Thyroid Overview
Objectives <ul><li>Recognize the clinical findings of hypothyroidism. </li></ul><ul><li>Understand how to diagnose hypothy...
Thyroid Hormone Physiology Review <ul><li>Thyroid gland releases T4 and T3 </li></ul><ul><li>Thyroid follicular cells upta...
Thyroid physiology
Labs <ul><li>Serum Total T4 ( Thyroxin)  reflects thyroid hormone activity. Measures both free and bound T4  in healthy pa...
Labs <ul><li>╬   Serum TSH is the best SCREENING test for the diagnosis of hypothyroidism or hyperthyroidism in healthy am...
╬   Possible Test Question <ul><li>Which of the following is the best screening test for the diagnosis of hypothyroidism o...
Objective 1 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothy...
Clinical Findings of Hypothyroidism (part 1) <ul><li>Skin:dry, rough, non-pitting edema in lower extremities (myxedema), c...
Clinical Findings of Hypothyroidism(part 2) <ul><li>Renal:  Glomerular filtration rate, renal plasma flow, tubular reabsor...
Hypothyroidism <ul><li>Epidemiology/pathophysiology; </li></ul><ul><li>5 to 10% over 65  </li></ul><ul><li>Causes: </li></...
Primary Hypothyroidism
Labs <ul><li>╬   In primary hypothyroidism (99% of hypothyroidism) TSH is elevated. </li></ul><ul><li>TSH is one of the mo...
Labs <ul><li>Order T4 after TSH if: </li></ul><ul><ul><li>hypothalamic/pituitary disease is suspected </li></ul></ul><ul><...
Primary Hypothyroidism <ul><li>Types of primary hypothyroidism </li></ul><ul><ul><li>Hashimoto’s thyroiditis </li></ul></u...
Objective 2 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothy...
Primary Hypothyroidism <ul><li>Types of primary hypothyroidism   </li></ul><ul><li>*Hashimoto’s thyroiditis: </li></ul><ul...
╬   Lab summary - hypothyroidism
Primary Hypothyroidism <ul><li>Types of primary hypothyroidism   </li></ul><ul><ul><li>Hashimoto’s thyroiditis: </li></ul>...
Subacute thyroiditis-hypothyroid phase <ul><li>Etiology:  destruction of the thyroid gland  </li></ul><ul><li>*(often due ...
╬   Lab summary - hypothyroidism
Primary Hypothyroidism <ul><li>Types of primary hypothyroidism   </li></ul><ul><ul><li>Hashimoto’s thyroiditis: </li></ul>...
Secondary Hypothyroidism <ul><li>Adults: </li></ul><ul><ul><li>Almost always due to pituitiary disease. </li></ul></ul><ul...
╬   Lab summary - hypothyroidism
Tertiary Hypothryroidism <ul><li>Due to hypothalamic disease: </li></ul><ul><ul><li>sarcoidosis  </li></ul></ul><ul><ul><l...
Resistance to Thyroid Hormone <ul><li>Peripheral resistance to thyroid hormone is very rare. </li></ul><ul><li>Beyond scop...
Functional Thyroid Imaging <ul><li>Radioactive iodine (I-123), administered orally </li></ul><ul><li>the radioisotope and ...
Imaging <ul><li>Radionuclide Imaging of the Thyroid  </li></ul><ul><li>The radiotracer uptake is  increased  whenever   th...
Imaging <ul><li>Radionuclide Imaging of the Thyroid  </li></ul><ul><li>The radiotracer uptake is  decreased  whenever   th...
Objective 3 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothy...
Imaging <ul><li>╬  Thyroid functional scans they are not helpful in the diagnosis of hypothyroidism and should not be used...
Imaging <ul><li>╬  Thyroid functional scans they are not helpful in the diagnosis of hypothyroidism and should not be used...
Other Thyroid Imaging <ul><li>CT and MRI:  </li></ul><ul><ul><li>structural imaging modalities and provide no functional i...
. . . Hypothyroidism and pregnancy <ul><li>Maternal hypothyroidism during pregnancy may lead to adverse fetal outcomes.  <...
Objective 4 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothy...
Hyperthyroidism: clinical findings <ul><li>Weight loss </li></ul><ul><li>Heat intolerance </li></ul><ul><li>Insomnia </li>...
Hyperthyroidism  - with low TSH <ul><li>Grave’s Disease </li></ul><ul><li>Toxic Multinodular Goiter </li></ul><ul><li>Hype...
Grave’s Disease <ul><li>60-70% of all cases of hyperthyroidism. </li></ul><ul><li>3% of population affected. </li></ul><ul...
Graves Disease Findings <ul><li>Weight loss </li></ul><ul><li>Heat intolerance </li></ul><ul><li>Insomnia </li></ul><ul><l...
Grave’s Disease <ul><li>May be cyclic with exacerbations and remissions. </li></ul><ul><li>Usually, ongoing destructive in...
Grave’s Disease <ul><li>Familial predisposition </li></ul><ul><li>Overlap with automimmune Hashimoto’s thyroiditis and the...
Grave’s Disease <ul><li>*Cause:  circulating antibodies against various thyroid antigens.  </li></ul><ul><ul><li>The most ...
Grave’s Disease <ul><li>Cause:  circulating antibodies against various thyroid antigens.   </li></ul><ul><ul><li>The most ...
