Thyroid DiseaseAnd OsteoporosisLisa Hays, MDEndocrinology Fellow

OutlineSigns and symptoms of hyperthyroidismDiagnostic studies for hyperthyroidismCauses and treatments of hyperthyroidismGeneral overview of hypothyroidismEvaluation of thyroid nodulesOverview of osteoporosis

Cellular effects of thyroid

Hyperthyroidism SymptomsAnxiety/irritabilityWeaknessTremorsDifficulty sleepingPalpitationsIncreased bowel movementsFatigueWeight loss Hyperkinetic movementsHeat intolerance

Case Presentation37 yo male presented to PCP w/ complaint of feeling poorly for past monthAlso complained of weakness, difficulty sleeping, increased heart rate. 10 stools per day.What else do we need to know before examining?

Case PresentationT 99.1, HR 92 irregular, RR 20, BP 153/75Physical examinationMild proptosisNontender goiter with thyroid bruit presentCV: Irregularly irregular rhythmExt: Brisk DTRs, mild resting tremorWhat labs or studies do we need?

Laboratory StudiesTSH 6 ng/dl (nl 0.71-1.85)Total T3 >600 ng/dl (nl 72-170)Thyroid Stimulating Antibody 130% (nl 0-125%)Negative Thyroid peroxidase and thyroglobulin antibodies

Case PresentationPatient was diagnosed with Graves DiseaseStarted on Methimazole 10 mg TIDPropranolol for symptom managementAnticoagulation for atrial fibrillation

Thyroid AntibodiesTSH receptor antibodiesCan be stimulating or inhibitoryThyroglobulin antibodiesThyroid peroxidase antibodies (formerly known as microsomal)

Anything else?Radioactive Iodine UptakeMeasures the amount of iodine taken up by the thyroid in 24 hoursNormal 15-30%Thyroid ScanGives an anatomic view of the thyroidTechnetium used to image

Differential DiagnosisHigh uptakeGraves DiseaseMultinodular GoiterToxic solitary NoduleTRH secreting Pituitary TumorHCG secreting tumorLow uptakeSubacute ThyroiditisSilent ThyroiditisIodine induced Exogenous L-ThyroxineStruma ovariiAmiodarone

Graves DiseaseMost common cause of hyperthyroidism60-80% of casesAutoimmune diseaseCaused by thyroid stimulating immunoglobulinsBind to TSH receptors on thyroidCause hypersecrection of thyroid hormoneCause hypertrophy & hyperplasia of thyroid follicles

Weetman, A. P. N Engl J Med 2000;343:1236-1248Pathogenesis of Graves' Disease

Clinical ManifestationsSymptoms and signs of hyperthyroidismOphthalmopathyPresent in 50% of patientsEyelid retractionPeriorbital edemaProptosis (exopthalmos)DiplopliaDermopathy (myxedema)

Weetman, A. P. N Engl J Med 2000;343:1236-1248Clinical Manifestations of Graves' Disease

Graves DiseaseAssociated ConditionsType I Diabetes MellitusAddisons DiseaseVitiligoPernicious anemiaAlopecia AreataMyasthenia GravisCeliac Disease

Graves TreatmentAntithyroid drugs (Thionamides)Proplythiouracil (PTU) 300-400 mg dailyMethimazole 30-40 mg dailyDecrease synthesis of hormone, PTU also decreases conversion of T4 to T3Permanent remission in 40-50% of treated patientsRisk of agranulocytosisPTU used in pregnancyBeta-Blockers for symptoms

Graves TreatmentThyroidectomyRapid cure but requires thyroid replacementRadioactive Iodine Iodine (131I) is givenEffect is typically seen in 3-6 monthsHypothyroidism often develops

Multinodular GoiterLess common than Graves and effects older individualsDiscrete nodules become autonomous and hyperfunctionTreatment with thyroidectomy (often poor surgical candidates) or iodine, thionamides

Subacute ThyroiditisEtiology is typically viralKnown as De Quervains thyroiditis or granulomatous thyroiditisThyroid is often enlarged, tender, painfulVery low radioactive iodine uptakeSelf-resolving within weeks to monthsTreatment with NSAIDS, steroids, Beta-blockers

