Reinterpreting patterns of variation in human thyroid function

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 personalised care, research into the causes of thyroid variation at multiple levels is needed.

Thyroid Hormone Signalling in Human Evolution and Disease: A Novel Hypothesis

“…Likewise, a single-nucleotide polymorphism in the DIO2 gene of Neanderthals [ 53 ] that resulted in a decreased capacity for conversion of T4 to T3 could have affected key developmental programmes and could potentially explain the significant phenotypical differences between Neanderthals and Homo sapiens despite their closeness in terms of genetic ancestry [ 53 , 54 ]. Most importantly, this variant may have enabled Neanderthals to hibernate and survive long and cold winters [ 55 ] (if this evidence is further confirmed), but when archaic humans switched to a high-carbohydrate diet, the variant became disadvantageous, as it is associated with an increased risk of diabetes [ 56 , 57 ].…”

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

“…TH, especially T3, inhibit TRH and TSH secretion [ 2 ]. However, very recently, the HPT axis has been suggested as a dynamic system with plasticity, allowing adaptation to demanding situations through regulating “life-history trade-offs between reproduction, growth, immunity and basal metabolic rate” in the setting of an evolutionary ecology framework [ 35 ].…”

Charting the Unknown Association of COVID-19 with Thyroid Cancer, Focusing on Differentiated Thyroid Cancer: A Call for Caution

“…The activity of TRH neurons is inhibited by negative energy balance situations such as fasting, inflammation or chronic stress [ 142 ]. Indeed, very recently, Keestra et al suggested an evolutionary ecology framework according to which HPT axis is considered a dynamic, adaptive system with a key role in “mediating life-history trade-offs between the functions of reproduction, growth, immunity and basal metabolic rate” [ 143 ] in the setting of demanding situations, including depression, psychosocial stress, and traumatic stress [ 144 , 145 ]. The absence of a causality between the psychosocial stress and the thyroid disorders in the setting of COVID-19 pandemic does not undermine the magnitude of an holistic approach to this issue, which will enable an integrated patient-oriented management of thyroid disorders, including DTC, during the challenging COVID-19 pandemic and beyond.…”