Thyroid DiseaseThyroid DiseaseAnd OsteoporosisAnd Osteoporosis

Lisa Hays, MDLisa Hays, MDEndocrinology FellowEndocrinology Fellow

OutlineOutline

Signs and symptoms of hyperthyroidismSigns and symptoms of hyperthyroidism

Diagnostic studies for hyperthyroidismDiagnostic studies for hyperthyroidism

Causes and treatments of hyperthyroidismCauses and treatments of hyperthyroidism

General overview of hypothyroidismGeneral overview of hypothyroidism

Evaluation of thyroid nodulesEvaluation of thyroid nodules

Overview of osteoporosisOverview of osteoporosis

Cellular effects of thyroidCellular effects of thyroid

Hyperthyroidism SymptomsHyperthyroidism Symptoms

Anxiety/irritabilityAnxiety/irritability

WeaknessWeakness

TremorsTremors

Difficulty sleepingDifficulty sleeping

PalpitationsPalpitations

Increased bowel Increased bowel movementsmovements

FatigueFatigue

Weight loss Weight loss

Hyperkinetic Hyperkinetic movementsmovements

Heat intoleranceHeat intolerance

Case PresentationCase Presentation

37 yo male presented to PCP w/ complaint 37 yo male presented to PCP w/ complaint of feeling poorly for past monthof feeling poorly for past month

Also complained of weakness, difficulty Also complained of weakness, difficulty sleeping, increased heart rate. 10 stools sleeping, increased heart rate. 10 stools per day.per day.

What else do we need to know before What else do we need to know before examining?examining?

Case PresentationCase Presentation

T 99.1, HR 92 irregular, RR 20, BP 153/75T 99.1, HR 92 irregular, RR 20, BP 153/75

Physical examinationPhysical examination Mild proptosisMild proptosis Nontender goiter with thyroid bruit presentNontender goiter with thyroid bruit present CV: Irregularly irregular rhythmCV: Irregularly irregular rhythm Ext: Brisk DTR’s, mild resting tremorExt: Brisk DTR’s, mild resting tremor

What labs or studies do we need?What labs or studies do we need?

Laboratory StudiesLaboratory Studies

TSH <0.010 uIU/ml (nl 0.47-5.0)TSH <0.010 uIU/ml (nl 0.47-5.0)

Free T4 >6 ng/dl (nl 0.71-1.85)Free T4 >6 ng/dl (nl 0.71-1.85)

Total T3 >600 ng/dl (nl 72-170)Total T3 >600 ng/dl (nl 72-170)

Thyroid Stimulating Antibody 130% (nl 0-Thyroid Stimulating Antibody 130% (nl 0-125%)125%)

Negative Thyroid peroxidase and Negative Thyroid peroxidase and thyroglobulin antibodiesthyroglobulin antibodies

Case PresentationCase Presentation

Patient was diagnosed with Graves’ Patient was diagnosed with Graves’ DiseaseDisease

Started on Methimazole 10 mg TIDStarted on Methimazole 10 mg TID

Propranolol for symptom managementPropranolol for symptom management

Anticoagulation for atrial fibrillationAnticoagulation for atrial fibrillation

Thyroid AntibodiesThyroid Antibodies

TSH receptor antibodiesTSH receptor antibodies Can be stimulating or inhibitoryCan be stimulating or inhibitory

Thyroglobulin antibodiesThyroglobulin antibodies

Thyroid peroxidase antibodies (formerly Thyroid peroxidase antibodies (formerly known as microsomal)known as microsomal)

Anything else?Anything else?

