Abstract
Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive biomarkers. The elonginB/C-cullin5-SOCS-box-complex (ECS-complex) (an intracellular five-protein complex) is stimulated by circulating growth hormone (GH) and regulates GH receptor levels through a negative feedback loop. It mediates the cells’ sensitivity for GH and therefore, represents a potent new biomarker for those diseases. In this study, individual ECS-complex proteins were measured in whole blood samples of patients with acromegaly (n = 32) or GHD (n = 12) via ELISA and compared to controls. Hierarchical clustering of the results revealed that by combining the three ECS-complex proteins suppressor of cytokine signaling 2 (SOCS2), cullin-5 and ring-box protein 2 (Rbx-2), 93% of patient samples could be separated from controls, despite many patients having a normal IGF-1 or not receiving medical treatment. SOCS2 showed the best individual diagnostic performance with an overall accuracy of 0.93, while the combination of the three proteins correctly identified all patients and controls. This resulted in perfect sensitivity and specificity for all patient groups, which demonstrates potential benefits of the ECS-complex proteins as clinical biomarkers for the diagnostics of GH-related diseases and substantiates their important role in GH metabolism.
Highlights
IntroductionGrowth hormone deficiency (GHD) and acromegaly are two growth hormone disorders caused by reduced or increased levels of growth hormone (GH), respectively
Growth hormone deficiency (GHD) and acromegaly are two growth hormone disorders caused by reduced or increased levels of growth hormone (GH), respectively. Those diseases are mainly triggered by pituitary neuroendocrine tumors (PitNETs) that slowly shift the physiological balance of hormone secretion to pathological levels
A GHD is often caused by a non-functioning PitNET and is reported to occur in 290–460 cases per million, being more frequent than acromegaly [8]
Summary
Growth hormone deficiency (GHD) and acromegaly are two growth hormone disorders caused by reduced or increased levels of growth hormone (GH), respectively. Those diseases are mainly triggered by pituitary neuroendocrine tumors (PitNETs) that slowly shift the physiological balance of hormone secretion to pathological levels. Because symptoms of GH-related disorders evolve very subtly over the course of many years, initial diagnoses are made only after 5–25 years [9]. This results in 73% of cases already being macroadenomas (>1 cm) upon diagnosis, which significantly reduces
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