هوالطیف. subclinical thyroid dysfunction is a common clinical problem (hypo > hyper) ...
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هوالطیف
Subclinical thyroid dysfunction Subclinical thyroid dysfunction
Is a common clinical problem
(Hypo > Hyper) Abnormal TSH
Normal T4, FT4, FT4I
Changing TSH Reference LimitsChanging TSH Reference Limits
0
2
4
6
8
10
12
~4.0
0.3-0.4
~5.0
0.5
~10.0
?
2004200420042004
~2.50.3-0.4
RIA1970-85
2nd gen IMA1985-90
3rd gen IMA1990-00
TSH(mIU/L)
National Health & Nutrition Examination Survey National Health & Nutrition Examination Survey NHANES IIINHANES III
0
5
10
15
20
25
30
35
0.30.3 1.01.0 2.02.0 3.03.0 4.04.0
Frequency(%)
No thyroid disease 13,344
95% TSH 0.3-2.5
Mean TSH 1.49
TSH (mIU/L)
Total 17,353 subjectsTotal 17,353 subjects
NHANES IIINHANES III Effect of Age on TSH Effect of Age on TSH
0.0
0.5
1.0
1.5
2.0
2.5
12-1912-19 20-2920-29 30-3930-39 40-4940-49 50-5950-59 60-6960-69 70-7970-79 8080 AvgAvg
Age (yr)
TSH(mIU/L
1.49
28.0 30.9 54.6 85.2 96.58.3 14.413.5 18.1 30.65.5 5.8
0
20
40
60
80
100
NHANES IIINHANES III Positive Correlation of TPOAb and Positive Correlation of TPOAb and TSH TSH
0.10.1 0.40.4 1.01.0 1.51.5 2.02.0 2.52.5 3.03.0 3.53.5 4.04.0 4.54.5 55 1010 >20>20
5.7
Subclinical/OvertHypothyroidismTypical TSH Reference Range
SubclinicalHyperthyroidism
TSH (mIU/L)
TP
OA
b (
%)
So What is Normal TSH Range?
• TSH reference range of 0.5-5.0 is considered normal based on results of general cross-sectional population studies
• More recent studies of rigorously screened normal euthyroid volunteers show serum TSH levels 0.5-2.5 mIU/L
• New TSH reference intervals should be established in studies that exclude subsets with goiter, TPOAb, FHx thyroid dis, meds
• Target TSH for T4 treatment is now 0.3-3.0
FT4, FT3
Low TSH
ClinicalHyper
ClinicalHypo
Low FT4
TSHNormalFT4 & FT3
SubclHyper
Normal FT4TPOAb +
SubclHypo
NewTSHrange
UnequivocallyEuthyroid
New Spectrum of Thyroid DysfunctionNew Spectrum of Thyroid Dysfunction
0.010.01 0.10.1 1010 100100
0.50.5 2.52.5
TSH (mIU/L)
Subclinical HypothyroidismSubclinical Hypothyroidism
• Serum TSH >5.0 mIU/L
• Normal FT4 and FT3
• Mild symptoms may be present
Definition :
Subclinical HypothyroidismPrevalence : Whickham Study
1.1 - 9% in 12 studies (1977-2002)
Women 2.7-11.6%; Men 1.9-3.4%;
Elderly women 8.8-11.6%
White, non-Hispanic 4.8%
Black, non-Hispanic 1.6%
Mexican-American 3.9%
75% with TSH = 5-10 mIu/l
Hollowell, 2002; Canaris, 2000; Vanderpump, 1995; Parle, 1991
Subclinical HypothyroidismSubclinical HypothyroidismWhickham Study: Risk of Progression
Annual risk 20-yr cumulative
Positive test (%) incidence (%)TSH N, Ab+ 2.1 27
TSH , Ab– 2.6 33
TSH , Ab+ 4.3 55
Subclinical HypothyroidismSubclinical Hypothyroidism Whickham Study: Follow-UpWhickham Study: Follow-Up
1,877 subjects Lower risk with young age, lower
TSH, Ab neg Prevalence increased in women with
age: 4.5% in <44; 17.4% in >75 Prevalence in men >65 was 6.2%
Subclinical HypothyroidismSubclinical Hypothyroidism Colorado StudyColorado Study
25,862 subjects surveyed Mean age 55 TSH > 5.0 in 9.5% TSH 5.0 -10 in 74% TSH >10 in 26%
Subclinical HypothyroidismSubclinical HypothyroidismCauses
• Autoimmune Thyroiditis
• Subacute Thyroiditis
• Post 131I or Surgery
• Postpartum Thyroiditis
