Point-of-Care Platform for Endocrine Disorders Detection in Low-/Middle-Income Countries

Endocrine pathology encompasses a wide range of disorders originating from diverse sites within the body. Some involve the endocrine glands themselves, while others arise from endocrine cells scattered within non-endocrine tissues. The endocrine cells can be divided broadly into three categories: neuroendocrine cells, steroidogenic cells, and thyroid follicular cells, each with its distinct embryological origin, morphological features, and biochemical pathways for hormone synthesis. Disorders of the endocrine system include developmental abnormalities, inflammatory conditions, whether infectious or autoimmune, hypofunction due to atrophy, hyperfunction often due to compensatory hyperplasia, and various types of neoplasia. Fully understanding endocrine pathology requires knowledge of both structural and functional aspects of the system, including biochemical signaling pathways controlling hormone synthesis and secretion. The advances made in molecular genetics have further elucidated both sporadic and hereditary diseases prevalent in this field. 1 The interplay between the endocrine system and neuropsychiatric function is a long-standing subject of scientific interest, particularly about thyroid and parathyroid disorders. Dysregulation of thyroid hormones can have a significant impact on mental state and cognitive performance, as observed in hypothyroidism and hyperthyroidism, conditions frequently associated with mood alterations, depression, anxiety, and cognitive impairment. Similarly, parathyroid dysfunction can lead to calcium metabolism fluctuations that may result in neuropsychiatric symptoms such as confusion, irritability or psychosis, highlighting the critical role of these glands in maintaining neurochemical balance. Thyroid and parathyroid hormones have historically been recognised not only for their metabolic and developmental roles, but also for their influence on emotional and cognitive regulation. Early clinical observations noted that severe hypothyroidism or hyperparathyroidism could mimic primary psychiatric illness. More recent studies have demonstrated that disturbances in thyroid hormone homeostasis during early development can impair brain maturation and behaviour, while chronic dysregulation in adulthood can alter neuroendocrine feedback and stress response pathways. 2 Diagnosis of diseases and monitoring of treatment through technological devices have evolved remarkably over the past two centuries. The origins of diagnostic devices in the 19th and early 20th centuries are simple mechanical tools, such as the stethoscope, which was invented by René Laennec in 1816, and the thermometer. Later, chemical assays enabled the detection of biomarkers in blood and urine-the first laboratory-based diagnostics. These formed the roots of quantitative medical evaluation 3. Then, in the mid-20th century, the advent of electronics gave medicine a new dimension, signaling the advent of the Age of Electrical and Electronic Instrumentation. Internal organs could now be investigated non-invasively with devices such as the electrocardiograph (ECG) and electroencephalograph (EEG), let alone imaging instruments like X-rays, CT scans and MRIs. Diagnostic medicine became more and more data-driven and objective. The miniaturization of electronics, starting from the 1970s through the 2000s, allowed the development of portable diagnostic tools, such as glucose meters for diabetes monitoring, by using electrochemical sensors. These are called biosensors and represent devices that combine biological recognition elements, such as enzymes, antibodies, or polymers, with transducers to detect specific analytes. 4,5 In recent years, starting from the 2010s up to today, advances in microfabrication, nanomaterials, and wireless communication have enabled the development of wearables and implantable capable of the continuous monitoring, in real time, of vital signs and metabolites such as glucose, lactate, and pH. Such technologies will represent the beginning of a new era for medicine: from a reactive approach to that of a preventive and personalized one, enabling diseases to be diagnosed early and treatments managed in an optimized fashion. This thesis will deal, according to the brief scope of this research, with the development of biosensors for the diagnosis and home monitoring of endocrine diseases. The thesis consists of an introductory chapter presenting the scope of the research and five main chapters. Chapter 1 introduces the physiological and clinical background of thyroid and parathyroid disorders and reviews the state of the art in biosensing field. Chapters 2 through 4 describe the different biosensors developed during the PhD work. The research can be divided into three main phases, roughly one per year, each progressively contributing to achieving the final objectives. Chapter 5 presents an Early Health Technology Assessment of the developed multiplexed CAD prototype device. Chapter 6 concludes with a summary of the work carried out and future perspectives.