Grave’s Disease <ul><li>Cause:  circulating antibodies against various thyroid antigens.   </li></ul><ul><ul><li>The most ...
Objective 5 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothy...
Grave’s Disease <ul><li>Labs </li></ul><ul><li>Increased T4 and T3 </li></ul><ul><li>sometimes only T3 is elevated </li></...
<ul><li>IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN.  IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU ...
. . . however . . .  <ul><li>IF TSH depressed, T3 T4 increased, & no ophthalmopathy: </li></ul><ul><li>Then get a Radioact...
Subacute Thyroiditis - hyperthyroid phase <ul><li>Etiology:  destruction of the thyroid gland  </li></ul><ul><li>*(often d...
Compare: Graves vs  Subacute Thyroiditis hyperthyroid phase ______________________________________________________________...
Toxic Multinodular Goiter (MNG) <ul><li>Frequency:  20-30%  of hyperthyroid patients. </li></ul><ul><li>Pathophysiology: f...
Toxic Multinodular Goiter (MNG) <ul><li>Labs:  </li></ul><ul><li>*TSH suppressed;  </li></ul><ul><li>*T4 and T3 (high, nor...
Toxic Ademoma <ul><li>3-5% of thyrotoxicosis </li></ul><ul><li>Cause:  </li></ul><ul><li>* a single hyperfunctioning folli...
Iodine-induced Thyrotoxicosis <ul><li>Administering iodine may cause thyrotoxicosis in patients with: </li></ul><ul><li>*i...
Troma Ovarii <ul><li>Ectopic thyroid tissue </li></ul><ul><ul><li>Dermoid tumors </li></ul></ul><ul><ul><li>Ovarian terato...
TSH producing Pituitary Tumor <ul><li>Very rare </li></ul><ul><li>TSH high; T4 T3 high </li></ul>
Other causes of thyrotoxicosis <ul><li>Metastatic Thyroid Carcinoma </li></ul><ul><li>Molar Hydatiform Pregnancy and Chori...
Nuclear Imaging for thyrotoxicosis summary
OBJECTIVES <ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute...
╬   Possible Test Question <ul><li>Which of the following is the best screening test for the diagnosis of hypothyroidism o...
╬
<ul><li>╬   In primary hypothyroidism (99% of hypothyroidism) TSH is elevated. </li></ul><ul><li>╬   Serum TSH is the best...
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Thyroid Overview

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  • Thyroid Overview

    1. 1. Thyroid Overview
    2. 2. Objectives <ul><li>Recognize the clinical findings of hypothyroidism. </li></ul><ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute Hypothyroidism. </li></ul><ul><li>Understand the role of thyroid functional scans in the diagnosis of hypothyroidism. </li></ul><ul><li>Know the specific cellular activities that are overactive in Grave’s disease. </li></ul><ul><li>Understand how to diagnose Grave’s disease. </li></ul>
    3. 3. Thyroid Hormone Physiology Review <ul><li>Thyroid gland releases T4 and T3 </li></ul><ul><li>Thyroid follicular cells uptake iodine. </li></ul><ul><li>Iodine oxidized & incorporated into MIT & DIT </li></ul><ul><li>Coupling of iodotyrosine with thyroglobuline forms T3 & T4. </li></ul><ul><li>Poteolysis of the thyroglbuline molecule releases MIRT, DIT, T3, T4 . </li></ul><ul><li>MIT and DIT are deiodinated and the liberated iodine is reused. </li></ul><ul><li>T4 & T3 (to a much lesser extent) released from thyroid. </li></ul><ul><li>TPO (thyroperoxidate) medicates thyroid hormone synthesis. </li></ul><ul><ul><li>(mediates both: Oxidation of iodine; incorporation into tyrosyl resudues). </li></ul></ul><ul><li>Thyroid hormones transported to carrier proteins. .04% of T4 is free; .4% of T3 is free; the free form is the biologically active form able to bind to thyroid receptors. </li></ul><ul><li>T3 has a much higher affinity for the thyroid receptor than T4. </li></ul><ul><li>The body regulates thyroid activity by converting T4 to T3 (by deiodinases). </li></ul><ul><li>Free thyroid hormone is transported through cell membrane by a carrier and binds to thyroid receptors (TR). </li></ul><ul><li>Thyroid function is regulated by the hypothalamic-pituitary-thyroid axis. </li></ul><ul><li>Synthesis of T4 and T3 regulated by TSH. </li></ul><ul><li>A negative feedback loop is present. </li></ul>
    4. 4. Thyroid physiology
    5. 5. Labs <ul><li>Serum Total T4 ( Thyroxin) reflects thyroid hormone activity. Measures both free and bound T4 in healthy patients. </li></ul><ul><li>Serum Total T3 (Triiodothyronine) measures both free and bound T3 . </li></ul><ul><li>(TBG) is the major thyroid hormone binding proteins. </li></ul><ul><ul><li>Other proteins with binding capacity: transthyretin (thyroxine-binding prealbumin) and albumin. </li></ul></ul><ul><li>TSH is the only test that can detect small changes of thyroid hormone excess or deficiency. </li></ul><ul><li>Free Thyroid Hormone </li></ul><ul><ul><li>(rarely ordered) Usually what is reported is an estimate of free T4 which is a calculated Free T4 Index (FT4 I) </li></ul></ul>
