Measurement of human growth hormone by immunoassays: Current status, unsolved problems and clinical consequences

Abstract

Measuring the concentration of growth hormone (GH) in blood samples taken during dynamic tests represents the basis for diagnosis of growth hormone related disorders, namely growth hormone deficiency and growth hormone excess. Today, a wide spectrum of immunoassays are in use, enabling rapid and sensitive determination of growth hormone concentrations in routine diagnostics. From a clinical point of view several difficulties exist with the use and interpretation of GH assay results in the assessment of GH related disorders: Many physiological factors such as fat mass, age and gender influence the outcome of dynamic tests, overall leading to significant inter-individual differences in GH responses. However, in addition to the physiological variability, considerable variability exists in GH assay results obtained by different immunoassays. Unfortunately, all the new technical advances in the field of GH measurement techniques have not reduced this methodological variability. To a large extent, the actual values reported for the GH concentration in a sample depend on the method used by the respective laboratory. Obviously, such discrepancies limit the applicability of consensus guidelines on diagnosis and treatment in clinical practice. This review summarizes current practices for GH measurement with respect to the methods used, their limitations and the clinical consequences of the existing heterogeneity in GH immunoassay results.

Failure to achieve disease control in acromegaly: cause analysis by a registry-based survey

“…In many uncontrolled patients, disease activity at this cross-sectional presentation was only moderate according to IGF1. With the well-known challenges of IGF1 and also GH assays (14,15,16,17), it is of no surprise that a considerable number of patients had, at previous visits, an IGF1 or GH level within the target range respectively. Obviously, fluctuating IGF1 or GH values due to interassay variations are a major reason as to why a substantial number of patients were cross-sectionally categorised as uncontrolled and yet received no medical therapy or seemingly inadequate low-dose drug monotherapy.…”

Long-term outcome in patients with acromegaly: analysis of 1344 patients from the German Acromegaly Register

“…Random GH values as either single determinations or as the first value of a profile or an oral glucose tolerance test are also documented in the register although in fewer patients. Since commercial GH-assays show a high interassay variability, the use of a given threshold for all centers to define disease control could therefore be misleading (29,30). As many centers guide their long-term treatment decisions especially in medically treated patients on IGF1 levels and in order to uniform the outcome definition for all treatment modalities, we used IGF1 normalization as the outcome parameter to define disease control in this nationwide retrospective analysis.…”

Quantification of growth hormone in serum by isotope dilution mass spectrometry

“…Diagnosis of growth hormone (GH) deficiency and -excess (acromegaly) is based on determination of circulating concentrations of GH in serum during dynamic tests [1,2]. In spite of efforts to standardization, decision making in clinical practice continues being hampered by significant discrepancies in assay results between different laboratories (test methods).…”