Download Disorders of Thyroid Function - Endocrinology

Disorders of Thyroid
Function: Hypo and
Hyperthyroidism
Thomas Repas D.O.
Diabetes, Endocrinology and Nutrition Center, Affinity Medical Group, Neenah, Wisconsin
Member, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control Program
Member, Inpatient Diabetes Management Committee, St. Elizabeth’s Hospital, Appleton, WI
Chairman, Diabetes Steering Committee, AMG/NHP, Appleton, WI
Tuesday March 15, 2005
Website: www.endocrinology-online.com
Anatomy of the Thyroid Gland
Follicles: the Functional Units of
the Thyroid Gland
Follicles Are the Sites
Where Key Thyroid
Elements Function:
• Thyroglobulin (Tg)
• Tyrosine
• Iodine
• Thyroxine (T4)
• Triiodotyrosine (T3)
The Thyroid Produces and
Secretes 2 Metabolic Hormones
• Two principal hormones
– Thyroxine (T4 ) and triiodothyronine (T3)
• Required for homeostasis of all cells
• Influence cell differentiation, growth, and
metabolism
• Considered the major metabolic hormones
because they target virtually every tissue
Thyroid-Stimulating Hormone
(TSH)
• Regulates thyroid hormone
production, secretion, and growth
• Is regulated by the negative feedback
action of T4 and T3
Hypothalamic-Pituitary-Thyroid Axis
Negative Feedback Mechanism
Production of T4 and T3
• T4 is the primary secretory product of the
thyroid gland, which is the only source of T4
• The thyroid secretes approximately 70-90 g
of T4 per day
• T3 is derived from 2 processes
– The total daily production rate of T3 is about
15-30 g
– About 80% of circulating T3 comes from
deiodination of T4 in peripheral tissues
– About 20% comes from direct thyroid secretion
T4: A Prohormone for T3
• T4 is biologically inactive in target
tissues until converted to T3
– Activation occurs with 5' iodination of the
outer ring of T4
• T3 then becomes the biologically
active hormone responsible for the
majority of thyroid hormone effects
Thyroid Hormones Stimulate
Metabolic Activities in Most Tissues
• Thyroid hormones (specifically T3) regulate
rate of overall body metabolism
– T3 increases basal metabolic rate
• Calorigenic effects
– T3 increases oxygen consumption by most
peripheral tissues
– Increases body heat production
Metabolic Effects of T3
• Stimulates lipolysis and release of free fatty
acids and glycerol
• Induces expression of lipogenic enzymes
• Effects cholesterol metabolism
• Stimulates metabolism of cholesterol to bile
acids
• Facilitates rapid removal of LDL from plasma
• Generally stimulates all aspects of
carbohydrate metabolism and the pathway for
protein degradation
Additional Effects of T3
• Initiates or sustains differentiation and growth
• Stimulates formation of proteins, which exert
trophic effects on tissues
• Essential for neural development and
maturation and function of the CNS
• Important for normal reproductive function
• T3 is considered the major regulator of
mitochondrial activity
Disorders of Thyroid Function
Overview of Thyroid Dysfunction
• Hypothyroidism
• Hyperthyroidism
Typical Thyroid Hormone Levels
in Thyroid Disease
TSH
T4
T3
Hypothyroidism
High
Low
Low
Hyperthyroidism
Low
High
High
Thyroid Disease Spectrum
Overt Hypothyroidism
TSH >4.7 IU/mL, Free T4 Low
Subclinical Hypothyroidism
TSH >4.7 IU/mL, Free T4 Normal
Euthyroid
TSH 0.5-4.7 IU/mL, Free T4 Normal
Hyperthyroidism
TSH <0.5 IU/mL, Free T3/T4 Normal or Elevated
0
10
5
TSH, IU/mL
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.
Vanderpump MP, et al. Clin Endocrinol (Oxf). 1995;43:55-68.
