In addition, the correlation between age and an increased prevalence of hypothyroidism, in a steadily ageing population, will contribute to an overall higher incidence of hypothyroidism in the near future. The exact pathological mechanism through which radiation induces primary hypothyroidism remains to be eluded but radiation is known to directly cause gland damage through induction of apoptosis, fibrosis of the gland capsule, atherosclerosis, thyroiditis, thyroglobulin antibodies ( 50– 54).Ĭonsidering the direct correlation between primary hypothyroidism and radiotherapy for head and neck cancer, as well as the observed significant increase in survival rates of cancer, rising from 24% to 50% over the last 40 years, and a latency period of up to 27 years for radiation-induced hypothyroidism, we can expect to see a significant increase in the incidence of primary hypothyroidism ( 55). The overall incidence of hypothyroidism following irradiation in the head or neck region varies widely between studies, ranging up to 92%, but most frequently lays between 20-60% ( 49). However, the majority of causes in developed countries are instead due to direct damage of the thyroid gland through processes like inflammation, autoimmune disease, or radiation ( 45– 47).įor example, the most common clinically late effect of radiation, when applied at a therapeutic dose (30-70Gy) within the cervical region, is primary hypothyroidism ( 46, 48). This can be attributed to a variety of reasons including medication and iodine deficiency ( 43, 44). Primary hypothyroidism, which accounts for 99% of all hypothyroidism cases, arises due to an inability of the thyroid to produce the thyroid hormones triiodothyronine (T3) and thyroxine (T4) ( 41). In accordance with its aetiology, hypothyroidism can be divided into three subtypes: primary central, comprised of secondary and tertiary and peripheral ( 42). This is proposed in the form of exploration and combination of materials used to fabricate these scaffolds, the addition of peptides which can aid restoration of tissue homeostasis and additional in vivo experimentation providing data on safety and efficacy of these implants. However, further work is needed until clinical translation can be achieved. Multiple of these scaffolds have successfully restored an athyroid phenotype in vivo. Those currently under investigation are composed of either biopolymers or native decellularized extracellular matrix (dECM) in conjunction with either primary thyrocytes or stem cells which have undergone directed thyroid differentiation.
Recently, these techniques have been adapted for thyroid tissue, primarily through the fabrication of regenerative scaffolds. Tissue engineering and regenerative medicine have been applied in conjunction with each other to restore function of various tissues. Here, issues are present regarding the lack of regulation concerning formulation and lack of data regarding safety and efficacy of these treatment methods. The alternative therapeutic approach employed in the past is combination therapy, which consists of administration of both T3 and T4, either synthetic or in the form of desiccated thyroid extract. Additional complications are also present in the form of dosage difficulties, extensive drug interactions and poor patience compliance.
However, there is mounting evidence that this is unable to restore thyroid hormone signaling in all tissues due to often persistent symptoms. The current standard of care encompasses thyroid hormone replacement therapy, traditionally in the form of synthetic T4. The incidence rate of primary hypothyroidism is expected to increase in the near future, partially due to increasing survival of patients that have undergone radiotherapy for head and neck cancer, which induces this disease in over half of those treated. Primary hypothyroidism severely impacts the quality of life of patients through a decrease in the production of the thyroid hormones T3 and T4, leading to symptoms affecting cardiovascular, neurological, cognitive, and metabolic function. 3Department of ENT, Head and Neck Surgery, NHS Lothian, Edinburgh, United Kingdom.2Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, United Kingdom.1Institute for Bioengineering, School of Engineering, The University of Edinburgh, Edinburgh, United Kingdom.
Nixon 3, Elaine Emmerson 2 and Anthony Callanan 1*
0 kommentar(er)
