1.
Disorder of thyroid hormone transport into the tissues.
Groeneweg, S, Visser, WE, Visser, TJ
Best practice & research. Clinical endocrinology & metabolism. 2017;(2):241-253
Abstract
Transport of thyroid hormone (TH) across the plasma membrane is essential for intracellular TH metabolism and action, and this is mediated by specific transporter proteins. During the last two decades several transporters capable of transporting TH have been identified, including monocarboxylate transporter 8 (MCT8), MCT10 and organic anion transporting polypeptide 1C1 (OATP1C1). In particular MCT8 and OATP1C1 are important for the regulation of local TH activity in the brain and thus for brain development. MCT8 is a protein containing 12 transmembrane domains, and is encoded by the SLC16A2 gene located on the X chromosome. It facilitates both TH uptake and efflux across the cell membrane. Male subjects with hemizygous mutations in MCT8 are afflicted with severe intellectual and motor disability, also known as the Allan-Herndon-Dudley syndrome (AHDS), which goes together with low serum T4 and high T3 levels. This review concerns molecular and clinical aspects of MCT8 function.
2.
Thyroid Hormones, Metabolic Syndrome and Its Components.
Delitala, AP, Fanciulli, G, Pes, GM, Maioli, M, Delitala, G
Endocrine, metabolic & immune disorders drug targets. 2017;(1):56-62
Abstract
Metabolic syndrome is a clustering of various metabolic parameters, which include diabetes, low high-density lipoprotein cholesterol, elevated triglycerides, abdominal obesity, and hypertension. It has merged as a worldwide epidemic and a major public health care concern. However, due to the different criteria used for the assessment, the frequency of metabolic syndrome in the general population is variable but it is more common in the older people. Metabolic syndrome is closely linked to cardiovascular risk and increases cardiovascular outcomes and all-cause mortality. Recent evidences showed that alterations of the thyroid function could have an impact on the components of the metabolic syndrome, suggesting that thyroid hormones have a variety of effects on energy homeostasis, lipid and glucose metabolism, and blood pressure. In this review, we summarize available data on the action of thyroid hormone on the components of metabolic syndrome.
3.
Thyroid hormone transporters and resistance.
Visser, TJ
Endocrine development. 2013;:1-10
Abstract
Cellular entry is an important step preceding intracellular metabolism and action of thyroid hormone (TH). Transport of TH across the plasma membrane does not take place by simple diffusion but requires transporter proteins. One of the most effective and specific TH transporters identified to date is monocarboxylate transporter 8 (MCT8), the gene of which is located on the X chromosome. Although MCT8 is expressed in many tissues, its function appears to be most critical in the brain. Hemizygous MCT8 mutations in males cause severe psychomotor retardation, known as the Allan-Herndon-Dudley syndrome (AHDS), and abnormal serum TH levels. AHDS thus represents a type of TH resistance caused by a defect in cellular TH transport.
4.
Nutritional epidemiology and thyroid hormone metabolism.
Vanderpas, J
Annual review of nutrition. 2006;:293-322
Abstract
Severe iodine deficiency was the main cause of endemic goiter and cretinism. Most of the previously iodine-deficient areas are now supplemented, mainly with iodized salt. The geographical distribution of severe endemic areas has been progressively reduced, and at present, approximately 200 million people living in remote places are still at risk of severe iodine deficiency. International public health programs should be focused first on reaching these populations, and second on auditing and monitoring the operational work of supplementation programs. This second point is essential to prevent iodine-induced hyperthyroidism or interruptions of iodine supplement distribution, which could be catastrophic for the fetus and the young infant. Echography brings a complementary tool to clinical assessment of goiter by palpation. Inductively coupled plasma-mass spectrometry brings at least a definitive gold standard for iodine measurement and thyroid hormone measurement. Thiocyanate overload has been clearly documented as a goitrogen in Central Africa, and when associated with selenium deficiency, it may be included as risk factor for endemic myxedematous cretinism. Variable exposure to different environmental risk factors is likely the explanation of the variable distribution of two types of endemic cretinism (neurological and myxedematous), and the clinical overlap of the pathogeny of both syndromes is more important than previously described. It is possible that Kashin-Beck osteoarthropathy is another evanescent endemic disease that will disappear with the correction of iodine deficiency.
5.
Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion.
Douyon, L, Schteingart, DE
Endocrinology and metabolism clinics of North America. 2002;(1):173-89
Abstract
Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is diminished and, in severe cases, thyroid-binding protein levels are decreased. In regards to GH, there is an increase in GH secretion with a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see text] changes in cortisol secretion in patients with anorexia nervosa resemble depression. They present with increased urinary free cortisol and serum cortisol levels but without changes in ACTH levels. In contrast to the findings observed in obesity, the ACTH response to CRH is suppressed, suggesting an increased secretion of CRH. The endocrine changes observed in obesity and starvation may complicate the diagnosis of primary endocrine diseases. The increase in cortisol secretion in obesity needs to be distinguished from Cushing's syndrome, the decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished from secondary hypothyroidism, and the increase in cortisol secretion observed in anorexia nervosa requires a differential diagnosis with primary depressive disorder.