Endocrinologists looking to quantify growth hormone in their patients frequently rely on laboratory tests for insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3). However, according to an article in Clinical Laboratory News, getting accurate readings is tricky for a variety of reasons, including biological and both intra- and inter-assay variations.
IGF-I, a protein stimulated by growth hormone that plays an important role in growth during childhood, is primarily produced by the liver. According to Ravinder Singh, Ph.D., Director of the Mayo Clinic Endocrine Laboratory, in Rochester, Minnesota, "It’s a useful marker for growth hormone deficiency or surplus because it is released fairly consistently, unlike growth hormone itself, which can fluctuate throughout the day."
However, measuring IGF-I accurately has its challenges. According to Dr. Singh, the reference range for IGF-I has been evolving, now getting as specific as providing norms for patients at almost every year of age to reflect how dramatically IGF-I varies with age. "Different assay manufacturers also may use different calibration materials and antibodies used for the assays may not be consistent, making it quite challenging to compare results from one assay to another," he said.
In addition to measurement challenges, the agents sent to clinical laboratories may not be consistent from lot to lot. According to Alicia Algeciras-Schimnich, Ph.D., Chair of Mayo Clinic's Division of Clinical Biochemistry and Immunology, this happened at Mayo Clinic a few years back, when the laboratory was using a commercial IGF-I assay. She and her colleagues were noticing elevated IGF-I results in some patients that were considered false positives once they reviewed patients’ clinical data. “The clinical picture was not consistent with growth hormone excess,” she said. “That created a challenge for us to try to figure out what was going on.”
Ultimately, they determined the problem to be related to inconsistent reagent lots. “It was an assay-performance issue, not a patient or sample-collection issue,” Dr. Algeciras-Schimnich said. Mayo Clinic subsequently switched to a lab-developed mass spectrometry assay to try to achieve better consistency over time.