MAUDE Adverse Event Report: SIEMENS HEALTHCARE DIAGNOSTICS PRODUCTS, LIMITED IMMULITE 2000 XPI ACTH; IMMULITE 2000 XPI ACTH

Model Number	IMMULITE 2000 XPI ACTH
Medical Device Problem Code	High Test Results (2457)
Health Effect - Clinical Code	No Code Available (3191)
Date of Event	07/19/2013
Type of Reportable Event	Malfunction
Additional Manufacturer Narrative
The prevalence of immunoassay interference is variable and dependent on the type of antibody interference.Interferences can be addressed by multiple techniques upon recognition of discordance with clinical presentation and/or results of concurrent assessments (e.G., imaging, other laboratory testing).Some common interferences include icterus, hemolysis, lipemia, heterophilic antibodies, and biotin.For example, biotin interference does not occur below 1500 ng/ml with the immulite acth assay.The immulite acth assay architecture and reagent formulation has remained unchanged since product launch.Although no immunoassay can be completely free from interference the immulite acth assay was designed to minimize the effect of interfering substances.In addition, the acth immulite assays have statements in the limitation section of the instructions for use indicating the following:- heterophilic antibodies in human serum can react with the immunoglobulins included in the assay components causing interference with in vitro immunoassays.Samples from patients routinely exposed to animals or animal serum products can demonstrate this type of interference potentially causing an anomalous result.These reagents have been formulated to minimize the risk of interference; however, potential interactions between rare sera and test components can occur.For diagnostic purposes, the results obtained from this assay should always be used in combination with the clinical examination, patient medical history, and other findings.Acth is used as an aid in assessing adrenal insufficiency and hypersecretion and is investigated in conjunction with other diagnostic laboratory testing such as cortisol measurements.Cortisol is used to first assess presence of a disease state, then additional work up is needed to determine etiology.Treatment decisions are not based on acth measurements alone, but rather are correlated with the patient's clinical history and presentation, such as blood cortisol, urinary free cortisol, dheas, stimulation and suppression testing and imaging.In scenarios where acth values are discordant with the clinical picture and/or other diagnostic testing, the results would be questioned and instigate repeat or further testing.Non-invasive tests (e.G.Crh, desmopressin stimulation, dexamethasone suppression) and/or mri are recommended as the subsequent steps for investigating elevated acth results.If the described non-invasive follow-up testing is inconclusive or discordant, only then would ipss testing be an option for further investigation.Ipss would not be performed based solely on an elevated acth result.There are known false positive and false negative causes of ipss results, with imaging studies used to confirm diagnosis of a pituitary or ectopic source needed to enable invasive treatment.Avs is not recommended for use in cushing's syndrome investigation, but rather is used for primary aldosteronism.Prior to surgery, the acth results were questioned, leading to testing for heterophile antibodies and use of an alternate assay.As stated in the immulite 2000 xpi ifu, the presence of heterophilic antibodies may cause anomalous acth results.Worst case, a falsely elevated or depressed result may cause delayed differential diagnosis of acth-related disorders such as cushing's syndrome, hypopituitarism, or adrenal insufficiency, and lead to additional testing.
Event or Problem Description
This mdr is being filed based on review of a publication cited by the fda based on recent communications about the immulite adrenocorticotropic hormone (acth) assay, titled "a diagnostic conundrum: heterophilic antibody interference in an adrenocorticotropic homrone immunoassay not detectable using a proprietary heterophile blocking reagent" dated april 2, 2013 by "jonathan grasko et.Al." the article states that a retired (b)(6) year old retired female nurse underwent extensive invasive investigations, which were ultimately unnecessary, as a result of initial analytical interference in the immulite 2000 xpi acth assay, which could not be resolved using a proprietary heterophilic binding reagent.The patient had a history of hypertension and depressive illness presented following the diagnosis and treatment of breast cancer which was deemed to be in clinical remission.The patient was noted to have bilateral adrenal gland enlargement on a recent abdominal ct scan.On initial presentation, there were a few clinical features suggestive of glucocorticoid excess; however, over the subsequent 12 months, classic features of cushing's syndrome developed including hypertension, weight gain, bruising and moon facies.The article states that plasma acth was consistently within the lower half of the reference interval on multiple analyses.The article did not provide dates of testing or the results.Cranial magnetic resonance imaging (mri) showed central nodular bulkiness of the pituitary gland without a discrete adenoma.Inferior petrosal sinus sampling (ipss) results showed an absent central to peripheral venous gradient.Consequently, adrenal venous sampling (avs) was undertaken to determine lateralization of cortisol secretion.These results suggested predominant, but not exclusive, right-sided production of cortisol, consistent with either acth-dependent cushing's syndrome or bilateral adrenal hyperplasia.The possibility of ectopic acth production was considered, but due to the protracted clinical presentation and biochemical investigations, this diagnosis became less likely and no further investigation for ectopic acth syndrome was undertaken.Initial clinical discussions were focused on surgical removal of the dominant site of cortisol production by unilateral right adrenalectomy in order to control the patient's signs and symptoms of glucocorticoid excess rather than bilateral adrenalectomy.Further investigation to exclude heterophilic antibody interference as a cause of possible discrepant acth results was recommended.Heterophilic antibody interference of acth measurement was investigated using heterophilic blocking tubes and analysed using an alternate method.The use of scantibodies led to a misleading increase in acth.As a consequence, the biochemical results post-scantibody treatment supported the initial diagnosis of acthdependent cushing's syndrome.However, measurements of acth by the alternative method, produced a clinically more likely acth result which was below the lower limit of detection for this assay.After obtaining all results, the patient underwent a right unilateral adrenalectomy based on the investigations and the results obtained on the alternate platform with a final diagnosis of acth independent cushing's syndrome.There was no report of negative outcome from the surgery.The customer did not raise a complaint with siemens.Statements and actions attributed to the physician(s) and customer are derived from information provided in the article and have not been verified.The date refers to the date the article was published.The date indicated in this mdr, is the date siemens was made aware of the article.

• Brand Name: IMMULITE 2000 XPI ACTH
• Common Device Name: IMMULITE 2000 XPI ACTH
• Manufacturer (Section D): SIEMENS HEALTHCARE DIAGNOSTICS PRODUCTS, LIMITED; glyn rhonwy; llanberis; gwynedd, LL55 4EL; UK LL55 4EL
• MDR Report Key: 9290144
• Report Number: 2432235-2019-00402
• Device Sequence Number: 11305733
• Product Code: CKG
• UDI-Device Identifier: 00630414963532
• UDI-Public: 00630414963532
• Combination Product (Y/N): N
• Initial Reporter State: NY
• Initial Reporter Country: US
• PMA/510(K) Number: K960066
• Number of Events Summarized: 1
• Summary Report (Y/N): N
• Reporter Type: Manufacturer
• Report Source: literature
• Initial Reporter Occupation: Other Health Care Professional
• Type of Report: Initial
• Report Date (Section B): 11/07/2019

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this a Product Problem Report?: Yes
• Operator of Device: Health Professional
• Device Model Number: IMMULITE 2000 XPI ACTH
• Device Lot Number: UNKNOWN
• Was Device Available for Evaluation?: No
• Type of Report(Section G): Initial
• Initial Date Received by Manufacturer: 10/17/2019
• Initial Report FDA Received Date: 11/07/2019
• Is This a Single-Use Device that was Reprocessed and Reused on a Patient? (Y/N): No
• Patient Sequence Number: 1
• Patient Age: 60 YR