Statement of DisclosuresThe following potential conflict of interest relationships are germane to this presentation. Event Support: RLCLabs manufacturers of Nature Throid, Westhroid and Westhroid PEmployment: NoneSpeakers Bureau: NoneStock Shareholder: None Grant/Research Support: None Consultant: NonePublications: Complete Idiot’s Guide to Thyroid Disease, Healing Hashimoto’s A Savvy Patient’s GuideInformation Products: Hypothyroid App, Hypothyroid App Pro Status of FDA devices used for the material beingpresented NA/Non-Clinical Status of off-label use of devices, drugs or other materials that constitute thesubject of this presentation NA/Non-Clinical
Health By Default • Fat • Sick • Epileptic kid
Healthy & Happy Health By Design• Physician• Author• Patient Advocate
Alan Christianson, NMD• SCNM Premier Class• Began Thyroid focused practice in 1996.• American Thyroid Association• American Academy of Clinical Endocrinology• Broda Barnes Foundation• Wilson Temperature Syndrome
IntroductionThe guidelines of conventional medicine tend to under-diagnoseand under-treat hypothyroid symptoms.The guidelines in alternative medicine tend to over-diagnose andover-treat hypothyroid symptoms.Emerging evidence will be used to evaluate both sides’ strengthsand weaknesses and create an evidence-based Integrativemodel.
Pre Event QuizWhich of the following would mandate thyroidreplacement in a symptomatic patient with a TSHbetween 2.5 to 4.5?A. Delayed Achilles reflexB. AM Axillary body temperature below 97.2C. Positive prior response to thyroid replacementD. Ultrasonographic signs of autoimmunity
Pre Event QuizMost hypothyroidism in the USA and Europe is caused by:A. Iodine deficiencyB. Autoimmune diseaseC. ObesityD. Bromide toxicity
Pre Event QuizThyroid dosing can be safely increased until:A. AM Axillary body temperature rises above 98.9B. Symptoms have resolvedC. TSH is suppressed below 0.4 mIU/LD. free T3 elevates above 4.8 pg/mL
Learning Objectives•Conventional diagnostic criteria for Hypothyroidism and theirshortcomings•Alternative diagnostic criteria for Hypothyroidism and theirshortcomings•Diagnostic guidelines that predict which non-‘Hypothyroid’ patientscan benefit from thyroid treatment and which may not.•Thyroid medications and dosing guidelines•Advanced strategies for managing Hashimoto’s
Hypothyroidism•> 30 Million American Adults•10% of population – undisputed•20% of population – hypothetical and probable•25-50% of those with disease have been diagnosed•50% of those diagnosed still symptomatic•8 Times more common in women
Hypothyroidism in Women•25% of Women will develop hypothyroidism in their lifespans (conservative estimates)•Scientists are not clear why women get more autoimmune diseases, top theories: • Microchimerism (persistent foreign cells from baby) • Lower Testosterone • Expression of X-linked immune abnormalities•Yet, Scientists do now know why women live longer . . .
•Thyroid Mass Average = 60-100 grams•Size = deck of cards•Shape = (approximate) Butterfly•Non-palpable when healthy
Thyroid Hormone Synthesis
Thyroid hormones◦ Triiodothyronine=T3=liothyronine = 30 micrograms/day ◦ 20% produced by thyroid gland ◦ 80% by deiodination ◦ 4 x as potent as T4◦ T1 and T2 in trace amounts
Williams Textbook of Endocrinology. Page: 312
Thyroid Physiology• Stimulates all cells to form energy• Burns carbohydrate and fat• Body temperature• Hair, skin and nails• Immune function• Regulates ovaries and adrenals• Repair of brain cells• Intestinal peristalsis
• Family History of Thyroid Disease - Any Type Genes • Variations in Sodium Iodine Symporter • Iodine, Fluoride, Perchlorate, Mercury, Cadmium Toxins • Vitamin D - Below optimal levels (50-70 ng/dl) Vit D • EBV, hepatitis C, human parvovirus B19, coxsackie,Infections herpes virus
Hashimotos ThyroiditisDr. Hakuru Hashimoto • Immune system attacks 1881 - 1934 thyroid • Both hyper/hypo symptoms • 97% of hypothyroidism
Hashimoto’sThyroiditis• Autoimmune• Most Common Thyroid Disease in America• Higher Risk of other Autoimmune diseases• 8 /1 Female to Male ratio• Higher risk of thyroid cancer• NAFL
Autoimmune Thyroid Disease: New Models of Cell Death in Autoimmunity. Giorgio Stassi & Ruggero De Maria Nature Reviews Immunology 2, 195-204 (March 2002).
Section 1 Part 2THYROID DIAGNOSIS
Hypothyroidism - Historical Perspective ". . there are a large number of patients who suffer fromthyroid poverty and who drift from physician to physicianwithout the cause of their symptoms being suspected. . . . Indoubtful cases thyroid extract may be given in small doses asa therapeutic test, and continued if it does good anddiscontinued if it does harm."The Profit and Loss Account of Modern Medicine, and OtherPapers By Stuart McGuire Published 1915 L. H. Jenkins
The condition in which hypothyroid symptoms are present without otherimmediate causes and can be improved with thyroid replacement therapy.•Hypothyroidism•Subclinical hypothyroidism•Type 2 hypothyroidism•Functional hypothyroidism•Sublaboratory hypothyroidism•(Clinical) Hypothyroid Syndrome
•TSH•T4/fT4•T3/fT3•Antithyroid antibodies (TPO, TG, TSI)Normal and abnormal defined by local referencelaboratory ranges
Value Normal low Normal highTSH 0.4 4.5 – 7.0 fT3 1.4 4.2 fT4 0.7 2.0
Thyroid reference ranges have been skewed to thehypo side by including the thyroid disease population.[Evidence Level A, RCT]Erden g, Oanzden A, Tezcan G, et al. Biological Variation and Reference Change Values of TSH, Free T3, andFree T4 Levels in Serum of Healthy Turkish Individuals. Turk J Med Sci 2008; 38 (2): 153-158.
The average TSH, free T3 and free T4 scores of healthy individuals without thyroiddisease was compared to current normal ranges. Those chosen were free ofthyroid disease and had no chronic disease such as diabetes, hypertensioncoronary artery disease or anemia. Subjects were excluded if they had any majormedical illness such as other endocrine or autoimmune disease, any medicationuse including oral contraceptives, pregnancy or history of substance abuse.This population showed less variation in thyroid blood levels than establishedreference ranges would predict. Most notably TSH levels did not exceed themiddle of the normal reference range.
By testing each individual 4 times over two weeksunder consistent conditions, the study also showedthat intra-individual variation in thyroid serology wasnearly identical to inter-individual variation in thishealthy population.
Value Median Min. MaxTSH 0.99 0.36 1.91 fT3 2.69 1.99 3.17 fT4 0.93 1.09 1.9
Obesity within normal TSH•Positive association between BMI and TSH (P < 0.001)•When TSH values all in normal ranges . . .•Highest to lowest TSH = 12.1 pound weight difference in women•Negative association between BMI and free T4 (P < 0.001)Knudsen N et al. Small differences in thyroid function may be important forbody mass index and the occurrence of obesity in the population.J Clin Endocrinol Metab. 2005 Jul;90(7):4019-24
Less stamina than others Requires naps in the afternoon Inability to work full-timeLess energy than others Sleep Apnea (which can also be associated Inability to stand on feet for longLong recovery period after any activity with low cortisol) Air Hunger (feeling like you can’t get enough periodsInability to hold children for very long Complete lack of motivationArms feeling like dead weights after air) Inability to concentrate or read long periods Slowing to a snail’s pace whenactivity walking up slight grade of timeChronic Low Grade Depression Forgetfulness Extremely crabby, irritable,Suicidal Thoughts Foggy thinking intolerant of othersOften feeling cold Inability to lose weight Handwriting nearly illegibleCold hands and feet Always gaining weight Internal itching of earsHigh or rising cholesterol Inability to function in a relationship with Broken/peeling fingernailsHeart disease anyone Dry skin or snake skinPalpitations NO sex drive Major anxiety/worryFibrillations Failure to ovulate and/or constant bleeding Ringing in earsPlaque buildup Moody periods PMS Lactose IntoleranceBizarre and Debilitating reaction to Inability to eat in the morningsexercise Inability to get pregnant; miscarriages Excruciating pain during period Joint painHard stools Carpal tunnel symptoms NauseaConstipation Swelling/edema/puffiness No AppetiteNo eyebrows or thinning outer eyebrows Aching bones/muscles Fluid retention to the point ofDry Hair Osteoporosis Congestive Heart FailureWhite hairs growing in Bumps Swollen legs that preventedNo hair growth, breaks faster than it Acne on face and in hair walkinggrows Breakout on chest and arms fluid on the inner earDry cracking skin HivesNodding off easily Exhaustion in every dimension–physical, mental, spiritual, emotional
Possible symptoms are far too numerous andnon-specific to be of diagnostic value.If you have possible thyroid symptoms but noobjective sign of thyroid disease,you just have symptoms.
