Subclinical Thyroid Disease

Microsoft PowerPoint - Subclinical thyroid Disease GR-2 (002) - Read-OnlyEndocrinology, Diabetes, Bone and Mineral Disorders Henry Ford Health System
Disclosures
Objectives
• Discuss the adverse effects on the cardiovascular system and bone
• Role of treatment in the elderly
• Importance of Subclinical thyroid disease in Pregnancy
Definition
Subclinical thyroid disease is defined as a serum T4 and a Total or Free T3 in their respective reference ranges, in the presence of abnormal serum TSH levels
Subclinical Hypothyroidism
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Approximate Changes of serum TSH with Aging
J. Endocr. Soc., Volume 3, Issue 1, January 2019, 146–158
For every decade increase in age over 30, TSH increases
by about 0.3 mIU/ml
13 million
50-60 million
The threshold at which levothyroxine is prescribed is now lower
Gutierrez, Lancet Vol 5; 246-248, April 2017
The cost of initiating and monitoring therapy is not trivial
Case • 58-year-old woman with family history of AITD
presents for an annual check up
• She has an elevated Total and LDL cholesterol
• TSH is 8.9 mIU/ml, and she has a normal FT4
• Has fatigue and dry skin
• She wants to know if she should be treated
Subclinical Hypothyroidism
• Circadian fluctuation of TSH
• Transient changes in TSH
• Risk of progression is 2-6% per year
• 46% of patients have a normalization of TSH in 2 years
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Prevalence of Subclinical Hypothyroidism
Whickham 1977 (n=2779)
Colorado 2000 ( n= 25,682)
NHANES 2002 (n=17,353)
Canaris G. Arch Internal Medicine. 160; 526 2000 Hollowell JJ Clin Endo Metab. 87; 489 2002
More common in women, older people and White ethnicity
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Effects of Subclinical Hypothyroidism Symptoms Related to SCH
• 1 in 3 patients have no symptoms Fatigue and muscle cramps
Dry skin and Cold sensitivity
Memory issues, depression
• 20-25% of euthyroid people report 2 or more of these symptoms
• Obesity and weight gain is not related to SCH
• Meta-analysis of 21 randomized clinical trials, including 2192 participants with subclinical hypothyroidism
• Thyroid hormone therapy was not significantly associated with improvement in general quality of life or thyroid related symptoms
• Study did not support routine use of thyroid hormone therapy in adults with SCH.
Feller, JAMA, 2018; 320 (13): 1349-1359 Feller, JAMA. 2018;320(13):1349-1359.
Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis
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Subclinical Hypothyroidism and Cholesterol Elevation
For every 1 mIU/ml rise in TSH, TC increases by 3.5 mg/dl in women and 6.2 mg/dl in men
25,862 participants screened in a statewide Health fair in 1995
-7.9
-10.3
-10.3 mg/dl
Danese M, J Clin Endo Metab 2000; 85: 2993
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• Thyroid hormone has an inotropic effect on cardiac muscle
• SCH is associated with impaired left ventricular diastolic function at rest
• Positive association between hypothyroidism and heart failure
• Increased carotid intimal thickness and endothelial dysfunction
Rodondi, JAMA. 2010;304(12):1365-1374.
Among 55,287 adult participants form 11 studies, 3450 had subclinical hypothyroidism (6.2%)
During a follow up between 1972- 2007, 9664 participants died, 4470 of CHD events
SCH was associated with an increased risk of CHD events and CHD mortality even after adjustment for traditional CV risk factors
CHD outcomes did not differ across age groups
Factor HR for CHD events
HR for CHD mortality
Razvi et al JCEM 2008; 93:2998-3007
Subclinical hypothyroidism and Ischemic Heart Disease
Razvi et al JCEM 2008; 93:2998-3007
Meta-Analysis (N=12): 2,399 SCH Subjects and 13,302 Controls Group 1: subjects <65 years; Group 2: Subjects >65 years
Studies with Subjects <65 IHD Increased
Subclinical Hypothyroidism and Cardiovascular Mortality
Meta-Analysis (N=8): 1,4172 SCH Subjects and 13,302 Controls Group 1: subjects <65 years; Group 2: Subjects >65 years
Studies with Subjects <65 Demonstrated increased CV mortality
Razvi et al JCEM 2008; 93:2998-3007
Data from the General Practitioner Research database in UK.
