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The Mighty ThyroidPresented by:Betsy Reynolds, RDH, MSPresenter Disclosures Betsy Reynolds, RDH, MS Acts as a Key Opinion Leader for Philips/DiscusIn that capacity, she receives educational grant funding for presentation development She is not an employee of either company and has no vested interest in sales of any product manufactured or distributed by Philips/DiscusAdditionally, she has received funding from GC American for her 2015 presentation at the ADA Annual SessionMs. Reynolds has received financial reimbursement from Parkell for authoring CE articles available at: parkell. and financial support to assist with presentation expendituresAgenda:IntroductionSystemic Disorders of the ThyroidHyperthyroidismHypothyroidismThyroid CancerOral Manifestations of Thyroid DiseaseTreatment RecommendationsHeadlinersThe American Thyroid Association (ATA) is the world’s leading professional association of medical specialists dedicated to education and research to improve thyroid disease prevention, diagnosis and treatment; improving thyroid patient care; and educating the public about thyroid health and diseasesPrevalence and Impact of Thyroid DiseaseAn estimated 20 million Americans have some form of thyroid disease and it has been suggested that more than 12% of the U.S. population will develop a thyroid condition during their lifetimeUp to 60% of those with thyroid disease are unaware of their conditionWomen are five to eight times more likely than men to have thyroid problems—one woman in eight will develop a thyroid disorder during her lifetimeUndiagnosed thyroid disease may put patients at risk for certain serious conditions such as cardiovascular diseases, osteoporosis and infertilityPregnant women with undiagnosed or inadequately treated hypothyroidism have an increased risk of miscarriage, preterm delivery, and severe developmental problems in their childrenMeet the Thyroid!The thyroid gland is located in the front of the neck attached to the lower part of the larynx and to the upper part of the tracheaThe thyroid has two sides called lobes that lie on either side of the trachea—the lobes are usually connected by a strip of thyroid tissue known as an isthmus (however, in some cases, there are two separate thyroid lobes without an isthmus)Through hormonal activity, the thyroid regulates metabolic functions such as:BreathingHeart rateCentral and peripheral nervous systemsBody weightMuscle strengthMenstrual cyclesBody temperatureCholesterol levelsMuch more!As an endocrine gland, the thyroid uses dietary iodine to produce hormones such as:Triiodothyronine (‘T3’)Thyroxine (‘T4’)The process by which the thyroid uses iodine is actually quite complicated and certain steps are still unclear—essentially, iodine is converted to its free elemental form (‘iodide’) and then enters the thyroid gland through a special transport mechanismIodide then undergoes a process called oxidation and is incorporated into intermediate hormones called MIT (Monoiodotyrosine, which contains 1 iodide) and DIT (Diiodotyrosine, which contains 2 iodides)—these compounds then combine to form the active hormones, tri-iodothyronine (T3) and thyroxine (T4)These hormones are then stored in the thyroid gland and released into the blood streamKEY: Without iodine, the thyroid cannot make hormones vital to healthTwo glands in the brain—the pituitary and hypothalamus—play important roles in maintaining thyroid hormone balanceWhen thyroid hormones are low, the hypothalamus produces Thyroid Releasing Hormone (‘TRH’) that signals the pituitary gland to release Thyroid Stimulating Hormone (‘TSH’)The increased levels of TSH ‘stimulate’ the thyroid to produce more thyroid hormone to bring blood hormone levels back to normalThe three glands and the hormones they produce make up the ‘Hypothalmic-Pituitary-Thyroid Axis’T3 and T4Although the thyroid gland produces more T4 (80%) compared with T3 (20%), T3 is 300% more active than T4—additionally, much of the T4 is converted into the more active T3 inside the cells of the body When the Thyroid MalfunctionsHyperthyroidism (‘Thyrotoxicosis’)Hyperthyroidism is a condition in which the thyroid gland is overactive and makes excessive amounts of thyroid hormoneIn simple terms, all the metabolic processes are ‘speeded up’—for example, the pulse rate is rapid (over 100) and occasionally irregular (atrial fibrillation), bowel function is increased (diarrhea), and the sweat glands work excessivelyThe nervous system is also stimulated so that the patient becomes irritable and anxiousDespite increased appetite, the patient usually loses weight because food intake cannot keep up with the increased breakdown of body proteinsCardiac Symptoms of Hyperthyroidism:TachycardiaChanges in heart rate and force of cardiac contractionSystolic heart murmurHypertensionOther symptoms of Hyperthyroidism include:Heat intoleranceTrouble sleepingHand tremors/Finger clubbingGoiter (side views are beneficial to detect goiter)Causes for Hyperthyroidism:Toxic nodular or multinodular goiter—lumps or nodules in the thyroid gland that cause the thyroid to produce excessive amounts of thyroid hormonesToxic nodular or multinodular goiter is the result of focal and/or diffuse hyperplasia of thyroid follicular cellsThe prevalence of toxic nodular goiter increases with age and in the presence of iodine deficiencyIn addition, inflammation of the thyroid gland—called thyroiditis—may result from a viral, bacterial or immune reaction which may temporarily cause symptoms of hyperthyroidism Medications containing iodine (such as amiodarone) may cause the thyroid gland to overproduce thyroid hormonesAmiodarone is a very effective anti-arrhythmic drug—and it causes thyroid dysfunction in about 15%–28% of patients after 2–3 years of treatmentIt is also an iodine-rich compound with some structural similarity to thyroxine (T4)Amiodarone contains approximately 37% iodine by weight—each 200-mg tablet is estimated to contain about 75 mg of organic iodide (8-17% of which is released as free iodide)Standard maintenance therapy with 200 mg amiodarone can provide more than 100 times the daily iodine requirementAmiodarone and its metabolites may have a direct cytotoxic effect on the thyroid follicular cellsPatients considering amiodarone therapy should have a full thyroid work-up prior to starting the medication regimeInstruct patients about the adverse effects of amiodarone therapy—because the development of thyrotoxicosis is sudden and explosive, instruct patients to watch for symptoms and to seek treatment promptlyHamburger ThyrotoxicosisCommunity-wide outbreaks of ‘hamburger thyrotoxicosis’ resulting from inadvertent consumption of beef contaminated with bovine thyroid gland have been reportedCase ReportSome women may develop hyperthyroidism during