Genes Are Not Always Our Destiny
Well-established environmental triggers for developing Hashimotos in those who are genetically predisposed include excessive iodine intake, bacterial and viral infections, hormonal imbalances, toxins, and therapy with certain types of medications. Cigarette smoking, surprisingly, has been associated with a reduced risk of Hashimotos and may somewhat delay or suppress the development of the condition.
In people with Hashimotos, only 50 percent of their identical twins presented with thyroid antibodies, meaning genes alone are not the single defining factor, and environmental triggers play a;critical role.
About Hypothyroidism And Resistance To Thyroid Hormone
Genes in the Hypothyroidism and Resistance to Thyroid Hormone Panel and their clinical significance
* Some, or all, of the gene is duplicated in the genome. Read more.
# The gene has suboptimal coverage reads), and/or the gene has exons listed under Test limitations section that are not included in the panel as they are not sufficiently covered with high quality sequence reads.
The sensitivity to detect variants may be limited in genes marked with an asterisk or number sign . Due to possible limitations these genes may not be available as single gene tests.
Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant , autosomal recessive , mitochondrial , X-linked , X-linked dominant and X-linked recessive ; ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database ; HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database . The list of associated, gene specific phenotypes are generated from CGD or Mitomap databases.
Non-coding variants covered by Hypothyroidism and Resistance to Thyroid Hormone Panel
- Single exon deletions or duplications
- Variants within pseudogene regions/duplicated segments
- Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis.
Thyroid Nodules Diagnosis And Treatment
Most nodules are detected during a normal physical exam. They can also be detected during an ultrasound, CT scan, or an MRI. Once a nodule is detected, other procedures a TSH test and a thyroid scan can check for hyperthyroidism or hypothyroidism. A fine needle aspiration biopsy is used to take a sample of cells from the nodule and determine whether the nodule is cancerous.
Benign thyroid nodules arent life-threatening and usually dont need treatment. Typically, nothing is done to remove the nodule if it doesnt change over time. Your doctor may do another biopsy and recommend radioactive iodine to shrink the nodules if it grows.
Cancerous nodules are pretty rare according to the National Cancer Institute , thyroid cancer affects less than 4 percent of the population. The treatment your doctor recommends will vary depending on the type of tumor. Removing the thyroid through surgery is usually the treatment of choice. Radiation therapy is sometimes used with or without surgery. Chemotherapy is often required if the cancer spreads to other parts of the body.
Children can also get thyroid conditions, including:
- thyroid nodules
- thyroid cancer
Sometimes children are born with a thyroid problem. In other cases, surgery, disease, or treatment for another condition causes it.
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Chromosomal Disorders With Aitd As A Component
Downs syndrome patients, with trisomy of chromosome 21, have a high prevalence of both autoimmune and congenital thyroid disease. AH is the commonest thyroid problem, affecting 1520% of adults with Downs syndrome . GD occurs less frequently, with a prevalence of 12%, which may not be increased compared with the general population . Turners syndrome, which is characterized by complete or partial loss of X chromosome material in a phenotypic female, is also associated with AITD. About 15% of Turners patients have AH, with 3040% having positive thyroid antibodies . There is a correlation between cytogenetic abnormalities and AITD in Turners syndrome, with an Xq isochromosome being associated with a prevalence of AH of up to 40% . GD prevalence is not increased in Turners syndrome . DiGeorge syndrome and the overlapping chromosome 22q11 deletion syndromes are associated with GD . One small study suggests that GD may occur in up to 20% of subjects with these chromosome 22q11 deletion syndromes . Overall, the association of AITD with these chromosomal disorders suggests that chromosomes 21, 22, and X may each harbor important AITD susceptibility or resistance genes. Alternatively, in the 22q11 deletion syndromes, the consequences of thymic hypoplasia on T lymphocyte maturation may have a specific but secondary effect to predispose to GD.
