Reinterpreting patterns of variation in human thyroid function

• Published in: Evolution, medicine, and public health Vol. 9; no. 1; pp. 93 - 112
• Main Authors: Keestra, Sarai, Högqvist Tabor, Vedrana, Alvergne, Alexandra
• Format: Journal Article
• Language: English
• Published: Oxford University Press 26.02.2021
• Subjects: hyperthyroidism; autoimmune thyroid diseases; hypothyroidism; evolutionary ecology; evolutionary medicine; thyroid hormones
• ISSN: 2050-6201; 2050-6201
• DOI: 10.1093/emph/eoaa043

Lay Summary Thyroid hormone reference intervals—used to determine normal thyroid function —currently don’t take into account many significant factors that can cause variation in thyroid hormone levels. These factors include age, sex, ethnicity, season, time of day, iodine content in the diet, socioeconomic status, stress levels, body composition, immune status, menstrual cycle phase, and overall health status. This paper shows how early life experiences as well as short term stressors may affect variation in thyroid function. These are energetic challenges to which the thyroid physiology can respond to. Our investigation shows that much variation in thyroid function is natural. It may result from a complex interplay of evolutionary, genetic, developmental, and physiological factors in response to energetic challenges in the environment, beyond what is currently considered in biomedicine. A new research agenda for thyroid health should explore the way that diversity in thyroid function has evolved as a response to different contexts people live in—like focusing on how people’s metabolisms adapt to the energetic requirements of their environments. Abstract Two hundred million people worldwide experience some form of thyroid disorder, with women being especially at risk. However, why human thyroid function varies between populations, individuals, and across the lifespan has attracted little research to date. This limits our ability to evaluate the conditions under which patterns of variation in thyroid function are best understood as ‘normal’ or ‘pathological’. In this review, we aim to spark interest in research aimed at understanding the causes of variation in thyroid phenotypes. We start by assessing the biomedical literature on thyroid imbalance to discuss the validity of existing reference intervals for diagnosis and treatment across individuals and populations. We then propose an evolutionary ecological framework for understanding the phylogenetic, genetic, ecological, developmental, and physiological causes of normal variation in thyroid function. We build on this approach to suggest testable predictions for how environmental challenges interact with individual circumstances to influence the onset of thyroid disorders. We propose that dietary changes, ecological disruptions of co-evolutionary processes during pregnancy and with pathogens, emerging infections, and exacerbated stress responses can contribute to explaining the onset of thyroid diseases. For patients to receive the best personalized care, research into the causes of thyroid variation at multiple levels is needed.