The Colorado Thyroid Disease Prevalence Study represents our best scholarlyexamination of which symptoms best predicted thyroid disease.In 1995, over 25,000 people participated in health fairs in Colorado to get somebasic medical screening for vision, blood pressure, colon cancer and skin cancer.Participants also had serum TSH measured and were given a thyroid symptomsurvey.
The thyroid scores were categorized into four ranges:1. Normal defined as TSH scores 0.3 - 5.12. Subclinical hypothyroid defined as TSH scores greater than 5.1 but with normalT4 levels3. Hypothyroid defined as TSH scores greater than 5.1 and low T4 levels4. Hyperthyroid defined as TSH scores lower than 0.01.Of many symptoms surveyed, the following were those that served as the bestpredictors of which patients would have significantly abnormal blood thyroidlevels:
Of many symptoms surveyed, the following were those thatserved as the best predictors of which patients would havesignificantly abnormal blood thyroid levels.Note high specificities and low sensitivities:
Hypothyroidism - Conventional DiagnosisPer Merck Manual:•TSH elevationand•T4/fT4 suppression•Dose titration until TSH normal, symptoms notfactored into dosing
Hypothyroidism - Conventional DiagnosisHypothyroid symptoms are known to often be present buttheir presence or absence does not change the diagnosis.Serology w/o symptoms = hypothyroidismSymptoms w/o serology ≠ Hypothyroidism
Conventional Diagnosis - Shortcomings• Thyroid symptoms can emerge with normal thyroid serology• Some patients with thyroid symptoms and normal serology can benefit from thyroid replacement.• Some patients with thyroid symptoms and normal serology are at higher medical risk without thyroid replacement• ‘Normal’ thyroid serology is biased to thyroid pathology
Thyroid symptoms with normal thyroid serologyIn America, hypothyroidism is caused primarily by Hashimoto’s thyroiditis.In most cases, clear signs of the disease can be documented several years beforehypothyroid serology manifests.Symptoms can be present at the earliest stages of the disease, prior to elevation of TSHand suppression of fT3 or fT4.[Evidence Level C, Expert Consensus]Tomer Y, Huber A. The etiology of autoimmune thyroid disease: a story of genes and environment. J Autoimmune. 2009; 32: 231-239.
Thyroid symptoms with normal thyroid serologyThe early stages of this disease can be documented via blood tests foranti thyroid antibodies, palpable thyroid changes on physical exam,ultrasound findings or tissue biopsy.Serum antibodies in their absence do not rule out Hashimoto’s.[Evidence level C, Expert Consensus]Thyroid Disease Manager. Chapter 8. Hashimotos Thyroiditis. Takashi Akamizu, Nobuyuki Amino, and Leslie J De Groot.http://www.thyroidmanager.org/Chapter8/8-frame.htm. Accessed 4.3.11.Stephanie L Lee, MD, PhD; Chief Editor: George T Griffing, M.Hashimoto Thyroiditis. http://emedicine.medscape.com/article/120937-overview accessed 4/9/11.
Patients benefit from early treatmentTreatment with thyroid replacement therapy at this early stage ofHashimoto’s can:•Reduce symptoms•Slow disease progression•Reduce the risk of nodules and goiter•Shrink existing nodules and goiter[Evidence Level B, Clinical Trial]Padberg S, et. al. ."One-year prophylactic treatment of euthyroid Hashimotos thyroiditis patients with levothyroxine: is there a benefit?" Thyroid. 2001 Mar;11(3):249-55.
Medical risks for untreated early Hashimoto’sPatients with Hashimoto’s disease, even without positive antithyroidantibodies and serum hypothyroidism still have higher risks for heartdisease. Patients with Hashimoto’s Thyroiditis whose TSH is above 2.0have an increased risk of thyroid cancer.Not only can these patients be treated, they are placed at greatermedical risk if not treated.[Evidence level B, Clinical Trial]Bastenie PA, Vanhaelst L, Golstein J, Smets P, et al. Asymptomatic autoimmune thyroiditis and coronary heart-disease. Lancet. 1977. 1:155.Heinonen OP, Aho K, Pyorala K, et al. Symptomless autoimmune thyroiditis in coronary heart disease. Lancet. 1972. 1:785.
Hypothyroidism - Alternative DiagnosisPer Broda Barnes:•Hypothyroid symptoms - including weight gain, fatigue,depression, hair loss but not stringently defined.•AM Axillary BBT <97.8•Dose increase until symptoms resolve or BBT >98.2•OK to ignore both hypothyroid serology at diagnosis andhyperthyroid serology with dose titration
Alternative Diagnosis - Shortcomings•Ranges used to evaluate BBT•Dangers of hyperthyroid serology
Alternative Diagnosis - ShortcomingsRanges used to evaluate BBTBBT can be suppressed by hypothyroidism, but:•Significant temperature suppression is not consistentwith early disease•Normal variance of BBT greater than Barnes estimates•Too many other factors influence BBT
Ranges used to evaluate BBTPer Barnes:“Thus, it seemed that axillary, or underarm, temperature might serve as a simpleguide to determining low thyroid function and the need for thyroid therapy. Andover the past thirty years, it has served as such.In that time, based on many thousands of readings, it has been established thatnormal values for underarm temperature are in the range of 97.8 - 98.2 degreesFahrenheit.”Barnes B. Hypothyroidism: The Unsuspected Illness, HarperCollins. 1976:46.
Ranges used to evaluate BBTIn 2002 a comprehensive review of credible papers on normal human body temperatures from1935 - 1999 was published.This paper showed that the range of normal temperatures was from 91.8 - 100.6 degreesFahrenheit for women and 96.2 - 99.9 for men. Axillary temperatures are held to be within adegree of oral temperatures.The conclusion of the meta-analysis was that: “The ranges of normal body temperature need tobe adjusted, especially for the lower values. When assessing body temperature it is important totake place of measurement and gender into consideration.”[Evidence level B, Clinical Trial]Sund-Levander M, Forsberg C, Wahren L, et al. Normal oral, rectal, tympanic and axillary body temperature in adult men and women: a systematicliterature review. Scand J Caring Sci. 2002 Jun;16(2):122-8.
Alternative Diagnosis - ShortcomingsDangers of hyperthyroid serologyBarnes claims that patients with any persistent possiblehypothyroid symptoms can safely increase thyroiddosing as long as BBT does not elevate above 98.2degrees.
Alternative Diagnosis - ShortcomingsDangers of hyperthyroid serologyYet in many cases, patients can end up on significantlysupraphysiologic doses of thyroid with complete TSHsuppression before BBT elevates. Barnes argues thatTSH suppression and T4/T3 elevations can be safelyignored.
Dangers of hyperthyroid serologySubstantial bodies of data tracking patients with suppressed TSHlevels show that even without obvious hyperthyroid symptoms,morbidity and mortality increase.The largest bodies of data come from three groups:1. Those found from screening to have sub-clinicalhyperthyroidism, meaning abnormally low TSH, normal T3 andT4 and no obvious hyperthyroid symptoms.
Dangers of hyperthyroid serology2. Patients with refractory endogenous hyperthyroidism, typicallyGraves disease.3. Patients with intentional endogenous hyperthyroidism,generally to lower risk of thyroid cancer recurrence.
Dangers of hyperthyroid serologySpecific problems that become apparent with hyperthyroid serology include:•Atrial fibrillation•Stroke•Osteoporosis•Dementia•Grave’s eye disease•Increase in Total Mortality[Evidence level A, RCT]Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. 2004.164(15):1675-1678.Woeber KA. Thyrotoxicosis and the heart. N Engl J Med. 1992;327(2):94-98.Petersen P, Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke. 1988. 19(1):15-18.Sun L, Davies T, Blair H, et al. TSH and Bone Loss. Annals of the New York Academy of Sciences. 1068: 1. 2006. 1749-6632.Bensenor I, Paulo L, Paulo M, et al. Subclinical hyperthyroidism and dementia: the Sao Paulo Ageing & Health Study (SPAH). J BMC Public Health.1. 2010. 1471-2458-10-298.Osman F, Gammage MD, Franklyn JA, et al. Hyperthyroidism and cardiovascular morbidity and mortality.Thyroid. 2002. Jun;12(6):483-7.