Silent ThyroiditisAlso called painless or lymphocytic thyroiditisNot painful like subacuteTransientLow iodine uptake

HypothyroidismWeaknessFatigueLethargy, sleepinessSlowness of speech and thoughtPuffy appearanceDry skin, coarse hairCold intoleranceConstipation

Physical FindingsPuffy featuresDry skinNonpitting edemaHypothermiaBradycardiaSlow return of deep tendon reflexesLoss of lateral portion of eyebrows

Causes of HypothyroidismPrimary HypothyroidismIodine deficiencyIatrogenic-surgery, radioablationAutoimmune thyroid destructionDrugs interfering with hormone synthesisInfiltrative diseasehemochromotosis, sarcoidosis, neoplastic diseaseCongenital thyroid agensis or defects in hormone synthesis

Hashimotos ThyroiditisMost common type of thyroid diseaseAutoimmune damageLymphocytic infiltrate, fibrosis, decreased thyroid hormone productionAutoantibodies (thyroglobulin and peroxidase)Can also be associated with polyglandular autoimmune diseaseAdrenal insufficiency, ovarian failure, vitiligo, diabetes

Thyroid ReplacementSynthetic levothyroxine (T4)Converted to T3 in the bodyStudies vary on utility of using T3 Typical replacement dose is 1.6 micrograms/kg (100-150 mcg typical)Start with reduced dose in elderly and patients with history of heart disease

Myxedema ComaSevere untreated hypothyroidismHypothermia, hypoglycemia, shock, hypoventilation, ileus50% mortalityTreat with IV levothyroxine, steroids

Thyroid Nodule21 yo male w/ no past medical history presents to his PCP complaining of gradually enlarging knot in his neckWhat questions do you have?Examination reveals a firm 3 cm nodule in right lobe of thyroidWhat is the next step?

Thyroid NodulesLifetime risk of palpable nodule 5-10%50% of the population has a nodule on autopsy or ultrasoundOnly 1 in 20 is malignant

Differential DiagnosisMalignancyPapillaryFollicularMedullaryAnaplasticMetastasisBenign follicular adenomaCystColloid Nodule

Hegedus, L. N Engl J Med 2004;351:1764-1771Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Hegedus, L. N Engl J Med 2004;351:1764-1771Clinical Findings Suggesting the Diagnosis of Thyroid Carcinoma in a Euthyroid Patient with a Solitary Nodule, According to the Degree of Suspicion

Evaluation of NoduleMeasure TSHIf Hyperthyroid (low TSH), do uptake and scanTreat with surgery or I-131 ablationIf normal thyroid function, next step is fine needle aspiration (FNA)Check Calcitonin level if family history of MEN2 or medullary carcinoma exists.

Hegedus, L. N Engl J Med 2004;351:1764-1771Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Fine Needle AspirationFNA is most effective way to distinguish between benign and malignant nodulesInexpensive, performed as outpatientUltrasound guided FNA if not palpable or less than 1.5 cm in diameterWhat results will I see?Benign-75% of the timeMalignant-4% of casesSuspicious or inadequate-22%

Hegedus, L. N Engl J Med 2004;351:1764-1771Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Management of NodulesMalignantTotal thyroidectomySuspiciousThyroidectomyBenignDiscuss with the patientUltrasound surveillanceSurgeryConsider levothyroxine suppression (varying results)

Case PresentationFNA revealed papillary thyroid carcinomaPatient underwent total thyroidectomyTreatment with I-131 ablation after surgery

Osteoporosis

Case Presentation70 year old female asks her PCP if she should have a bone density done.What questions should her PCP ask?No history of fracturesMenopause was surgical at age of 55Mother fractured her hip at 74

OsteoporosisDefinitionMicroarchitectural deterioration of bone tissue leading to decreased bone massBone fragilitySusceptibility to fractureA problem of decreased peak bone mass and accelerated bone lossAffects 10 million in the United States

