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Thyroid Disease And Osteoporosis. Lisa Hays, MD Endocrinology Fellow. Outline. Signs and symptoms of hyperthyroidism Diagnostic studies for hyperthyroidism Causes and treatments of hyperthyroidism General overview of hypothyroidism Evaluation of thyroid nodules Overview of osteoporosis.

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Thyroid DiseaseAnd Osteoporosis

Lisa Hays, MD

Endocrinology Fellow


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Outline

  • Signs and symptoms of hyperthyroidism

  • Diagnostic studies for hyperthyroidism

  • Causes and treatments of hyperthyroidism

  • General overview of hypothyroidism

  • Evaluation of thyroid nodules

  • Overview of osteoporosis



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Anxiety/irritability

Weakness

Tremors

Difficulty sleeping

Palpitations

Increased bowel movements

Fatigue

Weight loss

Hyperkinetic movements

Heat intolerance

Hyperthyroidism Symptoms


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Case Presentation

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

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

  • What else do we need to know before examining?


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Case Presentation

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

  • Physical examination

    • Mild proptosis

    • Nontender goiter with thyroid bruit present

    • CV: Irregularly irregular rhythm

    • Ext: Brisk DTR’s, mild resting tremor

  • What labs or studies do we need?


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Laboratory Studies

  • TSH <0.010 uIU/ml (nl 0.47-5.0)

  • Free T4 >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


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Case Presentation

  • Patient was diagnosed with Graves’ Disease

  • Started on Methimazole 10 mg TID

  • Propranolol for symptom management

  • Anticoagulation for atrial fibrillation


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Thyroid Antibodies

  • TSH receptor antibodies

    • Can be stimulating or inhibitory

  • Thyroglobulin antibodies

  • Thyroid peroxidase antibodies (formerly known as microsomal)


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Anything else?

  • Radioactive Iodine Uptake

    • Measures the amount of iodine taken up by the thyroid in 24 hours

    • Normal 15-30%

  • Thyroid Scan

    • Gives an anatomic view of the thyroid

    • Technetium used to image


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High uptake

Graves’ Disease

Multinodular Goiter

Toxic solitary Nodule

TRH secreting Pituitary Tumor

HCG secreting tumor

Low uptake

Subacute Thyroiditis

Silent Thyroiditis

Iodine induced

Exogenous L-Thyroxine

Struma ovarii

Amiodarone

Differential Diagnosis


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Graves’ Disease

  • Most common cause of hyperthyroidism

    • 60-80% of cases

  • Autoimmune disease

  • Caused by thyroid stimulating immunoglobulins

    • Bind to TSH receptors on thyroid

    • Cause hypersecrection of thyroid hormone

    • Cause hypertrophy & hyperplasia of thyroid follicles


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Pathogenesis of Graves' Disease

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


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Clinical Manifestations

  • Symptoms and signs of hyperthyroidism

  • Ophthalmopathy

    • Present in 50% of patients

    • Eyelid retraction

    • Periorbital edema

    • Proptosis (exopthalmos)

    • Diploplia

  • Dermopathy (myxedema)


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Clinical Manifestations of Graves' Disease

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


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Graves’ Disease

  • Associated Conditions

    • Type I Diabetes Mellitus

    • Addison’s Disease

    • Vitiligo

    • Pernicious anemia

    • Alopecia Areata

    • Myasthenia Gravis

    • Celiac Disease


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Graves Treatment

  • Antithyroid drugs (Thionamides)

    • Proplythiouracil (PTU) 300-400 mg daily

    • Methimazole 30-40 mg daily

    • Decrease synthesis of hormone, PTU also decreases conversion of T4 to T3

    • Permanent remission in 40-50% of treated patients

    • Risk of agranulocytosis

    • PTU used in pregnancy

  • Beta-Blockers for symptoms


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Graves Treatment

  • Thyroidectomy

    • Rapid cure but requires thyroid replacement

  • Radioactive Iodine

    • Iodine (131I) is given

    • Effect is typically seen in 3-6 months

    • Hypothyroidism often develops


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Multinodular Goiter

  • Less common than Graves and effects older individuals

  • Discrete nodules become autonomous and hyperfunction

  • Treatment with thyroidectomy (often poor surgical candidates) or iodine, thionamides