Prevalence of Abnormal Thyroid
Function
The Colorado Thyroid Disease Prevalence study
• Used thyroid stimulating hormone (TSH) levels as a
measure of thyroid function
• Prevalence of elevated TSH levels (hypothyroidism)
was 9.5% and the prevalence of decreased TSH
levels (hyperthyroidism) was 2.2%
• Lipid levels increased as thyroid function declined
• 40% of patients taking thyroid medications had
abnormal TSH levels
Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.
Prevalence of Elevated Serum TSH
by Decade of Age and Gender
Participants With
Elevated TSH, %
NHANES III Study (N=17 353)
18
16
14
12
10
8
6
4
2
0
Males
Females
13- 20- 30- 40- 50- 60- 70- >80
19 29 39 49 59 69 79
Age, y
• At <40 years of
age, prevalence is
relatively low and
similar between
males and
females
• At ≥40 years of
age, a higher
percentage of
female patients
have elevated
TSH levels
Hollowell JG, et al. J Clin Endocrinol Metab. 2002;87:489-499.
Thyroid-Stimulating
Hormone (TSH) Assays
• Key test for diagnosis of hypothyroidism and
hyperthyroidism
• TSH assay sensitivity has improved with
subsequent test generations
– First generation: RIA
Sensitivity: 1.0 IU/mL
– Second generation: IRMA
Sensitivity: 0.1 IU/mL
– Third generation: ELISA
Sensitivity: 0.03 IU/mL
Ladenson PW, et al. Arch Intern Med. 2000;160:1573-1575.
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text.
8th ed. 2000.
Zophel K, et al. Nuklearmedizin. 1999;38:150-155.
Additional Laboratory Tests for
Thyroid Function
Test
Normal Levels
When to Use
Serum total T4
5-11 µg/dL
DO NOT USE total T4/T3
Free T4
0.7-1.8 ng/dL
Use with TSH to
assess degree of
hypothyroidism
Free T3
2.77 – 5.27 ng/dL
Use when FT4 does
not confirm to TSH
TPOAb, TgAb
Negative
In combination with TSH,
predictor of disease
progression
Endocr Pract. 2002;8:457-469.
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at: http://www.nacb.org/lmpg/thyroid_lmpg.stm.
Accessed July 1, 2003.
Screening for Disorders of Thyroid
Function
Population
Men
Women
Pregnant women
Patients >60 years of age
Testing Frequency
Every 5 years beginning at
35 years of age
Every 5 years beginning at
35 years of age
As soon as possible after
conception; up to 3 months
after giving birth
Once a year
The Endocrine Society Web site. Available at: http://www.endosociety.org/pubrelations/pressReleases/archives/1999/hypothyroid.cfm. Accessed April 17, 2003.
Loyola University New Orleans Web site. Available at: http://www.loyno.edu/~msthomas/hypo.html.
Accessed April 17, 2003.
Hypothyroidism
Hypothyroidism
• Hypothyroidism is a disorder with multiple
causes in which the thyroid fails to
secrete an adequate amount of thyroid
hormone
– The most common thyroid disorder
– Usually caused by primary thyroid gland failure
– Also may result from diminished stimulation of the
thyroid gland by TSH
Clinical Features of
Hypothyroidism
Tiredness
Puffy Eyes
Forgetfulness/Slower Thinking
Enlarged Thyroid (Goiter)
Moodiness/ Irritability
Hoarseness/
Deepening of Voice
Depression
Inability to Concentrate
Persistent Dry or Sore Throat
Thinning Hair/Hair Loss
Difficulty Swallowing
Loss of Body Hair
Slower Heartbeat
Dry, Patchy Skin
Menstrual Irregularities/
Heavy Period
Weight Gain
Cold Intolerance
Infertility
Elevated Cholesterol
Constipation
Family History of Thyroid
Disease or Diabetes
Muscle Weakness/
Cramps
Hypothyroidism and Depression
Have Many Common Features
Hypothyroidism
Depression
• Sleep decrease
• Suicidal ideation
• Weight loss
• Appetite increase/
decrease
• Constipation
• Appetite decrease
• Decreased concentration
• Decreased libido
• Delusions
• Depressed mood
• Diminished interest
• Sleep increase
• Weight increase
• Fatigue
• Bradycardia
• Cardiac and lipid
abnormalities
• Cold intolerance
• Delayed reflexes
• Goiter
• Hair and skin
changes
Nemeroff CB, J Clin Psychiatry. 1989;50(suppl):13-20.