1. Consensus Development Conference. Am J Med. 1993;94:646-650.2. Riggs BL, Melton LJ III. Bone. 1995;17:505S511S.3. Ray NF et al. J Bone Miner Res. 1997;12(1):2435.4. Cummings SR et al. Arch Intern Med. 1989;149:24452448.Hip Fractures Can Lead to Disability, Loss of Independence, and Even DeathHip fracture is associated with increased risk of:Disability: 50% never fully recover1,2 Long-term nursing home care required: 25%2Increased mortality within 1 year due to complications: up to 24%3Lifetime risk of death: comparable to that of breast cancer4

OsteoporosisPrimary osteoporosisUnrelated to chronic illnessRelated to aging and decreased gonadal functionSecondary osteoporosisSecondary to chronic illnesses that cause accelerated bone lossExamples: Glucocorticoid use, celiac sprue, hyperthyroidism

Risk Factors for Osteoporotic FractureNonmodifiablePotentially ModifiableGold color denotes risk factors that are key factors for risk of hip fracture, independent of bone density.National Osteoporosis Foundation, Physicians Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.

Diagnosis of OsteoporosisHistory and physical examination to exclude secondary osteoporosisLaboratory studies if suspect secondary osteoporosisMeasurement of Bone Mineral Density (BMD)Dual X-ray Absorptiometry (DEXA scan)Provides most reproducible values of bone densityg/cm2

6070809010030405060708090AgeRelative BMD (%)ForearmSpineHip and Heel0100020003000400035-3985+Colles'VertebraeHipAgeAnnual Fracture IncidenceCooper C. Baillires Clin Rheumatol. 1993;7:459477.Faulkner KG. J Clin Densitom. 1998;1:279285.BMD and Fracture Risk Are Inversely Related

Central DXA MeasurementMeasures multiple skeletal sitesSpineProximal femurForearmTotal bodyOffice basedConsidered the clinical standard

National Osteoporosis Foundation, Physicians Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.National Osteoporosis Foundation GuidelinesWho Should Be Considered for BMD Testing?Women 65 years of age regardless of additional risk factorsPostmenopausal women

Other Populations To Consider for Assessment of OsteoporosisMenPatients on long-term high-dose glucocorticoids

T-Score Is KeyInterpreting BMD Measurement ReportsA clinically relevant value on the BMD reportDescribes bone mass compared with the mean peak bone mass of healthy young adult women in terms of Standard Deviation (SD)Can help confirm the diagnosis of low bone mass or osteoporosisFor every SD below the young adult normal, the risk of fracture approximately doubles

1. National Osteoporosis Foundation, Physicians Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998. 2. Marshall D. Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312:12541259.

SDAge (years)21012345620 30 40 50 60 70 80 90T-score = 3.0Peak Bone MassVisualizing a Patients T-ScoreT-score = Number of standard deviations (SDs) by which the patients bone mass falls above or below the mean peak bone mass for normal young adult women = T-score for patient, a 60-year-old woman; here, T = 3.0Light line: Change in mean bone mass over time in womenHeavy line: Mean peak bone mass for young normal adult women National Osteoporosis Foundation, Physicians Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.

National Osteoporosis Foundation, Physicians Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.T-SCOREACTION

< 2.0Initiate therapy

< 1.5Initiate therapy(with at least 1 additional risk factor)National Osteoporosis Foundation Guidelines for postmenopausal WomenRecommendations for Treatment Based on BMD Testing Results

Treatment of OsteoporosisAdequate Calcium (1200 mg elemental)Adequate Vitamin D (at least 400 IU)Weight-bearing exercise

Pharmacologic AgentsBisphosphonatesInhibit osteoclastic bone resorptionIncreased BMD and decreased fracturesEx: alendronate, risedronateCalcitoninNasal spray or injectionDecreased vertebral fracturesNo hip fracture dataRaloxifenSERMDecreased vertebral fracture

Osteoporosis SummaryOsteoporosis is a disease with serious consequences.Bone loss associated with osteoporosis increases fracture risk, which may lead to disability, loss of independence, and death.Patients at risk for osteoporotic fracture should be considered for BMD testing.T-score is the most clinically relevant measure of fracture risk.According to NOF guidelines, consider therapy in patients with a T-score of