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Wednesday, 11 December 2013

The Effects of Thyroid hormone (1)


 Thyroid hormone (triiodothyronine (T3) and thyroxine (T4)), produced by the thyroid gland, plays an important role in regulation of metabolism, including directly boosts energy metabolism and triggers rapid protein synthesis and regulates mitochondrial gene transcription, etc. Iodine is necessary for the production of T3 and T4, deficiency of Iodine can lead to enlarge thyroid grand and goitre.

1. Excessive iodine intake (or deficiency) and goitre 
In the study to investigate the associations between intakes of iodine and water chemicals and the thyroid gland status of schoolchildren living in the coastal city of Port Sudan, researchers at 1 Sudan Atomic Energy Commission, Khartoum, found that the coastal city of Port Sudan is a goitre-endemic area. In contrast to other Sudanese cities in which endemic goitre is related to iodine deficiency, goitre in Port Sudan is associated with iodine excess. Water chemicals seemed to have no effects on thyroid status(1)

2.  Thyroid hormones and lipid metabolism
Thyroid hormone (T3) and its receptor (TR) have the diverse effects on the lipid metabolism and hypothyroidism causes hypercholesterolaemia characterized by increased levels of low-density ripoproteins (LDL). In the study by Hamamatsu University School of Medicine, researchers described that the existence of the complex cross-talks in the lipid metabolism between TR and other nuclear hormone receptors including peroxisome proliferator -activated receptors (PPARs), liver X receptor alpha (LXRalpha) and farnesoid X receptors (FXRs). Understanding for the function of TRs and other nuclear factors may provide the new approach to the control of hypercholesterolaemia(2).

3. Thyroid hormones and Carbohydrate metabolism
 In the study to evaluate Carbohydrate metabolism in nine patients with subacute thyroiditis before treatment and after recovery, showed that Glucose area during oral glucose tolerance test was significantly correlated with the elevated thyroxine (r = 0.8, p less than 0.01), and triidothyronine (r = 0.66, p less than 0.05). The results indicated the importance of follow-up study of glucose tolerance in subacute thyroiditis as well as similarity of carbohydrate metabolism abnormalities in hyperthyroidism(3).

4. Insulin resistance in hyperthyroidism
Insulin-like growth factor binding-protein-1 (IGFBP-1) has a role in glucose homeostasis and is present at high concentrations in hyperthyroidism. In the study to investigate the relationship between IGFBP-1 concentration and glucose homeostasis in hyperthyroidism, showed that in hyperthyroidism thyroid hormones directly increase fasting IGFBP-1 concentration but acute regulation of IGFBP-1 by insulin is normal and that elevated fasting phosphorylated IGFBP-1 concentration is associated with insulin resistance(4).

5. Thyroid hormones (TH) and brain development
Thyroid hormones (TH) are essential for normal brain development. Even subclinical hypothyroidism experienced in utero can result in neuropsychological deficits in children despite normal thyroid status at birth, researchers summerized that epidemiological, preclinical and animal research has clearly identified the critical role of TH in brain development. Additional work is required to understand the impact of low level perturbations of the thyroid axis to evaluate the risk associated with environmental contaminants with thyroid action(5).

6. Thyroid autoimmunity (TA) and heigh of Children
In the study to assess the association between pancreatic and thyroid autoimmunity (TA) and determine impact of thyroid antibodies on statural growth in Seventy-two children with type 1 diabetes mellitus (TIDM) and no clinical evidence of thyroid disorders, showed that patients with TA had significantly higher prevalence of GADA and IA2A and significantly higher A1c vs. patients without TA. Our data suggest significant association between TA and height in children with T1DM. SDS was independently associated with diabetes duration and TSH(6).

7. Thyroid hormone and the cardiovascular system
Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias - namely, atrial fibrillation - whereas overt hypothyroidism is characterized by the opposite changes.In the study of Effects of thyroid hormone on the cardiovascular system, researchers suggested that
administration of thyroid hormone or its analogue 3,5-diiodothyropropionic acid greatly benefits these patients, highlighting the potential role of thyroid hormone treatment in patients with acute and chronic cardiovascular disease(7).

8. Thyroid hormone and Delayed development
In the study to investigate the phenotype of TTR(Transthyretin (TTR) is a TH distributor protein in the circulatory system and is the only TH distributor protein synthesised in the central nervous system) null mice during development by The University of Melbourne, showed that TTR null mice also displayed a delayed suckling-to-weaning transition, decreased muscle mass, delayed growth and retarded longitudinal bone growth. In addition, ileums from postnatal day 0 (P0) TTR null mice displayed disordered architecture and contained fewer goblet cells than wild type. Protein concentrations in cerebrospinal fluid from P0 and P14 TTR null mice were higher than in age-matched wild type mice(8).

9. Thyroid disease in pregnancy
Thyroid diseases are common in women of childbearing age and it is well known that untreated thyroid disturbances result in an increased rate of adverse events, particularly miscarriage, preterm birth and gestational hypertension. According to the study by Division of Endocrinology, "V. Fazzi" Hospital, Lecce, overt dysfunctions (hyper- or hypothyroidism) have deleterious effects on pregnancy, subclinical disease, namely subclinical hypothyroidism, has still to be conclusively defined as a risk factor for adverse outcomes. Additionally, other conditions, such as isolated hypothyroxinemia and thyroid autoimmunity in euthyroidism, are still clouded with uncertainty regarding the need for substitutive treatment(9).

10. Thyroid disease in pregnancy and childhood
Thyroid function in pregnancy is characterised by a T4 surge at 12 weeks declining thereafter. Serum thyroid hormone concentrations fall in the second half of pregnancy. According to the study by Cardiff University School of Medicine, Fetal brain development depends on T4 transport into the fetus which in turn depends on sufficient maternal iodine supply. There is current concern that adequate iodisation is not present in large parts of Europe. There is increasing evidence that thyroid autoimmunity is associated with fetal loss but the mechanism is unclear and therapy requires carefully conducted studies. While hyperthyroidism in pregnancy is uncommon, effects on both mother and child are critical if untreated. Screening for thyroid function in early pregnancy and levothyroxine intervention therapy for maternal subclinical hypothyroidism should be considered but evidence is awaited. Screening for both thyroid dysfunction and thyroid antibodies ideally at a preconception clinic but certainly in early gestation is recommended(10).

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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/23206325
(2) http://www.ncbi.nlm.nih.gov/pubmed/17154100
(3) http://www.ncbi.nlm.nih.gov/pubmed/7034290
(4) http://www.ncbi.nlm.nih.gov/pubmed/10671946 
(5) http://www.ncbi.nlm.nih.gov/pubmed/22138353
(6) http://www.ncbi.nlm.nih.gov/pubmed/23155700
(7) http://www.ncbi.nlm.nih.gov/pubmed/14749496
(8) http://www.ncbi.nlm.nih.gov/pubmed/23092911
(9) http://www.ncbi.nlm.nih.gov/pubmed/22115167
(10) http://www.ncbi.nlm.nih.gov/pubmed/15988403