Populations at Risk for
Hypothyroidism
• Women
• Prior history of Graves
disease or postpartum
thyroid dysfunction
• Elderly
• Other autoimmune disease
• Family history of
– Thyroid disease
– Pernicious anemia
– Type 1 Diabetes mellitus
Caraccio N, et al. J Clin Endocrinol Metab. 2002;87:1533-1538.
Carmel R, et al. Arch Intern Med. 1982;142:1465-1469.
Perros P, et al. Diabetes Med. 1995;12:622-627.
Hypothyroidism: Types
• Primary hypothyroidism
– From thyroid destruction
• Central or secondary hypothyroidism
– From deficient TSH secretion, generally due to sellar
lesions such as pituitary tumor or craniopharyngioma
– Infrequently is congenital
• Central or tertiary hypothyroidism
– From deficient TSH stimulation above level of pituitary—ie,
lesions of pituitary stalk or hypothalamus
– Is much less common than secondary hypothyroidism
Bravernan LE, Utiger RE, eds. Werner & Ingbar's The Thyroid.
8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000.
Persani L, et al. J Clin Endocrinol Metab. 2000; 85:3631-3635.
Primary Hypothyroidism:
Underlying Causes
• Congenital hypothyroidism
– Agenesis of thyroid
– Defective thyroid hormone biosynthesis due to enzymatic defect
• Thyroid tissue destruction as a result of
–
–
–
–
Chronic autoimmune (Hashimoto) thyroiditis
Radiation (usually radioactive iodine treatment for thyrotoxicosis)
Thyroidectomy
Other infiltrative diseases of thyroid (eg, hemochromatosis)
• Drugs with antithyroid actions (eg, lithium, iodine, iodinecontaining drugs, radiographic contrast agents, interferon alpha)
• In the US, hypothyroidism is usually due to chronic
autoimmune (Hashimoto) thyroiditis
Chronic Autoimmune Thyroiditis
(Hashimoto Thyroiditis)
• Occurs when there is a severe defect in thyroid
hormone synthesis
– Is a chronic inflammatory autoimmune disease characterized
by destruction of the thyroid gland by autoantibodies against
thyroglobulin, thyroperoxidase, and other thyroid tissue
components
– Patients present with hypothyroidism, painless goiter, and
other overt signs
• Persons with autoimmune thyroid disease may have
other concomitant autoimmune disorders
– Most commonly associated with type 1 diabetes mellitus
• Will often have significantly elevated anti-TPO ab
Subclinical Hypothyroidism
Definition of Subclinical
Hypothyroidism
• An isolated elevated TSH level in the
setting of normal T3 and T4 levels
• Symptoms may be present or absent
Cooper DS. N Engl J Med. 2001;345:260-265.
Progression of Thyroid Disease
Subclinical
Euthyroid Hypothyroidism
Overt
Hypothyroidism
TSH
Normal
Range
T3
T4
Years
Ayala AR, et al. Endocrinologist. 1997;7:44-50.
Subclinical Hypothyroidism
Prevalence
• Worldwide prevalence between 1%
and 10%
• Highest rates are in women older than
60 years of age
• Over the age of 74, 16% of men and
21% of women have the disorder
Cooper DS. N Engl J Med. 2001;345:260-264.
Subclinical Hypothyroidism May Be
Confused With Other Disorders
•
•
•
•
Hyperlipidemia
Depression
Gynecological conditions
Aging
Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.
