Thyroid Disease and Osteoporosis
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Transcript of Thyroid Disease and Osteoporosis
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.