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
Cellular effects of thyroid
Hyperthyroidism Symptoms
Anxiety/irritability
Weakness
Tremors
Difficulty sleeping
Palpitations
Increased bowel
movements
Fatigue
Weight loss
Hyperkinetic
movements
Heat intolerance
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?
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?
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 0125%)
Negative Thyroid peroxidase and
thyroglobulin antibodies
Case Presentation
Patient was diagnosed with Graves’
Disease
Started on Methimazole 10 mg TID
Propranolol for symptom management
Anticoagulation for atrial fibrillation
Thyroid Antibodies
TSH receptor antibodies

Can be stimulating or inhibitory
Thyroglobulin antibodies
Thyroid peroxidase antibodies (formerly
known as microsomal)
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
Differential Diagnosis
• 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 LThyroxine
Struma ovarii
Amiodarone
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
Pathogenesis of Graves' Disease
Weetman, A. P. N Engl J Med 2000;343:1236-1248
Clinical Manifestations
Symptoms and signs of hyperthyroidism
Ophthalmopathy

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


Present in 50% of patients
Eyelid retraction
Periorbital edema
Proptosis (exopthalmos)
Diploplia
Dermopathy (myxedema)
Clinical Manifestations of Graves' Disease
Weetman, A. P. N Engl J Med 2000;343:1236-1248
Graves’ Disease
Associated Conditions







Type I Diabetes Mellitus
Addison’s Disease
Vitiligo
Pernicious anemia
Alopecia Areata
Myasthenia Gravis
Celiac Disease
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
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
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
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
Silent Thyroiditis
Also called painless or lymphocytic
thyroiditis
Not painful like subacute
Transient
Low iodine uptake
Hypothyroidism
Weakness
Fatigue
Lethargy, sleepiness
Slowness of speech and thought
“Puffy” appearance
Dry skin, coarse hair
Cold intolerance
Constipation
Physical Findings
Puffy features
Dry skin
Nonpitting edema
Hypothermia
Bradycardia
Slow return of deep tendon reflexes
Loss of lateral portion of eyebrows
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
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
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
Myxedema Coma
Severe untreated hypothyroidism
Hypothermia, hypoglycemia, shock,
hypoventilation, ileus
50% mortality
Treat with IV levothyroxine, steroids
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?
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
Differential Diagnosis
Malignancy


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Papillary
Follicular
Medullary
Anaplastic
Metastasis
Benign follicular
adenoma
Cyst
Colloid Nodule
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
Hegedus, L. N Engl J Med 2004;351:1764-1771
Evaluation of Nodule
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.
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
Fine Needle Aspiration
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%
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
Management of Nodules
Malignant

Total thyroidectomy
Suspicious

Thyroidectomy
Benign

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Discuss with the patient
Ultrasound surveillance
Surgery
Consider levothyroxine suppression (varying results)
Case Presentation
FNA revealed papillary thyroid carcinoma
Patient underwent total thyroidectomy
Treatment with I-131 ablation after surgery
Osteoporosis
Case Presentation
70 year old female asks her PCP if she
should have a bone density done.
What questions should her PCP ask?
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No history of fractures
Menopause was surgical at age of 55
Mother fractured her hip at 74
Osteoporosis
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
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.
Osteoporosis
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
Risk Factors for Osteoporotic
Fracture
Nonmodifiable
Potentially Modifiable
Personal history of fracture
as an adult
Current cigarette smoking
History of fracture in
first-degree relative
Estrogen deficiency, including
menopause onset <age 45
Caucasian race
Alcoholism
Low body weight (<127 lbs)
Low calcium intake (lifelong)
Advanced age
Female sex
Impaired eyesight despite
adequate correction
Recurrent falls
Dementia
Poor health/frailty
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 Osteoporosis
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
Forearm
Relative BMD (%)
100
Spine
Hip and Heel
90
80
70
60
30
40
50
60
70
80
90
Age
Faulkner KG. J Clin Densitom. 1998;1:279–285.
Annual Fracture Incidence
BMD and Fracture Risk Are
Inversely Related
Colles'
4000
Vertebrae
Hip
3000
2000
1000
0
3539
85+
Age
Cooper C. Baillières Clin Rheumatol. 1993;7:459–477.
Central DXA Measurement
Measures multiple
skeletal sites
 Spine
 Proximal femur
 Forearm
 Total body
Office based
Considered the
clinical standard
Who Should Be Considered for BMD
Testing?
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.
Other Populations To Consider for
Assessment of Osteoporosis
Men
Patients on long-term high-dose
glucocorticoids
Interpreting BMD Measurement
Reports
T-Score Is Key
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
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.
Visualizing a Patient’s T-Score
2
1
Peak Bone Mass
SD
0
–1
–2
–3
–4
T-score = –3.0
–5
–6
20
90
30
40
50
60
70
80
Age (years)
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
National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of
Osteoporosis. Belle Mead, NJ: Excerpta Medica, Inc.; 1998.
Recommendations for Treatment
Based on BMD Testing Results
National Osteoporosis Foundation Guidelines for
postmenopausal Women
T-SCORE
< –2.0
< –1.5
(with at least 1
additional risk factor)
ACTION
Initiate therapy
Initiate therapy
National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis.
Belle Mead, NJ: Excerpta Medica, Inc.; 1998.
Treatment of Osteoporosis
Adequate Calcium (1200 mg elemental)
Adequate Vitamin D (at least 400 IU)
Weight-bearing exercise
Pharmacologic Agents

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
Osteoporosis Summary
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.