Linkage Scanning For Novel Aitd Loci
Over the last 5 yr, three different cohorts of AITD families have been examined for genetic linkage to a large number of anonymous chromosomal markers by U.S., UK, and Japanese investigators. The results of these studies need to be viewed in the context that with 56 families , 82 sib-pairs , and 123 sib-pairs , no individual study has been appropriately powered to detect susceptibility loci with modest effects . Thus, only highly significant linkages, or those that are replicated in a second cohort of AITD or autoimmune patients, are likely to stand the test of time.
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Genetic Variation In Genes Influencing Thyroid Hormone Action And Its Effect On Clinical Phenotypes
Whilst only a few genes have been found to influence thyroid function, it has become clear that genes involved in thyroid hormone action can have clinically detectable effects with no effect on circulating thyroid hormone concentrations. As can be seen in , there are many elements which can affect the final binding of T3 to the TR in the cell nucleus, and therefore circulating concentrations of thyroid hormones may be a poor reflection of individual tissue levels. This may be particularly pertinent in tissues such as the brain in which there are mechanisms in place to protect the local tissue from swings in circulating levels. In this section, genes which influence clinical phenotypes are discussed. These are more difficult to study, as SNPs generally result in small functional changes which may be difficult to detect using inaccurate clinical measures and small sample sizes. Therefore associations have only been shown in a few, well-studied genes. These are summarised in .
What Is Pendred Syndrome
Pendred syndrome is a genetic disorder that causes early hearing loss in children. It also can affect the thyroid gland and sometimes creates problems with balance. The syndrome is named after Vaughan Pendred, the physician who first described people with the disorder.
Children who are born with Pendred syndrome may begin to lose their hearing at birth or by the time they are three years old. Usually, their hearing will worsen over time. The loss of hearing often happens suddenly, although some individuals will later regain some hearing. Eventually, some children with Pendred syndrome become totally deaf.
Almost all children with Pendred syndrome have bilateral hearing loss, which means hearing loss in both ears, although one ear may have more hearing loss than the other.
Childhood hearing loss has many causes. Researchers believe that in the United States 50 to 60 percent of cases are due to genetic causes, and 40 to 50 percent of cases result from environmental causes. Health care professionals use different clues, such as when the hearing loss begins and whether there are anatomical differences in the ears, to help determine whether a child has Pendred syndrome or some other type of progressive deafness.
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Thyroid Dysgenesis And Non
The TSH receptor gene encodes a transmembrane receptor present on the surface of follicular cells which mediates the effects of TSH secreted by the anterior pituitary and is critical for the development and function of the thyroid gland. It belongs to a subfamily of heptahelical G protein coupled receptors that have a common structure consisting of seven transmembrane segments, three extracellular and three intracellular loops, an extracellular amino terminal domain, and an intracytoplasmic carboxyl terminal tail . The actions of TSH on the thyrocyte occur principally by receptor mediated activation of Gs and subsequent generation of intracellular cyclic adenosine monophosphate . The human TSHR gene is located on chromosome 14q31 and the extracellular domain of the receptor is encoded by nine exons, whereas the transmembrane and intracellular portions are encoded by a single large exon.
Cartoon of the TSH receptor showing the positions of all the loss of function mutations reported to date. Missense mutations are shown in the circles, frameshift and deletion mutations are indicated by arrows, and splice site mutations are marked.
Inactivating mutations of the human TSHR are therefore associated with three phenotypes:
fully compensated TSH resistance to TSH;
partially compensated TSH resistance to TSH;
severe uncompensated resistance to TSH.