pregnancy or in the first year after giving birthDuring pregnancy, the hormone HCG (‘human chorionic gonadotropin’) is produced—it has mild thyroid stimulating effects and, as a result, can cause some symptoms of hyperthyroidismIn situations of multiple pregnancies (twins, triplets) HCG levels are even higher, and symptoms can be more pronouncedHCG levels peak at ~10 weeks—temporary subclinical (no apparent symptoms) hyperthyroidism occurs in 10%-20% of normal pregnant women during this period and these women typically do not require treatmentThe most common cause of hyperthyroidism is the autoimmune disorder Graves’ disease—Graves' disease (GD) is caused by autoimmune stimulation of the TSH receptors leading to hyperthyroidismAbout 35% of individuals also develop Grave’s ophthalmopathy which is an inflammatory disease of the orbital tissues—in these cases, the immune system attacks the muscle and tissue behind the eye resulting in a buildup of adipocytes and fibroblasts resulting in bulging eyes and vision complicationsTidbit Time: Smoking significantly worsens the outcome of Graves’ ophthalmopathyGrave’s Disease is associated with neutropenia in one in seven patients at diagnosis—neutrophil counts increase with treatment with ATD and are related to reduction in thyroid hormone concentrationsOral Manifestations of HyperthyroidismIncreased susceptibility to cariesIncreased risk of periodontal diseasesEnlargement of extraglandular thyroid tissue (posterior tongue)****Mandibular and/or maxillary osteoporosisAccelerated dental eruptionBurning Mouth SyndromeOsteoporosis and Hyperthyroidism:Osteoporosis and increased fracture associated with thyroid malfunction is a hotly debated topic with no real consensus—although there appears to be a stronger link between increased thyroid hormone output and negative effects on bone metabolismA Great Resource:Tuchendler, D and Marek B: The Influence of Thyroid Dysfunction on Bone Metabolism. Thyroid Research 7 (2014): 12. PMC. Web. 13 May 2017Treatment of HyperthyroidismAntithyroid medications (primarily methimazole; propylthiouracil is now used only for women in the first trimester of pregnancy)—these medications interfere with the production of thyroid hormonesRadioactive iodine therapy to damage the cells that make thyroid hormonesSurgical removal of part of or the entire thyroid gland Treatment of hyperthyroidism secondary to Grave’s Disease aims to reduce serum thyroid hormone concentrations and often antithyroid drugs (‘ATDs’) are used initiallyKEY: Grave’s disease normally responds well to treatment—however hypothryroidism is commonly observedWorth Noting:Many people are unaware that in the first half of the 20th Century, fluoride was used medically as an anti-thyroid drug—administered to slow thyroid function in patients with hyperthyroidismFluoride was found to be extremely effective at suppressing thyroid function at very low doses—2-5 mg per day over a period of monthsHeadliners: Are Fluoride Levels in Drinking Water Associated with Hypothyroidism Prevalence in England? A Large Observational Study of GP Practice Data and Fluoride Levels in Drinking Water; Stephen Peckham et al; Centre for Health Services Studies, University of Kent (Canterbury); results appearing in J Epidemiol Community Health; published online first 24 February 2015; as reported by Becky McCall for Medscape; posted 04 Mar 2015; accessed on 11 Mar 2016 at: levels of fluoride in drinking water appear to be associated with an increased risk for hypothyroidism in a study from England—raising concerns about the validity of community fluoridation of water as a safe public-health measureIn particular, when a comparison was drawn between a completely fluoridated area (0.7 mg/L or more) and a non-fluoridated area (0.3 mg/L or less), nearly TWICE the risk for hypothyroidism was detected in the fluoridated area!‘I think the results clearly demonstrate an increased risk of hypothyroidism associated with areas of [high] water fluoridation. [The study also]…raises questions about the safety of community fluoridation.’‘The findings are meaningful and plausible and deserve to be taken seriously. [T]hese results should prompt a rethinking of the whole practice of adding fluoride to drinking water in all countries.’ ‘[T]he large size of the study population minimized bias and the researchers accounted for the major known predictors of thyroid function—including age, sex, iodine intake, and perchlorate exposure…The prior recommendation of a fluoridation range from 0.7 to 1.2 mg/L is still the operative one, with most US states targeting a fluoride level of about 1 mg/L—the same as in the UK. If a similar study were to be conducted in the US, I would expect to see similar results.’Levels of fluoridation in the United Kingdom are comparable to those in the United States—in 2011, there was a proposed recommendation to decrease fluoride levels in drinking water to 0.7 mg/L in the United States but the recommendation of 0.7 mg/L is still only a proposal and very few US states or municipalities have made any changesResearchers estimate that people today who live in communities with fluoridated water supplies have a range of exposure of 1.6 to 6.6 mg per dayAnother Fluoride Tidbit:Fluorine and iodine (both members of the halogen group of atoms) have an antagonistic relationship—in excess, fluoride can interfere with iodine uptake and prevent iodine from functioning properlyHypothyroidism Occurs when the thyroid gland does not make enough thyroid hormones (T3 and T4) to meet the body’s needsOver 10 million Americans have hypothyroidism—~2 out of 100 individuals—and many do not know they have it!Women are more likely to have it than men and the chances for developing hypothyroidism increases with age—over 10% of Caucasian women over 60 years of age in the United States and Canada have an under-functioning thyroid glandThe signs and symptoms associated with hypothyroidism occur because there is a deficiency of thyroid hormone secretion and all metabolic processes in the body slow down—resulting in poor appetite, intolerance to cold, dry skin, brittle hair, fatigue, constipation, muscle weakness, poor memory retention and hoarseness Examination may reveal dry, scaly skin with a thickening of surface and underlying tissues (‘myxedema’), very slow reflexes, and decreased heart rateProblems may arise when outside factors act upon the thyroid metabolism cycle which can lead to disruptions in TSH levels, decreased production of T4, incomplete conversion of T4 to T3 or imbalance in the ratio of T3 to reverse T3***Typically, when T4 loses an atom of iodine—a process known as ‘monodeiodination’ or ‘T4 to T3 conversion’—it becomes T3In some cases, the body conserves energy by converting the T4 instead into Reverse T3 (‘RT3’)—an inactive form of T3 that is incapable of delivering oxygen and energy to the cellsIf there is a preferential conversion of T4 to reverse T3, the reverse T3 can act as an antagonist to T3 at the receptor level—factors that may lead to a preferential conversion to reverse T3 include high cortisol levels, glucocorticoids, stress, excess estrogen and nutritional deficiencies such as selenium, iodine, zinc and ironConsidered a ‘stress hormone’, cortisol levels increase during periods of chronic stress—causing a decrease in TSH secretion (which lowers thyroid hormone production) and inhibiting the conversion of T4 to active T3 while increasing the conversion of T4 to reverse T3Headliners: The Impact of Sleep Deprivation on Hormones and Metabolism; Source: Eve Van Cauter, PhD et al; Medscape Neurology. 