Disorders of Thyroid Function

1
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. Elizabeths Hospital, Appleton, WI Chairman,
Diabetes Steering Committee, AMG/NHP, Appleton,
WI Tuesday March 15, 2005
Website www.endocrinology-online.com
2
Anatomy of the Thyroid Gland
3
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)

4
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

5
Thyroid-Stimulating Hormone (TSH)

• Regulates thyroid hormone production, secretion,
  and growth
• Is regulated by the negative feedback action of
  T4 and T3

6
Hypothalamic-Pituitary-Thyroid AxisNegative
Feedback Mechanism
7
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

8
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

9
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

10
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

11
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

12
Disorders of Thyroid Function
13
Overview of Thyroid Dysfunction

• Hypothyroidism
• Hyperthyroidism

14
Typical Thyroid Hormone Levels in Thyroid Disease

• TSH T4 T3
• Hypothyroidism High Low Low
• Hyperthyroidism Low High High

15
Thyroid Disease Spectrum
Overt Hypothyroidism TSH gt4.7 ?IU/mL, Free T4 Low
Subclinical Hypothyroidism TSH gt4.7 ?IU/mL, Free
T4 Normal
Euthyroid TSH 0.5-4.7 ?IU/mL, Free T4 Normal
Hyperthyroidism TSH lt0.5 ?IU/mL, Free T3/T4
Normal or Elevated
?10
0
5
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.
2000160526-534. Vanderpump MP, et al. Clin
Endocrinol (Oxf). 19954355-68.
16
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.
2000160526-534.
17
Prevalence of Elevated Serum TSH by Decade of
Age and Gender
NHANES III Study (N17 353)

• At lt40 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

Males
Females
Participants With Elevated TSH,
Hollowell JG, et al. J Clin Endocrinol Metab.
200287489-499.
18
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.
20001601573-1575. Braverman LE, et al. Werner
Ingbars The Thyroid. A Fundamental and Clinical
Text. 8th ed. 2000. Zophel K, et al.
Nuklearmedizin. 199938150-155.
19
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. 20028457-469. 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.
20
Screening for Disorders of Thyroid Function
The Endocrine Society Web site. Available at
http//www.endo-society.org/pubrelations/pressRele
ases/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.
21
Hypothyroidism
22
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

23
Clinical Features of Hypothyroidism
Tiredness
Puffy Eyes
Enlarged Thyroid (Goiter)
Forgetfulness/Slower Thinking
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
Constipation
Elevated Cholesterol
Muscle Weakness/Cramps
Family History of Thyroid Disease or Diabetes
24
Hypothyroidism and DepressionHave Many Common
Features
Hypothyroidism
Depression

• 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

• Sleep decrease
• Suicidal ideation
• Weight loss
• Appetite increase/ decrease

Nemeroff CB, J Clin Psychiatry.
198950(suppl)13-20.
25
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.
2002871533-1538. Carmel R, et al. Arch Intern
Med. 19821421465-1469. Perros P, et al.
Diabetes Med. 199512622-627.
26
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 853631-3635.
27
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

28
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

29
Subclinical Hypothyroidism
30
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. 2001345260-265.
31
Progression of Thyroid Disease
Overt Hypothyroidism
Subclinical Hypothyroidism
Euthyroid
TSH
Normal Range
T3
T4
Years
Ayala AR, et al. Endocrinologist. 1997744-50.
32
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. 2001345260-264.
33
Subclinical Hypothyroidism May Be Confused With
Other Disorders