Uniting the Models Best of Alternative Worst of Alternative Symptoms considered Patients over-diagnosedMultiple treatment options Patients over-treated
Uniting the Models Best of Conventional Worst of Conventional Serology considered Patients under-diagnosedAmbiguous symptoms given due Patients under-treated merit
Clinical Hypothyroid Syndrome•Clinical - data gathered from patient’s history, reported symptoms and physicalexamination are considered•Hypothyroid - the condition can improve from thyroid replacement likehypothyroidism•Syndrome - the diagnosis is not a single bio-medical finding but a constellationof findings and symptomsClosest current concept is early stage symptomatic Hashimotosthyroiditis.
Clinical Hypothyroid Syndrome = Hashimoto’sThyroid specific symptoms in the absence of other causes +Objective signs of autoimmune thyroid disease +Suboptimal thyroid serology
Hashimoto’s- Diagnosis1. Patient presents with thyroid suspicious symptoms, especially those of recentonset such as:•Fatigue•Dry Skin•Cold intolerance•Muscular weakness•Dysphagia•Chronic irritability•Nervousness•Mood swings
Hashimoto’s - Diagnosis2. Perform physical exam and blood tests to rule out otherconditions, including but not limited to:Addison’s Disease, Anemia, Cardiovascular disease, Diabetes, Infectiousmononucleosis, Malignancy, Medication side effects, Rheumatologic disease, Sleepapnea3. If thyroid exam abnormal, follow up with ultrasound/FNA
Hashimoto’s - DiagnosisThyroid exam, ultrasound, or antithyroid antibodies abnormal?TSH >2.0?If both of the above are yes, treat Hashimoto’sIf Ultrasound shows clear Hashimoto’s, OK to treat even if antibodiesare negative and TSH optimal.[Evidence level B, Clinical Trial]
Specific Symptoms = • Slower thinking • More constipation • Hoarser/deeper voice • Drier skin Specific Symptoms • Feeling colderTSH >2.0 • More tired • Puffier eyes • Cramping / Weaker muscles Signs of Hashimoto’s Signs of Hashimoto’s = • Positive Thyroid Antibodies • (Negative antibodies not a rule out) • Abnormal Physical Exam • Abnormal Ultrasound
Prescribing OverviewBlack Box Warnings (Epocrates)Not for Obesity/ Weight LossNot for obesity/weight loss alone or as combo tx; in euthyroid pts doseswithin range of hormonal requirements ineffective for weight loss; largerdoses may cause serious or life-threatening toxicity, especially given in combow/ sympathomimetic amines including those w/ anorectic effects.
Prescribing OverviewContraindications / Cautions (Epocrates) 1. hypersens. to drug/class/components 2. MI 3. adrenal insufficiency 4. thyrotoxicosis 5. caution if cardiovascular dz 6. caution if HTN 7. caution if diabetes mellitus 8. caution in elderly pts
Prescribing OverviewT4 Absorption timeframe: 40-80% within 6hoursT4 Biological Half-life: 5-7 days
Prescribing OverviewT3 Absorption timeframe: 95% within 4hoursT3 Biological Half-life: 60 hours on average
Prescribing OverviewPharmacology (Epocrates)Metabolism: tissues, liver minimally; CYP450: unknownExcretion: bile; Half-life: 2-7 daysMechanism of Action natural T3 and T4 mixture: produces various physiologiceffects, including increasing metabolism
NDT for Hashimoto’s?Medical literature searches from 1998 to January 5th 2013yielded zero primary sources for this concern.The literature on the topic is scant and dated but all of itshows NDT is helpful or of no harm to Hashimoto’sThyroiditis.
NDT for Hashimoto’s?“ . . . oral feeding of animal thyroglobulin (TG) might inducetolerance to antigen in human autoimmune thyroid disease (AITD)”Induction of oral tolerance in human autoimmune thyroid disease. Lee S, et. al. Thyroid. 1998Mar;8(3):229-34.
NDT for Hashimoto’s?“the goiters that were caused by lymphocytic thyroiditis(Hashimoto’s) responded to treatment with desiccated thyroid”Effect of Desiccated Thyroid in Lymphocytic (Hashimoto’s) Thyroiditis. McConahey W, et. al.Journal of Clinical Endocrinology & Metabolism. January 1, 1959 vol. 19 no. 1 45-52.
NDT for Hashimoto’s?“the goiters that were caused by lymphocytic thyroiditis(Hashimoto’s) responded to treatment with desiccated thyroid”Effect of Desiccated Thyroid in Lymphocytic (Hashimoto’s) Thyroiditis. McConahey W, et. al.Journal of Clinical Endocrinology & Metabolism. January 1, 1959 vol. 19 no. 1 45-52.
Typical Case report 39 YO female • + Hashimoto’s and symptomatic • On levothyroxine prior 4 years • Changed to NDT As part of overall plan • Antibodies reversed over following 6 months
Case report - intake labs
Case report follow up labs
NDT for Hashimoto’s • NDT can be helpful as part of a comprehensive approach • Hashimoto’s antibodies are inherently variable • Larger numbers of readings over longer timeframes are necessary
NDT RecallsRecalls on levothyroxine from 1990 – 2008: “10 (mandatory)recalls, 150 lots, and 100 million tablets.”Recalls on NDT from 1990 – 2008: 1 mandatory, 1 voluntary,both for Armour brand Thyroid.Stability, Effectiveness, and Safety of Desiccated Thyroid vs. Levothyroxine: ARebuttal to the British Thyroid Association. Lowe J. Thyroid Science 4(3):C1-12,2009.
P = Pure Full Ingredient List:1. USP NDT Powder2. Inulin (Jerusalem Artichoke)3. Medium Chain Triglycerides (Coconut)
OTC Thyroid GlandularsNot a viable option - Recent assay done on 10 OTC thyroidsupplements - amount of active hormone ranged from zero to 91.6mcg T4, and zero to over 10 mcg T3.Prior independent assays found similar variabilitys both from productto product and from batch to batch with the same productsVictor Bernet MD, Mayo Clinic, presented for ATA
OTC Thyroid Glandulars•Dietary thyroid powders can be derived from ANY animal –including pigs (as there are no “exclusions”)•Per FDA/FTC – Dietary supplement companies CANNOT claim thatthere are ANY presence of ANY hormones in the powder/product
OTC Thyroid Glandulars•Most reputable companies indicate that the powder is “Thyroxin-Free” to denote differentiation between dietary vs.. prescription, yet noknown t4 removal mechanism•Any claim as such would be making a drug reference to a dietarysupplement which is against the FTC and FDA law•When tested, consistencies of hormonal values greatly varied frombatch to batch (much more beyond USP reference for RX version)
Value Median Min. MaxTSH 0.99 0.36 1.91 fT3 2.69 1.99 3.17 fT4 0.93 1.09 1.9
Free T3 / Free T4 RegulationTSH = Central control of thyroid hormones.fT4 / fT3 = Peripheral control of thyroidhormones
Free T3 / Free T4 Regulation•TSH relative to fT3/fT3 is non-linear at the extremes•Adjusting T4 or T3 intake separately will not correct this . . .• . . . unless peripheral regulation becomes overwhelmed.
Reverse T3 - Issues•Fatigue•Difficulty losing fat•Brain Fog•Muscle aches•Increased with chronic illness CF/FM•Increased with yo-yo dieting•Increased with heavy metals, infections, mental and physical stress
Managing Reverse T3 High rT3 = Euthyroid Sick Syndrome rT3 is the body’s attempt to deliberately slow metabolism like a block under a gas pedal.
