Sterling Pc

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Sterling Pc

  1. 1. Subclinical Hyperthyroidism Cheryl P. Sterling, MD, MPH VCU/MCV Hospitals February 20, 2003
  2. 2. Case Presentation <ul><li>48 yo Black female with well controlled HTN, h/o borderline hyperthyroidism </li></ul><ul><ul><ul><li>No specific complaints or concerns </li></ul></ul></ul><ul><ul><ul><li>Meds: </li></ul></ul></ul><ul><ul><ul><ul><li>HCTZ for BP control </li></ul></ul></ul></ul><ul><ul><ul><li>FHx remarkable for HTN, DM, no other endocrine D/O’s, no known AIDz </li></ul></ul></ul><ul><ul><ul><li>SHx unremarkable </li></ul></ul></ul>
  3. 3. Case Presentation <ul><li>48 yo Black female with well-controlled HTN, h/o borderline hyperthyroidism </li></ul><ul><ul><ul><li>ROS positive for low but normal appetite, no wgt loss, no signif fatigue </li></ul></ul></ul><ul><ul><ul><li>Pap UTD </li></ul></ul></ul><ul><ul><ul><li>No prior BMD study </li></ul></ul></ul><ul><ul><li>Physical exam = nonobese female; no obvious features c/w hyperthyroid state </li></ul></ul>
  4. 4. Case Presentation <ul><li>LABS </li></ul><ul><ul><li>WBC 6.0, Hgb 12.4, Platelets 378 </li></ul></ul><ul><ul><li>BMP unremarkable except for Ca 8.9 </li></ul></ul><ul><ul><li>LFT’s wnl </li></ul></ul><ul><ul><li>Fasting Lipid Profile </li></ul></ul><ul><ul><ul><li>Chol 173, HDL 45 </li></ul></ul></ul><ul><ul><ul><li>TG 120, LDL 97 </li></ul></ul></ul><ul><li>Serial thyroid testing </li></ul><ul><ul><li>11/00 TSH – 0.15 </li></ul></ul><ul><ul><li>3/01 TSH – 0.35 </li></ul></ul><ul><ul><li>7/01 TSH – 0.22 </li></ul></ul><ul><ul><li>9/02 TSH – 0.16 </li></ul></ul><ul><ul><li>2/03 TFT’s </li></ul></ul><ul><ul><ul><li>TSH - 0.21 </li></ul></ul></ul><ul><ul><ul><li>Total T4 - 8.4 </li></ul></ul></ul><ul><ul><ul><li>T3RU – 37.2% </li></ul></ul></ul><ul><ul><ul><li>FTI - 10 </li></ul></ul></ul>
  5. 5. Clinical Question <ul><li>Premenopausal female patient with hx of “borderline” hyperthyroidism, no obvious clinical signs nor subjective symptoms of thyroid hormone excess </li></ul><ul><li>What are the management options for this patient in your practice? </li></ul>
  6. 6. The Thyroid <ul><li>Subclinical Hyperthyroidism </li></ul><ul><li>- Characterized by the presence of low or undetectable plasma TSH concentration and normal circulating free thyroid hormones . </li></ul><ul><li>Also referred to as mild hyperthyroidism </li></ul><ul><li>Exogenous vs. endogenous </li></ul>
  7. 7. Common Signs/Symptoms <ul><li>Fatigue </li></ul><ul><li>Weight loss </li></ul><ul><li>Heat intolerance </li></ul><ul><li>Hyperhidrosis </li></ul><ul><li>Nervousness </li></ul><ul><li>Insomnia </li></ul><ul><li>Muscle weakness </li></ul><ul><li>Hyperdefecation </li></ul><ul><li>Tremor </li></ul><ul><li>Dyspnea </li></ul><ul><li>Palpitations </li></ul><ul><li>Menstrual irregularity </li></ul><ul><li>Anxiety </li></ul><ul><li>Irritability </li></ul><ul><li>Exophthalmos </li></ul><ul><li>Lid lag or stare </li></ul>
  8. 8. Subclinical Hyperthyroidism Goiter Exophthalmos
  9. 9. Etiology <ul><li>Presage to overt hyperthyroidism </li></ul><ul><ul><li>Early Graves’ disease </li></ul></ul><ul><ul><li>Multinodular goiter </li></ul></ul><ul><ul><li>Hashimoto’s </li></ul></ul><ul><li>Thyroiditis </li></ul><ul><ul><li>Subacute </li></ul></ul><ul><ul><li>Silent </li></ul></ul><ul><ul><li>Postpartum </li></ul></ul><ul><li>Thyroid carcinoma </li></ul><ul><li>Iodine-associated hyperthyroidism </li></ul><ul><ul><li>e.g. amiodarone </li></ul></ul><ul><li>Solitary autonomous adenoma </li></ul><ul><li>Nonthyroidal illness </li></ul><ul><li>Steroid or dopamine administration </li></ul><ul><li>Health food supplement </li></ul>Shrier, D.K., Burman, K.D. American Family Physician , 2002; 65(3). Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism , 2000; 85(12):4701-4705.
