ipotiroidismo: target di terapia nell’anziano · extreme longevity and increased serum tsh value...
TRANSCRIPT
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IPOTIROIDISMO: TARGET DI TERAPIA NELL’ANZIANO
Fabio Vescini
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Invecchiamento e funzione tiroidea
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Surks et al. JCEM 2007
TSH distribution Comparison of U.S. disease-free populations by age groups
NHANES III (1988-1994) and NHANES 1999-2002
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Extreme Longevity and Increased Serum TSH Value
Atzmon et al. JCEM 2009
236 Ashkenazi Jewish centenarians living independently, median age: 97.7 yrs 188 younger unrelated Ashkenazi Jews (controls), median age: 71.0 yrs 605 NHANES controls, age range 60-79 yrs
Median FT4 (≈1.0 ng/dl) value was similar in each group
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Prevalence of Elevated Serum TSH by Decade of Age and Gender
0
2
4
6
8
10
12
14
16
18
13-19 20-29 30-39 40-49 50-59 60-69 70-79 >80
Age, y
• Up to 40 years of age, prevalence is relatively low and similar between males and females
• Between 40 and 70 years of age, a higher percentage of female patients have elevated TSH levels
• At >70 years of age, prevalence is high and similar between males and females
Males
Females
NHANES III Study (N=17 353)
Hollowell et al. JCEM 2002.
Part
icip
ants
With
Ele
vate
d TS
H, %
Age (yrs)
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Thyroid Status, Disability and Cognitive Function, and Survival in Old Age Gussekloo J, et al. JAMA. 2004;292(21):2591-2599
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Effetti dell’ipotiroidismo
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Serum FT3 levels and systemic vascular resistance
Biondi & Klein, Endocrine 2004
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Klein et al. Circulation 2007
Effects of thyroid hormone on cardiovascular system
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The Cardiovascular Health Study: 3044 adults >65 yrs of age Participants with TSH 10.0-19.9 mU/l who were untreated by LT4 replacement had a greater incidence of HF events compared with euthyroid participants (41.7 vs. 22.9 x 1,000 person/year, p=0.01)
Rodondi et al. JACC 2008
TSH and Incident Heart Failure Events
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TSH quartiles and LDLc value according to women’s age
0
50
100
150
200
0
50
100
150
200
0
50
100
150
200
p=0.05
mg/
dl
1st 2nd 3rd 4th
Age Groups A: 30-49 years B: 50-64 years C: >65 years
1st 2nd 3rd 4th
p=0.001 p=0.002
p=0.05 p=0.02
1st quartile: TSH <0.36 mUI/L 2nd quartile: TSH >0.36 <3.60 mUI/L 3rd quartile: TSH >3.60 <10 mUI/L 4th quartile: TSH >10 mUI/L
A
B C Similar data in men
mg/
dl
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?
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Khandelwal and Tandon. Drugs 2012; 72 (1): 17-33.
• Levo-tiroxina: 1 mcg/Kg/die
• Dosi scalari partendo da 25 mcg/die
(incremento posologia ogni 4-6 settimane)
• Target TSH: limiti superiori del range di
norma
TERAPIA NELL’ANZIANO
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Thyroid Status of Treated Patients Colorado Thyroid Disease Prevalence Study (1525 pts.)
Canaris et al. Arch Intern Med. 2000
0
20
40
60
80
100
Euthyroid
60.1
Part
icip
ants
, %
Hyperthyroid Subclinical Hyperthyroid
0.9
20.7
Overtreated
>20%
Subclinical Hypothyroid
Hypothyroid
17.6
0.7
Undertreated
>18%
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• The deleterious health effects of iatrogenic thyrotoxicosis include atrial fibrillation and osteoporosis.
• We recommend avoiding thyroid hormone excess and subnormal serum TSH values, particularly TSH values below 0.1 mIU/L, especially in older persons and postmenopausal women.
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Khandelwal and Tandon. Drugs 2012; 72 (1): 17-33.
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Should elderly patients be considered for treatment?
• Routine treatment is not recommended for elderly (> 65 yrs) and very-elderly
(> 80 yrs) patients with subclinical hypothyroidism at TSH levels < 10 mUI/L
(Grade A).
• Also treatment is not recommended for SH if the aim is to improve cognitive
function in elderly people (Grade A).
• However in > 65 years old, treatment can be considered on an individual basis
(Grade D).
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The clinical symptoms and signs of hypothyroid may be very confounding in elderly patients.
• Fatigue • slow cerebration • cold intolerance • dry skin • constipation • weight abnormalities • arthralgia and myalgia • depression • alterations of hair • dyspnoea and oedema
If caused by hypothyroidism respond
well to thyroid hormone replacement
therapy, whereas thyroid hormones
have no effect, apart from placebo,
on such abnormalities in euthyroid
individuals
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How to initiate and adjust doses in elderly and in patients with cardiopathy?
• In patients older than 60 yrs with SH and also in those with ischemic cardiac
disease or heart failure, start levothyroxine therapy at lower doses (12.5 – 25
mcg/day) (Grade B).
• LT4 dose should be increased slowly, while monitoring for the development of
angina or other cardiac symptoms such as tachyarrhythmias (Grade D).
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Laurberg P, et al. Drugs Aging 2005; 22 (1): 23-38
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Il dilemma del medico: Trattare o non trattare l’ipotiroidismo
subclinico dell’anziano?
PRO:
• Prevenire la progressione verso l’ipotiroidismo clinico (specie in caso di Ab+)
• Alleviare i sintomi
• Migliorare la dislipidemia • Probabilmente ridurre il rischio di
scompenso cardiaco
CONTRO:
• Un numero significativo di soggetti con forma subclinica non progredirà verso l’ipotiroidismo franco
• Spesso i sintomi “da ipotiroidismo” non sono dovuti ad esso
• Rischio di sovradosaggio della LT4 (tachiaritmie)
• L’ipo subclinico potrebbe avere “effetti protettivi” nei pazienti molto anziani
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The TRUST Study
(Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism: a
randomised placebo-controlled Trial)
Rodondi N, Bauer DC. Subclinical hypothyroidism and cardiovascular risk: how to end the controversy. J Clin Endocrinol Metab. 2013;98(6):2267–9
• European multicentre study
• Examines thyroid hormone replacement
therapy versus placebo in elderly individuals
with persisting subclinical hypothyroidism
• A total of 3,000 participants will be enrolled
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