(Peripheral Metabolism of Thyroid Hormones Kelly G. Altern Med Rev 2000;5(4):306-333) 108
Reverse T3 ManagementExcess cortisol blocks T4 to T3 conversion and increases T4 to rT3◦ Test Diurnal salivary levels of cortisol and correct◦ Correct the reasons for poor conversion – nutritional deficiencies, toxins, medicationsGrowth Hormone increases T3 production◦ Oral estrogen inhibits growth hormone; change to transdermal if appropriate◦ Modify lifestyle (exercise, sleep) and nutrition to increase natural growth hormone production
Physiologic DosingReplacement doses of thyroid within the amount of thyroidhormone normally secreted by healthy adults or the typicalmaintenance dose of individuals post thyroidectomy.• Most common ending dose = 1.5 – 2.25 grains NDT• Typical range of ending dose = 0.75 – 2.5 grains• Very rarely need doses above 2.5 grains (0.3% of patients)• Best dose increase rate = ¼ grain increments per 4-6 weeks
Supraphysiologic DosingReplacement doses of thyroid that exceed the full amount ofthyroid hormone secreted by healthy adults or the typicalmaintenance dose of individuals post thyroidectomy.Paradox of Hypothyroid symptoms when on supraphysiologicdoses
Supraphysiologic DosingEstimates of average normal secretion for euthyroid humans are 94-110 µg T4 and 10-22 µg T3 daily.This equals roughly 150-200 mcg of T4, 30-50 mcg of T3,1.5 - 2 grainsof NDT.Doses above these are supraphysiologic and rarely indicated.[Evidence Level B, Clinical Trial]Fisher, D. A., Oddie, T. H. & Thompson, C. S. (1971) Thyroidal thyronine and non-thyronine iodine secretion in euthyroidsubjects. J. Clin. Endocrinol. Metab 33: 647-652.
Supraphysiologic DosingCase report – NP ‘Allison’ 34 yo female, teacher. 7 year history ofhypothyroidism per labs, 3 year history of treatment. On NDT, frustrated because only times she was free of fatigue and brain fogwas when TSH <0.1. Hashimoto’s came on after 4 month viral illness.Treated repeatedly w/ antibiotics w/o success. Hx lymphocytosis eversince.Well received conversation regarding short term and long term goals.
Supraphysiologic DosingCase report – longer term patient ‘Amy’ 38 yo female, 3 year historyof debilitating fibromyalgia. Mixed responses to therapies, nonedramatic. Hypothyroid, stable on blood levels. Patient read MetabolicTreatment of Fibromyalgia and wishes to pursue intentionalsupraphysiologic dosing.Complication: Graves eye disease, lost to follow up.
Testing SchedulesInitial Retest - 6 weeks. Fasting, pre-AMthyroid dose: •TSH •Chem panel •Other significant abnormals Note that TSH may still drift by 25% more than it’s initial change before stabilizing.
Testing SchedulesSecond Retest – 3 Months. Fasting, pre-AMthyroid dose:•TSH, free T3, free T4, rT3•Chem panel, Cortisol•Other significant abnormalsNote that TSH may still drift by 25% morethan it’s initial change before stabilizing.
Testing SchedulesThird Retest – 6 months. Fasting, pre-AM thyroiddose: •Ultrasound if initial abnormal •TSH •Chem panel, Cortisol •Other significant abnormals Note that TSH may still drift by 25% more than it’s initial change before stabilizing.
Thyroid Dosing Summaries•Optimal TSH = 0.4 – 1.5•Optimal TSH with structural issues orcancer history = 0.4 – 0.9•fT3/fT4 related to peripheralmetabolism•rT3 related to metabolic stressors
Thyroid nutrients - TyrosineFound in most protein foods, especially:• Meats• Dairy• Fish• Eggs• Peanuts
Vitamin DActive Hashimoto’s Thyroiditis have vitamin D levels that are about halfof unaffected controls16 ng/ml versus 29 ng/ml92% to 63% = p <0.0001Tamer G. Relative Vitamin D Insufficiency in Hashimotos Thyroiditis. Thyroid.2011 Aug;21(8):891-6.
Thyroid Nutrients - IronLow ferritin ◦ Required for transport of T3 to nucleus of cell and utilization of hormone◦Optimal level for thyroid function is 60-110
Iodine – Case Report‘Bob’ 65 year old male, extremely educated and involved in health.Long term seasonal patient, ‘snow bird.’Early in winter new symptoms: sudden onsetanxiety, palpitations, insomnia, night sweats.
Iodine – Case ReportExam: thyroiditis + new nodule.Serology: TSH 0.01, fT3 8.2, fT4 3.0 Bob’s thyroid uptake scan:
Iodine – Case ReportBob’s Diagnosis: Toxic Nodular GoiterTypical onset in American elderly males is after iodine contrast exposure orafter amiodarone.Bob had neither but was taking 25 mg Iodoral daily after being found to be‘iodine deficient’ after an iodine challenge test.
Iodine – Case ReportSarah: 33 yo female, vegetarian, newly diagnosed hypothyroid. FHx neg.TSH 6.3; nml 0.5 - 4.50 mIU/LfT3 5.2; nml 1.4 – 4.2 pg/mLfT4 0.8; nml 0.8 -2.8 ng/dLThyroglobulin 97; nml </= 60 ng/mlThyroid Ab negThyroid exam negSarah had begun taking 12.5 mg Iodoral tablets 1 month prior in hopes for helpwith weight loss.
Iodine RequirementsSafe Upper Limit for Adults without ATD = 1100 mcg daily Adapted from Food and Nutrition Board, Institute of Medicine 2001 Dietary reference intakes. National Academy Press, Washington, D.C.
U-Shaped Curve of Iodine Intake and Thyroid Disease100 µg/l urinary iodine ≃150 mcg daily adult intakeImage Source: Comprehensive Handbook of Iodine Ed. Preedy V. Burrow G, Watson R. Elsevier 2009. Alan Christianson, NMD
Optimal Iodine Intake 30 healthy, elderly adult females, without evidence of thyroid peroxidase antibodies (TPA), received daily doses of 500 μg I/day (as potassium iodide) for 14 or 28 days (Chow et al. 1991). Serum concentrations of FT were significantly decreased (change from 4 pretreatment level, approximately -1 pmol/L) and serum TSH concentrations were significantly increased http://www.atsdr.cdc.gov/toxprofiles/tp158.pdf
Optimal Iodine Intake The results of several epidemiological studies suggest that chronic exposure to excess iodine can result in or contribute to hypothyroidism. Thyroid status was compared in groups of children, ages 7–15 years, who resided in two areas of China where drinking water iodide concentrations were either 462 μg/L (n=120) or 54 μg/L (n=51) (Boyages et al. 1989; Li et al. 1987). Although the subjects were all euthyroid with normal values for serum thyroid hormones and TSH concentrations, TSH concentrations were significantly higher in the high iodine group. The prevalence and severity of goiter in the population were evaluated, the latter based on a goiter severity classification scale (Grade 0, no visible goiter; Grade 1, palpable goiter that is not visible when the neck is not extended; Grade 2, palpable and visible goiter when the neck is not extended). The high iodide group had a 65% prevalence of goiter compared to 15% in the low iodine group.
Optimal Iodine Intake Subjects were from one of three regions where, based on reported urinary iodine levels of 72, 100, or 513 μg I/g creatinine, the iodine intakes were approximately 117, 163, or 834 μg/day (1.7, 2.3, or 12 μg/kg/day for low, n=119; moderate, n=135; or high intake, n=92, respectively). The prevalence of serum TSH concentrations above the normal range was 4.2, 10.4, and 23.9% in the low, moderate, and high iodine groups, respectively. The prevalence of elevated serum TSH concentrations together with serum FT concentrations below the 4 normal range was 0.95, 1.5, and 7.6% in the low, moderate, and high iodine groups, respectively.
Optimal Iodine Intake People who have autoimmune thyroid disease may be at increased risk of developing thyroid dysfunction when exposed to excess iodide. Euthyroid patients (37 females, 3 males) from an iodine-deficient region, who were diagnosed with Hashimoto’s thyroiditis and who were positive for antithyroid (thyroid peroxidase) antibodies, received an oral dose of 250 μg potassium iodide (190 μg I/day) for 4 months; a similar group of thyroiditis patients (41 females, 2 males) served as controls (Reinhardt et al. 1998). Based on urinary iodide measurements of 72 μg I/g creatinine before the iodide supplementation, the preexisting iodide intake was approximately 125 μg/day, for a total iodide dosage of 375 μg/day (5.8. μg/kg/day) in the treatment group.
Optimal Iodine Intake Seven patients in the treatment group developed elevated serum TSH concentrations (>4 mU/L) and one patient developed overt clinical hypothyroidism with a TSH concentration of 43.3 mU/L and a serum FT concentration of 7 pmol/L. One patient in the treatment group became4clinically hyperthyroid with a serum FT concentration of 30 pmol/L and TSH 4 concentration of <1 mU/L. One patient in the control group developed mild subclinical hypothyroidism.