  10. 10. Biochemical Assessment <ul><li>Thyroid stimulating hormone (TSH): </li></ul><ul><ul><ul><li>Is the single most reliable test to diagnose thyroid disease. </li></ul></ul></ul><ul><ul><ul><li>The assay is accurate, widely available, safe, and a relatively inexpensive diagnostic test. </li></ul></ul></ul><ul><li>Also serum free and total T 4 , free and total T 3 . </li></ul><ul><ul><ul><li>Free thyroxine index = indirect measure of free T 4 </li></ul></ul></ul><ul><ul><ul><li>T 3 resin uptake = indirect estimate of unsaturated binding sites on thyroxine binding globulin </li></ul></ul></ul>Ladneson, et al. Arch Intern Med , 2000; 160: 1573-1575. Supit, et al. South Med J , 2002; 95(5):481-485.
  11. 11. Diagnostic Assessment <ul><li>Thyroid scan or radioactive iodine ( 123 I) uptake </li></ul><ul><ul><ul><li>“Hot” versus “Cold” nodule </li></ul></ul></ul><ul><li>Thyroid ultrasound </li></ul><ul><ul><ul><li>Anatomic abnormalities </li></ul></ul></ul><ul><ul><ul><ul><li>Does not reveal information regarding thyroid function </li></ul></ul></ul></ul><ul><ul><ul><li>Serial examination </li></ul></ul></ul>
  12. 12. Diagram of thyroid testing www.medscape.com/viewarticle/433852
  13. 13. Evidence-based Research? <ul><li>Detection and management of subclinical thyroid disorders </li></ul><ul><ul><li>Small prospective, nonrandomized studies </li></ul></ul><ul><ul><li>Cross-sectional studies </li></ul></ul><ul><ul><li>Case reports </li></ul></ul><ul><ul><li>Meta-analyses </li></ul></ul><ul><ul><li>Subgroup analysis in Framingham study </li></ul></ul>Toft, A.D. New England Journal of Medicine , 2001; 345(7):512–516. Shrier, D.K., Burman, K.D. American Family Physician , 2002; 65(3).
  14. 14. Short/Long-term Effects <ul><li>Alteration in cardiac morphology and function </li></ul><ul><ul><li>Cross-sectional studies demonstrating: </li></ul></ul><ul><ul><ul><ul><li>Increased heart rate </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Increased LV mass </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Enhanced LV function </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Impaired diastolic filling </li></ul></ul></ul></ul><ul><ul><li>Increased risk of atrial fibrillation and stroke in older patients </li></ul></ul>Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism , 2000; 85(12):4701-4705. Shrier, D.K., Burman, K.D. American Family Physician , 2002; 65(3).
  15. 15. Adverse Effects <ul><li>Alteration in bone metabolism </li></ul><ul><ul><li>Postmenopausal women with subclinical hyperthyroidism have increased bone loss </li></ul></ul><ul><li>Neuropsychological effects </li></ul><ul><ul><li>Reduced quality of life </li></ul></ul><ul><ul><li>Anxiety, depression </li></ul></ul><ul><ul><li>Increased risk of dementia, Alzheimer’s disease </li></ul></ul>Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism , 2000; 85(12):4701-4705. Kalmijn, S., Mehta, K.M., et al. Clinical Endocrinology (Oxf) , 2000; 53: 733-737.
  16. 16. Journal Article <ul><li>Subgroup analysis from Framingham Study </li></ul><ul><ul><li>Prospective study w/10 yr follow-up </li></ul></ul><ul><ul><li>Purpose – Is low serum thyrotropin in clinically euthyroid older persons a risk factor for subsequent atrial fibrillation? </li></ul></ul><ul><ul><li>2007 persons, age > 60 years </li></ul></ul><ul><ul><li>4 groups: </li></ul></ul><ul><ul><ul><li>low, slightly low, normal, high thyrotropin levels </li></ul></ul></ul>Sawin, C.T., Geller, A., et al. New England Journal of Medicine , 1994; 331(19): 1249-1252.
  17. 17. Results Sawin, C.T., Geller, A., et al. New England Journal of Medicine , 1994; 331(19): 1249-1252.
  18. 18. Journal Article <ul><li>Cross-sectional, case-control study in Italy </li></ul><ul><ul><li>Purpose – Effects of endogenous subclinical hyperthyroidism in the young and middle-aged </li></ul></ul><ul><ul><li>23 patients, 23 controls from areas of mild-moderate iodine deficiency </li></ul></ul><ul><ul><li>Assessment of </li></ul></ul><ul><ul><ul><li>Thyroid status </li></ul></ul></ul><ul><ul><ul><li>S/sx of thyroid hormone excess and quality of life </li></ul></ul></ul><ul><ul><ul><li>Cardiac morphology and function </li></ul></ul></ul>Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism , 2000; 85(12):4701-4705.