2005;7(1); accessed on 12 May 2017 at: release of hormones by the pituitary is markedly influenced by sleepAs seen in the HPT Axis discussed earlier, the pituitary gland is greatly affected by substances made by the hypothalamus (and vice versa)Another example of this glandular relationship is the Hypothalmic-Pituitary-Adrenal Axis (‘HPA Axis’)Researchers discovered that partial sleep loss affected circulating levels of pituitary-dependent hormones which lead to an increase in early evening levels of the stress hormone cortisol produced in the adrenal glandsNormally, cortisol concentrations are rapidly decreasing to attain minimal levels shortly before habitual bedtime—the rate of decrease of cortisol concentrations in the early evening was approximately 6-fold slower in subjects who had undergone 6 days of sleep restriction than in subjects who were fully restedAfter 6 days of 4-hour sleep time, the normal nocturnal thyroid-stimulating hormone (TSH) rise was strikingly decreased and the overall mean TSH levels were reduced by more than 30%Additionally, free thyroxine index (‘FT4I’) was higher in the sleep-restricted study participants than in the fully rested cohort—strengthening the negative feedback mechanism to the thyroid glandExcess Estrogen and Thyroid FunctionExcess estrogen increases levels of thyroid binding globulin (TBG)—the proteins that thyroid hormone is attached to as it is transported through the bodyWhen thyroid hormone is bound to TBG, it is inactive—it must be cleaved from TBG before it can activate cellular receptorsWhen TBG levels are high, the percentage of free thyroid hormones dropsThe most common causes of elevated TBG secondary to excess estrogen are birth control pills and hormone replacement therapyConsiderations of Selenium in Thyroid HealthIn patients with Hashimoto's disease, selenium supplementation has been shown to decrease anti-thyroid antibody levels and improves the ultrasound structure of the thyroid glandThe National Institutes of Health lists selenium supplements as possibly effective for autoimmune thyroiditis (Hashimoto’s thyroiditis) but the agency deems the supplements possibly unsafe when taken in high doses or long-term—low-dose, long-term use has been shown to increase the risk of developing diabetes and likely may interact with medications including immunosuppressants, anticoagulants and antiplatelet drugs, statins and blood thinners‘The idea that everyone should be taking selenium supplements in the off-chance they could help is not warranted and potentially dangerous. People should focus on getting selenium from their diets, which isn’t difficult in places like the U.S. [and Canada].’--Jason Baker, M.D.; assistant professor of clinical medicine; Weill Cornell Medical College (New York)Iodine and Thyroid HealthHeadliners: What Causes Thyroid Disease?; Alan Christianson; naturapathic medical doctor; posted 22 Jun 2015; accessed 9 Mar 2016 at: thyroid is the only part of the body that needs iodine—this is unusual because every other nutrient we know of is used for many body processes with a large variety of reactions Another unusual thing about iodine uptake and the thyroid is that an iodine transport mechanism is needed to get the nutrient inside gland—all of the other nutrients the body uses are found in adequate amounts in the bloodstream but the bloodstream cannot carry adequate iodine for the thyroidFor that reason, the thyroid has a pump that pulls iodine inside of the gland at concentrations up to 100 times what is found in the blood—this pump can be part of the problem in thyroid disease because it can pull toxins inside the thyroid along with the iodineIronically, the best-documented toxins to trigger thyroid disease include iodine itself—other thyroid toxins (called ‘endocrine disruptors’) include perchlorate, lead, mercury and over 200 other environmental chemicalsFire Retardants (PBDEs)PBDEs (‘polybrominated diethyl ethers’) disrupt thyroid function by blocking the uptake of iodine—eventually taking its place in the thyroid (mimicking and disrupting thyroid hormones in the process)PBDEs have been linked to lower IQ and are proven to negatively affect neural and physical development in children and developing infantsPerchlorateFound in rocket fuel, explosives, fireworks, and fertilizers, this common environmental chemical noticeably disrupts thyroid functionSimilarly to PBDEs, perchlorate replaces iodine in the thyroid and leads to decreased thyroid activityWater contains the highest concentrations of perchlorate—using a high-quality water filter may also help filter out perchlorateOrganophosphate PesticidesConsuming vegetables and fruits that have pesticide residue is one of the most common ways endocrine disruptors enter the thyroidOrganophosphate pesticides have been shown to cause infertility in men, slow brain development in children, and have even been shown to affect thyroid functionAlways choose organic when purchasing food to avoid these pesticidesPhthalatesPhthalates are added to plastics to aid durability and flexibility; yet, their negative health effects have been constantly reported in various studies all across the worldResearch has confirmed that phthalates inhibit sperm cell developmentThese chemicals have also been linked to obesity, diabetes, and thyroid conditionsPhthalates can easily leach into water, and people drinking from water bottles are the most susceptible to chronic exposureAlways store foods and liquids in glass whenever possiblePerfluorinated Chemicals (PFCs)It has been estimated that 99% of Americans have PFC accumulation in their bodiesPFCs have the power to accumulate in the body and are extremely difficult to get rid of once they are storedPFCs are commonly used to make non-stick pans—during cooking, some of these chemicals escape into food Avoiding non-stick cookware is extremely importantPFCs disrupt hormone function and have been tied to infertility, ineffective sperm, heart disease, thyroid disease, high cholesterol, and low birth-weight in babiesResearch has confirmed PFCs (especially