Signal Transduction Pathways For Cell Surface Receptors
These are complex processes and unfortunately dogged by terminology that is confusing and not always logical – a legacy from the periodic discovery of intracellular factors that were subsequently assembled into a relatively complete sequence of signal tranduction processes. It is not in the scope of this book to pursue all the molecular events but a broad outline is pertinent to understanding hormone action and genetic mutations that can cause endocrine disorders.
Receptors that have inherent tyrosine kinase activity bind molecules that have a specific SH2 domain . In turn, another accessory protein may be activated such as SOS . This can activate a monomeric G-protein known as Ras that essentially acts as a signal transduction switch. Its activation can lead to phosphorylation of Raf, MEK and eventually to mitogen activated protein kinase which can initiate transcription .
The transcription factor targets for kinases that are activated by protein and peptide hormones include c-jun and c-fos which make up the heterodimeric AP-1 complex, the serum response factor , and nuclear CREB-P which is phosphorylated by protein kinase A and enhances transcriptional activity of closely positioned promoters .
What Common Symptoms Can Happen With Thyroid Disease
There are a variety of symptoms you could experience if you have a thyroid disease. Unfortunately, symptoms of a thyroid condition are often very similar to the signs of other medical conditions and stages of life. This can make it difficult to know if your symptoms are related to a thyroid issue or something else entirely.
For the most part, the symptoms of thyroid disease can be divided into two groups those related to having too much thyroid hormone and those related to having too little thyroid hormone .
Symptoms of an overactive thyroid can include:
- Experiencing anxiety, irritability and nervousness.
- Having trouble sleeping.
- Experiencing an intolerance to cold temperatures.
How Tsh Levels Change
TSH levels are not very intuitive. Why does a high TSH mean you have an underactive thyroid gland? Why do low levels means the gland is overactive?
Understanding exactly how the thyroid gland works can help.
Your thyroid gland produces thyroid hormone. When it functions properly, your thyroid is part of a feedback loop with your pituitary gland that involves several actions:
First, your pituitary gland senses the level of thyroid hormone that is released into the bloodstream.
Your pituitary then releases the special messenger hormone TSH, which makes the thyroid release more thyroid hormone. From there:
- If your thyroid doesn’t produce enough thyroid hormone, your pituitary triggers your thyroid to make more.
- If your thyroid is overactive and producing too much thyroid hormone, your pituitary senses that and slows or shuts down TSH production.
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How Your Thyroid Works
Your thyroid gland is a small gland, normally weighing less than one ounce, located in the front of the neck. It is made up of two halves, called lobes, that lie along the windpipe and are joined together by a narrow band of thyroid tissue, known as the isthmus.
The thyroid is situated just below your “Adams apple” or larynx. During development the thyroid gland originates in the back of the tongue, but it normally migrates to the front of the neck before birth. Sometimes it fails to migrate properly and is located high in the neck or even in the back of the tongue . This is very rare. At other times it may migrate too far and ends up in the chest .
The function of the thyroid gland is to take iodine, found in many foods, and convert it into thyroid hormones:thyroxine and triiodothyronine . Thyroid cells are the only cells in the body which can absorb iodine. These cells combine iodine and the amino acid tyrosine to make T3 and T4. T3 and T4 are then released into the blood stream and are transported throughout the body where they control metabolism .
The pituitary senses this and responds by decreasing its TSH production. One can imagine the thyroid gland as a furnace and the pituitary gland as the thermostat.
Patterns Of Thyroid Tests Associated With Thyroid Disease
Primary Hypothyroidism A high TSH and low thyroid hormone level can indicate primary hypothyroidism. Primary hypothyroidism occurs when the thyroid gland makes too little thyroid hormone. Symptoms of hypothyroidism can include feeling cold, constipation, weight gain, slowed thinking, and decreased energy. Causes of primary hypothyroidism include:
- Autoimmune thyroid disease, including Hashimoto’s thyroiditis
- Thyroid gland dysfunction due to a medication
- Removal of all or part of the thyroid gland
- Radiation injury to the thyroid
- Excess treatment with anti-thyroid medications
Early or mild hypothyroidism may present as a persistently elevated TSH and a normal FT4 hormone level. This pattern is called subclinical hypothyroidism and your doctor may recommend treatment. Over time, untreated subclinical hypothyroidism can contribute to heart disease.
It is important to remember that normal TSH levels in older individuals are higher than the normal ranges for younger individuals.
