Fibromyalgia and Thyroid Resistance
Fibromyalgia and Thyroid Resistance
Fibromyalgia is a syndrome that affects the muscles and soft tissues. The symptoms of fibromyalgia are chronic muscles pain, fatigue, painful tender points, sleep problems, stress management, changes in the everyday lifestyle. These things can be usually relieved to some average point with the help of medications. The pain can be deep, sharp, dull, throbbing, or aching. You feel it in your muscles, tendons, and ligaments around the joints. For some people, the pain comes and goes. It could travel throughout your body.
Although the exact pathogenesis and representing mechanisms which give rise to clinical manifestation are unrevealed, there is an increasing line of indications suggesting an association between fibromyalgia and thyroid dysfunction. Some of the studies have shown that patients with fibromyalgia have an increased incidence of hypothyroidism. Further, thyroid autoimmunity has also been connected with fibromyalgia symptom severity. Circulating thyroid hormones do not give an accurate status of thyroid function in patients with fibromyalgia; rather intracellular thyroid hormone levels are more relevant. Low levels of intracellular hormones may follow from mitochondrial dysfunction as active transport of hormones across cellular membranes is required. It is well known that mitochondrial dysfunction is associated with fibromyalgia. In order to correct thyroid dysfunction and manage symptoms presenting in fibromyalgia patients, a multi-disciplinary approach should be taken assimilating dietary supplements, nutraceuticals, dietary changes and complementary alternative therapies.
Hypothyroidism, autoimmunity, and fibromyalgia
Although the latent procedures for fibromyalgia are not completely known, it is often observed as a stress-related disorder that involves interactions between the autonomic central nervous system, hypothalamic-pituitary-adrenal axis, and immune system. Thyroid autoantibodies included in patients with fibromyalgia are reported to occur at twice the rate of healthy controls. Moreover, approximately 25% of patients with fibromyalgia present with Tg Ab (thyroglobulin antibody) and/or TPO Ab (thyroid peroxidase antibody). Although these differences seem to exist between populations, the precise mechanism is not clearly known. Interrelations between fibromyalgia, thyroid and an increased incidence of primary and central hypothyroidism have been reported. Compared to a 1–5% incidence of primary hypothyroidism in the regular population, the incidence among fibromyalgia patients is 10–44% and secondary hypothyroidism are prevalent in 44%.
A recent study identified that euthyroid patients with fibromyalgia had an increased prevalence of positive TPO Ab compared to age- and sex-matched controls (19% in fibromyalgia patients vs. 7% in control patients). Regardless of this finding, TPO Ab positivity was not associated with clinical manifestations, which the authors suggested may support a hypothesis that thyroid autoimmunity may influence the development of fibromyalgia; however, the severity of fibromyalgia may not relate to the presence of TPO Ab. While associations between thyroid autoimmunity, fibromyalgia, and symptom acutness have been reported, the relationship between thyroid dysfunction and fibromyalgia has not yet been fully elucidated.
It has also been proposed that the characteristic pain experienced by fibromyalgia patients may relate to increased antibodies to muscle proteins, which are present in thyroid autoimmune disease. Additionally, pain distribution and pressure-pain threshold in patients with fibromyalgia have been positively associated with hypothyroidism and inversely associated with intracellular free T3, respectively. Substance P, a neuropeptide signaling pain, is increased through the disinhibition of substance P synthesis and secretion by nociceptive afferent neurons with low T3 concentrations.
Most patients with fibromyalgia also have difficulties with both thyroid production and utilization. There is a line of collective evidence which indicates that inadequate thyroid hormone regulation, due to hypothyroidism (thyroid hormone deficiency) or peripheral resistance to thyroid hormone, may both be underlying mechanisms causing cellular thyroid deficiency. Both abnormalities cause symptoms mainly through the same subsequent common mechanism—inadequate thyroid hormone regulation of gene transcription in the cells of affected tissues.
Thyroid Hormone Resistance:
Specific mutations in the thyroid hormone receptor are connected with thyroid hormone resistance. General resistance to the thyroid is a form of thyroid hormone resistance due to receptor site damage occurred by a very rare genetic disorder. In general resistance, both the peripheral tissues and pituitary gland are partly resistant to thyroid hormones. In patients with this disorder, TSH is almost everytime normal or mildly elevated with elevated T3 and T4. Genetic anomalies of thyroid hormone receptors can result in lower heart rate (20% lower), lower body temperature (0.5°C lower) and mild hypothyroidism. Peripheral resistance is a condition in which the peripheral tissues are hyporesponsive to thyroid hormones. Patients with peripheral resistance present with normal serum T3, T4, and TSH but a clinical profile suggesting thyroid hormone deficiency. Metabolism accelerates to normal in patients with peripheral resistance when thyroid hormone concentrations within the cell are high enough to override the resistance. Another form of resistance is a resistance to endogenous and exogenous hormones, where hormones are incompletely synthesized or cleaved. Several factors are also involved in this form of thyroid hormone resistance, including physiological antagonism; antibodies to hormones or hormone receptors; or absence of target cells.
Thyroid Hormone Receptor Damage
Thyroid dysfunction may arise from thyroid hormone receptor damage resulting from multiple factors including genetic anomalies of thyroid hormone receptors, autoimmune, oxidative or toxic damage to thyroid hormone receptors or reasonable binding to thyroid-hormone receptors by environmental circumstances (e.g. pollutants, food additives, etc.). Some toxins appeared affecting thyroid function includes bisphenol A (BPA), polychlorinated bisphenols (PCBs), polybrominated diphenyl ethers (PBDEs), and Triclosan and organochlorine pesticides.
BPA stick to thyroid hormone receptors and estrogen receptors, antagonizing thyroid hormone receptor activation. BPA has also been shown to inhibit the regulation of most T3-dependent responsive genes and affect T3 signaling pathways. In an animal model, BPA exposure produced an endocrine profile similar to that observed in patients with T3 resistance syndrome.
PCBs are persistent organic pollutants that have paired phenol rings with different degrees of chlorination. Their structure is similar to thyroid hormone and can bind to interact with the thyroid hormone receptor acting as an agonist or antagonist to the thyroid hormone receptor. PCBs were widely used from 1930 to 1979, at which time they were banned in the US. They are lipophilic compounds that have a half-life of 7 years and have been found in high amounts in breast milk. Prenatal exposure to PCBs has been shown to be associated with a decreased cognitive function in children, impairing executive function, verbal abilities, visual recognition, and memory.
PBDEs have a structure similar to thyroid hormone and can displace T4 from serum thyroid-binding protein transthyretin (TTR). PBDEs are widely used as flame retardants and in plastics, foams and building materials, and have also been detected in foods (meat, fish, vegetables, and dairy). PBDEs are detectable in 97% of US residents at levels 20 times higher than those seen in European residents. Increased PBDEs have also been associated with lower free T3; TSH declines 16% for every ten-fold increase in PBDEs, increasing the risk of subclinical hyperthyroidism two-fold.
Triclosan is an antibacterial/anti-fungal agent containing chlorinated organic molecules similar to PCBs, PBDEs, and BPA. Triclosan suppresses serum thyroid hormone concentrations. According to NHANES-, Triclosan has been found in 75% of urine samples and has also been found at detectable levels in breast milk.
Other environmental toxins which affect thyroid function and hormone homeostasis include organochlorine pesticides, which activate hepatic uridine diphosphate glucuronyltransferases (UDPTGs) and increases T4 metabolism, and perchlorate, which lower both T3 and T4. Some stage of immunity has been seen with iodine addition.