Association Of Ctla4 With Gd
In 1995, Yanagawa et al. reported an association of GD with an allele of the CTLA4 gene, which was the first report showing allelic association of CTLA4 with any human autoimmune disorder. They found a significantly higher prevalence of the 106 mobility unit allele of the CTLA4n polymorphism in white GD patients compared with controls. Subsequently, the G allele of CTLA4A/G was also found to be associated with GD . The association of these two CTLA4 polymorphisms with GD has been reproduced by several subsequent studies in different populations, with relative risks between 1.4 and 3.2 . It is interesting to note that in the Tunisian population, GD was found to be associated with the A allele at CTLA4A/G, in contrast to the G allele in other populations . The association of GD with the promoter polymorphism CTLA4C/T is less consistent than with the CTLA4n and CTLA4A/G polymorphisms , suggesting that in white populations the minor allele at this polymorphism may be carried on a different haplotype to the disease susceptibility allele.
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What Research Is Being Conducted
The NIDCD is funding researchers who are working to understand hearing loss caused by inherited syndromes such as Pendred syndrome as well as from other causes. Researchers also are looking carefully at the characteristics of the disorder and how the syndrome might cause problems in different parts of the body such as the thyroid and inner ear.
Scientists continue to study the genetic basis of Pendred syndrome. The protein that the SLC26A4 gene makes, called pendrin, is found in the inner ear, kidney, and thyroid gland. Researchers have identified more than 150 deafness-causing mutations or alterations of this gene.
By studying mice, scientists are gaining a greater understanding of how an abnormal SLC26A4 gene affects the form and function of different parts of the body. For example, by studying the inner ears of mice with SLC26A4 mutations, scientists now realize that the enlarged vestibular aqueduct associated with Pendred syndrome is not caused by a sudden stop in the normal development of the ear. Studies such as this are important because they help scientists rule out some causes of a disorder while helping to identify areas needing more research. Researchers are hopeful these studies eventually will lead to therapies that can target the basic causes of the condition.
Molecular Genetics And Gene Function
Causative mutations in the SLC16A2 gene on Xq13.8 have now been identified in more than 170 males from 90 families and some heterozygote carrriers,, and probably also accounts for a proportion of adult males with unresolved X-linked intellectual disability.SLC16A2 belongs to the 14 members of the SLC16 family of genes and encodes the MCT8 protein. The majority of SLC16A2 mutations results in complete loss of function, although few mutations with clinically milder phenotypes may show residual transporter activity. Known pathogenic SLC16A2 missense mutations localize exclusively to the transmembrane helices within the MCT8 protein.
MCT8 is an active and specific thyroid hormone transporter with differential tissue expression.- In humans, MCT8 shows preferential substrate specificity for triiodothyronine and is early and widely expressed in the brain and other tissues including the heart, liver, kidneys, and skeletal muscle.,
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Hyperthyroidism Diagnosis And Treatment
A blood test measures levels of thyroid hormone and thyroid-stimulating hormone in your blood. The pituitary gland releases TSH to stimulate the thyroid to produce its hormones. High thyroxine and low TSH levels indicate that your thyroid gland is overactive.
Your doctor might also give you radioactive iodine by mouth or as an injection, and then measure how much of it your thyroid gland takes up. Your thyroid takes in iodine to produce its hormones. Taking in a lot of radioactive iodine is a sign that your thyroid is overactive. The low level of radioactivity resolves quickly and isnt dangerous for most people.
Treatments for hyperthyroidism destroy the thyroid gland or block it from producing its hormones.
- Antithyroid drugs such as methimazole prevent the thyroid from producing its hormones.
- A large dose of radioactive iodine damages the thyroid gland. You take it as a pill by mouth. As your thyroid gland takes in iodine, it also pulls in the radioactive iodine, which damages the gland.
- Surgery can be performed to remove your thyroid gland.
If you have radioactive iodine treatment or surgery that destroys your thyroid gland, you will develop hypothyroidism and need to take thyroid hormone daily.
