Macro-alkaline phosphatase: a discussion highlighting discrepancy between wet and dry chemistry assays via a unique case report

Background: Alkaline phosphatase (ALP) is a key biomarker of hepatobiliary and skeletal disease. Isolated elevations often prompt extensive investigations to rule out various pathologies, which can be invasive and to the detriment of the patient’s physical, financial, and emotional well-being. One benign diagnosis of exclusion for an isolated elevated ALP value is macro-ALP, an immunoglobulin-bound enzyme complex. However, very little literature exists describing this phenomenon, which may prevent its recognition by clinicians and laboratory directors. Additionally, macro-ALP can be difficult to distinguish from other pathologic etiologies, as standard colorimetric assays can only detect the quantity, but not the size, of the ALP enzyme. Case Description: A 48-year-old male with a history of hypothyroidism and erectile dysfunction demonstrated a persistent 3-year discrepancy in ALP values between our in-house dry chemistry platform (Vitros 7600, QuidelOrtho, microslide technique) and an outside laboratory wet chemistry assay (ARUP Laboratories, Roche Cobas 8000). In-house results were normal (63–91 U/L; reference range, 34–122 U/L), while outside laboratory testing showed persistent elevations (173–242 U/L; reference range, 40–120 U/L). Other markers were normal. Following evaluation by endocrinology and gastroenterology with no concrete diagnosis, our laboratory elected to perform a polyethylene glycol (PEG) precipitation test (Abbott Alinity CI), which confirmed macro-ALP (<40% recovery). The patient remained asymptomatic, and no pathology was identified. Conclusions: Macro-ALP is a rare cause of isolated ALP elevation. This case highlights a benign presentation in a healthy individual and underscores how methodological differences between wet and dry chemistry assays can yield discrepant results. Awareness of this benign variant and assay-dependent variability can prevent unnecessary investigations.