Disorders of Thyroid Function - Endocrinology

Transcript 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 (T 4 ) • Triiodotyrosine (T 3 )

The Thyroid Produces and Secretes 2 Metabolic Hormones

• Two principal hormones – Thyroxine (T 4 ) and triiodothyronine (T 3 ) • 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 T 4 and T 3

Hypothalamic-Pituitary-Thyroid Axis Negative Feedback Mechanism

Production of T

and T

3 • • • T 4 is the primary secretory product of the thyroid gland, which is the only source of T 4 The thyroid secretes approximately 70-90  g of T 4 per day T 3 – is derived from 2 processes The total daily production rate of T 3 is about 15-30  g – About 80% of circulating T 3 comes from deiodination of T 4 in peripheral tissues – About 20% comes from direct thyroid secretion

T

: A Prohormone for T

3 • • T 4 is biologically inactive in target tissues until converted to T 3 – Activation occurs with 5' iodination of the outer ring of T 4 T 3 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 T 3 ) regulate rate of overall body metabolism – T 3 increases basal metabolic rate Calorigenic effects – T 3 increases oxygen consumption by most peripheral tissues – Increases body heat production

Metabolic Effects of T

3 • • • • • • 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 T

3 • • • • • 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 T 3 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

Hypothyroidism Hyperthyroidism TSH High Low T 4 Low High T 3 Low High

Thyroid Disease Spectrum

Overt Hypothyroidism TSH >4.7  IU/mL, Free T 4 Low Subclinical Hypothyroidism TSH >4.7  IU/mL, Free T 4 Normal Euthyroid TSH 0.5-4.7  IU/mL, Free T 4 Normal Hyperthyroidism TSH <0.5  IU/mL, Free T 3 /T 4 Normal or Elevated 0 5  10 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

NHANES III Study (N=17 353) 18 16 14 12 10 8 6 4 2 0 13 19 20 29 Males Females 30 39 40 49 50 59 Age, y 60 69 70 79 >80 • 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 Serum total T 4 Free T 4 Free T 3 TPOAb, TgAb Normal Levels 5 11 µg/dL 0.7-1.8 ng/dL 2.77 – 5.27 ng/dL Negative When to Use DO NOT USE total T4/T3 Use with TSH to assess degree of hypothyroidism Use when FT4 does not confirm to TSH 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 Men Women Population 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.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 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 Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Inability to Concentrate Thinning Hair/Hair Loss Loss of Body Hair Dry, Patchy Skin Weight Gain Cold Intolerance Elevated Cholesterol Family History of Thyroid Disease or Diabetes Puffy Eyes Enlarged Thyroid (Goiter) Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Difficulty Swallowing Slower Heartbeat Menstrual Irregularities/ Heavy Period Infertility Constipation Muscle Weakness/ Cramps

Hypothyroidism and Depression Have Many Common Features

Depression Hypothyroidism • 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, 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 T 3 and T 4 levels Symptoms may be present or absent Cooper DS.

N Engl J Med

. 2001;345:260-265.

Progression of Thyroid Disease

Euthyroid Subclinical 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

300 250 Hypothyroid 200 150 100 Mild Thyroid Failure Euthyroid 50 0 Subclinical Hyperthyroid Hyperthyroid 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 100 Condition Present Condition Absent 50 0 Women With Subclinical Hypothyroidi sm Euthyroid Women Women With Subclinical Hypothyroid ism and Antibodies to Thyroid Euthyroid Women Without Antibodies to Thyroid Peroxidase 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 0 -5 -10 -15 -20 -25 -30 -35 -40 Gorman et al, 1979 Elder et al, 1990 Wiseman et al, 1993 Tanis BC, et al.

Clin Endocrinol.

1996;44:643-649.

Levothyroxine Therapy Reduces Cholesterol in Subclinical Hypothyroidism TSH Basel Thyroid Study (N=63) 250 Total Cholesterol 155 LDL-C 14 12 10 8 6 4 2 0 240 150 145 LT 4 Placebo 230 LT 4 Before Placebo After 140 LT 4 Placebo 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

TSH >3.0  IU/mL Initial Levothyroxine Dose 6-8 Weeks Repeat TSH Test TSH <0.5  IU/mL Increase Levothyroxine Dose by 12.5 to 25  g/d TSH 0.5- 2.0  IU/mL Symptoms Resolved 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 LT 4 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 LT 4 at 25-50  g/d with gradual dose increments at 6- to 8-week intervals For elderly patients with cardiac disease, start LT 4 at 12.5-25  g/d, with gradual dose increments at 4- to 6-week intervals The LT 4 dose is generally adjusted in 12.5-25 increments  g 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 surgery – – Short bowel syndrome Celiac disease • Drugs That Increase Clearance – Rifampin – – Carbamazepine Phenytoin Reduced Absorption – – – – – – – Colestipol hydrochloride Sucralfate Ferrous sulfate Food (eg, soybean formula) Aluminum hydroxide Cholestyramine Sodium polystyrene sulfonate • • Factors That Reduced T 4 to T 3 Clearance – – Other Mechanisms – – Amiodarone Selenium deficiency Lovastatin Sertraline Braverman LE, Utiger RD, eds.

The Thyroid: A Fundamental and Clinical Text

. 8 th ed. 2000.

Synthroid ® [package insert]. Abbott Laboratories; 2003.

6 5 1 0 4 3 2

Iron Ingestion and Levothyroxine Therapy

Ferrous Sulfate Effect on TSH Levels in Patients With Hypothyroidism

<.001

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.”

Disorders Characterized by Hyperthyroidism

Thyrotoxicosis and Hyperthyroidism Definitions

• • Thyrotoxicosis – The clinical syndrome of hypermetabolism that results when the serum concentrations of free T 4 , T 3 , 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 Difficulty Sleeping Bulging Eyes/Unblinking Stare/ Vision Changes Enlarged Thyroid (Goiter) Menstrual Irregularities/ Light Period Frequent Bowel Movements Warm, Moist Palms First-Trimester Miscarriage/ Excessive Vomiting in Pregnancy Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Difficulty Swallowing Palpitations/ Tachycardia Impaired Fertility Weight Loss or Gain Heat Intolerance Increased Sweating 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 131 I 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 h ESR 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 h FT4/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 T and T 3 levels 4 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

• • • Antithyroid drugs – Inhibit the synthesis of T 4 and T 3 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

TSH 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

FT4, 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

TSH,

FT4/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

TSH but

uptake on I123 U & S

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