Disorders of Thyroid

Function: Hypo and

Hyperthyroidism

Joseph Partogi Sibarani, SPPD

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 5 10
TSH, IU/mL
Braverman LE, et al. Werner & Ingbars 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
NHANES III Study (N=17 353)
At <40 years of
Males age, prevalence is
relatively low and
Elevated TSH, %

Females
Participants With

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 & Ingbars 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 g/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 & Ingbars 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 Testing Frequency

Every 5 years beginning at
Men
35 years of age
Every 5 years beginning at
Women
35 years of age
As soon as possible after
Pregnant women conception; up to 3 months
after giving birth
Patients >60 years of age Once a year

The Endocrine Society Web site. Available at: http://www.endo-

society.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
Persistent Dry or Sore Throat
Inability to Concentrate
Thinning Hair/Hair Loss Difficulty Swallowing

Loss of Body Hair Slower Heartbeat

Dry, Patchy Skin Menstrual Irregularities/

Heavy Period
Weight Gain Infertility
Cold Intolerance
Elevated Cholesterol Constipation
Muscle Weakness/
Family History of Thyroid Disease or
Cramps
Diabetes
 Hypothyroidism and Depression
Have Many Common Features
Depression Hypothyroidism

Constipation
Appetite decrease Bradycardia
Decreased concentration Cardiac and lipid
Sleep decrease Decreased libido abnormalities
Suicidal ideation Delusions Cold intolerance
Weight loss Depressed mood Delayed reflexes
Appetite increase/ Diminished interest Goiter
decrease Sleep increase Hair and skin
Weight increase changes
Fatigue

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 pituitaryie,
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, iodine-
containing 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 Overt
Euthyroid Hypothyroidism 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 & Ingbars 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

250 Hypothyroid
Lipid Levels, mg/dL

200 Mild Thyroid

Failure
150 Euthyroid

100 Subclinical
Hyperthyroid
50 Hyperthyroid

0
Total-C* LDL-C* HDL-C* Triglycerides

*Total-C indicates total cholesterol; LDL-C,

LDL-Cholesterol; HDL-C, HDL-Cholesterol
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
100
Condition Absent
Patients, %

50

0
Women With Euthyroid Women Euthyroid
Subclinical Women With Women
Hypothyroidi Subclinical Without
sm Hypothyroid Antibodies to
ism and Thyroid
Antibodies Peroxidase
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

Gorman et Elder et al, Wiseman et al,

al, 1979 1990 1993
0
Change in Total Cholesterol

-5
-10
(mg/dL), %

-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
14
12
TSH (IU/mL)

150

LDL-C (mg/dL)
10
TC (mg/dL)

240
8
6 145
4
2
0 230 140
LT4 Placebo LT4 Placebo LT4 Placebo

Before 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 & Ingbars 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 Continue Dose Decrease

Levothyroxine Levothyroxine
Dose by Dose by
12.5 to 25 g/d Measure TSH at 6 Months, 12.5 to 25 g/d
Then Annually or Singer PA, et al. JAMA. 1995;273:808-812.
When Symptomatic 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 & Ingbars 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 Drugs That Increase
Postjejunoileal bypass Clearance
surgery Rifampin
Short bowel syndrome Carbamazepine
Celiac disease Phenytoin
Reduced Absorption Factors That Reduced T4
Colestipol hydrochloride to T3 Clearance
Sucralfate Amiodarone
Ferrous sulfate Selenium deficiency
Food (eg, soybean formula)
Aluminum hydroxide
Other Mechanisms
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
Ferrous Sulfate Effect on TSH Levels in
Patients With Hypothyroidism
6
P<.001
5
TSH Level, IU/mL

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 & Ingbars 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
Hoarseness/
Nervousness/Tremor
Deepening of Voice

Persistent Dry or Sore Throat

Mental Disturbances/ Irritability
Difficulty Swallowing
Difficulty Sleeping
Bulging Eyes/Unblinking Stare/ Vision Palpitations/

Changes Tachycardia

Enlarged Thyroid (Goiter) Impaired Fertility

Menstrual Irregularities/ Weight Loss or Gain

Heat Intolerance
Light Period
Increased Sweating
Frequent Bowel Movements
Warm, Moist Palms
Sudden Paralysis

Family History of
First-Trimester Miscarriage/
Thyroid Disease
Excessive Vomiting in Pregnancy
or Diabetes
Initial Evaluation of a Patient with
Hyperthyroidism

TSH, FT4, FT3

Thyroid uptake and scan
Thyroid stimulating immunoglobulins (if
suspect Graves 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 & Ingbars 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 & Ingbars 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 Graves
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 Graves 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