Primary Hyperthyroidism A low TSH and a high thyroid hormone level can indicate primary hyperthyroidism. Primary hyperthyroidism occurs when the thyroid gland makes or releases too much thyroid hormone. Symptoms of hyperthyroidism can include tremors, palpitations, restlessness, feeling too warm, frequent bowel movements, disrupted sleep, and unintentional weight loss. Causes of primary hyperthyroidism include:
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How Is Goitre Diagnosed
Goitre is diagnosed when the thyroid gland is enlarged enough to be felt by external touch or is clearly visible without a scan. Usually a GP will undertake thyroid function tests to measure the levels of thyroid hormones and thyroid antibodies in the bloodstream. They may also arrange an ultrasound scan or make a referral to an endocrinologist for outpatient assessment. Where more complex tests are required, they may include:
Overview Of The Thyroid Gland
, MD, MS, David Geffen School of Medicine at UCLA
The thyroid is a small gland, measuring about 2 inches across, that lies just under the skin below the Adams apple in the neck. The two halves of the gland are connected in the middle , giving the thyroid gland the shape of a bow tie. Normally, the thyroid gland cannot be seen and can barely be felt. If it becomes enlarged, doctors can feel it easily, and a prominent bulge may appear below or to the sides of the Adams apple.
The thyroid gland secretes thyroid hormones, which control the speed at which the bodys chemical functions proceed . Thyroid hormones influence the metabolic rate in two ways:
Thyroid hormones affect many vital body functions, such as the heart rate, the rate at which calories are burned, skin maintenance, growth, heat production, fertility, and digestion.
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How Do I Know If My Thyroid Dose Is Correct
Monitoring thyroid levels on medication Correct dosing of thyroid hormone is usually assessed using the same tests for diagnosis of thyroid disease, including TSH and FT4. Thyroid tests are typically checked every 4-6 weeks initially and then every 6 to 12 months once stable. In special circumstances, such as pregnancy, a history of thyroid cancer, central hypothyroidism, amiodarone therapy, or use of combination T4 and T3 thyroid hormone replacement, your endocrinologist may check different thyroid tests. Additionally, your endocrinologist will evaluate for symptoms of hyperthyroidism and hypothyroidism and peform a physicial exam.
Women who are pregnant and women who may become pregnant should only be treated with levothyroxine . Only T4 efficiently crosses the placenta to provide thyroid hormone to the developing fetus. Thyroid hormone is critical in early pregnancy for brain development. Normal ranges for thyroid tests in pregnancy are different and change by trimester. Women with thyroid disease in pregnancy or who are considering pregnancy should be under the care of an endocrinologist to guide therapy.
Got Questions About Normal Thyroid Hormone Levels?
Diagnostic Tests Of The Thyroid Gland
Doctors first examine the person and feel the person’s neck to see whether the thyroid gland is enlarged.
Depending on the results of the examination, other tests may also be needed. Additional testing may also be necessary in rare cases in which doctors cannot determine whether the problem lies in the thyroid or in the pituitary gland.
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Is There A Higher Risk Of Developing Thyroid Disease If I Have Diabetes
If you have diabetes, youre at a higher risk of developing a thyroid disease than people without diabetes. Type 1 diabetes is an autoimmune disorder. If you already have one autoimmune disorder, you are more likely to develop another one.
For people with type 2 diabetes, the risk is lower, but still there. If you have type 2 diabetes, youre more likely to develop a thyroid disease later in life.
Regular testing is recommended to check for thyroid issues. Those with type 1 diabetes may be tested more often immediately after diagnosis and then every year or so than people with type 2 diabetes. There isnt a regular schedule for testing if you have type 2 diabetes, however your healthcare provider may suggest a schedule for testing over time.
If you have diabetes and get a positive thyroid test, there are a few things to you can do to help feel the best possible. These tips include:
- Getting enough sleep.
- Taking all of your medications as directed.
- Getting tested regularly as directed by your healthcare provider.
What Is Thyroid Disease
Thyroid disease is a general term for a medical condition that keeps your thyroid from making the right amount of hormones. Your thyroid typically makes hormones that keep your body functioning normally. When the thyroid makes too much thyroid hormone, your body uses energy too quickly. This is called hyperthyroidism. Using energy too quickly will do more than make you tired it can make your heart beat faster, cause you to lose weight without trying and even make you feel nervous. On the flip-side of this, your thyroid can make too little thyroid hormone. This is called hypothyroidism. When you have too little thyroid hormone in your body, it can make you feel tired, you might gain weight and you may even be unable to tolerate cold temperatures.
These two main disorders can be caused by a variety of conditions. They can also be passed down through families .
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What Is A Tsh Test
Thyroid testsBlood tests to measure thyroid hormones are readily available and widely used. Not all thyroid tests are useful in all situations.
TSH TestThe best way to initially test thyroid function is to measure the TSH level in a blood sample. Changes in TSH can serve as an “early warning system” often occurring before the actual level of thyroid hormones in the body becomes too high or too low.