    6. 6. Labs <ul><li>╬ Serum TSH is the best SCREENING test for the diagnosis of hypothyroidism or hyperthyroidism in healthy ambulatory individuals. </li></ul><ul><li>TSH is the initial test done to assess thyroid function and the only test needed if it is normal. </li></ul>
    7. 7. ╬ Possible Test Question <ul><li>Which of the following is the best screening test for the diagnosis of hypothyroidism or hyperthyroidism in healthy ambulatory individuals. </li></ul><ul><li>Radioiodine I-123 uptake </li></ul><ul><li>Free T3 </li></ul><ul><li>Free T4 Index </li></ul><ul><li>TSH (Correct answer) </li></ul><ul><li>TSH and functional scan </li></ul>
    8. 8. Objective 1 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute Hypothyroidism. </li></ul><ul><li>Understand the role of thyroid functional scans in the diagnosis of hypothyroidism. </li></ul><ul><li>Know the specific cellular activities that are overactive in Grave’s disease. </li></ul><ul><li>Understand how to diagnose Grave’s disease. </li></ul>
    9. 9. Clinical Findings of Hypothyroidism (part 1) <ul><li>Skin:dry, rough, non-pitting edema in lower extremities (myxedema), coarse hair, hair loss (lateral aspects of eyebrows). </li></ul><ul><li>Ocular: swelling of eyelids. </li></ul><ul><li>CV: Bradycardia, impared contraction with reduced cardiac output, cardiomegaly, pericardial effusion, increased incidence of coronary atherosclerosis. </li></ul><ul><li>Pulmonary: Shortnes of breath and resp. failure with mexedema coma. </li></ul><ul><li>ENT: Husky voice due to infiltration of vocal cords, enlarged tongue with associated garbled voice and sleep apnea. </li></ul><ul><li>GI: Reduced appetite, (increased weight is due to water retention), constipation, atrophic gastritis (50%), B12 malabsorption (12%). </li></ul><ul><li>CNS: severe brain damage in children born with hypothyroidism (cretinism) - the earlier the treatment the better the result. Reduced concentration, lethargy, coma, carpal tunnel. Slow relaxation phase of reflexes due to muscle dysfunction. </li></ul><ul><li>Muscles: Stiff, ache, elevated CPK and SGOT. </li></ul><ul><li>Anemia: mild normochromic normocitic is most common. Microcitic due to iron malabsorption; macrocitic due to B12 malabsorption. </li></ul>
    10. 10. Clinical Findings of Hypothyroidism(part 2) <ul><li>Renal: Glomerular filtration rate, renal plasma flow, tubular reabsorption are reduced (however - BUN and creatinine are normal); water excretion impaired. </li></ul><ul><li>Myxedema Coma: (decompensated hypothyroidism) </li></ul><ul><ul><li>end stage of severe long-standing hypothyroidism, </li></ul></ul><ul><ul><li>mental obtundation is profound. </li></ul></ul><ul><ul><li>an endocrine emergencies as the mortality is over 50%. </li></ul></ul><ul><ul><li>usually accompanied by a subnormal temperature, bradycardia, and hypotension are present. </li></ul></ul>
    11. 11. Hypothyroidism <ul><li>Epidemiology/pathophysiology; </li></ul><ul><li>5 to 10% over 65 </li></ul><ul><li>Causes: </li></ul><ul><li>*Defect within thyroid gland (Primary) </li></ul><ul><li>(accounts for ~98% of hypothyroidism) </li></ul><ul><li>*Deficiency of TSH (secondary) </li></ul><ul><li>*Deficiency of THR (tertiary or hypthalamic) </li></ul><ul><li>*Peripheral Tissue resistance to thyroid hormone </li></ul>
    12. 12. Primary Hypothyroidism
    13. 13. Labs <ul><li>╬ In primary hypothyroidism (99% of hypothyroidism) TSH is elevated. </li></ul><ul><li>TSH is one of the most sensitive tests in medicine. </li></ul>
    14. 14. Labs <ul><li>Order T4 after TSH if: </li></ul><ul><ul><li>hypothalamic/pituitary disease is suspected </li></ul></ul><ul><ul><ul><li>then a measure of free T4 (index or direct assay) is needed together with TSH. </li></ul></ul></ul><ul><ul><li>significant alterations in binding proteins are expected, </li></ul></ul><ul><ul><ul><li>then a measure of free T4 (index or direct assay) is needed together with TSH. </li></ul></ul></ul><ul><ul><ul><ul><li>Clinical conditions associated with elevation in thyroid hormone binding proteins include active hepatitis, pregnancy, drugs (estrogen, raloxifene, tamoxifen, 5-fluorouracil, perphenazine, clofibrate, heroin and methadone), acute intermittent porphyria and hereditary TBG excess. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Clinical conditions associated with reduction in thyroid hormone binding proteins include cirrhosis, nephrotic syndrome, protein losing enteropathies, malnutrition, severe illness, drugs (androgens, glucocorticoids), and hereditary TBG deficiency. </li></ul></ul></ul></ul>