• Medications (ATD,Lithium,I131 )
Potential Side EffectsPotential Side Effects
TC and LDLc Lpa Homocysteine LV diastolic dysfunction Atherosclerosis
5-10 10-15 15-20 20-40 40-60 60-80 >80150
200
250
Low150
200
250
Normal
Colorado StudyColorado StudyMean Cholesterol LevelsMean Cholesterol Levels
P<0.001P<0.001
TSH levels
Colorado StudyColorado StudyMean Cholesterol LevelsMean Cholesterol Levels
150
200
250
Normal 5-10
P<0.003
TSH levels
Rotterdam StudyRotterdam Study
Population study of 7,983
(1990-1993) 1,149 women evaluated for
Lpids, TSH, Aortic calcifications, ECG and MI
Follow-up chart review in 1996
Rotterdam StudyRotterdam Study
Association of MTF with Risk of Atherosclerosis and MIAssociation of MTF with Risk of Atherosclerosis and MI
1.0 1.0
1.7
2.3
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Aortic atherosclerosisAortic atherosclerosis Myocardial infarctionMyocardial infarction
** **
Euthyroid
Mild hypothyroidism (TSH >4.0)
Oddsratio
52-year-old woman with mild fatigue and obesity; thyroid exam is normal TSH= 5.6 FT4 = 1.1 TPO= 420Q: Do you Rx with T4?
a. Yesb. No
Case:
Prevent progression to overt hypothyroidism
Reduce TC and CV risk Improve symptoms
Subclinical HypothyroidismSubclinical Hypothyroidism
Why Treat?Why Treat?
RCT, 63 F 34 with SCH Mean TSH 11-14 (range 5-50) Duration of LT4 therapy = 48 wk TC 3.8%, LDL C 8.2% Risk reduction of CAD mortality 17%
Subclinical HypothyroidismSubclinical HypothyroidismBasel StudyBasel Study
Younger pt TSH >5 TPOAb+ cholesterol
Subclinical HypothyroidismSubclinical HypothyroidismFavoring TreatmentFavoring Treatment
■ Goiter■ Symptoms■ Infertility■ Pregnancy
Hypothyroidism:Hypothyroidism:Recommendations for therapyRecommendations for therapy
Thyroxin therapy= Euthyrox®
TPO-Antibodies positive
Elevated TSH
Symptoms, goiter, elevated total or LDL cholesterol, pregnancy,
or ovulatory dysfunction with infertility
TSH 10 mU/L
Check TSH, fT4, TPO-Abobtain lipid profile
TPO-Antibodies negative
Annual follow-up (TSH, fT4)or thyroxine therapy
TSH < 10 mU/L
No symptoms, goiter, elevated total or LDL-C, pregnancy, or
ovulatory dysfunction with infertility
Adapted fromCooper DS. Subclinical hypothyroidism. N Engl J Med 2001;345(4):260-5
Pharmacological Considerationson Thyroid Pharmacological Considerationson Thyroid HormonesHormones
• IIn the normal adultn the normal adult
– 100 µg T4 is secreted by the thyroid daily100 µg T4 is secreted by the thyroid daily– 30 µg T3 is produced daily (80% from peripheral de-iodination of 30 µg T3 is produced daily (80% from peripheral de-iodination of
T4, 20% from thyroid secretion)T4, 20% from thyroid secretion)
• Administration of Levothyroxine sodium closely mimics glandular Administration of Levothyroxine sodium closely mimics glandular secretionsecretion
– Conversion to T3 is appropriately regulated in the tissuesConversion to T3 is appropriately regulated in the tissues– Stable serum T3 concentrations between levothyroxine dosesStable serum T3 concentrations between levothyroxine doses
• Levothyroxine has a long half-life of approximately 7 daysLevothyroxine has a long half-life of approximately 7 days
– Small fluctuations in serum concentrations between dosesSmall fluctuations in serum concentrations between doses