Autoimmune Thyroid Disease In Children And Adolescents
The frequency of HT in the pediatric age ranges between 0.3 and 9.6% , occurring rarely before the age of 3 years and reaching a peak in early to mid-puberty. There is a strong female preponderance with a female-to-male ratio varying across studies between 2:1 and 9.7:1 . This female predominance is less pronounced in prepubertal children , suggesting the influence of sex hormones in the development of ATD . Diagnosis is established by detecting positive serum TPO and/or TG autoantibodies along with a heterogeneous echotexture and diffuse or irregular hypoechogenicity of the thyroid parenchyma on ultrasound scan .
Further data indicate that the presence of goiter and elevated TG autoantibodies at HT diagnosis may predict a deterioration of thyroid function over time . Moreover, in patients with HT, elevated TSH levels and TPO antibodies at diagnosis, a progressive increase in TSH during follow-up a well as the concomitant presence of celiac disease were shown to increase the risk of developing hypothyroidism after a 3 year period .
Overall, the natural course of SH is worse in patients with underlying HT compared to idiopathic ones . With regards to treatment, levothyroxine replacement therapy in patients with SH is generally recommended, if TSH levels are higher than 5 IU/ml in the presence of goiter or positive thyroid antibodies and in all cases where TSH levels exceed 10 IU/ml .
Can I Check My Thyroid At Home
You can do a quick and easy self-exam of your thyroid at home. The only tools you need to do this self-exam are a mirror and a glass of water.
To do the thyroid self-exam, follow these steps:
- Start by identifying where your thyroid is located. Generally, youll find the thyroid on the front of your neck, between your collar bone and Adams apple. In men, the Adams apple is much easier to see. For women, its usually easiest to look from the collar bone up.
- Tip your head back while looking in a mirror. Look at your neck and try to hone in on the space you will be looking once you start the exam.
- Once youre ready, take a drink of water while your head is tilted back. Watch your thyroid as you swallow. During this test, youre looking for lumps or bumps. You may be able to see them when you swallow the water.
Repeat this test a few times to get a good look at your thyroid. If you see any lumps or bumps, reach out to your healthcare provider.
Who Is Affected By Thyroid Disease
Thyroid disease can affect anyone men, women, infants, teenagers and the elderly. It can be present at birth and it can develop as you age .
Thyroid disease is very common, with an estimated 20 million people in the Unites States having some type of thyroid disorder. A woman is about five to eight times more likely to be diagnosed with a thyroid condition than a man.
You may be at a higher risk of developing a thyroid disease if you:
- Have a family history of thyroid disease.
- Have a medical condition .
- Take a medication thats high in iodine .
- Are older than 60, especially in women.
- Have had treatment for a past thyroid condition or cancer .
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Can I Live A Normal Life With A Thyroid Disease
A thyroid disease is often a life-long medical condition that you will need to manage constantly. This often involves a daily medication. Your healthcare provider will monitor your treatments and make adjustments over time. However, you can usually live a normal life with a thyroid disease. It may take some time to find the right treatment option for you and control your hormone levels, but then people with these types of conditions can usually live life without many restrictions.
Summary And Future Directions
Improved technology in genetic investigations have already provided us with a wealth of information on the genetic basis for normal thyroid function, autoimmune thyroid disease and the influence of thyroid genes on clinical phenotypes. Early optimistic expectations that all genes responsible would be rapidly discovered have had to be reined in, and researchers across many fields are searching for the reasons this has not happened. The need for larger sample sizes and collaboration between groups with access to large cohorts has now been understood, and these studies will undoubtedly discover further genes. Furthermore, whole genome sequencing may provide more information as other types of genetic variation, such as copy number variants may also be found to play a role. In addition, influences on accessibility of genes to transcription may be at work. However, what we have already discovered has increased our understanding of normal thyroid hormone action and physiology, and we are beginning to understand the complex origins of autoimmune thyroid disease. Important for future work is the need to replicate the early findings presented above and perform functional studies to identify the true associations and the mechanisms behind them. These mechanisms will increase our understanding of thyroid physiology and identify therapeutic targets.
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