    15. 15. Primary Hypothyroidism <ul><li>Types of primary hypothyroidism </li></ul><ul><ul><li>Hashimoto’s thyroiditis </li></ul></ul><ul><ul><li>Subacute thyroiditis </li></ul></ul><ul><ul><li>Iatragenic </li></ul></ul><ul><ul><li>Drugs </li></ul></ul><ul><ul><li>Iodine deficiency </li></ul></ul><ul><ul><li>Dyshormonogenesis </li></ul></ul><ul><ul><li>Primary and Metastatic Tumor to the Thyroid (rare) </li></ul></ul>
    16. 16. Objective 2 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute Hypothyroidism. </li></ul><ul><li>Understand the role of thyroid functional scans in the diagnosis of hypothyroidism. </li></ul><ul><li>Know the specific cellular activities that are overactive in Grave’s disease. </li></ul><ul><li>Understand how to diagnose Grave’s disease. </li></ul>
    17. 17. Primary Hypothyroidism <ul><li>Types of primary hypothyroidism </li></ul><ul><li>*Hashimoto’s thyroiditis: </li></ul><ul><ul><ul><li>Most common cause of primary hypothyrodism. </li></ul></ul></ul><ul><ul><ul><li>Etiology: autoimmune destruction of the thyroid gland </li></ul></ul></ul><ul><ul><ul><li>╬ TSH is elevated. </li></ul></ul></ul><ul><ul><ul><li>╬ Anti-thyroglobuline and/or anti-TPO antibodies are present in most (90%) patients. </li></ul></ul></ul><ul><ul><ul><li>Autoimmune thyroiditis may coexist with other autoimmune diseases: pernicious anemia, RA, DM, “Burnt out” Grave’s disease. </li></ul></ul></ul><ul><ul><li>Subacute thyroiditis </li></ul></ul><ul><ul><li>Iatragenic </li></ul></ul><ul><ul><li>Drugs </li></ul></ul><ul><ul><li>Iodine deficiency </li></ul></ul><ul><ul><li>Dyshormonogenesis </li></ul></ul><ul><ul><li>Primary and Metastatic Tumor to the Thyroid (rare) </li></ul></ul>
    18. 18. ╬ Lab summary - hypothyroidism
    19. 19. Primary Hypothyroidism <ul><li>Types of primary hypothyroidism </li></ul><ul><ul><li>Hashimoto’s thyroiditis: </li></ul></ul><ul><li>*Subacute thyroiditis (hypothryroid phase):Aka: granulomatous, lymphocytic or postpartum thyroiditis . . . . . . . . . . </li></ul><ul><ul><li>Iatragenic </li></ul></ul><ul><ul><li>Drugs </li></ul></ul><ul><ul><li>Iodine deficiency </li></ul></ul><ul><ul><li>Dyshormonogenesis </li></ul></ul>
    20. 20. Subacute thyroiditis-hypothyroid phase <ul><li>Etiology: destruction of the thyroid gland </li></ul><ul><li>*(often due to upper respiratory illness). </li></ul><ul><li>*Destruction leads to release of thyroid hormone in circulation (rather than from an increase in synthesis of hormone). </li></ul><ul><li>Symptoms: depends on phase </li></ul><ul><li>Radioiodine I-123 uptake: low </li></ul><ul><li>Outcome: </li></ul><ul><li>1. after thyrotoxic phase, </li></ul><ul><li>2. subacute thyroiditis may progress to transient (6 - 12 months) hypothyroidism (90% are transient) </li></ul><ul><li>3. return to euthyroidism </li></ul><ul><li>Supportive treatment only; no inhibitors of thyroid hormone synthesis are needed. </li></ul><ul><li>╬ TSH is elevated; Anti-thyroglobuline and/or anti-TPO antibodies are not present. </li></ul><ul><li>It is important not to erroneously diagnose these patients with Hashimoto's and commit them to life-long thyroid hormone replacement therapy. </li></ul>
    21. 21. ╬ Lab summary - hypothyroidism
    22. 22. Primary Hypothyroidism <ul><li>Types of primary hypothyroidism </li></ul><ul><ul><li>Hashimoto’s thyroiditis: </li></ul></ul><ul><ul><li>Subacute thyroiditis: </li></ul></ul><ul><li>*Iatragenic: </li></ul><ul><ul><li>Post ablative following radioactive iodine administration or after thyroidectomy. </li></ul></ul><ul><li>*Drugs: </li></ul><ul><ul><li>Lithium, amiodarone (~40% iodine), high intake of iodine such as in seaweed or algae tablets from health food stores. </li></ul></ul><ul><li>*Iodine deficiency: </li></ul><ul><ul><li>in some less developed countries - goiter is present . </li></ul></ul><ul><li>*Dyshormonogenesis: </li></ul><ul><ul><li>Enzymatic defects in thyroid hormone biosynthesis lead to poor hormone secretion and development of goiter. This is a rare cause of hypothyroidism, especially in the adult patient. Failure of the thyroid gland to descend during embryogenenesis may also cause congenital hypothyroidism. </li></ul></ul><ul><li>*Primary and Metastatic Tumor to the Thyroid (rare) </li></ul>
    23. 23. Secondary Hypothyroidism <ul><li>Adults: </li></ul><ul><ul><li>Almost always due to pituitiary disease. </li></ul></ul><ul><ul><li>╬ TSH is low or normal. </li></ul></ul><ul><ul><li>TSH may not be a biologically active as usual, but still detected in the TSH assay; TSH is called, “inappropriately normal.” </li></ul></ul><ul><li>Selective TSH deficiency: </li></ul><ul><ul><li>Very rare genetic cause of newborn hypothyroidism </li></ul></ul><ul><ul><li>May be seen in adults due to autoimmunity against thyrotrophs (cells that produce TSH). </li></ul></ul>