PFOA and PFHxS) negatively affect thyroid hormone levelsAccording to a 2017 report, some 16.5 MILLION Americans in 33 states may be drinking water containing unsafe levels of organic compounds known as PFAs—which has also been linked to high cholesterol, obesity and cancer--As reported in TIME; 30 JAN 2017Headliners: Researchers: Potentially dangerous chemicals found in fast-food wrappers; Study results published in Environmental Science & Technology Letters; 1 FEB 2017; As reported by Michael Hawthorne; Chicago Tribune; results appearing in the Idaho Statesman; 2 FEB 2017For over 30 years, fast-food companies have relied on the chemical industry to keep grease and oil from soaking through burger wrappers, French fry cartons, and pizza boxesResearchers began to realize that those compounds—PFCs—were causing cancer, liver damage, reproductive trouble and hormonal imbalances during developmentIt turned out that food wrappers were a MAJOR source of exposure—under oath, a former DuPont chemist described how customers ingested the chemicals every time they ate a French fryMcDonald’s, Burger King and other chains pledged to stop using PFCs and manufacturers began to phase them out—in 2016, the FDA followed up with a ban on three PFCs used in packagingIn a study released in 2017, a THIRD of samples collected from McDonald’s, Burger King, Starbuck’s and other restaurants contained FLUORINE—a key building block in PFCsBack to IodineBefore the 1920s, iodine deficiency was common in the Great Lakes, Appalachian, and Northwestern U.S. regions and in most of Canada—since the introduction of iodized salt, the ‘goiter belt’ has been virtually eliminatedHowever, many other parts of the world do not have enough iodine available through their diet and iodine deficiency continues to be an important public health problem globally—approximately 40% of the world’s population remains at risk for iodine deficiencyKEY:Both over- and under-production of thyroid hormone are associated with goiter!In hyperthyroidism, the goiter is the result of inflammation of the glandIn hypothyroidism, the goiter develops as the thyroid attempts to make more thyroid hormone in the absence of sufficient dietary iodineHeadliners: The Silent Epidemic of Iodine Deficiency; Nancy Piccone; appearing online at ; posted October 2011; accessed 11 Mar 2016 at: the developed world, iodine deficiency has increased more than fourfold over the past 40 years—nearly 74% of normal, ‘healthy’ adults may no longer consume enough iodineThe health benefits of reducing salt intake have been well established—millions of Americans have slashed their use of salt to protect themselves against high blood pressure and cardiovascular disease AND have cut iodine intake in the process Hashimoto’s ThyroditisIn the case of any autoimmune disease, the main feature is the production of antibodies that attack the healthy tissue of the bodyKEY:Patients first experience symptoms of hyperthyroidism (sudden weight loss, rapid heartbeat, anxiety, high blood pressure and hot flashes)—however, as levels of hormone clear from the blood and drop, patients experience hypothyroid symptoms like fatigue, depression, weight gain, constipation and mood swingsThis pattern repeats until thyroid hormones becomes depleted and patients are subsequently diagnosed with a low thyroid state Systemic Manifestations of HypothyroidismCold intoleranceConstipationForgetfulness and personality changes***Modest weight gain (mainly due to fluid retention and decreased metabolism)Paresthesias of the hands (carpel tunnel) and feet (caused by deposition of proteinaceous ground substance in the ligaments around the wrist and ankle) Women may experience irregular or absent menstrual cyclesDull facial expression Hoarse voice Slow speechFacial puffiness and periorbital swelling (due to infiltration with the mucopolysaccharides hyaluronic acid and chondroitin sulfate)Drooping eyelidsHair is sparse, coarse, and drySkin is coarse, dry, scaly, and thickHypothermiaBradycardia (slow heart rate)Facial rashHeadliners: Are You Living Life with Thyroid Brain Fog?; October 24, 2014 by Dana Trentini; posted on 24 Oct 2014; written by Dr. Hugh Melnick (); accessed 4 Mar 2016 at: 3/4/16Poorly managed hypothyroidism can have a powerful effect on the brainIncreased depression and anxiety—hypothyroidism has been shown to increase depression seven-fold!—have long been associated with thyroid disorders--Source: Larisch R et al: Depression and anxiety in different thyroid function states. Horm Metab. Res. 2004 Sep;36(9):650-3. Accessed on 11 Mar 2016 at: Mood Deterioration (‘CMD’)These three words are how medical experts and research analysts describe the mentally foggy state that many hypothyroid patients find themselves in—in fact, current studies indicate that an underactive thyroid can take a significant toll on mental health because EVERY system slows (including neurological functions)Symptoms of CMD include:Inability to concentrateDetachment from personal relationships and activitiesLow self-esteemDepressionInability to connect detailsShort-term memory problemsSlowed mental reactionsConfusionUnfortunately, the neurological symptoms that about 5% of all hypothyroidism patients suffer from are largely underestimated or outright ignored by a lot of practicing medical professionalsTreatment of Hashimoto’s:Levothyroxine (also known as Synthroid, Eltroxin, and some other trade names) is first line conventional medical therapy for hypothyroidismIdeally, levothyroxine provides synthetic T4 (thyroxine) which is subsequently converted to T3 by tissues throughout the body—supplementing only T4 depends on conversion to have effect at the tissue levelThis treatment also is designed to provide feedback to the pituitary gland which produces TSH—bringing down elevated TSH found in hypothyroidismGenerally speaking, thhe correct dose of thyroxine is determined by normal TSH (0.3-3.5milliU/L)***, a normal Total T3 (1.2-3.4 nmol/L) and a T4 level in the upper half of normal or just above (normal range 50-165 nmol/L)KEY:The correct dose of T4 can ‘normalize’ TSH levels but may not resolve symptoms of hypothyroidism or resolve the autoimmune process present in Hashimoto’s hypothyroidPatients often complain that even though they are in treatment for their thyroid condition, they do not feel better physically or mentallyAccording to Pamela Wartian Smith, MD, MPH, the standard test for low thyroid might not provide a clear understanding of thyroid function—a ‘normal’ test result that is in the lower range of acceptable TSH levels may be too low for some people!Typically, hypothyroidism is diagnosed with a simple blood test for TSH (if thyroxine is LOW, the body will produce higher levels of TSH to compensate)—therefore, a TSH reading of ≥5.0 mlU/L (milli-international units per liter) is