  19. 19. Results Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism , 2000; 85(12):4701-4705. <ul><li>Multinodular goiter, solitary autonomous nodule; no antithyroid Ab’s; significant difference in free T3 and free T4 between groups </li></ul><ul><li>Higher mean SRS score in patients as well as lower SF-36 scores (r = -0.84, p = 0.008) </li></ul><ul><li>No ECG abnormality; Holter showed higher average HR (p < 0.001) and higher prevalence of APC’s in patients (p = ns) </li></ul><ul><li>Doppler echo showed increased PWT and IVST in patients as well as higher indices of LV systolic function </li></ul>
  20. 20. Conclusions <ul><li>Patients were affected by endogenous subclinical hyperthyroidism as evidenced by increased symptoms and impaired quality of life. </li></ul><ul><li>Cardiac morphology and function affected by increased heart rate, LV mass, enhanced LV function and impaired diastolic filling </li></ul><ul><li>Untreated endogenous subclinical hyperthyroidism may have untoward effects in young and middle-aged so consider early treatment. </li></ul>Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism , 2000; 85(12):4701-4705.
  21. 21. Subclinical Hyperthyroidism Prevention of atrial fibrillation and osteoporosis are the main potential benefits of treating subclinical hyperthyroidism. Treatment options include: - Beta-blockers - Antithyroid medications - Radioactive iodine ( 131 I) - Surgery - Close clinical follow-up
  22. 22. Subclinical Hyperthyroidism <ul><li>Screening? Guidelines? </li></ul><ul><li>ATA (2000) recommends initial screen at age 35 with repeat testing every 5 years </li></ul><ul><li>RCP of London, ACP (1996, 1998) – no proven excess morbidity; women > 50 years </li></ul><ul><li>AACE – all women > age 35 and men over age 60 </li></ul>Toft, A.D. New England Journal of Medicine , 2001; 345(7):512–516. Ladneson, et al. Arch Intern Med , 2000; 160: 1573-1575. Helfand, M., Redfern, C.C. Annals of Internal Medicine , 15 July 1998. 129:141-143, 144-158.
  23. 23. Subclinical Hyperthyroidism <ul><li>- Individualize management </li></ul><ul><li>- Discuss benefits vs. risks </li></ul><ul><li>- Of each treatment option, e.g. periodic monitoring of CBC, LFT’s, TFT’s </li></ul><ul><li>- Financial considerations </li></ul><ul><li>- Drug interactions, potential toxicities </li></ul><ul><li>- Also consider potential issues of nonadherence </li></ul>Shrier, D.K., Burman, K.D. American Family Physician , 2002; 65(3).
  24. 24. The Answer (To My Clinical Question) <ul><li>Continue close observation with serial TFT’s, including total and free T3 </li></ul><ul><li>Discuss with patient possible treatment options </li></ul><ul><ul><li>Thyroid scan with RAIU </li></ul></ul><ul><ul><li>Antithyroid medications, if necessary </li></ul></ul><ul><li>Refer to endocrinology for management </li></ul>
  25. 25. References Biondi, B., Palmieri, E.A., Fazio, S., et al. Endogenous Subclinical Hyperthyroidism Affects Quality of Life and Cardiac Morphology and Function in Young and Middle-Aged Patients. Journal of Clinical Endocrinology and Metabolism , 2000; 85(12):4701-4705. Helfand, M., Redfern, C.C. Screening for Thyroid Disease: An Update (Parts 1 & 2). Annals of Internal Medicine , 15 July 1998. 129:141-143, 144-158. Kalmijn, S., Mehta, K.M., Pols, H.A.P., Hofman, A., et al. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam Study. Clinical Endocrinology (Oxf) , 2000; 53: 733-737. Ladneson, et al. ATA guidelines for Detection of Thyroid Dysfunction. Archives of Internal Medicine , 2000; 160: 1573-1575. Sawin, C.T., Geller, A., Wolf, P.A., Belanger, A.J., et al. Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons. New England Journal of Medicine , 1994; 331(19): 1249-1252.
  26. 26. References Shrier, D.K., Burman, K.D. Subclinical Hyperthyroidism: Controversies in Management. American Family Physician , 2002; 65(3). Supit, et al. Interpretation of Laboratory Thyroid Function Tests for the Primary Care Physician. Southern Medical Journal , 2002; 95(5):481-485. Toft, A.D. Subclinical hyperthyroidism. New England Journal of Medicine , 2001; 345(7):512–516. Utiger, R.D. Subclinical Hyperthyroidism – Just a Low Serum Thyrotropin Concentration, or Something More? New England Journal of Medicine , 1994; 331(19): 1302-1303.

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