Aldin V, et al. Am Fam Physician. 1998;57:776-780.
Nemeroff CB. J Clin Psychiatry. 1989;50(suppl):13-20.
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
Subclinical Hypothyroidism
and Cardiovascular Disease
• Cardiac manifestations
– Left ventricular systolic and diastolic dysfunction
– Increased systolic time interval
– Myocardial infarction
• Coronary artery disease
– Elevated total cholesterol levels, LDL-C levels,
and triglyceride levels
– Aortic atherosclerosis
– Hyperhomocysteinemia
Biondi B, et al. Ann Intern Med. 2002;137:904-914.
Ayala AR, et al. Cleve Clin J Med. 2002;69:313-320.
Aldin V, et al. Am Fam Physician. 1998;57:776-780.
Subclinical Hypothyroidism
Elevates Serum Lipid Levels
300
Hypothyroid
200
Mild Thyroid
Failure
150
Euthyroid
100
Subclinical
Hyperthyroid
50
Hyperthyroid
Lipid Levels, mg/dL
250
0
Total-C*
LDL-C*
*Total-C indicates total cholesterol; LDL-C,
LDL-Cholesterol; HDL-C, HDL-Cholesterol
HDL-C*
Triglycerides
Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.
The Rotterdam Study
Design and Objectives
• A population-based cross-sectional cohort study
conducted in a district of Rotterdam, the
Netherlands
– Cohort included 3105 men and 4878 women aged 55
and older
– Thyroid status was determined from a random sample
of 1149 elderly women (mean age 69 ± 7.5 years)
selected from the study
• The study's objective was to investigate whether
subclinical hypothyroidism and thyroid
autoimmunity are associated with aortic
atherosclerosis and myocardial infarction
Hak AE, et al. Ann Intern Med. 2000;132:270-278.
Subclinical Hypothyroidism Associated
With Aortic Atherosclerosis
Presence of Aortic Atherosclerosis
Condition Present
Condition Absent
Patients, %
100
50
0
Women With
Subclinical
Hypothyroidi
sm
Euthyroid
Women
Euthyroid
Women
Women
With
Without
Subclinical
Antibodies to
Hypothyroid
Thyroid
ism and
Peroxidase
Antibodies
to Thyroid
Peroxidase
Hak AE, et al. Ann Intern Med. 2000;132:270-278.
Subclinical Hypothyroidism Increases
Risk of Myocardial Infarction (cont.)
• Subclinical Hypothyroidism contributed
to 60% of MI cases in patients with
diagnosed subclinical hypothyroidism
• Subclinical Hypothyroidism contributed
to 14% of all MI instances in the study
population
• Subclinical Hypothyroidism is
independently associated with MI
Hak AE, et al. Ann Intern Med. 2000;132:270-278.
Rationale for Treating
Subclinical Hypothyroidism
• Potential benefits from treatment
– Prevent progression to overt
hypothyroidism
– Improve serum lipid profile, which may
reduce the risk of death from
cardiovascular causes
– Reduce symptoms, including psychiatric
and cognitive abnormalities
Cooper DS. N Engl J Med. 2001;345:260-264.
Subclinical Hypothyroidism Treated With
Levothyroxine Therapy: Effects on Total
Cholesterol
Change in Total Cholesterol
(mg/dL), %
Gorman et
al, 1979
Elder et al, Wiseman et al,
1990
1993
0
-5
-10
-15
-20
-25
-30
-35
-40
Tanis BC, et al. Clin Endocrinol. 1996;44:643-649.
Levothyroxine Therapy Reduces Cholesterol in
Subclinical Hypothyroidism
Basel Thyroid Study (N=63)
TSH
250
Total Cholesterol 155
LDL-C
10
8
6
LDL-C (mg/dL)
12
TC (mg/dL)
TSH (IU/mL)
14
240
4
150
145
2
0
230
LT4
Placebo
LT4
Before
Placebo
140
LT4
Placebo
After
Meier C, et al. J Clin Endocrinol Metab. 2001;86:4860-4866.
