MSACL 2024 Abstract

INTRODUCTION
Hormones are essential biological messengers, pivotal in regulating (human) homeostasis. As the human body needs constant adaptation to a changing environment, hormone concentrations constantly fluctuate in response. Adequate hormonal response to physiological and environmental stimuli is an essential marker of health. Although much money and effort are spent on discovering new biomarkers, relatively little attention is paid to the correct sampling of current endocrine biomarkers. Here we present for the first time a 24-hour profile of catecholamines, and metanephrines obtained by microdialysis from a healthy volunteer going about her normal daily routine.

METHODS
An healthy female participant, age 48 years was sampled for 24 hours. A 20-kDa cutoff linear microdialysis catheter (membrane length, 30 mm; mDialysis) was placed perpendicular to the midline in periumbilical subcutaneous tissue, flushed, and then perfused at 1 ul/min (107 microdialysis pump, mDialysis) with sterile isotonic fluid (T1 perfusion fluid, mDialysis). The outlet of the probe was adapted to conneced to our fraction collector (U-RHYTHM, Dynamic Therapeutics) using 20 cm of fluorinated ethylene propylene tubing, allowing the automated collection and storage of individual samples every 20 min. The pump and sampler assembly were placed in a flexible waist belt. Immediately following collection, catecholamines were stabilised in microdialysate through the continuous addition at 0.1ul/min of 0.3molar ascorbic acid. Liquid chromatography in combination with tandem mass spectrometry was used to simultaneously analyze the microdialysate and obtain high-resolution profiles of tissue catecholamines and metanephrines. Other wearables that were used were 24-hour blood pressure measurement, continuous glucose monitoring, heart rate measurement, light monitoring, activity monitoring and wrist temperature.

RESULTS
With the U-RHYTHM ambulatory microdialysis sampling system we obtained for the first time in human a 24 hour profile of catecholamines and metanephrines without need for blood samples, and in a naturalistic setting contextualized with wearable device data. In total 73 interstitial samples were collected. Collection started 11:10 am on the first day and ended 11:10 am the following day. Profiles were constructed for each individual hormone. Most hormones were detected in all samples, except for adrenaline which was detected in 60 % of all samples, metanephrine in 81 % of all samples, and 3-methoxytyramine in 74 % of all samples. Median [IQR] concentrations of the hormones were 0.072 [0.011 - 0.12], 0.083 [0.051 - 0.10], 0.006 [0.005 - 0.0087], 0.008 [0.006 - 0.011], 0.012 [0.005 - 0.018], and 0.008 [0.006 - 0.009] nmol/L for dopamine, noradrenaline, adrenaline, 3-methoxytyramine, normetanephrine and metanephrine, respectively. Noradrenaline concentrations showed a good correlation with heart rate binned per ten minutes (r = 0.86).

CONCLUSION
The innovative U-RHYTHM ambulatory microdialysis sampling system has successfully provided a comprehensive 24-hour profile for catecholamines and metanephrines for a healthy individual under normal daily conditions, not previously accomplished in human studies. The median concentrations of these hormones were lower or comparable to plasma concentrations. The strong correlation between noradrenaline concentrations and heart rate underlines the potential for such hormonal monitoring to reflect physiological states and changes. Although the presence of certain hormones like adrenaline and metanephrine was not detected in all samples, the collection and detection rate was significant enough to provide a useful profile for each hormone. This approach offers a novel perspective on the dynamics of hormone release and metabolism during normal daily activities. It underscores the importance of temporal resolution in understanding the complex endocrine system, and the findings can pave the way for improved sampling strategies in both research and clinical settings. By integrating the microdialysis method with other monitoring devices, we have moved closer to a multidimensional understanding of the physiological underpinnings of hormonal regulation. The implications for the field of endocrinology are profound, as this method could be adapted for the diagnostic evaluation of hormonal dysregulation in various diseases, potentially leading to more personalized and timely interventions.