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Subacute Thyroiditis

  • Etiology is typically viral

  • Known as De Quervain’s thyroiditis or granulomatous thyroiditis

  • Thyroid is often enlarged, tender, painful

  • Very low radioactive iodine uptake

  • Self-resolving within weeks to months

  • Treatment with NSAIDS, steroids, Beta-blockers


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Silent Thyroiditis

  • Also called painless or lymphocytic thyroiditis

  • Not painful like subacute

  • Transient

  • Low iodine uptake


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Hypothyroidism

  • Weakness

  • Fatigue

  • Lethargy, sleepiness

  • Slowness of speech and thought

  • “Puffy” appearance

  • Dry skin, coarse hair

  • Cold intolerance

  • Constipation


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Physical Findings

  • Puffy features

  • Dry skin

  • Nonpitting edema

  • Hypothermia

  • Bradycardia

  • Slow return of deep tendon reflexes

  • Loss of lateral portion of eyebrows


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Causes of Hypothyroidism

  • Primary Hypothyroidism

    • Iodine deficiency

    • Iatrogenic-surgery, radioablation

    • Autoimmune thyroid destruction

    • Drugs interfering with hormone synthesis

    • Infiltrative disease

      • hemochromotosis, sarcoidosis, neoplastic disease

    • Congenital thyroid agensis or defects in hormone synthesis


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Hashimotos Thyroiditis

  • Most common type of thyroid disease

  • Autoimmune damage

    • Lymphocytic infiltrate, fibrosis, decreased thyroid hormone production

    • Autoantibodies (thyroglobulin and peroxidase)

    • Can also be associated with polyglandular autoimmune disease

      • Adrenal insufficiency, ovarian failure, vitiligo, diabetes


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Thyroid Replacement

  • Synthetic levothyroxine (T4)

  • Converted to T3 in the body

  • Studies 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


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Myxedema Coma

  • Severe untreated hypothyroidism

  • Hypothermia, hypoglycemia, shock, hypoventilation, ileus

  • 50% mortality

  • Treat with IV levothyroxine, steroids


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Thyroid Nodule

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

  • What questions do you have?

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

  • What is the next step?


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Thyroid Nodules

  • Lifetime risk of palpable nodule 5-10%

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

  • Only 1 in 20 is malignant


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Malignancy

Papillary

Follicular

Medullary

Anaplastic

Metastasis

Benign follicular adenoma

Cyst

Colloid Nodule

Differential Diagnosis


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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


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

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


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Evaluation of Nodule Carcinoma in a Euthyroid Patient with a Solitary Nodule, According to the Degree of Suspicion

  • Measure TSH

    • If Hyperthyroid (low TSH), do uptake and scan

      • Treat with surgery or I-131 ablation

    • If normal thyroid function, next step is fine needle aspiration (FNA)

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


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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


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Fine Needle Aspiration a Clinically Detectable Solitary Thyroid Nodule

  • FNA is most effective way to distinguish between benign and malignant nodules

  • Inexpensive, performed as outpatient

  • Ultrasound guided FNA if not palpable or less than 1.5 cm in diameter

  • What results will I see?

    • Benign-75% of the time

    • Malignant-4% of cases

    • Suspicious or inadequate-22%


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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


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Management of Nodules a Clinically Detectable Solitary Thyroid Nodule

  • Malignant

    • Total thyroidectomy

  • Suspicious

    • Thyroidectomy

  • Benign

    • Discuss with the patient

    • Ultrasound surveillance

    • Surgery

    • Consider levothyroxine suppression (varying results)


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Case Presentation a Clinically Detectable Solitary Thyroid Nodule

  • FNA revealed papillary thyroid carcinoma

  • Patient underwent total thyroidectomy

  • Treatment with I-131 ablation after surgery


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Osteoporosis a Clinically Detectable Solitary Thyroid Nodule


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Case Presentation a Clinically Detectable Solitary Thyroid Nodule

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

  • What questions should her PCP ask?

