Graves’ disease (or Basedow-Graves disease) is an autoimmune disease. It most commonly affects the thyroid, frequently causing it to enlarge to twice its size or more (goiter), become overactive, with related hyperthyroid symptoms such as increased heartbeat, muscle weakness, disturbed sleep, and irritability. It can also affect the eyes, causing bulging eyes (exophthalmos). It affects other systems of the body, including the skin, heart, circulation and nervous system.
It affects up to 2% of the female population, sometimes appears after childbirth, and has a female:male incidence of 5:1 to 10:1. Hereditary factors are the major risk factor for the development of Graves disease, with “79% of the liability to the development of GD … attributable to genetic factors”. Smoking and exposure to second-hand smoke is associated with the eye manifestations but not the thyroid manifestations.
Diagnosis is usually made on the basis of symptoms, although thyroid hormone tests may be useful, particularly to monitor treatment.
Medical eponyms are often styled nonpossessively; thus Graves’ disease and Graves disease are variant stylings for the same term.
The signs and symptoms of Graves’ disease virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being Graves’ ophthalmopathy, goitre, and pretibial myxedema (which are caused by the autoimmune processes of the disease). Symptoms of the resultant hyperthyroidism are mainly insomnia, hand tremor, hyperactivity, hair loss, excessive sweating, shaking hands, itching, heat intolerance, weight loss despite increased appetite, diarrhea, frequent defecation, palpitations, muscle weakness, and skin warmth and moistness. Further signs that may be seen on physical examination are most commonly a diffusely enlarged (usually symmetric), nontender thyroid, lid lag, excessive lacrimation due to Graves’ ophthalmopathy, arrhythmias of the heart, such as sinus tachycardia, atrial fibrillation and premature ventricular contractions, and hypertension. People with hyperthyroidism may experience behavioral and personality changes including: psychosis, mania, anxiety, agitation, and depression.
The Immunoglobulin G antibody recognizes and binds to the thyrotropin receptor (TSH receptor). It mimics the TSH to that receptor and activates the secretion of thyroxine (T4) and triiodothyronine (T3), and the actual TSH level will decrease in the blood plasma. The TSH levels fall because the hypothalamus-pituitary-thyroid negative feedback loop is working. The result is very high levels of circulating thyroid hormones and the negative feedback regulation will not work for the thyroid gland.
The trigger for auto-antibody production is not known. There appears to be a genetic predisposition for Graves’ disease, suggesting that some people are more prone than others to develop TSH receptor activating antibodies due to a genetic cause. HLA DR (especially DR3) appears to play a significant role.
Since Graves’ disease is an autoimmune disease which appears suddenly, often quite late in life, it is thought that a viral or bacterial infection may trigger antibodies which cross-react with the human TSH receptor (a phenomenon known as antigenic mimicry, also seen in some cases of type I diabetes).
One possible culprit is the bacterium Yersinia enterocolitica (a cousin of Yersinia pestis, the agent of bubonic plague). However, although there is indirect evidence for the structural similarity between the bacteria and the human thyrotropin receptor, direct causative evidence is limited.Yersinia seems not to be a major cause of this disease, although it may contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals. It has also been suggested that Y. enterocolitica infection is not the cause of auto-immune thyroid disease, but rather is only an associated condition; with both having a shared inherited susceptibility. More recently the role for Y. enterocolitica has been disputed.
Emotional stress has been posited as a possible cause of Graves’ disease as well, based largely on anecdotal evidence. While there are theoretical mechanisms by which stress could cause an aggravation of the autoimmune response that leads to Graves’ disease, more robust clinical data are needed for a firm conclusion.
