ARUP Online Scientific Resource

Dr. Charles Hawker Contributions

Dr. Charles Hawker, an ARUP Medical Director, was involved in the discovery of the role of procalcitonin in diagnosing and monitoring septic shock.

Around 1980, Dr. Hawker’s laboratory (the Laboratory Procedures Esoteric Center at the Upjohn Company, Kalamazoo, Michigan) had one of the few radioimmunoassays for calcitonin in the United States. Dr. Hawker was contacted by Dr. Russell W. Chesney, an endocrinologist at the University of Wisconsin (Madison), who  indicated that many patients with toxic shock syndrome were experiencing lowered serum calciums that could not be explained. [This was before Medicare had prohibited multi-test panels; 27-test profiles that included serum calcium were frequently ordered when lab work was needed]. Dr. Hawker agreed to run calcitonin (CT) levels on specimens from some of these patients as a possible explanation for hypocalcemia.

All of the serum specimens subsequently tested had significantly elevated immunoreactive calcitonin values, with some being more than 100 times the upper reference limit and similar to levels seen in patients with medullary thyroid carcinoma (MTC). Dr. Hawker and a scientist in his laboratory, Dr. Francis P. DiBella, then carried out further research to determine whether the calcitonin in these patients was authentic calcitonin or some other form that was cross-reacting in the radioimmunoassay. They performed gel filtration studies to compare the elution profile of the calcitonin immunoreactivity in the serum of a patient with toxic shock syndrome to the elution profile of the calcitonin immunoreactivity in a patient with MTC producing similarly excessive amounts of calcitonin.

Because the form of calcitonin that eluted from the serum of the patient with toxic shock syndrome appeared much larger in size than authentic (intact) calcitonin, it was thought to have been a polymeric form. [At the time of these studies, the concept of prohormones had only been discovered for a few hormones, and calcitonin was not one of those]. In order to learn more about this potentially larger form of calcitonin, Drs. Hawker and DiBella performed the gel filtration studies before and after treatment of the patient serum specimens with 2-mercaptoethanol, a reducing agent that breaks disulfide bonds, which might disrupt a polymeric form. There was no change in the size of the authentic calcitonin from the patient with medullary thyroid carcinoma that eluted from the gel filtration column, but the 2-mercaptoethanol shifted the calcitonin immunoreactivity measured after gel filtration from the larger, perhaps polymeric, form of calcitonin to a somewhat smaller form that was still larger in size than authentic calcitonin.

This research was published in 1983 in the Journal of Laboratory and Clinical Medicine.¹ The authors included Drs. Chesney, Hawker, and DiBella, along with two well known endocrinologists, Dr. John Haddad of the University of Pennsylvania (a former President of the American Society for Bone and Mineral Research), and Dr. David McCarron of the University of Oregon, both of whom had also seen patients with toxic shock syndrome and lowered serum calcium levels. Two other physicians at the University of Wisconsin, Dr. Joan Chesney and Dr. Jeffrey Davis, were also included as authors of this publication.

An important 2004 review article on procalcitonin (CTpr) and sepsis²  stated : “An initial publication in 1983 first called attention to increased serum levels of immunoreactive CT in patients with the staphylococcal toxic shock syndrome, a severe form of sepsis.” The authors then credited the early research conducted by Dr. Hawker and his colleagues with providing “…the inspiration for multiple subsequent studies of CTpr in inflammation, systemic infection, and sepsis.” In this review, the authors noted that the two larger forms identified in the early report were likely procalcitonin and the 21-amino acid CT carboxyterminus peptide I (CCP-I), another CT precursor.