    24. 24. ╬ Lab summary - hypothyroidism
    25. 25. Tertiary Hypothryroidism <ul><li>Due to hypothalamic disease: </li></ul><ul><ul><li>sarcoidosis </li></ul></ul><ul><ul><li>tumors </li></ul></ul><ul><ul><li>radiation </li></ul></ul>
    26. 26. Resistance to Thyroid Hormone <ul><li>Peripheral resistance to thyroid hormone is very rare. </li></ul><ul><li>Beyond scope of this lecture. </li></ul>
    27. 27. Functional Thyroid Imaging <ul><li>Radioactive iodine (I-123), administered orally </li></ul><ul><li>the radioisotope and a scan (image) of the thyroid obtained 4 or 24 hours later. </li></ul><ul><li>I-123 is accumulated by thyroid follicular cell & incorporated into thyroglobulin (trapped and organified). </li></ul>
    28. 28. Imaging <ul><li>Radionuclide Imaging of the Thyroid </li></ul><ul><li>The radiotracer uptake is increased whenever thyroid under increased stimulus: </li></ul><ul><li>*Raised TSH </li></ul><ul><li>*Stimulating antibody of Grave’s disease </li></ul><ul><li>*When thyroid becomes autonomous (“hot” nodule or toxic multinodular goiter). </li></ul>
    29. 29. Imaging <ul><li>Radionuclide Imaging of the Thyroid </li></ul><ul><li>The radiotracer uptake is decreased whenever the thyroid is under decreased stimulus: </li></ul><ul><li>decreased TSH in hypopituitarism </li></ul><ul><li>exogenous thyroid hormone administration </li></ul><ul><li>when thyroid cells are damaged so that the uptake mechanism is defective </li></ul><ul><li>Hashimoto's thyroiditis: </li></ul><ul><li>autoimmune destruction of the thyroid gland; </li></ul><ul><li>Anti-thyroglobuline and/or anti-TPO antibodies are present in most (90%) patients </li></ul><ul><li>Subacute thyroiditis: </li></ul><ul><li> Destruction leads to release of thyroid hormone in circulation (rather than from an increase in synthesis of hormone). </li></ul><ul><li>When excess iodine &quot;swamps&quot; the radioactive tracer. </li></ul>
    30. 30. Objective 3 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute Hypothyroidism. </li></ul><ul><li>Understand the role of thyroid functional scans in the diagnosis of hypothyroidism. </li></ul><ul><li>Know the specific cellular activities that are overactive in Grave’s disease. </li></ul><ul><li>Understand how to diagnose Grave’s disease. </li></ul>
    31. 31. Imaging <ul><li>╬ Thyroid functional scans they are not helpful in the diagnosis of hypothyroidism and should not be used for this indication. </li></ul><ul><li>Hashimoto's thyroiditis : </li></ul><ul><li>autoimmune destruction of the thyroid gland; </li></ul><ul><li>Anti-thyroglobuline and/or anti-TPO antibodies are present in most (90%) patients. </li></ul><ul><li>DECREASED UPTAKE </li></ul><ul><li>Subacute thyroiditis: </li></ul><ul><li> Destruction leads to release of thyroid hormone in circulation (rather than from an increase in synthesis of hormone). </li></ul><ul><li> DECREASED UPTAKE </li></ul><ul><li>Thyroid functional scans are helpful in the differential diagnosis of hyperthyroidism and in determining the function of a thyroid nodule </li></ul>
    32. 32. Imaging <ul><li>╬ Thyroid functional scans they are not helpful in the diagnosis of hypothyroidism and should not be used for this indication. </li></ul><ul><li>Hashimoto's thyroiditis : </li></ul><ul><li>DECREASED UPTAKE </li></ul><ul><li>Subacute thyroiditis: </li></ul><ul><li> DECREASED UPTAKE </li></ul>
    33. 33. Other Thyroid Imaging <ul><li>CT and MRI: </li></ul><ul><ul><li>structural imaging modalities and provide no functional information. </li></ul></ul><ul><ul><li>NO role in the initial evaluation of thyroid dysfunction. </li></ul></ul><ul><li>Ultrasound: </li></ul><ul><ul><li>modality of choice for evaluation of thyroid structure (e.g. evaluation of thyroid nodules). </li></ul></ul><ul><li>CT or MRI: </li></ul><ul><ul><li>may be used to: </li></ul></ul><ul><ul><ul><li>visualize a large substernal goiter </li></ul></ul></ul><ul><ul><ul><li>evaluate tracheal compression. </li></ul></ul></ul>
    34. 34. . . . Hypothyroidism and pregnancy <ul><li>Maternal hypothyroidism during pregnancy may lead to adverse fetal outcomes. </li></ul><ul><ul><li>lower IQ as adolescents. </li></ul></ul><ul><ul><li>It is controversial whether all pregnant women should be screened for hypothyroidism. </li></ul></ul><ul><ul><li>Women with known hypothyroidism prior to pregnancy should have their dose of levothyroxine adjusted to maintain normal thyroid levels before conception and during pregnancy. </li></ul></ul>
    35. 35. Objective 4 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute Hypothyroidism. </li></ul><ul><li>Understand the role of thyroid functional scans in the diagnosis of hypothyroidism. </li></ul><ul><li>Know the specific cellular activities that are overactive in Grave’s disease. </li></ul><ul><li>Understand how to diagnose Grave’s disease. </li></ul>