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Graves’ disease – Wikipedia, the free encyclopedia
The following are some of the risks and symptoms of various thyroid conditions and diseases. Hypothyroidism Symptoms The symptoms of hypothyroidism — an underactive thyroid — tend to mirror the slowing down of physical processes that results from insufficient thyroid hormone. Common symptoms include fatigue, weight gain, constipation, fuzzy thinking, low blood pressure, fluid retention, depression, body pain, slow reflexes, and much more. A more detailed list of symptoms and risks is featured in the Hypothyroidism Risks/Symptoms Checklist. It can also be helpful to identify risks and symptoms using this interactive online test: Quiz: Could You Be Hypothyroid?. Hyperthyroidism Symptoms The symptoms of hyperthyroidism tend to reflect the rapid metabolism that results from an oversupply of thyroid hormone. Common symptoms include anxiety, insomnia, rapid weight loss, diarrhea, high heart rate, high blood pressure, eye sensitivity/bulging and vision disturbances, and many other concerns. A lengthier list of symptoms and risks is featured in Graves’ Disease and Hyperthyroidism: Risks and Symptoms. To pinpoint symptoms of an overactive thyroid, you may also want to take this online test: Quiz: Could You Be Hyperthyroid?. Autoimmune Thyroid Disease Symptoms The two autoimmune diseases that directly affect the thyroid are Hashimoto’s disease and Graves’ disease. The symptoms of Hashimoto’s disease usually parallel the hypothyroidism that is a result of the disease. Occasionally, however, while the thyroid is failing, it can have periods where it sputters into life and even becomes temporarily overactive. This is known as Hashitoxicosis. Symptoms then can be confusing, with cycling over a period of days or weeks between hypothyroidism and hyperthyroidism symptoms. To understand the difference between hypothyroidism and Hashimoto’s disease, read: Hashimoto’s vs. Hypothyroidism: What’s the Difference? Graves’ disease symptoms typically mirror hyperthyroidism. For more information, read this review of important things to know about Graves’ disease. Goiter/Nodules Symptoms Symptoms of goiter — an enlarged thyroid — include a swollen, tender or tight feeling in the neck or throat, hoarseness or coughing, and difficulty swallowing or breathing. Sometimes, the goiter is visbible to yourself or others.
Symptoms of nodules depend on what action they are having. Some cause no symptoms, while others may cause difficulty swallowing, a feeling of fullness, pain or pressure in the neck, a hoarse voice, or neck tenderness. Some nodules trigger hyperthyroid-like symptoms such as palpitations, insomnia, weight loss, anxiety, and tremors. Nodules can also trigger hypothyroidism, and symptoms might include weight gain, fatigue, depression. Nodules can sometimes cause cycling back and forth between hyperthyroid and hypothyroid symptoms.
Here is more information on Thyroid Nodules, Lumps and Goiter. Sometimes you can detect goiter or a nodule yourself by performing a Thyroid Neck Check. Here are instructions on how to do a neck check.
Mary Shomon, About.com’s Thyroid Guide since 1997, is a nationally-known patient advocate and best-selling author of 10 books on health, including “The Thyroid Hormone Breakthrough: Overcoming Sexual and Hormonal Problems at Every Age,” “The Thyroid Diet: Manage Your Metabolism for Lasting Weight Loss,” “Living Well With Hypothyroidism: What Your Doctor Doesn’t Tell You…That You Need to Know,” “The Thyroid Guide to Hair Loss,” “Living Well With Graves’ Disease and Hyperthyroidism,” “Living Well With Autoimmune Disease,” and “Living Well With Chronic Fatigue Syndrome and Fibromyalgia.” Click here for more information on Mary Shomon.
Thyroid Disease Symptoms and Risk Factors
The structural formula (left) and a space-filling model (right) of (S)-triiodothyronine (T3, also called liothyronine in the pharmaceutical industry)
The structural formula (left) and a space-filling model (right) of (S)-thyroxine (T4.)
The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are tyrosine-based hormones produced by the thyroid gland that are primarily responsible for regulation of metabolism. Iodine is necessary for the production of T3 and T4. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as goitre. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. The ratio of T4 to T3 released into the blood is roughly 20 to 1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5′-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). All three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production.
The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body’s sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
Thyroid hormone leads to heat generation in humans. However, the thyronamines function via some unknown mechanism to inhibit neuronal activity; this plays an important role in the hibernation cycles of mammals and the moulting behaviour of birds. One effect of administering the thyronamines is a severe drop in body temperature.
Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland. The effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues). T3 is 3- to 5- fold more active than T4.
Thyroxine (3,5,3′,5′-tetraiodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin (this is not the same as TBG), which is cleaved by enzymes to produce active T4.
The steps in this process are as follows:
Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules. Thyroxine (T4) contains four iodine atoms. Triiodothyronine (T3) is identical to T4, but it has one less iodine atom per molecule.