Radioactive Iodine UptakeRadioactive Iodine Uptake Measures the amount of iodine taken up by Measures the amount of iodine taken up by

the thyroid in 24 hoursthe thyroid in 24 hours Normal 15-30%Normal 15-30%

Thyroid ScanThyroid Scan Gives an anatomic view of the thyroidGives an anatomic view of the thyroid Technetium used to imageTechnetium used to image

Differential DiagnosisDifferential Diagnosis

• High uptakeHigh uptake

Graves’ DiseaseGraves’ Disease

Multinodular GoiterMultinodular Goiter

Toxic solitary NoduleToxic solitary Nodule

TRH secreting Pituitary TRH secreting Pituitary TumorTumor

HCG secreting tumorHCG secreting tumor

Low uptakeLow uptake

Subacute ThyroiditisSubacute Thyroiditis

Silent ThyroiditisSilent Thyroiditis

Iodine induced Iodine induced

Exogenous L-Exogenous L-ThyroxineThyroxine

Struma ovariiStruma ovarii

AmiodaroneAmiodarone

Graves’ DiseaseGraves’ Disease

Most common cause of hyperthyroidismMost common cause of hyperthyroidism 60-80% of cases60-80% of cases

Autoimmune diseaseAutoimmune diseaseCaused by thyroid stimulating Caused by thyroid stimulating immunoglobulinsimmunoglobulins Bind to TSH receptors on thyroidBind to TSH receptors on thyroid Cause hypersecrection of thyroid hormoneCause hypersecrection of thyroid hormone Cause hypertrophy & hyperplasia of thyroid Cause hypertrophy & hyperplasia of thyroid

folliclesfollicles

Weetman, A. P. N Engl J Med 2000;343:1236-1248

Pathogenesis of Graves' Disease

Clinical ManifestationsClinical Manifestations

Symptoms and signs of hyperthyroidismSymptoms and signs of hyperthyroidism

OphthalmopathyOphthalmopathy Present in 50% of patientsPresent in 50% of patients Eyelid retractionEyelid retraction Periorbital edemaPeriorbital edema Proptosis (exopthalmos)Proptosis (exopthalmos) DiplopliaDiploplia

Dermopathy (myxedema)Dermopathy (myxedema)

Weetman, A. P. N Engl J Med 2000;343:1236-1248

Clinical Manifestations of Graves' Disease

Graves’ DiseaseGraves’ Disease

Associated ConditionsAssociated Conditions Type I Diabetes MellitusType I Diabetes Mellitus Addison’s DiseaseAddison’s Disease VitiligoVitiligo Pernicious anemiaPernicious anemia Alopecia AreataAlopecia Areata Myasthenia GravisMyasthenia Gravis Celiac DiseaseCeliac Disease

Graves TreatmentGraves Treatment

Antithyroid drugs (Thionamides)Antithyroid drugs (Thionamides) Proplythiouracil (PTU) 300-400 mg dailyProplythiouracil (PTU) 300-400 mg daily Methimazole 30-40 mg dailyMethimazole 30-40 mg daily Decrease synthesis of hormone, PTU also decreases Decrease synthesis of hormone, PTU also decreases

conversion of T4 to T3conversion of T4 to T3 Permanent remission in 40-50% of treated patientsPermanent remission in 40-50% of treated patients Risk of agranulocytosisRisk of agranulocytosis PTU used in pregnancyPTU used in pregnancy

Beta-Blockers for symptomsBeta-Blockers for symptoms

Graves TreatmentGraves Treatment

ThyroidectomyThyroidectomy Rapid cure but requires thyroid replacementRapid cure but requires thyroid replacement

Radioactive Iodine Radioactive Iodine Iodine (131I) is givenIodine (131I) is given Effect is typically seen in 3-6 monthsEffect is typically seen in 3-6 months Hypothyroidism often developsHypothyroidism often develops

Multinodular GoiterMultinodular Goiter

Less common than Graves and effects Less common than Graves and effects older individualsolder individualsDiscrete nodules become autonomous Discrete nodules become autonomous and hyperfunctionand hyperfunctionTreatment with thyroidectomy (often poor Treatment with thyroidectomy (often poor surgical candidates) or iodine, thionamidessurgical candidates) or iodine, thionamides