significantly elevated to confirm a diagnosis of hypothyroidismIf a person remains symptomatic even when TSH levels are within the ‘normal’ range, the problem could be with the laboratory used to analyze the blood draw (many laboratories use different reference ranges)Mainstream medicine generally relies on a normal TSH range from 0.5 mlU/L to 5.0 mlU/L—other doctors will only diagnose hypothyroidism once TSH is above 10.0!For these reasons, it is extremely important to demand a COMPLETE thyroid panel when seeing a physicianAccording to endocrineweb: thyroxine T4 4.6-12 ug/dl Free thyroxine fraction FT4F 0.03-0.005% Free Thyroxine FT4 0.7-1.9 ng/dl Thyroid hormone binding ratio THBR 0.9-1.1 Free Thyroxine index FT4I 4-11 Serum Triiodothyronine T3 80-180 ng/dl Free Triiodothyronine l FT3 230-619 pg/d Free T3 Index FT3I 80-180 Radioactive iodine uptake RAIU 10-30% Serum thyrotropin TSH 0.5-6 uU/ml*** Thyroxine-binding globulin TBG 12-20 ug/dl T4 +1.8 ugm TRH stimulation test Peak TSH 9-30 uIU/ml at 20-30 min Serum thyroglobulin l Tg 0-30 ng/m Thyroid microsomal antibody TMAb Varies with method Thyroglobulin antibody titer TgAb Varies with method Reverse T3 rT310-24 ng/dL***Excessive intake of thyroid supplements resulting in subclinical hyperthyroidism may occur in as many as 20% of patients (particularly the elderly)! Patients who begin taking levothyroxine in middle age may need lower doses with advancing age—and overtreatment is common despite requirements for regular thyroid-stimulating hormone (TSH) monitoringSomething to ponder:Use of levothyroxine is increasing—in the United States, the number of prescriptions for levothyroxine increased from 97 million in 2007 to 120 million in 2014 making levothyroxine the most prescribed drug in the USA for the first time--Source: Rodriguez-Gutierrez, Rene et al: Levothyroxine overuse: time for an about face?; appearing in The Lancet Diabetes & Endocrinology; Vol 5 (4): p.246 - 248 ; accessed 13 May 2017 at: 2016, doctors handed out 123 million prescriptions for Synthroid and its generic equivalent levothyroxine—slightly edging out atorvastatin (Lipitor) for the top spotRecommendations:TSH levels should be obtained at least annually in patients taking levothyroxineLevothyroxine should not be taken concomitantly with multivalent cations (ie, iron and calcium) or foodPatients should be instructed on how to take levothyroxine properlyLevothyroxine should be taken at a consistent time to avoid fluctuations in TSH levelsSome research suggests bedtime administration of levothyroxine may be more effective than morning administrationKEY:Standard prescription hormones (like Synthroid) only contain T4—if symptoms of hypothyroidism persist, medications containing T4 and T3 (generally in a 4:1 ration) may be prescribedDesiccated Thyroid: The Rising Star!Desiccated thyroid at one point was the ONLY medication option for underactive thyroid and has been around the longestUnlike synthetic levothyroxine, desiccated thyroid extracts contain T4 plus T3 as well as small amounts of thyroid co-factors T1, T2, calcitonin and iodine—proponents say this suite of ingredients is more ‘natural’ while others say they just feel better taking itMade from dried and powdered pig thyroid glands, the thyroid extract medications Armour, NP Thyroid, Nature-Thyroid and WP Thyroid seem to be making a comeback—in a 2017 American Thyroid Association survey of more than 12,000 people with hypothyroidism, early results showed that about 30% reportedly took natural or compounded thyroid medicationsBecause desiccated thyroid is NOT synthetic and is derived from a natural source that will vary from batch to batch, it is very important to use a reputable brand that is standardized and formulated carefully—in the United States, there are many products with desiccated thyroid in non-standardized amounts and pose a major health riskWhy does Hashimoto’s occur?Trigger TheoriesTriggers like poor diet, stress, toxins and illness can create negative changes in the microbiome—friendly bacteria that normally support health become suppressed while opportunistic and pathogenic bacteria take center stageThis can lead to a whole host of health conditions including autoimmunity Microbe triggers include the bacteria Yersinia Enterocolitica—which has surface peptides that mimic receptors on the thyroidThe receptors are so similar that when the immune system mounts a response to yersinian, it also attacks thyroid tissueHeadliners: Organization Finds Yersinia enterocolitica in Most Pork Samples; As reported by Greg Cima for The American Veterinary Medical Foundation; posted on 31 Dec 2012; accessed on 10 Mar 16 at: product testing organization found Yersinia enterocolitica in 69% of pork samples tested—the test results from Consumer Reports indicated the organization tested for the presence of certain bacteria in about 200 samples from pork chops and ground pork bought in six U.S. cities—the article also noted that 121 of 132 Yersinia isolates tested for drug resistance were resistant to at least one antimicrobialAbout 98,000 people in the U.S. were sickened (generally diarrhea and abdominal pain) by Y. enterocolitica annually from 2000-2008—the bacteria are most often spread to humans through contaminated food (particularly undercooked or raw pork)Yersinia enterocolitica cross the epithelial barrier in the ileal portion of the small intestine—to survive, these bacteria resist phagocytosis by macrophages and downregulate inflammationAs a result, bacteria resist host immune defenses in subepithelial tissues which allows them to invade and infect distant tissues--Source: War and peace at mucosal surfaces by Philippe J. Sansonetti; appearing in Nature Reviews Immunology. 4, 953-964 (December 2004)Once yersinia has disseminated throughout the body, the immune system mounts an antibody-mediated attack that affects BOTH the microbe and thyroid cells Viruses (such as HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus) are linked with Hashimoto's thyroiditis—these tiny microbes promote inflammation, provoke overstimulation of the immune system and may create the same type of molecular mimicry seen with yersiniaResearch is still working on finding the exact mechanisms that trigger the self-immune attack in the presence of these virusesHeadliners: Virologic and Immunologic Evidence Supporting an Association Between HHV-6 and Hashimoto's thyroiditis; E. Caselli, M. C. Zatelli, R. Rizzo, et al. PLOS Pathogens, vol. 8, no. 10, Article ID 100295, 2012; accessed on 8 Mar 16 at 2012 study linking Human Herpes Virus 6A (‘HHV-6A’) to Hashimoto’s thyroiditis (‘HT’) found that HHV-6A was detected significantly more frequently among thyroid fine needle aspirates from HT individuals than controls (82% versus 10%)The presence of HHV-6A infection was found localized in