Subjects with TSH between 5-10 mIU/ml
50% were treated with LT4 and followed over 9 years
Evaluated Incident fatal and nonfatal IHD events and mortality
A) Age 40-70 yr. (n=3093) 5.3% event rate
B) Age over 70 yr. (n=1642) 11.7% event rate
Razvi, Archives of Internal Medicine May 2012; vol 172
LT4 therapy of Subclinical Hypothyroidism, Fatal and Nonfatal CV events and Mortality
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TSH rises with age • TSH set point is altered
• Half-life of T4 increases with age
• Reduction in follicles and gland weight
• Increase in autoimmunity
232 centenarians
188 controls
• 15% had a TSH above 2.5
Study Population: Longevity Genes Study Group
Atzmon JCEM 94:1251-1254, 2009
599 subjects
209 died
Subjects with high TSH and low FT4 had the lowest mortality
Thyroid Status and Survival in Old Age
Leiden 85-plus study
No association between thyroid Status and ADL, depression and Cognitive performance
Gussekloo JAMA:292:2591-2599
Physiological Changes that Influence Thyroid Function in Pregnancy
Taylor, Peter N., PhD; Lazarus, John H., MD. 2019. Volume 48, 3. P 547-556
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• Recurrent miscarriages
• Impaired intellectual and psychomotor development of the baby
Testing before Pregnancy
• High risk women should be screened
• All women on treatment should be tested for abnormal TSH before pregnancy
• Preconception counseling
• Third Trimester: Between 3-3.5 mIU/ml
• Monitor thyroid function every 4 weeks in the first half of pregnancy and again at around 30 weeks' gestation
Screening in Adults
• History of head and neck irradiation
• History of RAI treatment
• Abnormal thyroid exam
Garber, Endocrine Practice: 2012; (18) 989
Goals for LT4 Treatment
ATA/AACE Hypothyroidism Guidelines 2012
Evidence does not support targeting specific TSH Values within the normal reference range. (Grade B, BEL 2)
Most People Age >65-75
Age>75
presents for an annual check up
• She has an elevated Total and LDL cholesterol
• TSH is 8.9 mIU/ml, and she has a normal FT4
• Has fatigue and dry skin
• She wants to know if she should be treated
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Subclinical Hyperthyroidism
check up
• TSH: <0.01 with free hormones in the reference range
• Asymptomatic
Subclinical Hyperthyroidism
• Mild - TSH 0.1-0.4 uIU/ml
• Severe - TSH <0.1 uIU/ml
• 6% of individuals progress to overt hyperthyroidism in one year
• Over treatment with exogenous supplementation
Subclinical Hyperthyroidism
• Bone loss is mostly cortical
• Risk of fracture is high in postmenopausal women but not in pre-menopause
• Propensity to falls
Blum M. JAMA. 2015;313(20):2055-2065.
13 studies with 70,298 participants; 4092 (3.2%) with subclinical hyperthyroidism Primary outcome: Hip Fracture
Risk for Fracture in Women with Low TSH
Factor Relative Hazard Ratio (Hip)
Relative Hazard Ratio (Spine)
Borderline low TSH (0.2-0.4)
1.9 (0.7-4.8) 2.8 (1.0-8.5)
332 women had a hip fracture
389 women had an incident vertebral fracture
Bauer, Annals of Internal Medicine, 2001; 134: 561-568
Study of Osteoporotic Fractures
Years
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High Thyrotropin
Normal Thyrotropin
Sawin CT et al. New Engl J Med. 1994;331:1249.
Subclinical Hyperthyroidism and Atrial Fibrillation
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2007 subjects > 60 y (1193 women, 814 men) TSH measured; 10-year follow-up 2007 subjects > 60 yr (1193 women, 814 men)
TSH measured; 10-year follow-up
0.1-0.4TSH mIU/L 0.4-5.0 > 5.0
Cumulative incidence of atrial fibrillation in relation to thyroid dysfunction at baseline thyroid screening (age >65 years).
Christian Selmer et al. BMJ 2012;345:bmj.e7895
Case • 70-year-old woman presents for a yearly
check up
• TSH: <0.01 with free hormones in the reference range
• Asymptomatic
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symptoms
Premenopausal, age less than 60, no osteoporosis and no symptoms
TSH <0.1
Therapy Optional
TSH 0.1-0.4
No therapy
dysfunction and hypercholesterolemia
• Do not treat the “very old”
• Treat SCH if TSH is over 2.5 mIU/ml and subject is planning a pregnancy
• Treat subclinical hyperthyroidism if there is risk for osteoporosis and atrial fibrillation
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