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Subclinical Hyperthyroidism

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Slide 1 :

Subclinical Hyperthyroidism Cheryl P. Sterling, MD, MPH VCU/MCV Hospitals February 20, 2003

Slide 2 :

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

Slide 3 :

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

Slide 4 :

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

Slide 5 :

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?

Slide 6 :

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

Slide 7 :

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

Slide 8 :

Subclinical Hyperthyroidism Goiter Exophthalmos

Slide 9 :

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.

Slide 10 :

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 T4, free and total T3. Free thyroxine index = indirect measure of free T4 T3 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.

Slide 11 :

Diagnostic Assessment Thyroid scan or radioactive iodine (123I) uptake “Hot” versus “Cold” nodule Thyroid ultrasound Anatomic abnormalities Does not reveal information regarding thyroid function Serial examination

Slide 12 :

Diagram of thyroid testing www.medscape.com/viewarticle/433852

Slide 13 :

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).

Slide 14 :

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).

Slide 15 :

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.

Slide 16 :

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.

Slide 17 :

Results Sawin, C.T., Geller, A., et al. New England Journal of Medicine, 1994; 331(19): 1249-1252.

Slide 18 :

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.

Slide 19 :

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

Slide 20 :

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.

Slide 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 (131I) - Surgery - Close clinical follow-up

Slide 22 :

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.

Slide 23 :

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).

Slide 24 :

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

Slide 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.

Slide 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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Helfand, M., Redfern, C.C. Annals of Internal Medicine, 15 July 1998. 129:141-143, 144-158. Subclin more Helfand, M., Redfern, C.C. Annals of Internal Medicine, 15 July 1998. 129:141-143, 144-158. Subclinical Hyperthyroidism.Individualize management …www.womenshealthtrack.vcu.edu/PPT/Sterling-PC.ppt less

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