thyrocytes (rather than in lymphocytes) infiltrating the lesionAdditionally, the study demonstrated that thyroid cells infected with both HHV-6A and HHV-6B became susceptible to Natural Killer Cell-mediated killing—providing evidence of a potential mechanism for HHV-6A/B-induced autoimmunityA 2015 study led by Rizzo and Caselli from the University of Ferrara also analyzed fine needle thyroid aspirates and found HHV-6 in 100% of the tests of HT sufferers (compared to only 25% in control)Considerations of IodineFor adults who are not lactating or pregnant, the US Institute of Medicine, and jointly by the WHO, United Nations Children’s Fund (UNICEF) and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD), recommend a daily iodine intake of 150 μg and state a tolerable upper level of 1,100 μg per daySources of iodine exposure and potential excess:DietKelp (per g): 16–8,165 μgBread (per slice): 2.2–587.4 μgMilk (per 8 oz): 88–168 μgFish fillet (per g, dry weight): 0.73 μgIodized salt: VariableOther sourcesVitamins (prenatal, labelled content per daily serving): 75–200 μgAmiodarone (per 200 mg): 75,000 μgIodinated contrast (free iodine content, per CT scan): 13,500 μgTopical iodine (povidone iodine): variable, usually 1–5%Expectorants, mouthwashes, vaginal douches: variableSaturated solution of potassium iodide (per drop): 50,000 μgKEY:Hydrogen peroxide is created in the thyroid to help convert iodine to its usable form—this can be inflammatory without adequate selenium levels to protect tissue by neutralizing free radicalsDietary Alert!Excessive iodine intake on its own can fuel autoimmunity by causing even more hydrogen peroxide to be made—while deficiency can lead to goiter and low thyroid function, too much can make autoimmunity worse When selenium is taken in from the diet it is used to synthesize proteinsThere are 3 classes of selenoproteins that the body makes—one of which is iodothyronine deiodinases (DDIs) which are involved with converting T4 into the active T3 form Selenium deficiency will increase cellular damage and set off autoimmunity—explaining why the thyroid is so susceptible to the development of Hashimoto's in a selenium deficient dietary state Gluten TriggerMany believe that there is a clear link between gluten consumption and Hashimoto's Thyroiditis—according to study investigations, the structure of gliadin (a component of gluten) is very similar to thyroid cellsThe more gluten that is consumed, the more the immune system responds by making antibodies to the thyroidHeadliners: Two of a Kind—Research Connects Celiac and Thyroid Diseases and Suggests a Gluten-Free Diet Benefits Both; Cheryl Harris, MPH, RD and Gary Kaplan, DO; appearing in Today’s Dietitian; Vol. 12 No. 11 P. 52; 11/2010; as reported by Breana Noble; News Max; posted 08 Mar 2016; accessed at: 3/10/16Research demonstrated that the autoimmune disorder Hashimoto’s thyroiditis and Celiac Disease are linked—once diagnosed with one autoimmune disease, many people are at risk of developing anotherToday’s Dietician reported that, in one research project, half of the patients with Celiac illness also had Hashimoto’sAccording to Beyond Celiac, patients with the gluten-related disorder are four times more likely to have Hashimoto’s than the average populationThe Celiac Support Association reported that Celiac Disease causes difficulty with absorption of thyroid hormonesMany patients with Celiac Disease are on a gluten-free diet—the diet not only lessens symptoms of Celiac illness, it also enhances the absorption of medications for Hashimoto’s disease--(Source: National Center for Biotechnological Information) Oral Manifestations of HypothyroidismSalivary gland enlargementCompromised periodontal health***Macroglossia***GlossitisDysgeusiaDelayed eruptionEnamel hypoplasia (especially in deciduous dentition)Anterior open biteMicrognathiaThick lipsMouth breathingDelayed wound healing***Thickening of the tongue and lips occurs due to an increase in accumulation of subcutaneous mucopolysaccharides (such as glycosaminoglycans)—these substances cannot be degraded in a hypothyroid stateCase Report (Source: Kothiwale S, Panjwani V. Impact of thyroid hormone dysfunction on periodontal disease. J Sci Soc 2016; 43:34-7. Accessed on 11 Mar 2016 at: )Studies have shown that the stress inflammatory cytokines (specifically IL-1β, IL-6 and TNF-α) down-regulate the HPT axis and reduce levels of thyroid stimulating hormone (TSH)It has also been demonstrated that one single injection of tumor necrosis factor alpha (TNF-α) reduced serum TSH, T3, free T4, free T3 and hypothalamic TRH for 5 daysTNF-α was also found to decrease the conversion of T4 to T3, reduce thyroid hormone uptake, and decrease the sensitivity of the thyroid to TSHIn order for thyroid hormone circulating in blood to have a physiological effect, it must first activate receptors on cells—inflammatory cytokines have been shown to suppress thyroid receptor site sensitivityThyroid Dysfunction and Cardiovascular HealthThyroid dysfunction creates unfavorable disturbances in lipid profiles—elevating low-density lipoprotein (LDL) and total cholesterol levels and raising the risk of atherosclerosisHypothyroidism also weakens the heart muscle and decreases contractile strength—arrhythmias can occur during exerciseRestoring normal thyroid function helps reverse multiple cardiovascular risk factors (especially adverse lipid profiles)—yet, mainstream medicine traditionally relies on thyroid hormone therapy for hypothyroidism which may increase cardiac metabolic rate*** Adrenal glands secrete noradrenaline (‘norepinephrine’) to compensate for a lack of thyroid hormone—and noradrenaline raises the heart rateUnfortunately, it’s hard to secrete just a little norepinephrine, so the heart rate becomes elevated, blood pressure rises, and anxiety increasesOften, medications like beta blockers are prescribed for hypertension and benzodiazepines for anxiety, when what is needed is thyroid hormone—lab results will show a ‘normal’ TSH level but low Free T3 and Free T4 levels in conjunction with a low body temperature confirm the hypothyroid stateControlling oral inflammation is extremely beneficial!Dental Alerts!Benzodiazepines, barbiturates, and narcotic analgesics may cause respiratory and cardiac depression in patients with hypothyroidismThyroxine (T4) replacement drugs can be synergistic with adrenergic agents (such as epinephrine used in anesthetic agents)Headliners: Beware of Biotin; Eric Seaborg; Endocrine News; Jan 2016Many physicians are encountering an increasing number of confounding thyroid hormone lab results caused by patients taking large doses of biotinThe problem is that almost all immunoassays today contain biotin because they rely on the biotin–streptavidin attraction to either anchor the assay’s antibodies to a capture surface or capture them once they have reacted with a patient sample--Stefan K. Grebe, MD, PhD; professor, laboratory medicine & pathology; co-director, the endocrine laboratory at the Mayo Clinic in Rochester, MNIn the case of competitive immunoassays—usually used for low molecular weight targets (such as T4, T3, and cortisol)—biotin interference causes a falsely high or low result‘I saw somebody just yesterday who has had an extensive workup for hyperthyroidism. A lot of her tests look like she has Graves’, but she is taking massive doses of biotin. She probably doesn’t have any thyroid problem. We could be treating people for Graves’ disease who don’t have it, and that’s really scary.’