What is a Normal TSH?
A controversial topic….
• In their 2002 position statement, AACE used an
upper limit of normal for TSH of 3.0mIU/L
established in a population of patients carefully
screened for thyroid disease by the National
Academy of Biochemistry in 2002.
• However, in 2004 a statement was published in
JAMA maintaining that the upper limit of TSH
should remain at 4.5 mIU/L, rather than 3.0-3.5
as some other organizations have suggested.
AACE MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE EVALUATION AND TREATMENT OF HYPERTHYROIDISM AND
HYPOTHYROIDISM. ENDOCRINE PRACTICE Vol 8 No. 6 2002
JAMA 2004; 291:228-238
Treatment of Hypothyroidism
Hypothyroidism Treatment Goal
Euthyroidism
• The goal of hypothyroidism therapy is to
replace thyroxine to mimic normal,
physiologic levels and alleviate signs,
symptoms, and biochemical
abnormalities
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
Therapy Initiation and Titration
• Therapy with levothyroxine sodium products
requires individualized patient dosing
– Careful titration: use a formulation with consistent doses
– Clinical evaluation: symptoms resolve more slowly than
TSH response
– Laboratory monitoring: need consistent, sensitive TSH
measurements
• Individualized patient dosing is influenced by
–
–
–
–
Age and weight
Cardiovascular health
Severity and duration of hypothyroidism
Concomitant disease states and treatment
Endocr Pract. 2002;8:457-469.
Singer PA, et al. JAMA. 1995;273:808-812.
Hypothyroidism Treatment
• Levothyroxine sodium is the treatment of choice for
the routine management of hypothyroidism
– Adults: about 1.7 g/kg of body weight/d
– Children up to 4.0 g/kg of body weight/d
– Elderly <1.0 g/kg of body weight/d
• Clinical and biochemical evaluations at 6- to 8-week
intervals until the serum TSH concentration is
normalized
• Given the narrow and precise treatment range for
levothyroxine therapy, it is preferable to maintain the
patient on the same brand throughout treatment
Singer PA, et al. JAMA. 1995;273:808-812.
Endocr Pract. 2002;8:457-469.
AACE 2002 Position Statement on
the Management of Hypothyroidism
“Bioequivalence of levothyroxine preparations is
based on total T4 measurement and not TSH
levels; therefore, bioequivalence is not the
same as therapeutic equivalence.
Furthermore, various brands of levothyroxine
are not compared against a levothyroxine
standard.
Preferably, the patient should receive the same
brand of levothyroxine throughout treatment.”
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE
FOR THE EVALUATION AND TREATMENT OF HYPERTHYROIDISM AND HYPOTHYROIDISM. ENDOCRINE PRACTICE Vol 8 No. 6
November/December 2002
Joint Position Statement on the Use and
Interchangeability of Thyroxine Products
According AACE, TES, and ATA:
“Patients should be maintained on the
same brand name levothyroxine product.”
“If the brand of levothyroxine medication is
changed, either from one brand to
another brand, from a brand to a generic
product, or from a generic product to
another generic product, patients should
be retested by measuring serum TSH in
six (6) weeks.”
2004 AACE, TES, and ATA Joint Position Statement on the Use and Interchangeability ofThyroxine Products
Primary Hypothyroidism
Treatment Algorithm
Initial Levothyroxine Dose
6-8 Weeks
TSH >3.0 IU/mL
Repeat TSH Test
TSH <0.5 IU/mL
TSH 0.5- 2.0 IU/mL
Symptoms Resolved
Increase
Levothyroxine
Dose by
12.5 to 25 g/d
Continue Dose
Measure TSH at 6 Months,
Then Annually or
When Symptomatic
Decrease
Levothyroxine
Dose by
12.5 to 25 g/d
Singer PA, et al. JAMA. 1995;273:808-812.
