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

Model Number IMMULITE 2000 ACTH

Device Problem High Test Results (2457)

Patient Problem No Code Available (3191)

Event Date 02/20/2019

Event Type  malfunction  

Manufacturer Narrative

In the article it was indicated that since the elevated plasma acth results obtained on the immulite system were inconsistent with the other clinical results, a heterophile blocking reagent study was carried out and the result was lower by >50% indicating the possible presence of heterophile antibody interference.The study was carried out again on a fresh plasma sample several months later and the results were similar.Dilution studies of the plasma sample was linear.Treatment of the sample with buffered phosphate solution resulted in decreased acth results consistent with precipitation of interfering immunoglobulins.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.As outlined in the "summary" section of the publication, despite the documentation of heterophile antibody assay interference and/or the absence of a pituitary or ectopic source of acth, providers proceeded with additional work up.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.Mdr 2432235-2019-00323, mdr 2432235-2019-00328, mdr 2432235-2019-00329, and mdr 2432235-2019-00330 were also filed for this event.

Event Description

This mdr is being filed based on review of a publication by the head of siemens commercial product quality in the endocrine society journal article titled "assay-specific spurious acth results lead to misdiagnosis, unnecessary testing, and surgical misadventure - a case series" dated january 18, 2019 by "loren wissner greene, md, ma, face, facp, eliza b.Geer, md, gabrielle page-wilson, md, ms, james w.Findling, md, facp, hershel raff, phd, faaas, faps".In one case falsely elevated acth (immulite) results were obtained on a 21 year old female due to interfering antibodies, which resulted in several invasive differential diagnostic procedures (including inferior petrosal sinus sampling), mris, and unnecessary pituitary surgery.Acth results on the patient sample tested on an alternate platform were normal and further studies excluded the diagnosis of cushing's syndrome.A 21 year old female presented after evaluation by several other physicians.She reported a 45-50 lb.Weight gain after taking clomiphene alone or in combination with dexamethasone for irregular menses with infertility.She had a history of hypertension, headaches, fever, insomnia, fatigue, abdominal pain, rashes, edema, early satiety, mild anorexia, and easy bruisability.Early morning plasma acth levels on the immulite were consistently elevated, and morning serum cortisol values were normal.Low and high dose of overnight dexamethasone suppressed morning serum cortisol levels, as were late night salivary cortisol values.However corresponding plasma acth concentrations remained elevated.Normal resolution (performed twice) and high resolution pituitary mri's with and without gadolinium were unremarkable.Since the elevated acth results were inconsistent with other clinical results, evaluation of possible acth assay interferences was carried out.The sample was treated with heterophilic blocking reagent and the result was >50% different from the untreated sample indicating the possible presence of heterophile antibody interference.The testing was repeated on a fresh plasma sample several months later and the results were similar.Dilutions of the plasma sample using the acth immulite assay was linear.An elevated acth sample decreased in result following treatment with a buffered phosphate solution, consistent with precipation of interfering immunoglobulins.Despite the lack of evidence for clinical cushing's syndrome, the patient's symptoms and consistently elevated plasma acth, led the patient to self refer to another physician at another medical center which resulted in a third pituitary mri which was suggestive of a right superior pituitary microadenoma.This led to inferior petrosal sinus sampling (ipss) using the acth immulite assay which showed an ips to peripheral gradient and lateralized to the left side.Because the ipss results ruled out ectopic cushing's and suggested the diagnosis of cushing's disease, pituitary surgery was performed.No adenoma was found, and the anatomic pathology report of the tissue removed, (which included immunohistochemistry for gh, prolactin, acth, fsh, lh and tsh) was consistent with normal anterior pituitary tissue.Additional follow-up confirmed that this patient did not have cushing's syndrome.One week after surgery and two months after surgery plasma acth levels were still elevated on the immulite.A pituitary mri performed two months after surgery suggested a residual pituitary adenoma and/or postoperative changes.As concerns with the immulite acth assay were raised the sample was tested on an alternate platform and the results were normal.Additional follow-up has confirmed that this patient does not have cushing's syndrome.The information provided in the article did not indicate if the acth assay was run on the immulite/immulite 1000 or the immulite 2000 system(s).Multiple acth results for the patient was provided in the article, but the dates of testing are unknown.Therefore multiple mdr's were filed for this event 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 (date of event) refers to the date the article was published.This mdr is being filed for the fifth result for acth.

• Brand Name: IMMULITE 2000 ACTH
• Type of Device: IMMULITE 2000 ACTH
• Manufacturer (Section D): SIEMENS HEALTHCARE DIAGNOSTICS PRODUCTS, LIMITED; glyn rhonwy; llanberis; gwynedd, LL55 4EL; UK LL55 4EL
• Manufacturer (Section G): SIEMENS HEALTHCARE DIAGNOSTICS PRODUCTS, LIMITED; uk registration #: 3002806944; glyn rhonwy; llanberis, LL55 4EL; UK LL55 4EL
• Manufacturer Contact: aarti aziz ; 511 benedict avenue; tarrytown, NY 10591 ; 9145242683
• MDR Report Key: 9115532
• MDR Text Key: 220532021
• Report Number: 2432235-2019-00331
• Device Sequence Number: 1
• Product Code: CKG
• UDI-Device Identifier: 00630414963532
• UDI-Public: 00630414963532
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: K960066
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: literature
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial
• Report Date: 09/25/2019

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 09/25/2019
• Is this an Adverse Event Report?: No
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Model Number: IMMULITE 2000 ACTH
• Device Lot Number: UNKNOWN
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 09/11/2019
• Was Device Evaluated by Manufacturer?: No
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Age: 21 YR