--Carol Greenlee, MD; endocrinologist; Grand Junction, Colorado‘When your lab results don’t make sense in terms of the clinical picture, or in terms of the constellation of lab results you have received, you should always think first of an assay interference—one of which is biotin—before you think of really exotic reasons for this to have happened, such as TSH-secreting pituitary tumors.’--Stefan K. Grebe, MD, PhD; professor, laboratory medicine & pathology; co-director, endocrine laboratory; Mayo Clinic (Rochester, MN)‘We have huge signs in my office that ask people if they are taking biotin—in each exam room, over the phlebotomy chair, and at the front desk. We had all these nice pictures on our walls, but the biotin thing alarmed us so much that we don’t care about our decorations in our office anymore.’--Carol Greenlee, MD; endocrinologist; Grand Junction, ColoradoWhen treating thyroid patients in the dental setting, be sure and ask about biotin supplementation!Other Treatment Recommendations: If a suspicion of thyroid disease arises for an undiagnosed patient, ALL elective dental and dental hygiene treatment should be put on hold!Avoid BPA-containing composite materialBisphenol A is a known endocrine disruptor and should be avoided in endocrine disorders such as thyroid disfunction Speaking of BPA:Over the past two decades, the number of children with defective enamel has been increasing—affecting 15%-20% of children 6 to 9 years of age--Source: Sylvie Babajko; French National Institute of Health and Medical Research (Paris); as reported in Science News; 17 September 2016Babajko and her colleagues concluded that BPA is a likely culprit in the enamel anomalies and is found in food packaging, store receipts and some dental sealantsPain ManagementAspirin is contraindicated in patients with hyperthyroidism because the medication promotes an increase in free forms of both T4 and T3—potentially worsening the symptoms of thyrotoxicosisNSAIDs should also be used with caution in patients who have hyperthyroidism and take β-Blockers (ibuprofen can decrease the effect of β-Blockers)Fluoride RecommendationsTopical is MUCH better than systemic but ingestion of ANY fluoride product should be minimized in cases of thyroid disfunctionStress Reduction Protocol Avoid the use of central nervous system depressants like benzodiazepines and barbiturates in hypothyroid patients Home Care RecommendationsExcellent plaque control Avoid alcohol mouthwashThyroid CancerFast Facts:Females are more likely to have thyroid cancer at a ratio of 3:1Thyroid cancer can occur in any age group—although it is most common after age 30 and its aggressiveness increases significantly in older patientsThyroid cancer does not always cause symptoms; often, the first sign of thyroid cancer is a thyroid nodule***It is estimated by the American Thyroid Association that Americans develop 250,000 thyroid nodules each yearBecause the thyroid gland is right under the skin, changes in its size and shape can often be felt or seen—for that reason, members of the dental team can play an important role in detecting thyroid diseaseThyroid Examination (Source: Dianne Glasscoe-Watterson, RDH, MBA; Thyroid Cancer: The dental professional’s role in early detection; online RDH; accessed on 11 Mar 2016 at: )The thyroid exam should begin with a visual inspection of the neck area for enlargement or asymmetry while the patient is in a supine positionThe clinician should then move to the 12 o’clock position and use both hands to conduct a bilateral tactile examination—working up both sides of the trachea to the angle of the jaw and ending with the TMJ areaA thorough check of the lymph nodes should be done as wellOther things to look for:Unwarranted anxiety or hyperactivity (hyperthyroidism)Inspect the patient’s hands for dry skin (hypothyroid), increased sweating (hyperthyroid), palmar erythema (reddening of the palms indicative of hyperthyroidism)Assess the radial pulse (assess rate and rhythm)Inspect the face for dry skin (hypothyroidism), sweating (hyperthyroidism) and eyebrows (loss of the outer third; possible hypothyroidism), rash (hypothyroidism)Inspect the eyes for redness/dryness (hypothyroidism) or bulging (Grave’s disease)Thyroid Cancer can be divided into four types: Follicular Thyroid CancerMedullary Thyroid CancerAnaplastic Thyroid CancerPapillary Carcinoma***Follicular Thyroid CancerRisk factors include radiation exposure, iodine deficiency, and older age75% of follicular thyroid cancer cases are women Medullary Thyroid CancerGrows faster than either papillary carcinoma or follicular thyroid cancerUsually appears in members of the same familyNot associated with radiation exposureMore common in females than malesCan be controlled if found early enough to prevent it spreading to the rest of the bodyRegional metastases (spread to neck lymph nodes) occurs early in the disease; spread to distant organs occurs late and can be to the liver, bone, brain, and adrenal medullaAnaplastic Thyroid CancerLeast common type of thyroid cancer (~1%) and the most deadlyUndifferentiated thyroid cancerGrows and spreads very quicklyMost common type of thyroid cancer found in people 60 years and olderMore common in males than females by a 2:1 ratioTypically presents as a rapidly growing neck massMay arise many years (more than 20) following radiation exposureCervical metastasis is present in the vast majority (more than 90%) of cases at the time of diagnosis!Papillary CarcinomaMost common type of thyroid cancer (~80%)Well-differentiated Grows slowlyGreat prognosis is if found early enough (~100% for small lesions in young patients)Peak onset ages are 30 to 50 years oldMore common in females than in males by a 3:1 ratio.Prognosis directly related to tumor size (<1.5 cm [1/2 inch] has a good prognosis)Accounts for 85% of thyroid cancers due to radiation exposureIn more than 50% of cases, it spreads to lymph nodes of the neck (distant spread is uncommon)Treatment for Thyroid Cancer:Surgery is the main treatment in nearly every case of thyroid cancer (either complete or partial thyroidectomy)KEY:After thyroidectomy, the patient will be on thyroid replacement therapy for lifeAnother KEY:Early detection is VERY important!Headliners: Who Let the Dogs Out?; Glenda Fauntleroy; reporting for Endocrine News (January 2016)Much cheaper, less invasive, and whole lot cuter than a fine-needle aspiration biopsy, thyroid cancer-sniffing dogs have a remarkable success rateMeet Frankie: The First Dog trained to Detect Thyroid CancerFound as an emaciated stray, this German shepherd mix was easily trained to be a search and rescue dog by his owner‘Being a search and rescue dog meant that he already understood looking for a scent and signaling when he found it. It was just a matter of changing the scent for him. So training to signal for thyroid cancer just took a few months.’