• Hyperlipidemia
• Depression
• Gynecological conditions
• Aging

Canaris GJ, et al. Arch Intern Med.
2000160526-534. Aldin V, et al. Am Fam
Physician. 199857776-780. Nemeroff CB. J Clin
Psychiatry. 198950(suppl)13-20. Braverman LE,
et al. Werner Ingbars The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
34
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.
2002137904-914. Ayala AR, et al. Cleve Clin J
Med. 200269313-320. Aldin V, et al. Am Fam
Physician. 199857776-780.
35
Subclinical Hypothyroidism Elevates Serum Lipid
Levels
300
250
200
150
Lipid Levels, mg/dL
100
50
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.
2000160526-534.
36
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. 2000132270-278.
37
Subclinical Hypothyroidism Associated With Aortic
Atherosclerosis
Presence of Aortic Atherosclerosis
Condition Present
100
Condition Absent
Patients,
50
0
Euthyroid Women Without Antibodies to Thyroid
Peroxidase
Women With Subclinical Hypothyroidism
Euthyroid Women
Women With Subclinical Hypothyroidism and
Antibodies to Thyroid Peroxidase
Hak AE, et al. Ann Intern Med. 2000132270-278.
38
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. 2000132270-278.
39
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. 2001345260-264.
40
Subclinical Hypothyroidism Treated With
Levothyroxine Therapy Effects on Total
Cholesterol
Gorman et
Elder et al,
Wiseman et al,
al, 1979
1990
1993
0
-5
-10
-15
Change in Total Cholesterol (mg/dL),
-20
-25
-30
-35
-40
Tanis BC, et al. Clin Endocrinol. 199644643-649.
41
Levothyroxine Therapy Reduces Cholesterol in
Subclinical Hypothyroidism
Basel Thyroid Study (N63)
TSH
Total Cholesterol
LDL-C
250
155
14
12
150
10
TSH (?IU/mL)
TC (mg/dL)
240
8
LDL-C (mg/dL)
6
145
4
2
0
230
140
LT4
Placebo
Placebo
Placebo
LT4
LT4
Meier C, et al. J Clin Endocrinol Metab.
2001864860-4866.
42
What is a Normal TSH?
43
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 291228-238
44
Treatment of Hypothyroidism
45
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.
46
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. 20028457-469. Singer PA, et al.
JAMA. 1995273808-812.
47
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 lt1.0 ?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. 1995273808-812. Endocr
Pract. 20028457-469.
48
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
49
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
50
Primary Hypothyroidism Treatment Algorithm
Initial Levothyroxine Dose
6-8 Weeks
TSH gt3.0 ?IU/mL
TSH lt0.5 ?IU/mL
Repeat TSH Test
TSH 0.5- 2.0 ?IU/mL Symptoms Resolved
Increase Levothyroxine Dose by 12.5 to 25 ?g/d
Decrease Levothyroxine Dose by 12.5 to 25 ?g/d
Continue Dose
Measure TSH at 6 Months, Then Annually or When
Symptomatic
Singer PA, et al. JAMA. 1995273808-812. 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.
51
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. 1995273808-812. 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/thyro
id_lmpg.stm. Accessed July 1, 2003.
52
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 lt50 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.
200148565-572. Synthroid package insert.
Abbott Laboratories 2003.
53
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. 1999341549-555.
54
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. 19995367-368. Man
del SJ, et al. N Engl J Med. 199032391-96.
55
Factors That May Reduce Levothyroxine
Effectiveness

• Malabsorption Syndromes
• Postjejunoileal bypass surgery
• Short bowel syndrome
• Celiac disease
• Reduced Absorption
• Colestipol hydrochloride
• Sucralfate
• Ferrous sulfate
• Food (eg, soybean formula)
• Aluminum hydroxide
• Cholestyramine
• Sodium polystyrene sulfonate

• Drugs That Increase Clearance
• Rifampin
• Carbamazepine
• Phenytoin
• Factors That Reduced T4 to T3 Clearance
• Amiodarone
• Selenium deficiency
• Other Mechanisms
• Lovastatin
• Sertraline

Braverman LE, Utiger RD, eds. The Thyroid A
Fundamental and Clinical Text. 8th ed.
2000. Synthroid package insert. Abbott
Laboratories 2003.
56
Iron Ingestion and Levothyroxine Therapy
Ferrous Sulfate Effect on TSH Levels in
Patients With Hypothyroidism
6
Plt.001
5
4
TSH Level, ?IU/mL
3
2
1
0
Before Ingestion
After Ingestion
Campbell NR, et al. Ann Intern Med.
19921171010-1013.
57
Is there any role for T3 supplementation in the
management of hypothyroidism?
58
NO!
59
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
60
Disorders Characterized by Hyperthyroidism
61
Thyrotoxicosis and HyperthyroidismDefinitions

• 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.
62
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

63
Signs and Symptoms of Hyperthyroidism
Hoarseness/Deepening of Voice
Nervousness/Tremor
Mental Disturbances/ Irritability
Persistent Dry or Sore Throat
Difficulty Swallowing
Difficulty Sleeping
Palpitations/Tachycardia
Bulging Eyes/Unblinking Stare/ Vision Changes
Impaired Fertility
Enlarged Thyroid (Goiter)
Weight Loss or Gain
Menstrual Irregularities/Light Period
Heat Intolerance
Increased Sweating
Frequent Bowel Movements
Sudden Paralysis
Warm, Moist Palms
Family History ofThyroid Diseaseor Diabetes
First-Trimester Miscarriage/ Excessive Vomiting
in Pregnancy
64
Initial Evaluation of a Patient with
Hyperthyroidism

• TSH, FT4, FT3
• Thyroid uptake and scan
• Thyroid stimulating immunoglobulins (if suspect
  Graves disease)

65
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

66
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.
67
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

68
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.

69
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

70
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

71
Subclinical Hyperthyroidism
72
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
20001001.
73
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

74
Should Subclinical Hyperthyroidism be Treated?

• Depends on the individual circumstances and
  presentation of the patient
• Usually will treat if TSH lt 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

75
Treatment of Hyperthyroidism
76
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.
77
Adjunctive Therapy of Hyperthyroidism

• Beta blockers
• Corticosteroid therapy
• Bile acid sequestrants
• Iodide

78
Which Treatment to choose?

• Depends on
• Patient preference
• Severity of hyperthyroidism
• Evidence of complications of hyperthyroidism
• Pregnancy
• The cause of hyperthyroidism

79
Unusual Thyroid Studies
80
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

81
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

82
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

83
iTSH but i uptake on I123 U S

• Thyroiditis
• Iodine induced thyrotoxicosis
• Factitious Hyperthyroidism
• Central Hypothyroidism