Demers LM, Spencer CA, eds. The National Academy of
Clinical Biochemistry Web site. Available at:
http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed
July 1, 2003.
Therapy Monitoring
• Clinical and laboratory monitoring enable
– Evaluation of the clinical response
– Assessment of patient compliance
– Assessment of drug interactions, if applicable
– Adjustment of dosage, as needed
• Clinical and laboratory evaluations should be performed
– At 6- to 8-week intervals while titrating
– Every 6 – 12 months once a euthyroid state is established
Singer PA, et al. JAMA. 1995;273:808-812. Demers LM, Spencer CA, eds.
Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site.
Available at: http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.
Caution in Patients With Underlying
Cardiac Disease
• Using LT4 in those with ischemic heart disease increases
the risk of MI, aggravation of angina, or cardiac
arrhythmias
• For patients <50 years of age with underlying cardiac
disease, initiate LT4 at 25-50 g/d with gradual dose
increments at 6- to 8-week intervals
• For elderly patients with cardiac disease, start LT4 at
12.5-25 g/d, with gradual dose increments at 4- to 6-week
intervals
• The LT4 dose is generally adjusted in 12.5-25 g
increments
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
Kohno A, et al. Endocr J. 2001;48:565-572.
Synthroid® [package insert]. Abbott Laboratories; 2003.
Impact of Maternal Hypothyroidism on Subsequent
Neuropsychological Development of Offspring
• Undiagnosed hypothyroidism in pregnant
women may adversely affect fetuses
• Treating maternal hypothyroidism during
pregnancy appears to be beneficial, even
when treatment falls short of euthyroid status
• Screening for hypothyroidism before or very
early in pregnancy may be warranted
Haddow JE, et al. N Engl J Med. 1999;341:549-555.
Treating Hypothyroidism Before and
During Pregnancy
• Encourage adherence with levothyroxine replacement
therapy before conception
• Monitor TSH levels before conception and during first
trimester
• Monitor TSH levels every 6 weeks throughout
pregnancy
• Remember, that during first trimester in a euthyroid
pregnancy, TSH will normally fall slightly.
• A goal TSH of 0.1 to 0.5 is acceptable for most
pregnant patients.
• Also, may use FT4/FT3 to confirm appropriate thyroid
status.
Gharib H, et al. Endocr Pract. 1999;5:367-368.
Mandel SJ, et al. N Engl J Med. 1990;323:91-96.
Factors That May Reduce
Levothyroxine Effectiveness
• Malabsorption Syndromes
– Postjejunoileal bypass
• Drugs That Increase
Clearance
surgery
– Short bowel syndrome
– Celiac disease
– Rifampin
– Carbamazepine
– Phenytoin
• Reduced Absorption
–
–
–
–
–
–
–
• Factors That Reduced T4
Colestipol hydrochloride
to T3 Clearance
Sucralfate
– Amiodarone
Ferrous sulfate
– Selenium deficiency
Food (eg, soybean formula) • Other Mechanisms
Aluminum hydroxide
– Lovastatin
Cholestyramine
– Sertraline
Sodium polystyrene
sulfonate
Braverman LE, Utiger RD, eds. The Thyroid: A
Fundamental and Clinical Text. 8th ed. 2000.
Synthroid® [package insert]. Abbott Laboratories; 2003.
Iron Ingestion and
Levothyroxine Therapy
TSH Level, IU/mL
Ferrous Sulfate Effect on TSH Levels in
Patients With Hypothyroidism
P<.001
6
5
4
3
2
1
0
Before Ingestion
After Ingestion
Campbell NR, et al. Ann Intern Med. 1992;117:1010-1013.
Is there any role for T3
supplementation in the
management of
hypothyroidism?
NO!