    36. 36. Hyperthyroidism: clinical findings <ul><li>Weight loss </li></ul><ul><li>Heat intolerance </li></ul><ul><li>Insomnia </li></ul><ul><li>Sweating </li></ul><ul><li>Anxiety </li></ul><ul><li>Hyperkinesis </li></ul><ul><li>Dyspena </li></ul><ul><li>Palpitations </li></ul><ul><li>Atrial fibrilation </li></ul><ul><li>Irregular menses </li></ul><ul><li>Infertility </li></ul><ul><li>Increased frequency of bowel movements </li></ul><ul><li>Myalgia </li></ul>
    37. 37. Hyperthyroidism - with low TSH <ul><li>Grave’s Disease </li></ul><ul><li>Toxic Multinodular Goiter </li></ul><ul><li>Hyperthyroid phase of thyroiditis </li></ul><ul><li>Toxic Adenoma </li></ul><ul><li>Iodine-induced </li></ul><ul><li>Metastatic thyroid carcinoma, rare. </li></ul><ul><li>Excess beta-HCG from a molar pregnancy or choriocarcinoama </li></ul><ul><li>Ectopic/Exogenous, rare </li></ul>
    38. 38. Grave’s Disease <ul><li>60-70% of all cases of hyperthyroidism. </li></ul><ul><li>3% of population affected. </li></ul><ul><li>Female:Male ratio is 5:1 in 3rd or 4th decade. </li></ul>
    39. 39. Graves Disease Findings <ul><li>Weight loss </li></ul><ul><li>Heat intolerance </li></ul><ul><li>Insomnia </li></ul><ul><li>Sweating </li></ul><ul><li>Anxiety </li></ul><ul><li>Hyperkinesis </li></ul><ul><li>Dyspena </li></ul><ul><li>Palpitations </li></ul><ul><li>Atrial fibrilation </li></ul><ul><li>Irregular menses </li></ul><ul><li>Infertility </li></ul><ul><li>Increased frequency of bowel movements </li></ul><ul><li>Myalgia </li></ul><ul><li>Proximal Muscle weakenss </li></ul><ul><li>Eye findings: </li></ul><ul><li>*lid retraction </li></ul><ul><li>*lid lag </li></ul><ul><li>*stare </li></ul>
    40. 40. Grave’s Disease <ul><li>May be cyclic with exacerbations and remissions. </li></ul><ul><li>Usually, ongoing destructive inflammation of thyroid gland. </li></ul><ul><li>Eventually leads to “burn out” form of the disease and resulting hypothyroidism. </li></ul><ul><li>Getting to hypothyroid state may take many years. </li></ul>
    41. 41. Grave’s Disease <ul><li>Familial predisposition </li></ul><ul><li>Overlap with automimmune Hashimoto’s thyroiditis and the associated: </li></ul><ul><ul><li>Pernicious anemia </li></ul></ul><ul><ul><li>Myasthenia gravis </li></ul></ul><ul><ul><li>Vitiligo </li></ul></ul><ul><ul><li>Addisons disease </li></ul></ul><ul><ul><li>Type 1 Diabetes Mellitus </li></ul></ul>
    42. 42. Grave’s Disease <ul><li>*Cause: circulating antibodies against various thyroid antigens. </li></ul><ul><ul><li>The most important antibody: </li></ul></ul><ul><ul><ul><li>The TSH receptor antibody (TSH-R Ab) is directed against the TSH receptor on the thyroid follicular cell membrane. </li></ul></ul></ul><ul><ul><ul><li>Other antibodies present: </li></ul></ul></ul><ul><ul><ul><ul><li>Antibodies agains thyroid peroxidase (TPO) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Antibodies against thyroglobulin (TG </li></ul></ul></ul></ul><ul><ul><li>TSH-R Ab most often act as TSH receptor agonists. </li></ul></ul><ul><ul><ul><li>increasing the activity of adenylate cyclase </li></ul></ul></ul><ul><ul><ul><li>increasing intracellular cyclic AMP levels </li></ul></ul></ul><ul><li> ╬ result in cellular overactivity: </li></ul><ul><ul><ul><ul><ul><li>increased iodine uptake </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Increased thyroid hormone synthesis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Increased thyroid release </li></ul></ul></ul></ul></ul>
    43. 43. Grave’s Disease <ul><li>Cause: circulating antibodies against various thyroid antigens. </li></ul><ul><ul><li>The most important antibody: </li></ul></ul><ul><ul><ul><li>The TSH receptor antibody (TSH-R Ab) is directed against the TSH receptor on the thyroid follicular cell membrane. </li></ul></ul></ul><ul><ul><ul><li>Other antibodies present: </li></ul></ul></ul><ul><ul><ul><ul><li>Antibodies agains thyroid peroxidase (TPO) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Antibodies against thyroglobulin (TG </li></ul></ul></ul></ul><ul><ul><li>* TSH-R Ab most often act as TSH receptor agonists. </li></ul></ul><ul><ul><ul><li>increasing the activity of adenylate cyclase </li></ul></ul></ul><ul><ul><ul><li>increasing intracellular cyclic AMP levels </li></ul></ul></ul><ul><li> ╬ result in cellular overactivity: </li></ul><ul><ul><ul><ul><ul><li>increased iodine uptake </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Increased thyroid hormone synthesis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Increased thyroid release </li></ul></ul></ul></ul></ul>
