Elvar Theodorsson¹, Jin Ye Yeo²

¹Linkoping University, Sweden; ²JLPM Editorial Office, AME Publishing Company

Correspondence to: Jin Ye Yeo. JLPM Editorial Office, AME Publishing Company. Email: jlpm@amegroups.com

Expert introduction

Prof. Elvar Theodorsson (Figure 1) is a professor emeritus at Linköping University in Sweden, whose main research interests are neuroendocrinology of regulatory peptides and neurosteroids, the applied metrology in clinical chemistry, and health technology assessment (HTA). In the clinical chemistry laboratory, he has especially shouldered the responsibilities of measuring and interpreting hormones, hematology, electrolytes, and blood gases. He has also been engaged in information technologies in the clinical laboratory and their interactions with clinical users. He has chaired HTA for the three county Councils in Eastern Sweden for ten years.

Elvar Theodorsson has served in working group- and/or leadership roles, e.g., in the Swedish Society for Clinical Chemistry (SFKK), The Nordic Society of Clinical Chemistry (NFKK), the European Union of Medical Specialists (UEMS) Section and Board of Laboratory Medicine, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), Eurachem, and the Joint Committee for Traceability in Laboratory Medicine (JCTLM) and in the Clinical and Laboratory Standards Institute (CLSI).

An overview of his publications is available here: http://orcid.org/0000-0003-0756-7723, https://www.researchgate.net/profile/Elvar-Theodorsson

Figure 1 Prof. Elvar Theodorsson

Interview

JLPM: What drove you to pursue neuroendocrinology?

Prof. Theodorsson: I was particularly interested in pharmacology during medical school. After the internship, I applied for PhD opportunities in the Nordic countries' pharmacology departments and had a six-month trial period at the Karolinska Institute in Stockholm in early 1980. This led to a PhD project and engagements in teaching pharmacology, clinical chemistry, and medical diagnosis to medical students.

Several research groups at the Karolinska Institute were engaged in research on regulatory peptides/neuropeptides in the 1980s, including Victor Mutt, Tomas Hökfelt, Jan Lundberg, and my tutor Sune Rosell, who kindled my interest in the neuropeptide neurotensin. When Sune Rosell moved to Astra early on, later Astra Zeneca, as head of research, I moved to the clinical chemistry department at the Karolinska Hospital in Stockholm where the opportunities for pursuing further research were optimal.

JLPM: Could you provide a brief overview of the applications of clinical chemistry in neuroendocrinology?

Prof. Theodorsson: Neurotransmitters, paracrine agents, and hormones all play crucial roles in regulating the functions of living organisms and are, therefore, of diagnostic interest. Their diverse chemistries range from small amines to large protein molecules, and they usually require measurement procedures able to measure exceptionally low concentrations, such as advanced immunochemical measurement systems, chromatographic, and mass spectrometric systems. Amongst the measurands in these categories, which are widely available in laboratories of clinical chemistry, are N-terminal pro-brain natriuretic peptide (NT-ProBNP) for the diagnosis and monitoring of cardiac failure, procalcitonin as an acute phase reactant, and chromogranin A as a general marker of endocrine tumors. Specialized laboratories of clinical chemistry use the measurement of individual amines and regulatory peptides for diagnosing and monitoring specific endocrine tumors.

JLPM: Has there been any recent advancements in the application of clinical chemistry in neuroendocrinology? Are there any examples that you believe hold significant promise?

Prof. Theodorsson: The currently most promising field of research and clinical practice in this field is the measurement of markers for brain and neuronal damage. It has earlier been possible to measure such markers in cerebrospinal fluid. Still, new immunochemical, molecular biology, and mass spectrometric measurement techniques are creating a paradigm shift, enabling measurements in plasma of molecules originating in the brain. The degree of automation of such techniques promises to make them available for common clinical chemistry laboratories. This is particularly promising in the diagnosis of degenerative diseases of the brain and for diagnosing traumatic brain damage.

JLPM: Your research focus on regulatory peptides and neurosteroids. What are some surprising findings derived from your studies on these substances?

Prof. Theodorsson: We demonstrated that carcinoid tumors excrete tachykinins such as neuropeptide K (NPK) and neurokinin A (NKA). In addition to their effects when normally secreted from primary afferent neurons, these substances were also shown to stimulate the growth of fibroblasts, contributing to the cardiac fibrosis accompanying advanced carcinoid syndromes.

JLPM: In your recent research work, your team highlighted the need to re-evaluate the 95% inclusion criteria for defining reference intervals (1). In your opinion, what are some ways the inclusion criteria can be re-evaluated and modified to reduce false positives while minimizing false negatives? Do you foresee increasing the inclusion criteria beyond 95% to pose any problems?

Prof. Theodorsson: Population-based reference intervals employing 95% inclusion criteria have been widely adopted. A process to change that practice is likely controversial in the laboratory and clinical community. In fact, clinicians are accustomed to the substantial number of false positives the current criteria of health, exclusion of outliers and 95% inclusion criteria invite. The widening of inclusion criteria to 99% we and others suggest may be useful in some situations. However, the improved estimates of biological variation established by the EFLM (European Federation of Clinical Chemistry and Laboratory Medicine) working group, including individual reference individuals and the current developments of methods for developing reference individuals based on big data, hold the most promise.

JLPM: As the Editorial Board Member, what are your expectations for JLPM?

Prof. Theodorsson: Journal editors, editorial board members, and reviewers have a difficult role when they find reasons to reject a manuscript. However, they frequently find reasons and spend substantial effort aiding the authors in improving their manuscripts and studies. That is the most satisfying role for all involved.

Reference

1. El-Khoury JM, Badrick T, Theodorsson E. Time to Reevaluate the 95% Inclusion Criteria for Defining Reference Intervals?. Clin Chem. 2024;70(5):700-702. doi:10.1093/clinchem/hvae026