Clinical hypothyroidism is a pervasive deficit in thyroid hormone actions, leading to the alteration of calorigenesis and oxygen consumption throughout the body and organ-specific effects. Deficiency of T3 actions at the genomic level cause hormonal, biochemical, ion-transport, and mechanical changes in target tissues. T4 is the principal hormone produced by the thyroid gland and in circulation.
Monodeiodination of its outer ring in both the cytoplasm and nucleus of target tissues converts it to T3 by the function of three tissue-specific deiodinases [72]. The actions of T3 are mediated by its binding to one of three receptor isoforms (TRα1, TRβ1, and TRβ2), which in turn form dimers with another T3 receptor or with other nuclear receptors. Subsequent DNA binding with specific orientations occurs at the 5′ regulatory regions of thyroid hormone-responsive genes to either activate or repress transcription [73].
Based on this genetic description, some clinical manifestations are understood at the molecular level, including short stature as a result of failure to stimulate the growth hormone gene in pituitary somatotrophs, decreased low-density lipoprotein (LDL) cholesterol clearance because of a deficit in the expression of the hepatic LDL receptor gene regulated by sterol regulatory element binding transcription factor 2 and impaired diastolic and systolic ventricular function resulting from decreased myocardial sarcoplasmic reticulum ATPase and α-myosin heavy chain expression.
T3 also regulates cellular uptake of glucose and amino acids, augments cardiomyocyte calcium-ATPase activity, and alters adenosine triphosphate generation by the mitochondria [74]. As novel therapies continue to be identified for the treatment of neuroendocrine malignancies, hypothyroidism may also result because of the interaction of thyroid hormone with G protein-coupled membrane receptors and the mitogen activated protein kinase pathways.
Diagnosis
Signs and Symptoms
Common clinical features associated with hypothyroidism are tiredness and fatigue, weight gain, dry skin, cold intolerance, constipation, muscle weakness, facial edema, hoarse voice, and poor memory (Table 4). These symptoms can be present in other diseases, including malignancy, and can be side effects of cancer therapies.
Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6.
Our study confirms that metabolic syndrome in both euthyroid and subclinical hypothyroid women is connected with obesity, visceral fat accumulation, and higher TSH and IL-6 concentrations. Immune thyroiditis is associated with higher TSH and IL-6 levels. Obese subclinical hypothyroid women with Hashimoto`s thyroditis have a higher prevalence of metabolic syndrome when compared with subclinical hypothyroid women without thyroid autoimmunity. It is possible that in the crosstalking between subclinical hypothyroidism and metabolic syndrome, enhanced proinflammatory cytokine release in the course of immunological thyroiditis plays a role.