Iodide is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium is cotransported with iodide from the basolateral side of the membrane into the cell and then concentrated in the thyroid follicles to about thirty times its concentration in the blood. Via a reaction with the enzyme thyroperoxidase, iodine is bound to tyrosine residues in the thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces thyroxine. Combining one particle of MIT and one particle of DIT produces triiodothyronine.
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Thyroid hormone – Wikipedia, the free encyclopedia
Personalized Female Hormone Replacement Therapy Programs – Matching Solutions with Symptoms
By: nikhil dudeja
Estrogen Hormone Replacement Therapy and Alzheimer’s Disease
Hormone Replacement Therapy can do a lot of amazing things. In the early twenty-first century, scientists are just exploring the tip of the iceberg when it comes to the benefits of various hormone treatments, including Estrogen, Testosterone, and Human Growth Hormone.
Although research has shown no evidence that Estrogen Replacement Treatments can alleviate the symptoms of Alzheimer’s disease, there is promising evidence that Estrogen Therapy can reduce the risk of Alzheimer’s disease in women, even women that are otherwise healthy.
As we all know, Menopause is a period of great Hormone Imbalance. From puberty to menopause, women experience a fairly predictable pattern of hormone levels, and their body ultimately benefits from this stability. Upon Menopause, however, hormone levels start to change significantly. Primarily, Estrogen Levels drop like a rock as the Ovaries greatly reduce their production.
There are multiple symptoms associated with Menopause, and they all have a negative impact on both life and health. Among these symptoms are:
Loss of Sexual Desire and Ability
These are the symptoms that women experience explicitly during the period of Menopause. For the most part (with the exception of sexual issues), these symptoms of Menopause dissipate slowly over time.
Long Term Symptoms of Hormone Deficiency
In recent years, however, researchers are discovering that there are many issues related to Hormone Deficiency that put women at risk for the rest of their lives. One risk that seems highly correlated with Estrogen Deficiency after Menopause is Alzheimer’s disease.
Alzheimer’s is a disease which is much more common among women than men. The risk for a woman to develop Alzheimer’s is almost double that of a man. Of course, part of that increased risk is due to the fact that women, on average, have a longer lifespan than their male counterparts, but that only explains away a small portion of the difference.
Why do Women Get Alzheimer’s More than Men?
In recent years, there have been a limited amount of studies conducted regarding the connection between Estrogen Deficiency and Cognitive Decline, but the research has been illuminating, to say the least. This research suggests that the administration of Estrogen Hormone Replacement Therapy can have a stimulative effect upon mental health in women, both assuaging Age-Related Cognitive Decline and even postponing or reducing the risk of Alzheimer’s Disease.
For many patients, especially those that are experiencing Estrogen Deficiency before Menopause, Estrogen Replacement Therapy can be combined with Progestin in order to maximize the effectiveness and safety profile of the treatment.
How Many People Struggle with Alzheimer’s in America?
Alzheimer’s is one of the worst medical issues plaguing modern American society. It is estimated that four million men and women are afflicted with Alzheimer’s today. Considering that twice as many women as men will experience Alzheimer’s in their lifetime, this is a significant portion of aging women.
Nearly every person in America intimately knows someone that has struggled with Alzheimer’s, whether they had to take care of an immediate family member, or were simply an acquaintance. A few years ago, several research teams sought to answer once and for all, if Estrogen Replacement Therapy could be a legitimate treatment option for women that are at risk of Alzheimer’s.
Can Estrogen Treat Alzheimer’s?
As a result of their research, they found that Estrogen was ultimately not effective as a means to directly treat Alzheimer’s Disease. Although they were unable to establish Estrogen as a potential Alzheimer’s treatment, their research still strongly suggested that Estrogen Therapy could reduce the risk of developing Alzheimer’s for women across the world.
Can Estrogen Prevent Alzheimer’s?
There is potential that Estrogen Replacement could significantly delay the onset of Alzheimer’s Disease, or, at a minimum, postpone the onset of the disease. Even if Estrogen only postpones Alzheimer’s, it could still be an amazingly useful tool in combination with other treatments that would all but eliminate the risk of Alzheimer’s Disease someday in the future.
The Benefits and Risks of Estrogen Replacement Therapy
There are countless women across America that have turned to Estrogen Treatments as a means to relieve the symptoms of Menopause. Every woman experiences Menopause in a different way, and some women are either more sensitive to the changes that take place, or produce lower baseline levels of Estrogen after Menopause.