Iodine Toxicology – Largest Resource http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=479&tid=85
Iodine in NDT 0.17-0.23% Iodine1 grain of Desiccated Thyroid contains: 0.20% x 60mg = 120µg Iodine
Assessment of Iodine Status•Thyroid Size•Thyroid Serology•Random Urinary Iodine•Topical Iodine•24 hour Urinary Iodine•24 hour Urinary Iodine Post Iodine Challenge•Serum/Blood spot Thyroglobulin - poor w/ TG Ab
Assessment of Iodine StatusThyroid VolumeVia Ultrasound or skilled examiner. Volume inversely correlates with iodinestatus.Accurate only in the absence of autoimmune disease, thyroiditis or thyroidcancer.Not practical as screening method. Alan Christianson, NMD
Assessment of Iodine StatusThyroid SerologyHelpful to measure as part of routine assessment.Does predict iodine status in the absence of:•Autoimmune thyroid disease•Anemias•Environmental toxins•Infections
Assessment of Iodine StatusFrom Preedy V, Burrow G, et al. Comprehensive Handbook of Iodine. Elsevier. 2009. pg 51.
At risk for Iodine Insufficiency - VegansMain sources of iodine: Seafood, Dairy, Iodine fortified salt.Along with avoiding animal foods, many vegetarians andvegans use specialty sea salts which are predominately non-iodized.Those with over 33% of their calories from raw foods areespecially at risk due to low iodine intake and concomitanthigh intake of goitrogens and phytates.
Iodine ToxicityIodine toxicity occurs in three different ways:• Simple chronic overexposure in excess of 1100 mcg.• From an increase of iodine in a population with a previously stable butlow intake. This can be a change as little as 150 mcg. Most pathologyoccurs in those with latent thyroid antibodies.• A single bolus dose, usually in excess of 10,000 mcg. Merck Manual Last full review/revision August 2008 by Larry E. Johnson, MD, PhD Content last modified August 2008
Iodine ToxicityNatural products with unsafe levels of iodine:• Kelp: AKA Fucus vesiculosus, Kombu• Iodoral: 12,500, 25,000 and 50,000 mcg tablets• Potassium Iodine, AKA SSKI, NoRad
Iodine Toxicity - the Japan QuestionDon’t the Japanese consume much more iodine than us and do finewith it?It has been specifically claimed that the Japanese safely consume13,800 mcg daily and enjoy less thyroid disease.. . . They don’t consume close to this much, but they do consumemore iodine than we do, and they have proportionately higher ratesof all types of thyroid disease.
Iodine Toxicity - the Japan QuestionSource of the 13800 mcg intake was a 1967 paper stating average Japaneseconsumed 4.6 grams of seaweed daily. This number was used with a 0.3% iodinecontent of seaweed from another source to get the 13,800 mcg.Yet the 4.6 grams daily was wet weight of seaweed. While the 0.3% iodine wasfor dry seaweed.J Clin Endocrinol Metab 1967; 27:638-47Alan Gaby, MD, lecture notes, AANP 2011.
Iodine Toxicity - the Japan QuestionThe average Japanese adult consumes 1200 mcg of iodineper day based on 2008 data.Over four times the typical American intake.Large amounts of seaweed is considered to be the largestreason.Shigenobu Nagataki. Thyroid. June 2008, 18(6): 667-668.doi:10.1089/thy.2007.0379.
Iodine Toxicity - the Japan QuestionAfter controlling for radiation exposure, the Japanese experience higher rates ofall types of thyroid disease including:•Hypothyroidism•Hyperthyroidism•Subclinical hypothyroidism•Subclinical hyperthyroidism•Goiter•Nodules•Thyroid cancer.Koike, A. and Naruse, T. (1991), Incidence of thyroid cancer in Japan. Seminars in Surgical Oncology, 7: 107-111.Kanji Kasagi, Norihiro Takahashi, Gen Inoue, Toyohiko Honda, Yasunori Kawachi and Yoichiro Izumi. Thyroid.September 2009, 19(9): 937-944. doi:10.1089/thy.2009.0205.
Iodine Guidelines For All Adult Patients•Consume primarily iodized salt in the form of iodizedsea salt or iodized Lite Salt (Potassium chloride/SodiumChloride blend)•Minimize salt from packaged and restaurant foods•Maintain Iron status•Consume 200 - 400 mcg selenium daily•Avoid iodine supplements
Iodine Guidelines For Patients with Thyroid Disease•Avoid daily iodine intake above 600 mcg combined from allsources.•Avoid kelp products•If taking desiccated thyroid, consider iodine-free multivitamins and avoiding all sea vegetables
Referenced peer reviewed article on Iodoral: Iodine, not too much, not too little. Published in NDNR July 2009 http://alturl.com/7usy3
Optimal NutritionTHYROID SPECIFIC TOPICS
Goitrogens•Goitrogens are chemicals that can block thyroidal iodine utilization orimpair hormone production.•These occur through distinct mechanisms, not all of which have clinicalsignificance
Goitrogens•This is most pronounced in indole compounds as found in cruciferousvegetables (cabbage, broccoli, cauliflower, and Brussels sprouts).•Soy and millet are often categorized as a goitrogens but their effects areindependent of iodine status.•Goitrogens are not of clinical importance unless they are consumedraw, in large amounts or with coexisting iodine deficiency.
Goitrogens•Jake was a previously healthy young man who was brought to mypractice by his father who was concerned that he was getting apatheticand weak and was having difficulty swallowing. Several months earlierJake embarked on a 100% raw produce diet. Jake went from a lean 170pounds to an emaciated 152 pounds.•His meals consisted mostly of blended raw vegetables with smallamounts of fruit. This made it easy for him to consume 3-5 pounds ofbroccoli a day.
GoitrogensFindings:• Iron and B-12 deficiencies• Non autoimmune Hypothyroidism• Homogenous goiterTreatment• Resumed low mercury fish and sea vegetables• Avoided raw cruciferous vegetables above 6 ounces.• Avoided soy foods and millet.
Goitrogens – Action StepsAvoid for all thyroid patients:• Soy• Fermented soy (?)• MilletSafe for those with Hashimoto’s• Cruciferous• Flax• Lima
Celiac Thyroid Connectionsthe prevalence of celiac disease in patients with autoimmune thyroid disease is approximately 4-15 timeshigher than the general population, thus suggesting that patients with autoimmune thyroid diseaseshould be routinely screened for celiac disease. However, the performance of these screening programshas never been evaluated in everyday, clinical-practice setting. We invited newly diagnosed patients withautoimmune thyroid disease, seen at our Hospital, to participate in a serological screening for celiacdisease. Two-hundred and thirty-one patients, female to male ratio 8.89:1, mean age 41.3 +/- 18.1years, range 7.1-80.5 years were included. The number of diagnosed celiac disease was 0. Our results donot support the usefulness of a screening for celiac disease in patients with autoimmune thyroid diseasein daily practice, despite the favorable results obtained in Research-setting studies. Since screening is aresource-consuming activity, for both patients and clinicians, we suggest that a careful evaluation of theyield of a screening is always warranted before its adoption in the clinical practice.Ann Ital Med Int. 2005 Jan-Mar;20(1):39-44.Screening for celiac disease in patients with autoimmune thyroid disease: from Research studies to dailyclinical practice.
Celiac Thyroid ConnectionsThyroid. 2008 Nov;18(11):1171-8. doi: 10.1089/thy.2008.0110.Tissue transglutaminase antibodies in individuals with celiac disease bind to thyroidfollicles and extracellular matrix and may contribute to thyroid dysfunction.CONCLUSIONS:Anti-TGase II antibodies bind to TGase II in thyroidtissue, and titers correlate with TPO antibody titers.These findings suggest that anti-TGase II antibodiescould contribute to the development of thyroid diseasein celiac disease.
Celiac Thyroid ConnectionsAmong autoimmune disorders, increased prevalence of CD has been found inpatients with autoimmune thyroid disease, 2% to 5% in autoimmune thyroiddisordersCeliac disease and autoimmune thyroid disease.Ch’ng CL, Jones MK, Kingham JG. Clin Med Res. 2007 Oct;5(3):184-92.
Celiac Thyroid Summary• No one thrives on processed wheat• No one thrives on gluten-free junk food • Your patients capacity for change is a finite commodity • Be strategic with it
Thyroid Nutrition–Action Steps• Thyroid Friendly Multi (Fe, Iodine free, CCM)• Screen for Celiac• Screen MTHFR• Avoid Soy• Minimize Iodine
Thyroid imaging: Nodules and beyondJane Sohn, M.D.