AACE Position Statement on the
Management of Hypothyroidism
“Desiccated thyroid hormone, combinations
of thyroid hormones, or triiodothyronine
(T3) should not be used as replacement
therapy.”
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE
FOR THE EVALUATION AND TREATMENT OF HYPERTHYROIDISM AND HYPOTHYROIDISM. ENDOCRINE PRACTICE Vol 8 No. 6
November/December 2002
Disorders Characterized by
Hyperthyroidism
Thyrotoxicosis and Hyperthyroidism
Definitions
• Thyrotoxicosis
–The clinical syndrome of hypermetabolism that
results when the serum concentrations of free
T4, T3, or both are increased
• Hyperthyroidism
–Sustained increases in thyroid hormone
biosynthesis and secretion by the thyroid gland
The 2 terms are not synonymous
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
Hyperthyroidism
Underlying Causes
• Signs and symptoms can be caused by any
disorder that results in an increase in circulation
of thyroid hormone
–
–
–
–
–
–
Toxic diffuse goiter (Graves disease)
Toxic uninodular or multinodular goiter
Painful subacute thyroiditis
Silent thyroiditis
Toxic adenoma
Iodine and iodine-containing drugs and radiographic
contrast agents
– Trophoblastic disease, including hydatidiform mole
– Exogenous thyroid hormone ingestion
Signs and Symptoms of
Hyperthyroidism
Nervousness/Tremor
Mental Disturbances/
Irritability
Hoarseness/
Deepening of Voice
Persistent Dry or Sore Throat
Difficulty Swallowing
Difficulty Sleeping
Bulging Eyes/Unblinking Stare/
Vision Changes
Enlarged Thyroid (Goiter)
Menstrual Irregularities/
Light Period
Palpitations/
Tachycardia
Impaired Fertility
Weight Loss or Gain
Heat Intolerance
Increased Sweating
Frequent Bowel Movements
Warm, Moist Palms
First-Trimester Miscarriage/
Excessive Vomiting in Pregnancy
Sudden Paralysis
Family History of
Thyroid Disease
or Diabetes
Initial Evaluation of a Patient with
Hyperthyroidism
• TSH, FT4, FT3
• Thyroid uptake and scan
• Thyroid stimulating immunoglobulins (if
suspect Grave’s disease)
Graves Disease
(Toxic Diffuse Goiter)
• The most common cause of
hyperthyroidism
– Accounts for 60% to 90% of cases
– Incidence in the United States
estimated at 0.02% to 0.4% of the
population
– Affects more females than males,
especially in the reproductive age
range
• Thyroid stimulating
immunoglobulins may be
positive in some patients and
helpful for diagnosis
Toxic Multinodular Goiter
• More common in places with lower iodine
intake
– Accounts for less than 5% of thyrotoxicosis cases
in iodine-sufficient areas
• Evolution from sporadic diffuse goiter to toxic
multinodular goiter is gradual
• Thyrotropin receptor mutations and TSH
mutations have been found in some patients
with toxic multinodular goiters
• Surgery or 131I is recommended treatment
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
Thyroiditis
• Different types: subacute, chronic, other
• RAI imaging will show decreased uptake
• In subacute thyroiditis: thyroid may be
exquisitely tender on exam
• Some may have + anti TPO ab, + anti-TG ab
and hESR
• Does not respond to anti-thyroid medication
or RAI treatment
• TOC is steroids and other adjunctive therapy
Iodine Induced Hyperthyroidism
• RAI imaging will show decreased uptake
• Usual presentation is a patient with history of MNG
who receives IV contrast
• Other causes include amiodarone treatment or a
patient moving from a previously iodine deficient
area to one of high iodine intake
• Can be very difficult to treat, TOC is steroids and
adjunctive tx.
• If possible stop the offending agent (ie amiodarone).
• Often does not respond well to anti-thyroid
medications, but may try.
• There is no place for RAI treatment.
