Evaluating health outcomes in the treatment of hypothyroidism

Abstract

Clinical hypothyroidism is defined by the inadequate production of thyroid hormone from the thyroid gland to maintain normal organ system functions. For nearly all patients with clinical hypothyroidism, lifelong treatment with thyroid hormone replacement is required. The primary goal of treatment is to provide the appropriate daily dose of thyroid hormone to restore normal thyroid function for each individual patient. In current clinical practice, normalization of thyrotropin (TSH) level is the primary measure of effectiveness of treatment, however the use of a single biomarker to define adequate thyroid hormone replacement is being reevaluated. The assessment of clinical health outcomes and patient-reported outcomes (PROs), often within the context of intensity of treatment as defined by thyroid function tests (i.e., undertreatment, appropriate treatment, or overtreatment), may play a role in evaluating the effectiveness of treatment. The purpose of this narrative review is to summarize the prominent health outcomes literature in patients with treated hypothyroidism. To date, overall mortality, cardiovascular morbidity and mortality, bone health and cognitive function have been evaluated as endpoints in clinical outcomes studies in patients with treated hypothyroidism. More recent investigations have sought to establish the relationships between these end results and thyroid function during the treatment course. In addition to clinical event outcomes, patient-reported quality of life (QoL) has also been considered in the assessment of adequacy of hypothyroidism treatment. From a health care quality perspective, treatment of hypothyroidism should be evaluated not just on its effectiveness for the individual patients but also to the extent to which patients of different sociodemographic groups are treated equally. Ultimately, more research is needed to explore differences in health outcomes between different sociodemographic groups with hypothyroidism. Future prospective studies of treated hypothyroidism that integrate biochemical testing, PROs, and end result clinical outcomes could provide a more complete picture into the effectiveness of treatment of hypothyroidism.

Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis

“…Syndrome T or SORSHOT, i.e., continued symptoms and reduced quality of life in treated www.nature.com/scientificreports/ hypothyroidism and AIT continues to be a challenge in about 10% of patients with thyroid diseases 2,9,26,44-46 . Multiple hypotheses have been proposed for an explanation of this common, yet poorly understood condition, but up to now no satisfactory solution is available [47][48][49][50][51] . Therefore, research programs addressing potential pathophysiological mechanisms of syndrome T are highly needed.…”

Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation

“…Our findings demonstrate that thyroid hormone deficiency during hibernation is restricted to the CNS and does not extend to peripheral levels of T3 and T4. Hibernating squirrels thus present a remarkable animal model in which central thyroid hormone function is depressed while essential peripheral thyroid function on internal organs and general metabolic processes is preserved 49 , 50 . Central thyroid hormone has been implicated in the seasonal shifts in reproduction and food intake in non-hibernating animals, including Siberian hamsters, sheep, photoperiodic F344 rats 51 – 54 and hibernating arctic ground squirrels 55 .…”

Hypothalamic hormone deficiency enables physiological anorexia

“…In this study, we found that squirrels exhibit T3 deficiency in the hypothalamus during IBA, and that restoration of T3 reverses anorexia, demonstrating that long-term suppression of hunger during hibernation is, at least partially, due to central hypothyroidism. Thyroid hormone deficiency is specific to the CNS and does not affect peripheral levels of T3 and T4, obviating the adverse effects of hypothyroidism on internal organs 35,36 and preserving the involvement of thyroid hormones in increasing thermogenic capacity prior to squirrels entering hibernation.…”

“…Our findings demonstrate that thyroid hormone deficiency during hibernation is restricted to the CNS and does not extend to peripheral levels of T3 and T4. Hibernating squirrels thus present a remarkable animal model in which central thyroid hormone function is depressed while essential peripheral thyroid function on internal organs and general metabolic processes is preserved 49,50 . Central thyroid hormone has been implicated in the seasonal shifts in reproduction and food intake in non-hibernating animals, including Siberian hamsters, sheep, photoperiodic F344 rats [51][52][53][54] and hibernating arctic ground squirrels 55 .…”