Subacute ThyroiditisSubacute Thyroiditis

Etiology is typically viralEtiology is typically viralKnown as De Quervain’s thyroiditis or Known as De Quervain’s thyroiditis or granulomatous thyroiditisgranulomatous thyroiditisThyroid is often enlarged, tender, painfulThyroid is often enlarged, tender, painfulVery low radioactive iodine uptakeVery low radioactive iodine uptakeSelf-resolving within weeks to monthsSelf-resolving within weeks to monthsTreatment with NSAIDS, steroids, Beta-blockersTreatment with NSAIDS, steroids, Beta-blockers

Silent ThyroiditisSilent Thyroiditis

Also called painless or lymphocytic Also called painless or lymphocytic thyroiditisthyroiditis

Not painful like subacuteNot painful like subacute

TransientTransient

Low iodine uptakeLow iodine uptake

HypothyroidismHypothyroidism

WeaknessWeaknessFatigueFatigueLethargy, sleepinessLethargy, sleepinessSlowness of speech and thoughtSlowness of speech and thought““Puffy” appearancePuffy” appearanceDry skin, coarse hairDry skin, coarse hairCold intoleranceCold intoleranceConstipationConstipation

Physical FindingsPhysical Findings

Puffy featuresPuffy features

Dry skinDry skin

Nonpitting edemaNonpitting edema

HypothermiaHypothermia

BradycardiaBradycardia

Slow return of deep tendon reflexesSlow return of deep tendon reflexes

Loss of lateral portion of eyebrowsLoss of lateral portion of eyebrows

Causes of HypothyroidismCauses of Hypothyroidism

Primary HypothyroidismPrimary Hypothyroidism Iodine deficiencyIodine deficiency Iatrogenic-surgery, radioablationIatrogenic-surgery, radioablation Autoimmune thyroid destructionAutoimmune thyroid destruction Drugs interfering with hormone synthesisDrugs interfering with hormone synthesis Infiltrative diseaseInfiltrative disease

hemochromotosis, sarcoidosis, neoplastic diseasehemochromotosis, sarcoidosis, neoplastic disease Congenital thyroid agensis or defects in hormone Congenital thyroid agensis or defects in hormone

synthesissynthesis

Hashimotos ThyroiditisHashimotos Thyroiditis

Most common type of thyroid diseaseMost common type of thyroid disease

Autoimmune damageAutoimmune damage Lymphocytic infiltrate, fibrosis, decreased Lymphocytic infiltrate, fibrosis, decreased

thyroid hormone productionthyroid hormone production Autoantibodies (thyroglobulin and peroxidase)Autoantibodies (thyroglobulin and peroxidase) Can also be associated with polyglandular Can also be associated with polyglandular

autoimmune diseaseautoimmune diseaseAdrenal insufficiency, ovarian failure, vitiligo, Adrenal insufficiency, ovarian failure, vitiligo, diabetesdiabetes

Thyroid ReplacementThyroid Replacement

Synthetic levothyroxine (T4)Synthetic levothyroxine (T4)

Converted to T3 in the bodyConverted to T3 in the body

Studies vary on utility of using T3 Studies vary on utility of using T3

Typical replacement dose is 1.6 Typical replacement dose is 1.6 micrograms/kg (100-150 mcg typical)micrograms/kg (100-150 mcg typical)

Start with reduced dose in elderly and Start with reduced dose in elderly and patients with history of heart diseasepatients with history of heart disease

Myxedema ComaMyxedema Coma

Severe untreated hypothyroidismSevere untreated hypothyroidism

Hypothermia, hypoglycemia, shock, Hypothermia, hypoglycemia, shock, hypoventilation, ileushypoventilation, ileus

50% mortality50% mortality

Treat with IV levothyroxine, steroidsTreat with IV levothyroxine, steroids

Thyroid NoduleThyroid Nodule

21 yo male w/ no past medical history 21 yo male w/ no past medical history presents to his PCP complaining of presents to his PCP complaining of gradually enlarging “knot” in his neckgradually enlarging “knot” in his neck

What questions do you have?What questions do you have?

Examination reveals a firm 3 cm nodule in Examination reveals a firm 3 cm nodule in right lobe of thyroidright lobe of thyroid

What is the next step?What is the next step?