Transient Thyroxicosis of
Pregnancy
• Occasionally a suppressed but detectable TSH and
normal or hFT4/FT3 is found early in pregnancy
• Due to structural homology between B-HCG and TSH
• More severe in twin pregnancies and hyperemesis
gravidum (higher B-HCG)
• Usually self limited and resolves on own
• May treat with PTU and B blockers if severe or
symptomatic
• Be aware of the possibility of a primary thyroid disorder
also occurring in pregnancy, this may be suggested by:
– Undetectable TSH
– Goiter
– History of pre-existing thyroid disease
Factitious Hyperthyroidism
• Some patients will place themselves on LT4 or
“thyroid extracts” and other supplements without
telling you
• Alternative health care practitioners and mental
health care providers may also use LT4 or T3
therapy for dubious or unproven reasons
• Thyroid may be small on exam or US, especially if
history of long term use
• RAI uptake will be low
• Thyroglobulin will also be unexpectedly low; TG is
elevated in ALL other causes of hyperthyroidism
Subclinical Hyperthyroidism
Definition of Subclinical
Hyperthyroidism
• Subnormal TSH level
• Normal total or free serum T4
and T3 levels
• Few or no signs or symptoms of
hyperthyroidism
Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8th ed.
Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000;1001.
Potential Consequences of
Subclinical Hyperthyroidism
• Decreased bone density with increase
risk of osteopenia or osteoporosis
• Increased risk of cardiac arrhythmias,
especially in the elderly
• Increased risk of miscarriage in
pregnancy
• May or may not have obvious
symptoms
Should Subclinical
Hyperthyroidism be Treated?
Depends on the individual circumstances and
presentation of the patient:
• Usually will treat if TSH < 0.1
• If TSH between 0.1 and 0.5:
– May initially observe only and follow for development of
overt hyperthyroidism (especially if young and otherwise
healthy patient)
– Should consider treatment if evidence of potential
complications of hyperthyroidism (osteopenia or
osteoporosis, a-fib), if frail/elderly or (possibly) if
symptoms
Treatment of Hyperthyroidism
Treatment of Hyperthyroidism
• Antithyroid drugs
– Inhibit the synthesis of T4 and T3
• Radioactive iodine therapy
– Iodine 131 taken up by functioning thyroid tissue
can decrease thyroid hormone production
• Surgical resection
– Remove hyperplastic and adenomatous tissues
– Restore normal thyroid function and,
consequently, pituitary function
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
Adjunctive Therapy of
Hyperthyroidism
•
•
•
•
Beta blockers
Corticosteroid therapy
Bile acid sequestrants
Iodide
Which Treatment to choose?
Depends on:
• Patient preference
• Severity of hyperthyroidism
• Evidence of complications of
hyperthyroidism
• Pregnancy
• The cause of hyperthyroidism
Unusual Thyroid Studies
iTSH but FT4 also i
Get FT3
• T3 toxicosis is not uncommon in Grave’s
disease- an elevated or high normal FT3
would be suggestive, as would a positive TSI
and diffuse goiter
• Sometimes seen in acute/chronic illness
• Central hypothyroidism is very rare in the
absence of risk factors or suspicious history
but would be suggested if FT3 also low
iFT4, but Normal TSH and FT3
• Most of these patients are normal and
do not need LT4 supplementation to
bring FT4 to normal range
• This is also occasionally seen in
patients with chronic disease or
depression, clinical significance
unknown, but LT4 supplementation not
recommended
Clinical Hyperthyroidism with iTSH,
hFT4/FT3 but RAI Uptake “Normal”
• Early/subclinical Grave’s disease could
present this way
• Remember that many medications can
interfere with RAI uptake
• High iodine diet or previous iodine
exposure (IV contrast, amiodarone)
could also reduce thyroid RAI uptake
iTSH but i uptake on I123 U & S
•
•
•
•
Thyroiditis
Iodine induced thyrotoxicosis
Factitious Hyperthyroidism
Central Hypothyroidism