Endocrine Abstracts

Introduction: Hormone macromolecules are complexes of hormones with other compounds, most often with IgG immunoglobulin. They show variable immunoreactivity in immunochemical tests (IRMA, ELISA, CLIA, ECLIA) and usually have a weak biological effect. They can interfere with immunological assays of various hormones. Some known hormone macrocomplexes are: BB-PRL (24% - 34%), macro-TSH (0.6% - 1.2%) and very rare macromolecules of various hormones: calcitonin, PTH, insulin (single reports). Presentation of a new hormone macromolecule – macro-GH (GH- growth hormone), that may interfere with different GH assays leading to false-high results in serum samples.

Case presentation: A 61-year-old female was admitted to our department with suspected acromegaly. Laboratory test showed increased fasting GH level without suppression on oral glucose tolerance test and normal IGF-1. A trial 3-month treatment with the long-acting somatostatin analogue was initiated. Despite the treatment, elevated GH with normal IGF-1 levels persisted. No visible decrease in pituitary adenoma size on MRI was detected. Finally, the patient underwent a transsphenoidal resection of a pituitary tumor. After the surgery, laboratory tests remained unchanged with elevated GH level and normal IGF-1. Interference in the determination of GH level was suspected.

Methods and results: We found a different immunoreactivity (different results) in the determination of GH by routine immunochemical methods: ECLIA, CLIA and IRMA. A serial dilution test showed non-linearity. Rheumatoid factor (RF) was absent. The test for the presence of heterophile antibodies was performed. GH recovery after incubation was 95%, indicating no interference from heterophile antibodies. In the penultimate stage, a sample of the patient’s serum was incubated with the serum of an acromegalic patient with a high concentration of GH. The GH recovery after incubation was 98%. Next the sample was precipitated with 25% PEG. The GH recovery was 12%, which means that 88% of growth hormone was in the form of macrocomplex (macro-GH). The last step in confirming the presence of the macrocomplex GH (macro-GH) was the use of the reference method - size-exclusion chromatography (SEC).

Conclusions: In the analyzed case, we confirmed a very rare type of interference - a presence of macro-GH. In each case of suspected inconsistency of laboratory test results with the clinical picture and/or other tests, it is advisable to start the procedure of excluding/looking for various types of interference that may impede the diagnosis and/or treatment of patients with various endocrine diseases.