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
Iodine-associated
hyperthyroidism
– Early Graves’ disease – Multinodular goiter – Hashimoto’s
hyperthyroidism
– e.g. amiodarone
Solitary autonomous
Thyroiditis
– Subacute – Silent – Postpartum
Thyroid carcinoma
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 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.
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
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
1. Multinodular goiter, solitary autonomous nodule; no antithyroid Ab’s; significant difference in free T3 and free T4 between groups 2. Higher mean SRS score in patients as well as lower SF-36 scores (r = -0.84, p = 0.008)
3. No ECG abnormality; Holter showed higher average HR (p < 0.001) and higher prevalence of APC’s in patients (p = ns)
4. Doppler echo showed increased PWT and IVST in patients as well as higher indices of LV systolic function
Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism, 2000; 85(12):4701-4705.
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 (131I) - Surgery - Close clinical follow-up
Subclinical Hyperthyroidism
Screening? Guidelines?
1. ATA (2000) recommends initial screen at age 35 with repeat testing every 5 years 2. RCP of London, ACP (1996, 1998) – no proven excess morbidity; women > 50 years 3. 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, 144158. 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.