samples were also evaluated using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) for comparison. We found that while the results by ELISA were reproducible, they were not accurate when compared to LC‐MS/MS. It is possible that medications or supplements may cross‐react with the ELISA reagents and confound the assessment; however, those were often not the reason for the discrepancy. Our results highlight the need for developing novel, reliable, and clinically accessible assays to measure ultra‐low estradiol levels to improve care of breast cancer survivors. At this stage, based on our findings, we recommend using MS‐based assays for estradiol quantitation for breast cancer survivors, whenever necessary.

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“…Likewise, the aromatase inhibitor exemestane is a structural analog of estradiol prescribed in breast cancer therapy. Biochemical evaluations of estradiol in exemestane therapy cause false-positive results in most estradiol immunoas-says because of cross-reaction with exemestane metabolites [12].…”

Section: Cross-reaction/assay Specificitymentioning

confidence: 99%

Hormone Immunoassay Interference: A 2021 Update

et al. 2022

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Immunoassays are powerful qualitative and quantitative analytical techniques. Since the first description of an immunoassay method in 1959, advances have been made in assay designs and analytical characteristics, opening the door for their widespread implementation in clinical laboratories. Clinical endocrinology is closely linked to laboratory medicine because hormone quantification is important for the diagnosis, treatment, and prognosis of endocrine disorders. Several interferences in immunoassays have been identified through the years; although some are no longer encountered in daily practice, cross-reaction, heterophile antibodies, biotin, and anti-analyte antibodies still cause problems. Newer interferences are also emerging with the development of new therapies. The interfering substance may be exogenous (e.g., a drug or substance absorbed by the patient) or endogenous (e.g., antibodies produced by the patient), and the bias caused by interference can be positive or negative. The consequences of interference can be deleterious when clinicians consider erroneous results to establish a diagnosis, leading to unnecessary explorations or inappropriate treatments. Clinical laboratories and manufacturers continue to investigate methods for the detection, elimination, and prevention of interferences. However, no system is completely devoid of such incidents. In this review, we focus on the analytical interferences encountered in daily practice and possible solutions for their detection or elimination.

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Falsely elevated serum oestradiol due to exemestane therapy

Cited by 19 publications

References 13 publications

Analytical bias of automated immunoassays for six serum steroid hormones assessed by LC-MS/MS

Analytical bias of automated immunoassays for six serum steroid hormones assessed by LC-MS/MS

Challenges of measuring accurate estradiol levels in aromatase inhibitor‐treated postmenopausal breast cancer patients on vaginal estrogen therapy

Hormone Immunoassay Interference: A 2021 Update

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