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Sterling Pc

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    Sterling Pc Sterling Pc Presentation Transcript

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