    44. 44. Grave’s Disease <ul><li>Cause: circulating antibodies against various thyroid antigens. </li></ul><ul><ul><li>The most important antibody: </li></ul></ul><ul><ul><ul><li>The TSH receptor antibody (TSH-R Ab) is directed against the TSH receptor on the thyroid follicular cell membrane. </li></ul></ul></ul><ul><ul><ul><li>Other antibodies present: </li></ul></ul></ul><ul><ul><ul><ul><li>Antibodies agains thyroid peroxidase (TPO) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Antibodies against thyroglobulin (TG </li></ul></ul></ul></ul><ul><ul><li>TSH-R Ab most often act as TSH receptor agonists. </li></ul></ul><ul><ul><ul><li>increasing the activity of adenylate cyclase </li></ul></ul></ul><ul><ul><ul><li>increasing intracellular cyclic AMP levels </li></ul></ul></ul><ul><li> ╬ result in cellular overactivity: </li></ul><ul><ul><ul><ul><ul><li>increased iodine uptake </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Increased thyroid hormone synthesis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Increased thyroid release </li></ul></ul></ul></ul></ul>
    45. 45. Objective 5 <ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute Hypothyroidism. </li></ul><ul><li>Understand the role of thyroid functional scans in the diagnosis of hypothyroidism. </li></ul><ul><li>Know the specific cellular activities that are overactive in Grave’s disease. </li></ul><ul><li>Understand how to diagnose Grave’s disease. </li></ul>
    46. 46. Grave’s Disease <ul><li>Labs </li></ul><ul><li>Increased T4 and T3 </li></ul><ul><li>sometimes only T3 is elevated </li></ul><ul><li>Decreased TSH </li></ul><ul><li>╬ IF TSH depressed, T3 T4 increased, & patient has Grave’s ophthalmopathy: </li></ul><ul><li>*lid retraction, </li></ul><ul><li>*stare, </li></ul><ul><li>*lid lag, </li></ul><ul><li>Then - your evaluation is finished; your diagnosis is made. </li></ul>
    47. 47. <ul><li>IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW;T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF:TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYESIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. IF: TSH LOW; T3 T4 HIGH; EYE SIGNS; THEN, YOU DO NOT ORDER A SCAN. </li></ul>
    48. 48. . . . however . . . <ul><li>IF TSH depressed, T3 T4 increased, & no ophthalmopathy: </li></ul><ul><li>Then get a Radioactive (I-123) scan: </li></ul><ul><li>Graves I-123 scan results will be: </li></ul><ul><li>elevated, diffuse, symmetric, </li></ul><ul><li>In Grave’s: I-123 uptake Thyroid autoantibodies may also be present: </li></ul><ul><li>anti-TPO (measured in clinical practice) </li></ul><ul><li>anti-TG </li></ul><ul><li>TSH-R Ab (not readily available) </li></ul><ul><li>In Graves: Orbital CT or MRI retro-orbital inflammation. </li></ul>
    49. 49. Subacute Thyroiditis - hyperthyroid phase <ul><li>Etiology: destruction of the thyroid gland </li></ul><ul><li>*(often due to upper respiratory illness). </li></ul><ul><li>*Destruction leads to release of thyroid hormone in circulation (rather than from an increase in synthesis of hormone). </li></ul><ul><li>Symptoms: same without Grave’s eye findings (in hyperthyroid phase. </li></ul><ul><li>Radioiodine I-123 uptake: low </li></ul><ul><li>Outcome: </li></ul><ul><li>after thyrotoxic phase, </li></ul><ul><li>subacute thyroiditis may progress to transient (6 - 12 months) hypothyroidism </li></ul><ul><li>Supportive treatment only; no inhibitors of thyroid hormone synthesis are needed. </li></ul>
    50. 50. Compare: Graves vs Subacute Thyroiditis hyperthyroid phase ______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ Graves : Subacute Thyroiditis hyperthyroid phase <ul><ul><li>TSH-R Ab most often act as TSH receptor agonists </li></ul></ul><ul><ul><ul><li>result in cellular overactivity: </li></ul></ul></ul><ul><ul><ul><ul><li>Increased thyroid hormone synthesis. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Increased thyroid release </li></ul></ul></ul></ul><ul><ul><li>Etiology: destruction of the thyroid gland </li></ul></ul><ul><ul><ul><li>Result in cellular underactivity </li></ul></ul></ul><ul><ul><ul><ul><li>leads to release of thyroid hormone in circulation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>(rather than from an increase in synthesis of hormone ). </li></ul></ul></ul></ul>Radioiodine I-123 uptake: high Radioiodine I-123 uptake: low Eye signs: present Eye signs: not present
    51. 51. Toxic Multinodular Goiter (MNG) <ul><li>Frequency: 20-30% of hyperthyroid patients. </li></ul><ul><li>Pathophysiology: follicles - with some degree of autonomy - become large enough to increase overall hormone production. (Large doses of iodide can precipitate thyrotoxicosis in patients with non-toxic multinodular goiters). </li></ul>