--Arny Ferrando, PhD; professor; Center for Translational Research in Aging and Longevity; University of Arkansas for Medical Sciences (UAMS)Ferrando and his colleagues at UAMS presented their pilot study at ENDO 2015 in San Diego that showcased Frankie’s diagnostic skills—before the pilot test, Frankie was imprinted with urine, blood, and thyroid tissue obtained from several different patients with metastatic thyroid carcinomaHe was then trained over six months to decipher between urine from thyroid cancer patients and those without cancerThen, in a first-of-its-kind project, he was asked to ‘diagnose’ the presence or absence of cancer in the urine of 34 patients who initially presented to UAMS with ≥ 1 thyroid nodule(s)—he matched 30 out of 34 samples (88.2% accuracy, two false negatives, two false positives)‘This study is highly novel, and the concept of a noninvasive, rapid, inexpensive test is quite appealing and might be of particular use on low-resource settings. The reported sensitivity and specificity are fairly robust relative to fine needle aspiration biopsy. We routinely make use of dog’s olfactory prowess in other potentially life-and-death situations, for example, bomb-sniffing, so I don’t think that the eventual use of this testing is beyond the realm of possibility.’--Elizabeth Pearce, MD; thyroid specialist; Boston Medical Center; commenting on Frankie’s abilitiesHeadliners: Don't Screen For Thyroid Cancer, Task Force Says; Journal of the American Medical Association; 9 May 2017; As reported on NPR’s ‘All Things Cionsidered’; 9 May 2017; accessed on 14 May 2017 at: U.S. Preventive Services Task Force oversight group puts thyroid cancer screening in its don't-do-it category in recommendationsThe task force concluded that, although screening for cancer would seem to be an obvious way to save lives, in the case of thyroid cancer screening, efforts actually backfire—‘the screening process almost always detects cancers that would never grow into life-threatening tumors’ ‘The harms outweigh the benefits. We would recommend against screening for thyroid cancer in adults who have no symptoms.’--Source: Dr. Seth Landefeld; member of the USPS Task Force; chairman; Department of Medicine; University of Alabama (Birmingham) ‘If you look early, you just find a whole new category of patients that has the disease but is never going to suffer from it at all. But they will suffer from the treatment.’--Source: Dr. H. Gilbert Welch; Dartmouth Institute for Health Policy and Clinical PracticeOnce growths are discovered, surgeons almost always remove the patient's thyroid gland—the surgery can have significant side-effects:Surgeons can sever the nerves that help control swallowing and speechRemoval of the parathyroid glands (which regulate calcium levels)Patients go on a lifelong prescription of thyroid hormoneThyroid cancer rates have also been climbing in the U.S. since the 1990s—but mortality rates have stayed flat (a possible indication that doctors are identifying and treating cancers that don't need to be treated)Here’s the kicker:‘As soon as somebody has symptoms, such as a swelling in the neck or change in their voice or swallowing, or pain in the neck ... you're in a different ballpark. You really want to sort those symptoms out.’--LandefeldIt was believed that most cancer developed primarily as a defect in genetic material—damage to cellular DNA occurred primarily through environmental carcinogenic factors such as tobacco smoke, UV radiation, etc.More recently, researchers have discovered that certain types of infections can also lead to cancer development—because infections can also cause damage to DNAAccording to WHO, about six in every 100 cancer deaths in developed countries are linked to an infectionPorphyromonas Gingivalis As a non-motile, Gram-negative, rod-shaped, anaerobic bacterial organism, P. gingivalis has surface fimbrae which allow the bacteria to adhere (‘stick’) to epithelial AND tooth surfaces making it a very important pathogen for periodontal diseasesThe main feature of periodontal diseases is inflammation of oral tissues in response to Gram negative pathogenic bacteria such as Porphyromonas gingivalis—an increase in secretion of gingival crevicular fluid (‘GCF’) accompanies the inflammatory responseThe rise in GCF raises the local pH which allows periopathic bacteria such as P. gingivalis to overgrow and crowd out other microbesP. gingivalis, as a hemin-dependent bacteria, enjoys the hemin that is abundantly found in GCF—the increased production of GCF accompanying inflammation of periodontal tissues provides a competitive advantage to the so-called ‘red-complex’ bacteria (of which P. gingivalis is a member) over commensalsAn investigation demonstrated that Porphyromonas gingivalis was present in 61% of study participants with esophageal squamous cell carcinoma (ESCC)--Source: Gao S et al: Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer; Infect Agent Cancer (2016); 11: 3. Published online 2016 Jan 19; accessed on 3/14/16 at: researchers also found the presence of P. gingivalis correlated with other factors—including cancer cell differentiation, metastasis and overall survival rateThere are two likely explanations: either ESCC cells are a preferred niche for P. gingivalis to thrive or the infection of P. gingivalis facilitates the development of esophageal cancer ‘These findings provide the first direct evidence that P. gingivalis infection could be a novel risk factor for ESCC and may also serve as a prognostic biomarker for this type of cancer. These data, if confirmed, indicate that eradication of a common oral pathogen may contribute to a reduction in the significant number of people suffering with ESCC. It would suggest that improving oral hygiene may reduce ESCC risk; screening for P. gingivalis in dental plaque may identify susceptible subjects; and using antibiotics or other anti-bacterial strategies may prevent ESCC progression.’--Source: Huizhi Wang; University of Louisville; School of DentistryTHANK YOU! ................
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