Macrohormones in endocrinology: prevalence, clinical impact, and diagnostic approaches

Macrohormones also called macromolecules or macrocomplexes are described as an antigen-antibody complex, consisting of monomeric hormones bound to immunoglobulins. These molecules exhibit minimal or no biological activity. However, their presence may falsely indicate elevation of active hormones levels which can lead to significant diagnostic challenges. Currently, polyethylene glycol precipitation (PEG) is one of the most recognized methods for identifying macrohormones and it has been widely used in diagnosing macroprolactinemia as awareness of its clinical implications is well recognized. Macrohormone assessment is particularly recommended when clinical symptoms are incompatible with laboratory findings, as it may help avoid unnecessary diagnostic procedures and treatments. Recently, there has been an increasing number of reports highlighting diagnostic challenges associated with other macrohormones, including macro-TSH, macro-FSH, macro-LH, macro-PTH, macro-GH, macro-ACTH, macro-insulin, and macro-calcitonin. The presence of these molecules can lead to overdiagnosis. This review aims to summarize the latest findings and highlight the importance of considering the presence of macrohormones in patients with discrepancies between clinical presentation and hormonal laboratory tests.