A high TSH level indicates that the thyroid gland is not making enough thyroid hormone . On the other hand, a low TSH level usually indicates that the thyroid is producing too much thyroid hormone . Occasionally, a low TSH may result from an abnormality in the pituitary gland, which prevents it from making enough TSH to stimulate the thyroid . In most healthy individuals, a normal TSH value means that the thyroid is functioning properly.
Expression And Signaling Pathways Of Th Receptors In The Early Nervous System
To affect transcription of target genes TRs bind DNA as either homodimers or heterodimers with retinoid-X-receptors and recognize TH response elements in promoter regions of regulated genes . TRs lacking bound THs can bind DNA as aporeceptors, which represses target gene transcription by recruiting corepressor complexes with histone deacetylase activity . T3 binding lifts this repression and leads to target gene transcription, which is necessary for normal nervous system development . While T3/TR interaction results in coactivator recruitment, chromatin restructuring, and transcriptional activation for most targets, some genes can also be repressed by TRs with bound THs . Accordingly, a meta-analysis study of genes transcriptionally regulated by THs in the nervous system identified over 700 curated targets, however the extent and mode of their regulation is likely to differ during development and in specific cell types . More targeted studies are needed to explain the differential cellular responses to THs in various contexts. The interplay between various TR isoforms, chromatin re-modeling and transcriptional machinery leads to complex tissue and cell-specific responses in various contexts and comprehensive reviews on the mechanistic aspects of the genomic pathway are available .
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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.
What Happens If I Have Too Much Thyroxine
The release of too much thyroxine in the bloodstream is known as thyrotoxicosis. This may be caused by overactivity of the thyroid gland , as in Graves’ disease, inflammation of the thyroid or a benign tumour. Thyrotoxicosis can be recognised by a goitre, which is a swelling of the neck due to enlargement of the thyroid gland. Other symptoms of thyrotoxicosis include intolerance to heat, weight loss, increased appetite, increased bowel movements, irregular menstrual cycle, rapid or irregular heartbeat, palpitations, tiredness, irritability, tremor, hair thinning/loss and retraction of the eyelids resulting in a staring appearance.
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How Does The Thyroid Gland Function
The major thyroid hormone secreted by the thyroid gland is thyroxine, also called T4 because it contains four iodine atoms. To exert its effects, T4 is converted to triiodothyronine by the removal of an iodine atom. This occurs mainly in the liver and in certain tissues where T3 acts, such as in the brain. The amount of T4 produced by the thyroid gland is controlled by another hormone, which is made in the pituitary gland located at the base of the brain, called thyroid stimulating hormone . The amount of TSH that the pituitary sends into the bloodstream depends on the amount of T4 that the pituitary sees. If the pituitary sees very little T4, then it produces more TSH to tell the thyroid gland to produce more T4. Once the T4 in the bloodstream goes above a certain level, the pituitarys production of TSH is shut off. In fact, the thyroid and pituitary act in many ways like a heater and a thermostat. When the heater is off and it becomes cold, the thermostat reads the temperature and turns on the heater. When the heat rises to an appropriate level, the thermostat senses this and turns off the heater. Thus, the thyroid and the pituitary, like a heater and thermostat, turn on and off. This is illustrated in the figure below.
Hormones And The Immune System
Since the discovery that surgical ablation of the pituitary gland caused atrophy of the thymus gland, experimental evidence from animal studies has indicated that there is a complex network of interactions between these two systems. The thymus gland, which is essential for orchestrating immune responses, has two regions – one in which T cell precursors from bone marrow mature and the other that secretes thymic hormones . The physiological role of thymic hormones is not clear but they are postulated to promote T cell maturation .
Simplified overview of the organization of the immune system. *The interaction of antigen-presenting cells that present peptide antigens bound to class II MHC molecules to T cells that express
The immune system can be considered a sensory system as it responds to stimuli such as bacteria, viruses, tumors and other antigens. When stimulated, cell-mediated or humoral immune responses are activated and this information is sent to the hypothalamus by cytokines and peptide hormones secreted from cells of the immune system. In addition neural and non-neural cells in the brain also synthesize cytokines. The neuroendocrine system responds to these signals which, in many ways, may be considered a stress response.
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Hormones And Gene Transcription
The receptors of all classes of hormones may regulate gene transcription either by activating transcription factors or by acting as transcription factors in their own right. Transcription is not, however, a simple process of a factor or receptor binding to DNA and activating RNA polymerase at an initiation site. It also requires a complex of enzymes, referred to as the holo-enzyme complex, before transcription is initiated down-stream of the factors and promoters. Thus, for example, a steroid receptor may have transcriptional activity but only when promoters bind with a particular part of the molecule. Sometimes these factors may act independently of ligand binding, others require ligand binding before they can be activated.