Decades of research have proven the effectiveness of Estrogen at reducing the potential tempest associated with Menopause, and medical researchers have discovered powerful links between Estrogen Replacement Therapy and a reduced risk of Osteoporosis.
Cautious links have also been made between Estrogen Replacement Therapy and reduced risk of heart disease, although this link has not been confidently established. For some women, however, Estrogen Replacement Therapy can increase the risk of breast cancer, although the exact level of risk is not fully discerned. Although there are certain risks involved with Estrogen HRT, for a huge number of women, it seems likely and clear that the benefits far outweigh the costs.
Before new research regarding memory and cognition, this was essentially the state of play in regard to the potential benefits and risks of Estrogen Deficiency and Estrogen Replacement. Today, researchers are becoming keenly aware of the way that Estrogen and Estrogen Deficiency affect the brain and mental health.
Estrogen and Acetylcholine
In research utilizing both laboratory animals and cultivated brain matter, there is evidence that supports the notion that Estrogen has the ability to protect and support the health of neurons in the brain. One means by which it accomplishes this is by boosting resting levels of Acetylcholine in the brain.
Acetylcholine acts as a protective force in the brain, which safeguards against the breakdown of brain tissue associated with Alzheimer’s disease. One of the physiological symptoms of Alzheimer’s is that Acetylcholine Levels drop significantly among patients that suffer from the disease. In addition to this, Estrogen Replacement Therapy also seems to be able reduce the rate at which Beta-Amyloids form in the brain.
What are Beta-Amyloids?
Beta-Amyloid is the primary actor which leads to the physiological deterioration associated with Alzheimer’s Disease. Although you have probably never heard of Beta-Amyloid, you probably know what it is whether you realize it or not. Beta-Amyloids are proteins which, when produced in the brain, lead to the clumps of tangled Amino Acids which are referred to as Plaques.
Estrogen Research in the 1990s
Before the turn of the century, there were only a small set of studies regarding the connection between Estrogen Supplementation and Alzheimer’s. These studies suggested that Estrogen Replacement Therapy could restore some memory and cognitive ability in women suffering from Alzheimer’s.
The problem with these studies is that they were for the most part small studies, and they also only evaluated patients over a short period of time. Although the studies showed some promise, they were not powerful enough to establish a significant link between Estrogen and the improvement of Alzheimer’s.
In the years following these initial studies, however, three new studies were conducted which intended to explore these potential benefits in a way that could more firmly establish the potential effects of Estrogen Treatment on Memory and Alzheimer’s. The biggest and longest of these studies was released in the Journal of the American Medical Association.
Testing the Hypothesis: Estrogen and Alzheimer’s
This study was conducted by Ruth Mulnard of Cal-Irvine, a representative of the Institute for Brain Aging and Dementia. This study had a participant pool of 120 patients, half of whom had been discovered to have Alzheimer’s disease. Half of the women in both groups were treated with Estrogen Replacement Therapy, the other half of both groups was treated with a placebo.
All patients received treatment for twelve months, and were regularly tested for alterations in language ability, mood, memory, and other cognitive abilities, in order to monitor any symptoms of cognitive decline. If Estrogen Replacement Therapy were able to improve the function of patients with Alzheimer’s disease, then the treatment would cause women taking Estrogen to decline more slowly than the patients that did not receive the treatment.
Estrogen Ineffective at Treating Alzheimer’s
Sadly, results showed that Estrogen has no effect upon patients that were already experiencing symptoms of Alzheimer’s. Among the ninety-seven women that finished the study, the women with Alzheimer’s taking Estrogen did not experience any improvement greater than placebo.
Two other studies displayed similar results, no conclusive evidence that Estrogen could relieve Alzheimer’s. Dr. Henderson, a medical researcher from USC Los Angeles, said that he felt the studies were fairly conclusive, and that Estrogen Therapy alone probably doesn’t have any significant benefits in regard to patients currently experiencing Alzheimer’s Disease.
Estrogen May Benefit Alzheimer’s Patients in Combination with other Treatments
Although these studies appear to put that aspect of the Estrogen-Alzheimer’s Care debate to rest, that does not mean that Estrogen Replacement Therapy does not have other beneficial effects. Even Dr. Henderson feels that there may be a place for Estrogen Treatments when combined with other forms of therapy.
