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 Fatigue
Weakness Weight loss
Tremors Hyperkinetic
Difficulty sleeping movements
Palpitations Heat intolerance
Increased bowel
movements
 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 DTRs, 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 0-
125%)
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 Low uptake
Graves Disease Subacute Thyroiditis
Multinodular Goiter
Silent Thyroiditis
Toxic solitary Nodule
TRH secreting Pituitary
Iodine induced
Tumor Exogenous L-
HCG secreting tumor Thyroxine
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
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
Addisons 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 Quervains 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 Benign follicular
Papillary adenoma
Follicular Cyst
Medullary Colloid Nodule
Anaplastic
Metastasis
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
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?
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;17:505S511S.
3. Ray NF et al. J Bone Miner Res. 1997;12(1):2435.
4. Cummings SR et al. Arch Intern Med. 1989;149:24452448.
 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 Current cigarette smoking
as an adult
Low body weight (<127 lbs)
History of fracture in Estrogen deficiency, including
first-degree relative menopause onset <age 45

Caucasian race Alcoholism

Low calcium intake (lifelong)
Advanced age
Impaired eyesight despite
adequate correction
Female sex
Recurrent falls
Dementia
Inadequate physical activity
Poor health/frailty Poor health/frailty

Gold 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 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
 BMD and Fracture Risk Are
Inversely Related

Annual Fracture Incidence

100 Forearm Colles'
Relative BMD (%)

Spine 4000 Vertebrae

Hip and Heel Hip
90
3000

80
2000

70
1000

60
0
30 40 50 60 70 80 90 35- 85+
39
Age Age

Faulkner KG. J Clin Densitom. 1998;1:279285. Cooper C. Baillires Clin Rheumatol. 1993;7:459477.
 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, Physicians 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, 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.
 Visualizing a Patients T-Score
2
1
0 Peak Bone Mass
1
SD

2
3
4
T-score = 3.0
5
6
20 30 40 50 60 70 80
90 Age (years)
T-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 = 3.0
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, Physicians 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 ACTION

< 2.0 Initiate therapy

< 1.5 Initiate therapy

(with at least 1
additional risk factor)

National Osteoporosis Foundation, Physicians 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.