Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism

Yener, Serkan; Demir, Leyla; Demirpençe, Mustafa; Barış, Mustafa; Şimşir, Ilgın Yıldırım; Özışık, Seçil; Çömlekçi, Abdurrahman; Demir, Tevfik

doi:10.1007/s12020-017-1268-7

Cited by 27 publications

(22 citation statements)

References 28 publications

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“…It is extremely rare that falsely high or low ACTH levels by a substance in the specimen interfering with the ACTH measurements are confirmed. There have been only 23 such cases, to our knowledge [3][4][5][6][7][8][9][10] (Table 3). Of the 23 cases, 22 exhibited erroneously elevated ACTH levels.…”

Section: Discussionmentioning

confidence: 99%

“…Of the 23 cases, 22 exhibited erroneously elevated ACTH levels. In some of these reports, the elevated ACTH levels measured on the Immulite platforms were proved to be false, either by pretreatment with heataggregated rabbit IgG, which is known to adsorb assayinterfering heterophilic antibodies [3], or by adoption of different assay platforms [4,[7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

“…In the field of endocrinology, falsely elevated levels of free thyroxine by anti-reagent or anti-analyte antibodies [1,2] and falsely elevated PRL or TSH levels due to formation of macromolecular complexes (such as "macro-PRL" or "macro-TSH") by anti-analyte antibodies [2] are well known. In the case of ACTH, however, there are extremely few reports only on the Siemens Immulite ACTH and the Abbott Architect ACTH [3][4][5][6][7][8][9][10].…”

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confidence: 99%

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Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency

et al. 2019

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A 49-year-old woman with membranous nephropathy was referred to our hospital during the tapering of oral prednisolone, because of suspicion of primary adrenal insufficiency based on a plasma ACTH level of 399.1 pg/mL in the Elecsys assay and a serum cortisol level of 3.1 μg/dL. A rapid ACTH stimulation test revealed a suboptimal response, whereas a prolonged ACTH simulation test showed a sufficient increase in her urinary free cortisol. Also, big ACTH was not detected by gel exclusion chromatography. Therefore, we speculated that ACTH levels were falsely elevated due to some interference substances. Pretreatment of her plasma with either polyethylene glycol precipitation or a heterophilic blocking tube substantially reduced her ACTH values. When either the Immulite ACTH II or the TOSOH II ACTH was tried instead of the Elecsys ACTH, her plasma ACTH values turned out to be lower and appropriate for her clinical status. These results indicated that heterophilic antibodies interfered only with the Elecsys ACTH assay presumably by bridging the capture and tracer antibodies. To our knowledge, this is the first case in which the Elecsys ACTH assay yielded falsely elevated results. Regardless of the measurement system used, if there is a discordance between assay results and clinical findings, it should be considered to adopt additional procedures and/or another assay.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency

et al. 2019

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“…However, high assay variability should be considered when interpreting low ACTH values (11). Reasons for the assay variability include the pulsatility of ACTH secretion, lack of an international reference standard, as well as technical issues associated with the assay methodology and analysis (e.g., interfering antibodies) (12,13). These issues can contribute to poor assay performance in patients, particularly in those with expected low ACTH levels.…”

Section: Discussionmentioning

confidence: 99%

Nonfunctional Adrenal Adenomas: Truth or Myth? Presentation and Treatment of 2 Patients

Moraitis

2018

AACE Clinical Case Reports

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Objective: Autonomous adrenal cortisol secretion is associated with increased frequency of cardiovascular events; however, there is little consensus on what clinical/biochemical criteria should be employed to establish its diagnosis and treatment. Reported here are two cases of autonomous adrenal cortisol secretion that challenge the currently recommended post-dexamethasone suppression test (post-DST) threshold (>1.8 µg/dL) for diagnosing hypercortisolism.Methods: Patient 1, a 64-year-old Caucasian man, presented with hypertension, nephrolithiasis, obesity, and history of a left adrenal tumor (2.1 × 2.9 cm). Baseline morning adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) were normal; 2-day low-dose DST (LDDST) cortisol was 1.2 µg/dL. Patient 2, a 58-year-old Caucasian woman, presented with bilateral adrenal hyperplasia, obesity, depression, and diabetes. Biochemical evaluation showed low-normal morning ACTH (9 pg/mL), low DHEA-S (<15 µg/dL), and 2-day LDDST cortisol of 1.5 µg/dL.Results: Patient 1 underwent left adrenalectomy because of an increase in the size of his tumor. Postoperatively, he developed adrenal insufficiency, which was treated with hydrocortisone. By 3 months postsurgery, he had lost 35 pounds and his blood pressure had improved substantially. Patient 2, based on the equivocal LDDST cortisol results, was treated medically, rather than surgically, with mifepristone (600 mg daily final dose) for 6 months. During treatment, her diabetes and psychological well-being improved, and she lost 18 pounds. Conclusion:The diagnosis of hypercortisolism is evolving. In cases where a link between autonomous adrenal cortisol secretion and related comorbidities is difficult to establish, a therapeutic trial of a glucocorticoid receptor antagonist may be a useful diagnostic/treatment approach. (AACE Clinical Case Rep. 2018;4:e75-e79) Abbreviations: ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; DHEA-S = dehydroepiandrosterone sulfate; DST = dexamethasone suppression test; GR = glucocorticoid receptor; HPA = hypothalamic-pituitary-adrenal; UFC = urine free cortisol

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“…Particularly, negative impact of antibody interference in ACTH measurements was recently reported in adrenal adenomas incidentally detected 21 . As no single routine test is available to identify immunoassay interference, the same authors suggest to ensure collaboration between clinical and laboratory staff to avoid clinical misjudgments.…”

Section: Definition Of Autonomous Acth-independent Hypercortisolismmentioning

confidence: 95%

Autonomous hypercortisolism: definition and clinical implications

et al. 2018

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In current practice, an adrenal adenoma usually comes as an unexpected byproduct of an imaging study performed for unrelated reasons, without any prior suspect of adrenal disease. Therefore, these tumors currently represent a public health challenge because they are increasingly recognized due to the widespread use of high-resolution cross-sectional imaging for diagnostic purposes. In radiology series, the prevalence of adrenal adenomas increases steeply with age, from around 3% below the age of 50 years up to 10% in the ageing population. These tumors may have clinical relevance because they are able to secrete cortisol autonomously, independently from the pituitary control, in up to 20%-30% of patients. In most of the cases the resulting cortisol excess is insufficient to produce a typical Cushing phenotype but may have clinical consequences, such as hypertension, diabetes, obesity, dyslipidemia and osteoporosis. Despite some controversy on the most effective diagnostic algorithm to define this subtle hypercortisolism, there is mounting evidence that a simple approach by using the 1-mg overnight dexamethasone suppression test (DST) may stratify patients for their cardiovascular risk. Crosssectional, retrospective studies showed that patients with increasingly higher cortisol following DST have an adverse cardiovascular risk profile and are at increased risk of death. Therefore, also a subtle autonomous cortisol excess is associated with increased morbidity and mortality, mainly of cardiovascular origin.

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Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism

Cited by 27 publications

References 28 publications

Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency

Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency

Nonfunctional Adrenal Adenomas: Truth or Myth? Presentation and Treatment of 2 Patients

Autonomous hypercortisolism: definition and clinical implications

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