Thyroid NodulesThyroid Nodules

Lifetime risk of palpable nodule 5-10%Lifetime risk of palpable nodule 5-10%

50% of the population has a nodule on 50% of the population has a nodule on autopsy or ultrasoundautopsy or ultrasound

Only 1 in 20 is malignantOnly 1 in 20 is malignant

Differential DiagnosisDifferential Diagnosis

MalignancyMalignancy PapillaryPapillary FollicularFollicular MedullaryMedullary AnaplasticAnaplastic MetastasisMetastasis

Benign follicular Benign follicular adenomaadenoma

CystCyst

Colloid NoduleColloid Nodule

Hegedus, L. N Engl J Med 2004;351:1764-1771

Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Hegedus, L. N Engl J Med 2004;351:1764-1771

Clinical Findings Suggesting the Diagnosis of Thyroid Carcinoma in a Euthyroid Patient with a Solitary Nodule, According to the Degree of Suspicion

Evaluation of NoduleEvaluation of Nodule

Measure TSHMeasure TSH If Hyperthyroid (low TSH), do uptake and scanIf Hyperthyroid (low TSH), do uptake and scan

Treat with surgery or I-131 ablationTreat with surgery or I-131 ablation If normal thyroid function, next step is fine If normal thyroid function, next step is fine

needle aspiration (FNA)needle aspiration (FNA)

Check Calcitonin level if family history of Check Calcitonin level if family history of MEN2 or medullary carcinoma exists.MEN2 or medullary carcinoma exists.

Hegedus, L. N Engl J Med 2004;351:1764-1771

Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Fine Needle AspirationFine Needle Aspiration

FNA is most effective way to distinguish FNA is most effective way to distinguish between benign and malignant nodulesbetween benign and malignant nodulesInexpensive, performed as outpatientInexpensive, performed as outpatientUltrasound guided FNA if not palpable or Ultrasound guided FNA if not palpable or less than 1.5 cm in diameterless than 1.5 cm in diameterWhat results will I see?What results will I see? Benign-75% of the timeBenign-75% of the time Malignant-4% of casesMalignant-4% of cases Suspicious or inadequate-22%Suspicious or inadequate-22%

Hegedus, L. N Engl J Med 2004;351:1764-1771

Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Management of NodulesManagement of Nodules

MalignantMalignant Total thyroidectomyTotal thyroidectomy

SuspiciousSuspicious ThyroidectomyThyroidectomy

BenignBenign Discuss with the patientDiscuss with the patient Ultrasound surveillanceUltrasound surveillance SurgerySurgery Consider levothyroxine suppression (varying results)Consider levothyroxine suppression (varying results)

Case PresentationCase Presentation

FNA revealed papillary thyroid carcinomaFNA revealed papillary thyroid carcinoma

Patient underwent total thyroidectomyPatient underwent total thyroidectomy

Treatment with I-131 ablation after surgeryTreatment with I-131 ablation after surgery

OsteoporosisOsteoporosis

Case PresentationCase Presentation

70 year old female asks her PCP if she 70 year old female asks her PCP if she should have a bone density done.should have a bone density done.

What questions should her PCP ask?What questions should her PCP ask? No history of fracturesNo history of fractures Menopause was surgical at age of 55Menopause was surgical at age of 55 Mother fractured her hip at 74Mother fractured her hip at 74

OsteoporosisOsteoporosis

DefinitionDefinition Microarchitectural deterioration of bone tissue Microarchitectural deterioration of bone tissue

leading to decreased bone massleading to decreased bone mass Bone fragilityBone fragility Susceptibility to fractureSusceptibility to fracture

A problem of decreased peak bone mass A problem of decreased peak bone mass and accelerated bone lossand accelerated bone loss

Affects 10 million in the United StatesAffects 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;17:505S–511S.3. Ray NF et al. J Bone Miner Res. 1997;12(1):24–35.4. Cummings SR et al. Arch Intern Med. 1989;149:2445–2448.