Dosing Other Nutrition glands Toxicology ImmunologySection 5THYROID IMMUNOLOGY
Thyroid antibodies•Antibodies can cause symptoms independent of thyroid hormones • Anxiety • Brain fog•Antibodies can raise medical risks independent of thyroid hormones • Miscarriage • Thyroid cancer Obstetrics and Gynecology 1997 Volume 90:364-369
Thyroid Antibodies•Antibodies can cause symptoms independent of thyroid hormones • Anxiety • Brain fog•Antibodies can raise medical risks independent of thyroid hormones • Miscarriage • Thyroid cancer•Antibody tests can be falsely negative up to 40% of the time Obstetrics and Gynecology 1997 Volume 90:364-369
Immunologic FactorsTH-1 / TH-2 Dominance•Immune dysfunction of several types can trigger Auto Immune Thyroid Disease•Immune dysfunction can be identified by testing key cytokines including•IL-2, IL-12, TNFα, Interferon, IL-4, IL-13, IL-10•Natural and prescription medicines can be used to influence immune cells.•Ultimately, the cause of immune dysfunction needs to be identified and addressed.•Prime causes include allergies, infections, toxins and deficiencies.
Immunologic Factors - AllergiesAirborne•Airborne allergies involve up-regulation of antibody formation•Antibody formation against any specific antigen heightens the antibody response against other antigens against which the host is already sensitized•Consequently lowering ‘total antigenic load’ and reactivity to one antigen can confer greater tolerance to other antigens
Immunologic Factors - AllergiesCase Study: Fredrique, 41 year old female•Over a 4 month period, Fredrique’s TSH scores ranged from 41 – 158 despite thyroid dose modifications and other steps•Her TPO antibodies during this time were never lower than >1000•After 4 months of SLIT, TPO antibodies lowered to 41•TSH was able to be brought to 1.7
Immunologic Factors - AllergiesDietary•Food allergies involve up-regulation of antibody formation and alterations in bowel flora•Food allergies can be: • Not relevant • Innate • Functional
Immunologic Factors - AllergiesDietary•Heightened antibodies from food allergies can raise thyroid antibodies and effect whole body inflammation effecting peripheral thyroid metabolism•Food allergies can be assessed by • Testing • Elimination – Reintroduction Diets
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Immunologic Factors - Allergies•Gluten can be culprit but not alwaysCase Study: Monique, 31 year old female•Gluten-free for 2 years•TPO antibodies never lower than >200•Testing showed Dairy, Almonds to be allergenic•After 6 months of allowing ‘healthy’ version of gluten and avoiding reactive foods, TPO antibodies became negative
EBV andThyroidSteps to AutoimmuneThyroiditis: (1) CD8+ T-celldeficiency, (2) primary EBVinfection, (3) decreased CD8+ T-cell control of EBV, (4) increasedEBV load and increased anti-EBVantibodies, (5) EBV infection inthe target organ, (6) expansionof EBV-infected B cells in thetarget organ, (7) infiltration ofautoreactive T cells into thetarget organ, and (8)development of ectopiclymphoid follicles in the targetorgan.http://www.hindawi.com/journals/ad/2012/189096/
Immune Repair for Hashimoto’s•History of known food intolerance, IBS, malabsorption, consider dietary allergies:•Key Labs: IgG panel (plan divided samples)•Treatments: • Avoidance • NAG / Glutamine • GI Antihistamines
Are YourPatientsToxic?Some ThingsYou JustWon’t KnowUnless YouLook!
Mercury – TG AntibodiesAbstract . . . associations between total blood mercury and thyroglobulin autoantibody antibodypositivity and thyroid peroxidase autoantibody positivity in . . . Women . . . (n=2047). Relative towomen with the lowest mercury levels (≤0.40 μg/L), women with mercury >1.81 μg/L (upperquintile) showed 2.24 (95% CI=1.22, 4.12) greater odds for thyroglobulin autoantibody positivity(p(trend)=0.032);this relationship was not evident for thyroid peroxidase autoantibody positivity. Results suggestan association between mercury and thyroglobulin autoantibody positivity.http://www.ncbi.nlm.nih.gov/pubmed/22280926
Environmental FactorsPCB’s Suppress T4 and raise TSHMETHODS:The sample consists of youth from the Akwesasne Mohawk Nation (n=232) who reside inproximity to several industries that have contaminated the local environment. We used multipleregression analysis to examine the effect of PCB groupings, p,p-DDE, HCB, lead, and mercury onthyroid hormones after adjusting for sociodemographic covariates and controlling for all othertoxicants.RESULTS:Exposure to PCBs affects the thyroid hormone profile in adolescents. The group of persistentPCBs was positively associated with TSH but inversely related to FT(4). Nonpersistent PCBs weresignificantly and negatively related to FT(4) only.http://www.ncbi.nlm.nih.gov/pubmed/18560538
Environmental FactorsThiocyanateAbstractThiocyanate [SCN-] is a complex anion which is a potent inhibitor of iodide transport. It is thedetoxification product of cyanide and can easily be measured in body fluids. Consumption ofnaturally occurring goitrogens, certain environmental toxins and cigarette smoke cansignificantly increase SCN- concentrations to levels potentially capable of affecting thethyroid gland.. Iodine supplementation completely reverses the goitrogenic influence of SCN-. SCN- is also generated from cigarette smoking as a detoxifying product of cyanide. Duringthe past two decades many reports dealt with the possible effects of cigarette smoking onthyroid hormone synthesis, thyroid gland size and thyroid autoimmunity including infiltrativeophtalmopathy of Graves disease.http://www.ncbi.nlm.nih.gov/pubmed/14757960
Environmental FactorsBisphenol AAbstractThe globally escalating thyroid nodule incidence rates may be only partially ascribed to betterdiagnostics, allowing for the assessment of environmental risk factors on thyroid disease.Endocrine disruptors or thyroid-disrupting chemicals (TDC) like bisphenol A, phthalates, andpolybrominated diphenyl ethers are widely used as plastic additives in consumer products. Thiscomprehensive review studied the magnitude and uncertainty of TDC exposures and theireffects on thyroid hormones for sensitive subpopulation groups like pregnantwomen, infants, and children. Our findings qualitatively suggest the mixed, significant (α = 0.05)TDC associations with natural thyroid hormoneshttp://www.ncbi.nlm.nih.gov/pubmed/22690712
Environmental Factors – SpecificSteps•UTM post challenge – treat specifically•Repeat results can be non-linear•Mineral replacement
Environmental Repair forHashimoto’s•History of chemical sensitivity (detergent aisle), neurologic symptoms, high exposure, consider Toxicology•Key Labs: • UTM • Chem (low Uric Acid, ALT) • RBC elements • PCBs • Bowel Transit Time • Urine specific gravity (hydration)
Environmental Repair forHashimoto’s•Treatments: • Avoidance • General Detox • Cleansing diet / Medical Food • Sauna • Maintain elimination • Spinach + Brown Rice • Cholestyramine • Targeted Chelation Therapy
Dosing Other Nutrition glands Toxicology ImmunologySection 7ENDOCRINE CONNECTIONS
Thyroid / Endocrine InteractionsKey Hormones with thyroid Interactions:•Cortisol•DHEA•Estradiol•Pregnenolone•Progesterone•Testosterone
Thyroid / Adrenal Interactions – Paradox of CortisolCellular Thyroid Function Functional Functional Hypometabolism Hypometabolism Optimal Thyroid Function Physiological Cortisol Range Cortisol
Thyroid / Adrenal Interactions Excess cortisol ◦ Inhibits T4 to T3 conversion ◦ Suppresses TSH ◦ Decreases thyroid receptor responsiveness Low cortisol ◦ Decreases thyroid receptor responsiveness ◦ May inhibit T4 to T3 conversion ◦ Transport across the membrane is energy dependent & modified by cortisol ◦ Cortisol regulates T3 receptor density ◦ May have to give cortisol to make thyroid supplementation work properly
Thyroid / Endocrine - Cortisol•Excess cortisol: inhibits actions of T2 and T3 onmitochondria•Low cortisol: cell membranes becomeinconsistently permeable to T3•Hypoadrenalism = absolute contraindication tothyroid replacement therapy
Thyroid / Endocrine - Cortisol•Suspect when: Fatigue, hypotension, salt craving•Test via: Combination of blood and saliva (confirmation)•Ideal Levels: Serum AM Fasting before 9 AM = 12-20 ng/dl