There are researchers that feel that Estrogen HRT may have beneficial effects when combined with a common Alzheimer’s treatment known as Aricept (scientific name: Donepezil). Estrogen shares an important aspect in common with these common Alzheimer’s medications: They all have the effect of increasing Acetylcholine in the brain, and there is strong reason to believe that Alzheimer’s may have the ability to increase the effectiveness of these other forms of treatment.
Today, there is a limited amount of data supporting this hypothesis, but the data is promising. There have been two studies thus far conducted with regard to Estrogen’s ability to supplement existing Alzheimer’s treatments. Data-analysis after the studies were completed showed that a small segment of participants were taking Estrogen Treatments in combination with other forms of Alzheimer’s medication. Although there were not enough women to lend significance to the results, it does show a certain level of potential, although we should be cautiously optimistic, perhaps.
Using Estrogen to Prevent Alzheimer’s Disease
Although no studies today are able to confirm Estrogen Replacement as a means to alleviate the effects of Alzheimer’s, there are a number of studies which provide evidence that Estrogen may be able to postpone Alzheimer’s in women that do not suffer from the disease. There is even some hope that it may be a tool in Alzheimer’s prevention.
In one of the most recent studies, 472 women were monitored over the course of sixteen years of their lives in the Baltimore Longitudinal Study of Aging. Although this study was not intimately concerned with Hormone Replacement Therapy as an Anti-Aging Treatment, the study was performed in a way which allowed a broad scope of analysis to be conducted.
Among the 472 subjects, there were a number which chose Estrogen Hormone Replacement Therapy, while many others went without such treatment. Looking back at the data, researchers found that women that chose to utilize Estrogen during and after menopause experienced Alzheimer’s disease at half the rate of women that did not.
Small Pool of Participants Still Provides Promise
Although this research shows an immense amount of promise, more work needs to be done in order to more accurately assess the viability of Estrogen to Prevent Alzheimer’s. At this point, the findings of the BLSA study amount simply to an exciting observation: Estrogen may be one of the most powerful tools that women have against both Alzheimer’s and general Cognitive Decline.
Although we should be excited at such a prospect, we must also realize that there are other factors which may be at play. Women that choose Estrogen Replacement Therapy may experience these benefits for other reasons not fully associated with treatment, including genetics or nutrition. In addition to this, the reduced risk of Alzheimer’s could also be the result of other factors which help them live a healthier life.
In general, women that choose Estrogen Replacement tend to be more conscientious about their health. Women that take Estrogen also tend to have stronger health care plans which allow them access to better treatments and health and wellness programs.
More Estrogen-Alzheimer’s Studies Underway
Today, there are three more studies being conducted in order to more clearly show the benefits of Estrogen Replacement Therapy in regard to Alzheimer’s. Of these three studies, two are being conducted by scientists in the United States, and a third by researchers in Great Britain.
Because these studies were designed specifically to uncover the potential benefit of Estrogen Replacement for Alzheimer’s, they will be able to declare, once and for all, the Effect of Estrogen on Alzheimer’s Patients.
All three of these studies will be placebo-controlled and double-blind in order to maximize the predictive value of the data. At random intervals, the patients will be tested and analyzed for cognitive ability. Researchers hypothesize that the combination of Estrogen and modern Alzheimer’s care will slow down the rate at which the disease progresses.
As we all well know, Alzheimer’s is a dreadful disease for which there is no known cure. If it indeed does have the ability to benefit women with regard to Alzheimer’s risk or treatment, then it will completely change the way that we think about Estrogen Replacement Therapy in the future.
The Potential of Hormone Replacement
Even if Estrogen simply delays Alzheimer’s or slows down the rate of decline associated with the disease, it will likely become a recommended treatment, especially for women that have a high risk for the disease as a result of genetics or other factors. Even if the link between Estrogen and Alzheimer’s Prevention is weak, it will still significantly broaden our knowledge of the disease and how it should be most effectively treated.
Who Should Consider Estrogen Replacement Today?
Until the benefits of Estrogen for Alzheimer’s can be fully proven, women should consider Estrogen Replacement Therapy in regard to other benefits that are more concrete, including cardiovascular health, Osteoporosis prevention, and to relieve the harshness of Menopause.
Although conclusive evidence regarding Alzheimer’s and Estrogen Treatment are still years away, there are numerous reasons to consider Estrogen for Your Health.
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Estrogen Hormone Replacement Therapy and Alzheimers Disease
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