Hip Fractures Can Lead to Disability, Hip Fractures Can Lead to Disability, Loss of Independence, and Even DeathLoss of Independence, and Even Death

Hip fracture is associated with Hip fracture is associated with increased increased risk of:risk of:

Disability: 50% never fully Disability: 50% never fully recoverrecover1,21,2

Long-term nursing home Long-term nursing home care required: 25%care required: 25%22

Increased mortality within 1 Increased mortality within 1 year due to complications: year due to complications: up to 24%up to 24%33

Lifetime risk of death: Lifetime risk of death: comparable to that comparable to that of breast cancerof breast cancer44

OsteoporosisOsteoporosis

Primary osteoporosisPrimary osteoporosis Unrelated to chronic illnessUnrelated to chronic illness Related to aging and decreased gonadal Related to aging and decreased gonadal

functionfunction

Secondary osteoporosisSecondary osteoporosis Secondary to chronic illnesses that cause Secondary to chronic illnesses that cause

accelerated bone lossaccelerated bone loss Examples: Glucocorticoid use, celiac sprue, Examples: Glucocorticoid use, celiac sprue,

hyperthyroidismhyperthyroidism

Risk Factors for Osteoporotic Risk Factors for Osteoporotic FractureFracture

Nonmodifiable Potentially ModifiablePersonal history of fracture as an adult

History of fracture infirst-degree relative

Caucasian race

Advanced age

Female sex

Dementia

Poor health/frailty

Current cigarette smoking

Low body weight (<127 lbs)

Estrogen deficiency, including menopause onset <age 45

Low calcium intake (lifelong)

Alcoholism

Impaired eyesight despiteadequate correction

Recurrent falls

Inadequate physical activity

Poor health/frailty

Gold color denotes risk factors that are key factors for risk of hip fracture, independent of bone density.National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.

Diagnosis of OsteoporosisDiagnosis of Osteoporosis

History and physical examination to History and physical examination to exclude secondary osteoporosisexclude secondary osteoporosisLaboratory studies if suspect secondary Laboratory studies if suspect secondary osteoporosisosteoporosisMeasurement of Bone Mineral Density Measurement of Bone Mineral Density (BMD)(BMD) Dual X-ray Absorptiometry (DEXA scan)Dual X-ray Absorptiometry (DEXA scan)

Provides most reproducible values of bone densityProvides most reproducible values of bone densityg/cmg/cm22

60

70

80

90

100

30 40 50 60 70 80 90

Age

Re

lati

ve

BM

D (

%)

Forearm

Spine

Hip and Heel

0

1000

2000

3000

4000

35-39

85+

Colles'

Vertebrae

Hip

Age

An

nu

al F

rac

ture

Inc

ide

nc

e

Cooper C. Baillières Clin Rheumatol. 1993;7:459–477.Faulkner KG. J Clin Densitom. 1998;1:279–285.

BMD and Fracture Risk Are BMD and Fracture Risk Are Inversely RelatedInversely Related

Central DXA MeasurementCentral DXA Measurement

Measures multipleMeasures multipleskeletal sitesskeletal sites SpineSpine Proximal femurProximal femur ForearmForearm Total bodyTotal body

Office basedOffice based

Considered theConsidered theclinical standardclinical standard

National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.

National Osteoporosis Foundation Guidelines

Who Should Be Considered for BMD Who Should Be Considered for BMD Testing?Testing?

Women Women 65 years of age regardless of additional risk factors65 years of age regardless of additional risk factors

Postmenopausal women <65 years of age with at least one Postmenopausal women <65 years of age with at least one risk factor for osteoporosis (in addition to menopause)risk factor for osteoporosis (in addition to menopause)

Postmenopausal women Postmenopausal women 65 years of age with fractures 65 years of age with fractures (to confirm diagnosis and determine disease severity)(to confirm diagnosis and determine disease severity)

Women considering therapy for osteoporosis, if BMD Women considering therapy for osteoporosis, if BMD testing would facilitate the decisiontesting would facilitate the decision