Thyroid / Endocrine - CortisolSalivary Cortisol is now done by major regional labs(Quest Diagnostics and Lab Corp)Measurement of salivary cortisol in 2012 - laboratory techniques and clinical indications.. . . Several studies have shown diagnostic sensitivities and specificities of over 90%, . . .. . . There are emerging roles for the use of salivary cortisol in diagnosing adrenalinsufficiency, particularly in conditions associated with low cortisol-binding globulin levels, andin the monitoring of glucocorticoid replacement. . . salivary cortisol has been used extensively as a biomarker of stress in a researchsetting, especially in studies examining psychological stress with repeated measurements.http://www.ncbi.nlm.nih.gov/pubmed/22812714
Thyroid / Endocrine - Cortisol The Journal of Clinical Endocrinology & Metabolism May 1, 2011 vol. 96 no. 5 1478-1485
Thyroid / Endocrine - Cortisol Action steps when abnormal:•Meditation – 10 minutes: http://alturl.com/g9tsm•Hourly Movement Breaks: http://alturl.com/5p6mu•Acupuncture•Glycemic Control•Avoidance of stimulants (Slow clearance with Hashimoto’s)•Sleep Hygiene•Cortisol replacement rarely conducive to long-term health in non- Addison’s population
Thyroid / Endocrine - DHEA•Thyroid Interactions: Can weakly potentiate thyroid hormones – may need dose modification•Suspect when: Adrenal dysfunction, fatigue, hypoglycemia, thinning of body hair, poor libido, female androgenic symptoms (excessive)•Test via: Serum•Ideal Levels: ◦ Female Adult – 80 – 260 mg/dl ◦ Male Adult – 220 – 515 mg/dl
Thyroid / Endocrine - DHEAAction steps when abnormal: Gender High Low Female Glycemic management, Stress reduction, Dietary weight loss, ovarian protein increase, function management Replacement therapy (2.5 – 10 mg) Male Rare – Cushings, Stress reduction, Dietary protein increase, Replacement Therapy (5 – 50 mg)
Thyroid / Endocrine - Pregnenolone•Thyroid Interactions: Lack of can weekly inhibit utilization of thyroid hormones•Suspect when: Adrenal symptoms + short term memory issues•Test via: Serum•Ideal Levels: • Female Adult – 30 – 180 ng/dl • Male Adult – 45 – 280 ng/dl
Thyroid / Endocrine - PregnenoloneAction steps when abnormal: Gender High Low Female Rare - Cushings Stress reduction, Dietary protein increase, Replacement therapy (10 – 50 mg) Male Rare – Cushings, Stress reduction, Dietary protein increase, Replacement Therapy (50 – 200 mg)
Thyroid / Endocrine - Progesterone•Thyroid Interactions: Progesterone potentiates uptake and conversion of thyroid hormones•Suspect when: Insomnia, anxiety, irregular cycles • PMS • PCOS • Peri-menopause • Menopause•Test via: Serum days 17-23 for menstruating women•Ideal Levels: 8 – 20 ng / dl (~1/10 Estradiol)•Action steps when abnormal: • Low: Replacement oral micronized or topical (lack of endometrial effect topical) • High: Liver function, DIM, Bowel flora regulation
Thyroid / Endocrine - Testosterone•Thyroid Interactions: • Lack of can weaken efficacy of endogenous and exogenous thyroid hormones • Replacement can increase efficacy of endogenous and exogenous thyroid hormones•Suspect when: Fatigue, Poor Libido, Low exercise recovery, Tendonitis, Lack of enthusiasm•Test via: Serum (consider free and bioavailable)•Ideal Levels: • Female Adult: 40 – 90 ng/dl • Male Adult: 450 – 850 ng/dl
Thyroid / Endocrine - TestosteroneAction steps when abnormal: Gender High Low Replacement Female Glycemic Stress reduction, IM / Subdermal – management, Dietary protein 16 – 50 mg / weight loss, ovarian increase, Strength Month function Training management Male Rare – Cushings, Stress reduction, IM / Subdermal – Sleep Hygiene, 200 – 400 mg / Strength Training, Month Dietary protein increase
Thyroid / Endocrine – Estradiol•Thyroid Interactions • Exogenous and Endogenous Estradiol increases thyroid binding globulin, lowering the effects of thyroid hormones • Decrease of Estradiol potentiates thyroid hormones. Consider when discontinuing NHRT or OCP•Suspect when: • PMS • Perimenopause • Menopause • Male on Testosterone replacement therapy•Test via: Serum
Thyroid / Endocrine - EstradiolAction steps when abnormal:Gender Blood levels High Low ReplacementFemale Menstruating Hepatic Stress reduction, w/o uterus: IM / (day 17-23) Function, lower Dietary protein Subdermal – 3 – 65 – 200 pg/ml sugar increase, 8 mg / Month, Strength Training w/ uterus NHRT: 45-130 consider pg/ml testosteroneMale 10 – 35 pg/ml Generally Stress reduction, n/a complication of Sleep Hygiene, TRT – dose Strength modification Training, Dietary protein increase
Thyroid / Endocrine – IGF-1•Thyroid Interactions: Lack of may slow T4 to T3 conversion in liver.•Can be cancer risk factor when elevated•Suspect when: • Poor immunity • Poor skin repair • Poor exercise recovery • Fatigue • Low cognitive function • Unexpected osteoporosis•Test via: Serum AM Fasting
Thyroid / Endocrine – IGF-1Action steps when abnormal:Gender Blood levels High LowFemale 100 – 250 pg/ml Glycemic control Sleep Hygiene, HIIT, Testosterone, secretogoguesMale 110 – 295 pg/ml Glycemic control Sleep Hygiene, HIIT, Testosterone, secretogogues
Section 8CASE REVIEW – Q AND A
Participant Case Review #139yo femaleHistory: trip abroad in 07-unwittingly contracted multiple microbes. Within a few months of returnhome became pregnant. Family history of Hashimotos.09 finally diagnosed w/microbes after multiple visits to multiple doctors. After treatment of microbesby natural means she was rid of all but one microbe which she still has; Blastocysts Hominus-evenafter hi dose Flagyl for 2wks population didnt budge but liver enzymes went out of range.Fatigue was still very present and she knew her family history and requested TPO and TSH-TPO was offcharts and remains so to this day. TSH was at 32 for years with other practitioner.
Participant Case Review #1con’t Shes finally medicated but not leveled yet. Last TSH 3wks ago was 8 and TPO remains at <1,000. Dosed up from Levothyroxine 125mcg to 137mcg On Levothyroxine 137 x 3wks. Retest in 5wks. She observes a gluten free dairy free organic diet. Low grain high veg medium amount of meat protein. We are working at building gut/immune system and slow steady detox-liver function normal again. Recent investigations into heavy metal shows mercury and she is seeing a biological dentist for amalgam removal by Huggins protocol. Then we will begin heavy metal detox slowly. Also one root canal tooth on thyroid meridian and she will have that extracted prior to amalgam removal.
Participant Case Review #239 year old female Diagnosed with Hashimotos age 26.Age 26-31 gained 80 lbs. and was on Levothyroxine. 5-10 mcg cytomel was added for a year or two . Wassuffering from fatigue and depression since diagnosis and was given Citalopram, then Wellbutrin. StoppedWellbutrin on her own and fatigue returned.Tried blood type diet and eliminating gluten in 2005, no change noticed.Went to see Dr. XXXX in 05/06. Dr. XXXX put her on Naturethroid, titrated dose using ThyroFlex andRMR, and optimal dose was between 3.5-4g QD in divided doses. Also treated adrenals. Initially lost 25 lbs.after the change of meds. Did well for a long time on this dose but weight continued to creep back up.TSH must be kept suppressed to feel normal. When TSH approaches normal range is not functional- hasdepression and apathy, fatigue, brain fog, and sleeps all the time. Adrenals tested, were within normal rangewith a dip around noon that was treated. Stopped doing thyroid labs, feels best with Free T3 above normalrange, TSH stays around .02, TPO stays around 3-400 and TG stays around 50. Docs always try to reduce herthyroid dose, so she self- treats
Participant Case Review #2 cont.Difficulty losing weight, and when she has hypo symptoms, her weight can increase by up to 6 lbs.overnight. Did hCG diet and successfully lost 75 lbs. over a year, after which she developedcholecystitis. After this, she stopped gluten, dairy, eggs and notices edema on eating gluten and othergrains. Re-gained about 50% of weight.Irregular menses X 10+ years, more recently cycles last from 10- 45 days, often has a “double period” about9-10 days apart. Hormones, when tested, showed low normal progesterone and estradiol.Chronic fatigue, chronic tonsillitis, chronic BV, acne, extensive dental work, and gums bleed around crowns.Chronic tonsillitis treated + prevented successfully by daily lymphatic tincture. Menses improving withbiphasic botanical formula, but continues to be erratic. Skips menses when hypo symptoms return.Currently planning to do food sensitivity testing.March 2012 started T3SR only therapy. Went to a max dose of 70 mcg BID and stayed there for ayear. Initially lost about 10 lbs. and energy/mood improved significantly. After about 9 months, hyposymptoms began returning, weight went up 10 lbs., bowel movements slowed, and depression had beenreturning since 12/12. FT3 in 01/14/13 was 4.5. She didn’t respond to an increase in T3 at this time.
