Thyroid function plays a crucial role in metabolic homeostasis, in the regulation of blood pressure, energy expenditure and in glucose and lipid metabolism. Thyroid alteration patterns, particularly hypothyroidism, are widely known to be associated with metabolic syndrome. However, more recently, different thyroid hormone release patterns have shown not to fit within the classic definitions of hypothyroidism or hyperthyroidism, patterns in which hormone levels may often be within the normal range. A condition defined as thyroid hormone resistance syndrome has been identified as a state characterized by thyroid hormones within the upper limits of the normal range but with normal to high TSH levels. In fact, many studies have shown an association between this condition and pathologies such as obesity, metabolic syndrome, diabetes and NAFLD. Recent studies have hypothesized that thyroid hormone resistance might be present in patients with disabilities, therefore they also investigated whether and how all those conditions may influence one another. Furthermore, given the important role that TSH and thyroid hormones play in the development of various diseases, and the consequent implications for the health system, the creation of reliable algorithms that support the interpretation of thyroid homeostasis in the clinical setting is therefore pivotal.