• Levothyroxine is the treatment of choice for the routine Levothyroxine is the treatment of choice for the routine management of hypothyroidismmanagement of hypothyroidism
Initial Dosing of Levothyroxine in Primary Initial Dosing of Levothyroxine in Primary HypothyroidismHypothyroidism
• NewbornsNewborns– 10 - 15 µg/kg/day, i.e. 50 µg/day10 - 15 µg/kg/day, i.e. 50 µg/day
• ChildrenChildren– 4-5 µg/kg/day, i.e. 12.5 - 50 µg/day4-5 µg/kg/day, i.e. 12.5 - 50 µg/day
• Adults:Adults:– approximately 1.6 µg/kg/day (e.g., 100-125 µg/day for a 70 approximately 1.6 µg/kg/day (e.g., 100-125 µg/day for a 70
kg adult) kg adult) – Patients with known coronary disease: up to 25 µg/dayPatients with known coronary disease: up to 25 µg/day
• Older patientsOlder patients– Patients > 60 years with long duration of hypothyroidism:Patients > 60 years with long duration of hypothyroidism:
50 µg/day or less50 µg/day or less– Patients without clinically overt cardiac disease: 50 µg/dayPatients without clinically overt cardiac disease: 50 µg/day
• Treatment may aggravate angina in ~20% of patientsTreatment may aggravate angina in ~20% of patients
Factors That Increase Levothyroxine Factors That Increase Levothyroxine RequirementRequirement
• Pregnancy, estrogen, tamoxifen, raloxifenePregnancy, estrogen, tamoxifen, raloxifene
• Small bowel diseaseSmall bowel disease
• Drugs or dietary supplements that reduce absorptionDrugs or dietary supplements that reduce absorption– Large amounts of fiber, bran, soy proteinLarge amounts of fiber, bran, soy protein– Aluminium- or iron-containing drugs, calcium carbonateAluminium- or iron-containing drugs, calcium carbonate
• Drugs that increase metabolismDrugs that increase metabolism– Rifampin, carbamazepine, phenytoin, phenobarbitalRifampin, carbamazepine, phenytoin, phenobarbital
• Drugs that reduce T4 to T3 conversionDrugs that reduce T4 to T3 conversion– Amiodarone, betablockers, pAmiodarone, betablockers, propylthiouracil, glucocorticoids and iodine ropylthiouracil, glucocorticoids and iodine
containing contrast mediacontaining contrast media
• Others (mechanism not known)Others (mechanism not known)– Sertraline, chloroquine/proguanil, lovastatinSertraline, chloroquine/proguanil, lovastatin
Case: 46-year-old woman with hypothyroidism is on thyroxine (T4) 0.125 mg daily
Q: What do you consider optimal target TSH?
a. 0.1 b. 1.0c. 5.0 d. 10.0
CONCLUSION :
Subclinical thyroid dysfunction is a common (hypo > hyper) clinical problem
Lab TSH reference range should be reset at
0.3-3.0 TSH therapeutic goal should be at 0.3-3.0 Patients with TSH >5 would likely benefit form
T4 Rx TSH >2.5 is associated with a higher risk for
clinical hypothyroidism
تقویتی و انتهایی اهداف طراحی و تقویتی استخراج و انتهایی اهداف طراحی و استخراجماتریس ماتریس از CPCP از
ماتريس تكميل از ماتريس پس تكميل از استخراج CPCP پس در قدم استخراج اولين در قدم اولينهدايت كننده سواالت طـــــرح را ترمينال هدايت كننده اهداف سواالت طـــــرح را ترمينال اهداف
( ( Leading QuestionsLeading Questions ) ) ( به مي شود آغاز ) زير به مي شود آغاز زير) کنید توجه بعد (اسالیدهای کنید توجه بعد اسالیدهای
قانون بكمك سواالت اين به پاسخ از قانون بعد بكمك سواالت اين به پاسخ از و و ABCDABCD بعدرا SMARTSMART چك ليستچك ليست آنها تکمیلی چك ليست را و آنها تکمیلی چك ليست و
درآوريم واضح اهداف درآوريم بصورت واضح اهداف بصورت