Participant Case Review #2 cont.In 03/13 switched back to NT 3g in divided doses, depression lifting and energy returning. Notices worseningof fatigue and depression in winter, October-May.ANA done about 10 years ago was +, homogenous, RF negative+ MTHFR Mutation : heterozygous for C677T+ COMT Mutation : Heterozygous+ TNF-a heterozygousHomozygous negative for Interleukin-6Recently hypo symptoms accompanied by arthralgias (fibromyalgia-type symptoms), diminished with switch ofmedication.
Participant Case Review #2 cont.No change on Thyrosol or Thyrocsin, had some initial improvement on iodine and took for a few monthsbefore stopping. Restarted and had no results. Some improvement with Beta-carotene/Vitamin Asupplementation. Considerable improvement on Xymogen’s Mitochondrial Renewal Kit (especially the L-Arginine) in energy and exercise tolerance. Considerable difficulty with detoxification protocols(fatigue, irritability, headaches). Does best on Paleo-type diet.Meds:NatureThroid 2g QAM, 1g QPMProgesterone: 25 mg dailySupplements:Flax oil 2 Tbsp. QDNutrient IV monthly (50g Vitamin C, high dose Bs, and minerals)5-MTHF 1-2g QD100b CFU probioticMetagenics Kaprex AIBiphasic botanical formula with daily phytolacca, iris, and ocimum sanctumVitamin D3: 10K IU daily
Participant Case Review #344 Year old female with symptoms of anxiety, racing heart, insomnia and weight gain.Labs confusing:TSH 0.2 (low)Free T4 1.2 (normal)Free T3 3.3 (normal)Anti TPO Antibodies: 97 (elevated)Endocrinologist says she may have Hashimoto’s but can’t be treated until her thyroid slows down enoughSupplements:Thyroid supportFish OilWomen’s multivitaminL-CarnitinePassofloria tincture
Participant Case Review #432 Year old maleFatigue, depression weight gainTSH 1.9Thyroid antibodies negativeFree T4 1.1 (normal)Free T3 3.5 (normal)Endocrinologist says she may have Hashimoto’s but can’t be treated until her thyroid slows down enoughSupplements:Thyroid supportFish OilWomen’s multivitaminL-CarnitinePassofloria tincture
Participant Case Review #554 year old female12 year history of hypothyroidism without HashimotosOn Armour thyroid 120 mg and cytomel 5 mg to help low t3 levelsLabs all over the boardTsh 0.001Free t3 3.9Tsh 0.1Free t3 2.9Tsh 0.02Free T3 2.8Why wont her t3 levels go up, why are her labs so inconsistent?
Participant Case Review #6* I directly responded instantly on this case28 year old woman, pregnant for last 6 weeksOn synthroid 112 mcgIodoral 12.5 mgPrenatal vitaminsShe is always tired and anxiousHer tsh goes too low without IodoralWith it she can take a higher dose of synthroid and feels better(Reference iodine w preg cases)
Iodoral in Pregnancy Leads to Congenital Hypothyroidism - 3 Recent casesCase 1 is a term infant with CH; TSH = 102.8 mU/LCH confirmed with serum free T4 = 0.47 μg/dL (n 0.9-2.3 μg/dL) and TSH >100. The infants mother tookIodoral tablets containing 12.5 mg of iodine daily throughout pregnancy. Infants urine iodine was normal (70 μg/dL, n 42-350 μg/L) after mother discontinued supplementaliodine, but breast milk iodine was elevated (3,228 µg/L, n 5-180 μg/L).Cases 2 and 3 are twins whose mother took Iodoral 12.5 mg daily throughout pregnancy. TSH >200 mU/L [n1.7-9.1 mU/L]; case 3: T4 = 4.64 [n 7.2-15.7], TSH >200 mU/L [n 1.7-9.1 mU/L]) and confirmed by serumsample (case 2: free T4 = 0.5 μg/dL *n 0.9-2.3 μg/dL+, TSH 420 *n 1.7-9.1 mU/L]; case 3: free T4 = QNS, TSH217 [n 1.7-9.1 mU/L]).Mother had elevated serum and urine iodine levels. These infants also had elevated urinary iodine (case 2:10,474 μg/L; case 3: 693 μg/L, n 42-350 μg/L).
Participant Case Review #7 Patient is a 60 year old male. Dx with OCD at age 29, at about the same time he was DX with Hashimoto’s. Hashimoto’s had been monitored by his PCP over the years and treated with Synthroid. In the last 5-6 months, patient reports: extreme fatigue, brittle nails, sinus drainage in back of throat making him hoarse (he is a drama teacher) and extreme cold hands (though this appears to be “settling down”). After a while he went in to see PCP and labs showed elevated TSH. PCP increased Synthroid to 175mcg and then to 200mcg and included Sildenafil 25mg.
Participant Case Review #7 As of today, blood tests “leveled out” (according to PCP) but all symptoms continue. Patient is convinced issue is Hashimoto’s and sleep-related. Sleep is where this case gets complicated: with OCD he has a reversed sleep schedule: he is up all night and sleeps during day until 2-3:30. This is largely due to rituals & associated anxiety related to preparing for bed. He is working on changing this with his psychiatrist. But it is a very slow process. His OCD also worsened 3 years ago when his Mom passed. Working with two therapists. His sleep is further disturbed by GERD and pain due to rotator cuff injury!
Participant Case Review #7 12/12 TSH 6.25 uIU/ml fT4 1.51 ng/dL 01/13 TSH 2.25 uIU/ml fT4 1.66 ng/dL T4 total 11.7 ug/dL T3 total 0.71 ng/dL TG antibodies WNL TPO antibodies 176.0 IU/mL T3 total 157 ng/dL
Participant Case Review #7 02/13 TSH 0.11 mIU/L – his PCP is keeping him here which seems too low to me? fT4 1.9 ng/dL FTI 3.5 T3 uptake 37 T4 9.4 mcg/dL
Participant Case Review #8 54 yo female Oct 31/12 Jan 28/13 Oct 31/212 TSH 4.12 TPO 300, thyroglobin antibody 326 Jan 28/13 TSH 3.94 TPO 241 thyroglobulin antibody 327 Allergies: sulpha 1988, clindamycin 2011 post dental implant
Participant Case Review #8 Treatment/medication: Nessman lycopus drainage for thyroid, cactus for heart palpitations Allergy research Thyroid plus 1pill/day 5 days/week (Non-Rx Thyroid Glandular) Pure north Vit, multivit, fish oil, digestive enz, probiotic, vit D 6,00 IU, selenium MB 150ug/day ALA, glutathione, magnesium citrate, NAC 200 mg/day Symptoms (4 minimum): Afternoon fatigue better with thyroid plus Memory loss Constipation, Eczema when eating dairy, food sensitivity test negative for glutein and dairy 2012 and 2013 How do I lower the thyroid antibodies?
Post Event QuizWhich of the following can justify thyroid replacementin a symptomatic patient with a TSH between 2.5 to4.5?A. Ultrasonographic signs of autoimmunityB. AM Axillary body temperature below 97.2C. Delayed Achilles reflexD. Positive prior response to thyroid replacement
Post Event QuizMost hypothyroidism in the US is caused by:A. ObesityB. Bromide toxicityC. Iodine deficiencyD. Autoimmune disease
Post Event QuizThyroid dosing can be safely increased untilA. Free T3 elevates above 4.8 pg/mLB. TSH is suppressed below 0.4 mIU/LC. Symptoms have resolvedD. AM Axillary body temperature rises above 98.9
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