    • No history of fractures

    • Menopause was surgical at age of 55

    • Mother fractured her hip at 74


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Osteoporosis a Clinically Detectable Solitary Thyroid Nodule

  • Definition

    • Microarchitectural deterioration of bone tissue leading to decreased bone mass

    • Bone fragility

    • Susceptibility to fracture

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

  • Affects 10 million in the United States


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

  • Hip fracture is associated with increased risk of:

    • Disability: 50% never fully recover1,2

    • Long-term nursing home care required: 25%2

    • Increased mortality within 1 year due to complications: up to 24%3

    • Lifetime risk of death: comparable to that of breast cancer4

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.


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Osteoporosis and Even Death

  • Primary osteoporosis

    • Unrelated to chronic illness

    • Related to aging and decreased gonadal function

  • Secondary osteoporosis

    • Secondary to chronic illnesses that cause accelerated bone loss

    • Examples: Glucocorticoid use, celiac sprue, hyperthyroidism


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Current cigarette smoking and Even Death

Personal history of fracture as an adult

Low body weight (<127 lbs)

History of fracture infirst-degree relative

Estrogen deficiency, including menopause onset <age 45

Alcoholism

Caucasian race

Low calcium intake (lifelong)

Advanced age

Impaired eyesight despiteadequate correction

Female sex

Recurrent falls

Dementia

Inadequate physical activity

Poor health/frailty

Poor health/frailty

Risk Factors for Osteoporotic Fracture

Nonmodifiable

Potentially Modifiable

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.


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Diagnosis of Osteoporosis and Even Death

  • History and physical examination to exclude secondary osteoporosis

  • Laboratory studies if suspect secondary osteoporosis

  • Measurement of Bone Mineral Density (BMD)

    • Dual X-ray Absorptiometry (DEXA scan)

      • Provides most reproducible values of bone density

      • g/cm2


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BMD and Fracture Risk Are Inversely Related and Even Death

Forearm

100

Colles'

Spine

Vertebrae

4000

Hip

Hip and Heel

90

3000

Relative BMD (%)

80

Annual Fracture Incidence

2000

70

1000

60

0

35-

85+

30

40

50

60

70

80

90

39

Age

Age

Faulkner KG. J Clin Densitom. 1998;1:279–285.

Cooper C. Baillières Clin Rheumatol. 1993;7:459–477.


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Central DXA Measurement and Even Death

  • Measures multipleskeletal sites

    • Spine

    • Proximal femur

    • Forearm

    • Total body

  • Office based

  • Considered theclinical standard


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Who Should Be Considered for BMD Testing? and Even Death

National Osteoporosis Foundation Guidelines

  • Women 65 years of age regardless of additional risk factors

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

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

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

  • Women who have been on HRT for prolonged periods

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


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Other Populations To Consider for Assessment of Osteoporosis and Even Death

  • Men

  • Patients on long-term high-dose glucocorticoids


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Interpreting BMD Measurement Reports and Even Death

  • A clinically relevant value on the BMD report

  • Describes 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 osteoporosis

  • For every SD below the young adult normal, the risk of fracture approximately doubles

T-Score Is Key

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.


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Visualizing a Patient’s T-Score and Even Death

2

1

0

–1

–2

–3

–4

–5

–6

  • 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 young adult women

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

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

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

Peak Bone Mass

SD

T-score = –3.0

20 30 40 50 60 70 80 90

Age (years)

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


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Recommendations for Treatment and Even DeathBased on BMD Testing Results

National Osteoporosis Foundation Guidelines for

postmenopausal Women

T-SCORE ACTION

< –2.0 Initiate therapy

< –1.5 Initiate therapy

(with at least 1 additional risk factor)

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


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Treatment of Osteoporosis and Even Death

  • Adequate Calcium (1200 mg elemental)

  • Adequate Vitamin D (at least 400 IU)

  • Weight-bearing exercise


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Pharmacologic Agents and Even Death

  • Bisphosphonates

    • Inhibit osteoclastic bone resorption

    • Increased BMD and decreased fractures

    • Ex: alendronate, risedronate

  • Calcitonin

    • Nasal spray or injection

    • Decreased vertebral fractures

    • No hip fracture data

  • Raloxifen

    • SERM

    • Decreased vertebral fracture


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Osteoporosis Summary and Even Death

  • Osteoporosis 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 <–2.0 and those with a T-score of <–1.5 with at least one risk factor.


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