Women who have been on HRT for prolonged periodsWomen who have been on HRT for prolonged periods

Other Populations To Consider for Other Populations To Consider for Assessment of OsteoporosisAssessment of Osteoporosis

MenMen

Patients on long-term high-dose Patients on long-term high-dose glucocorticoidsglucocorticoids

T-Score Is Key

Interpreting BMD Measurement Interpreting BMD Measurement ReportsReports

A clinically relevant value on the BMD reportA clinically relevant value on the BMD report

Describes bone mass compared with the mean peak Describes bone mass compared with the mean peak bone mass of healthy young adult women in terms of bone mass of healthy young adult women in terms of Standard Deviation (SD)Standard Deviation (SD)

Can help confirm the diagnosis of low bone mass or Can help confirm the diagnosis of low bone mass or osteoporosisosteoporosis

For every SD below the young adult normal, the risk For every SD below the young adult normal, the risk

of fracture approximately doublesof fracture approximately doubles 1. National Osteoporosis Foundation, Physician’s 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;312:1254–1259.

SD

Age (years)

2

1

0

–1

–2

–3

–4

–5

–6

20 30 40 50 60 70 80 90

T-score = –3.0

Peak Bone Mass

Visualizing a Patient’s T-ScoreVisualizing a Patient’s T-Score

T-score = Number of standard deviations (SDs) by which the patient’s T-score = Number of standard deviations (SDs) by which the patient’s bone mass falls above or below the mean peak bone mass for normal bone mass falls above or below the mean peak bone mass for normal young adult womenyoung adult women

= T-score for patient, a 60-year-old woman; here, T = –3.0= T-score for patient, a 60-year-old woman; here, T = –3.0

Light line: Change in mean bone mass over time in womenLight line: Change in mean bone mass over time in women

Heavy line: Mean peak bone mass for young normal adult women Heavy line: Mean peak bone mass for young normal adult women

National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.

National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.

T-SCORE ACTION

< –2.0 Initiate therapy

< –1.5 Initiate therapy

(with at least 1 additional risk factor)

National Osteoporosis Foundation Guidelines for postmenopausal Women

Recommendations for Treatment Recommendations for Treatment Based on BMD Testing ResultsBased on BMD Testing Results

Treatment of OsteoporosisTreatment of Osteoporosis

Adequate Calcium (1200 mg elemental)Adequate Calcium (1200 mg elemental)

Adequate Vitamin D (at least 400 IU)Adequate Vitamin D (at least 400 IU)

Weight-bearing exerciseWeight-bearing exercise

Pharmacologic AgentsPharmacologic Agents

BisphosphonatesBisphosphonatesInhibit osteoclastic bone resorptionInhibit osteoclastic bone resorption

Increased BMD and decreased fracturesIncreased BMD and decreased fractures

Ex: alendronate, risedronateEx: alendronate, risedronate CalcitoninCalcitonin

Nasal spray or injectionNasal spray or injection

Decreased vertebral fracturesDecreased vertebral fractures

No hip fracture dataNo hip fracture data RaloxifenRaloxifen

SERMSERM

Decreased vertebral fractureDecreased vertebral fracture

Osteoporosis SummaryOsteoporosis Summary

Osteoporosis is a disease with serious consequences.Osteoporosis is a disease with serious consequences. Bone loss associated with osteoporosis increases Bone loss associated with osteoporosis increases

fracture risk, which may lead to disability, loss of fracture risk, which may lead to disability, loss of independence, and death.independence, and death.

Patients at risk for osteoporotic fracture should be Patients at risk for osteoporotic fracture should be considered for BMD testing.considered for BMD testing.

T-score is the most clinically relevant measure of T-score is the most clinically relevant measure of fracture risk.fracture risk.

According to NOF guidelines, consider therapy in According to NOF guidelines, consider therapy in patients with a T-score of <patients with a T-score of <––2.0 and those with a T-score 2.0 and those with a T-score of <of <––1.5 with at least one risk factor.1.5 with at least one risk factor.