    52. 52. Toxic Multinodular Goiter (MNG) <ul><li>Labs: </li></ul><ul><li>*TSH suppressed; </li></ul><ul><li>*T4 and T3 (high, normal, slightly elevated) </li></ul><ul><li>Radioiodine (I-123) scan: </li></ul><ul><li>*Areas of “hot” or “warm” </li></ul><ul><li>*With areas of “cold” uptake (corresponding to multiple nodules). </li></ul>
    53. 53. Toxic Ademoma <ul><li>3-5% of thyrotoxicosis </li></ul><ul><li>Cause: </li></ul><ul><li>* a single hyperfunctioning follicular thyroid adenoma </li></ul><ul><ul><ul><li>~50% have an activating mutation in the TSH receptor causing overproduction of thyroid hormone in the monoclonal tumor </li></ul></ul></ul><ul><li>Excess thyroid hormone is produced; </li></ul><ul><li>Reduces TSH; </li></ul><ul><li>Remainder of thyroid gland remains quiet </li></ul><ul><li>Radiodine I-123 scan: </li></ul><ul><li>*One “hot” nodule; </li></ul><ul><li>*Remainder of gland is suppressed. </li></ul>
    54. 54. Iodine-induced Thyrotoxicosis <ul><li>Administering iodine may cause thyrotoxicosis in patients with: </li></ul><ul><li>*iodine deficiency (endemic) goiter </li></ul><ul><li>*Multinodular goiter (with areas of autonomy or an Autonomous nodule) </li></ul><ul><li>Pathogenesis: ? Perhaps loss of normal adaptation of thyroid to iodine excess. (Usually mild and remits after stopping the iodine therapy). </li></ul>
    55. 55. Troma Ovarii <ul><li>Ectopic thyroid tissue </li></ul><ul><ul><li>Dermoid tumors </li></ul></ul><ul><ul><li>Ovarian teratoma </li></ul></ul><ul><li>Radioiodide scan of neck: decreased uptake </li></ul><ul><li>Radioiodid scan of pelvic area: shows increased uptake </li></ul><ul><li>Tx: remove tumor. </li></ul>
    56. 56. TSH producing Pituitary Tumor <ul><li>Very rare </li></ul><ul><li>TSH high; T4 T3 high </li></ul>
    57. 57. Other causes of thyrotoxicosis <ul><li>Metastatic Thyroid Carcinoma </li></ul><ul><li>Molar Hydatiform Pregnancy and Choriocardinoma </li></ul><ul><li>Thyrotoxicosis Factitia: serrupticious ingestion of thyroid hormone. Seen in psychiatric patients, medical professionals, or people wanting to lose weight. </li></ul><ul><li>Decreased: </li></ul><ul><ul><li>TSH </li></ul></ul><ul><ul><li>Radioiodid I-123 uptake </li></ul></ul><ul><ul><li>secretion of thyroglobulin </li></ul></ul>
    58. 58. Nuclear Imaging for thyrotoxicosis summary
    59. 59. OBJECTIVES <ul><li>Understand how to diagnose hypothyroidism: distinguish between Primary Hashimoto’s and Primary Subacute Hypothyroidism. </li></ul><ul><li>Understand the role of thyroid functional scans in the diagnosis of hypothyroidism. </li></ul><ul><li>Recognize the clinical findings of hypothroidism. </li></ul><ul><li>Know the specific cellular activities that are overactive in Grave’s disease. </li></ul><ul><li>Understand how to diagnose Grave’s disease . </li></ul>
    60. 60. ╬ Possible Test Question <ul><li>Which of the following is the best screening test for the diagnosis of hypothyroidism or hyperthyroidism in healthy ambulatory individuals. </li></ul><ul><li>Radioiodine I-123 uptake </li></ul><ul><li>Free T3 </li></ul><ul><li>Free T4 Index </li></ul><ul><li>TSH (Correct answer) </li></ul><ul><li>TSH and functional scan </li></ul>
    61. 61.
    62. 62. <ul><li>╬ In primary hypothyroidism (99% of hypothyroidism) TSH is elevated. </li></ul><ul><li>╬ Serum TSH is the best SCREENING test for the diagnosis of hypothyroidism or hyperthyroidism in healthy ambulatory individuals. </li></ul><ul><li>╬ Thyroid functional scans they are not helpful in the diagnosis of hypothyroidism and should not be used for this indication. </li></ul><ul><li>Hashimoto’s thyroiditis: </li></ul><ul><ul><ul><li>╬ TSH is elevated. </li></ul></ul></ul><ul><ul><ul><li>╬ Anti-thyroglobuline and/or anti-TPO antibodies are present in most (90%) patients. </li></ul></ul></ul><ul><li>Subacute thyroiditis - hypothyroid phase: </li></ul><ul><ul><ul><li>╬ TSH is elevated. </li></ul></ul></ul><ul><ul><ul><li>╬ Anti-thyroglobuline and/or anti-TPO antibodies are NOT present. </li></ul></ul></ul><ul><ul><ul><li>Radioiodine I-123 uptake: low (may order in hyperthyroid phase) </li></ul></ul></ul><ul><li>╬ RECOGNIZE THE CLINICAL FINDINGS OF HYPOTHYROIDISM (TOO MANY TO LIST). </li></ul><ul><li>╬ C ellular overactivities of Grave’s disease: increased iodine uptake, Increased thyroid hormone synthesis, Increased thyroid release (as a result of the TSH receptor agonist, TSH-R Ab). </li></ul><ul><li>╬ IF TSH depressed, T3 T4 increased, Grave’s ophthalmopathy (lid retraction, stare, lid lag) are present, then - your evaluation is finished; your diagnosis is made. (You do not need a functional scan for the diagnosis). </li></ul>
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