Subclinical Hypothyroidism Mitchell S. Parker, MD Disclosure - I - - PowerPoint PPT Presentation

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Subclinical Hypothyroidism Mitchell S. Parker, MD Disclosure - I - - PowerPoint PPT Presentation

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Subclinical Hypothyroidism Mitchell S. Parker, MD Disclosure - I am on the Speakers Bureau for Abbott. I have limited my presentation to evidence that is supported by peer- reviewed studies and will provide a balanced view of

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SLIDE 1

Subclinical Hypothyroidism

  • Mitchell S. Parker, MD
  • Disclosure - I am on the Speaker’s Bureau

for Abbott. I have limited my presentation to evidence that is supported by peer- reviewed studies and will provide a balanced view of available therapeutic

  • ptions, where applicable.
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SLIDE 2
  • Subclinical Hypothyroidism
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SLIDE 3

Subclinical Hypothroidism

  • Affects 5 – 10% of the general population
  • Affects 10% 0f the elderly population
  • More common in females
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SLIDE 4

Case Presentation

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SLIDE 5

Screening For Thyroid Disease

Normal TSH = normal thyroid function Low TSH = Hyperthyroidism. High TSH = Primary Hypothyroidism

  • When the TSH is abnormal, follow with a serum

Free T4 for confirmation.

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SLIDE 6

Thyroid Disease-free Population: 0.44 to 5.5 mIU/L Total Population: 0.33 to 5.8 mIU/L Reference Population (no thyroid risk factors): 0.45 to 4.1mIU/L

0.5 5.0

TSH

NHANES III: TSH Normal Range

%

4.0 3.0 2.0 1.0

Hollowell JG, et al. J Clin Endocrinol Metab. 2002;87:489-499

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SLIDE 7

Recommended TSH Normals

  • Most labs .4 – 4.5
  • AACE .3 – 3.0
  • NACB .5 – 2.0
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SLIDE 8

Routine TSH Screening Recommendations

  • American Academy of Family Physicians –

patients over age 60 or with risk factors

  • American Thyroid Association – all

patients over 35 every 5 years

  • AACE – women before or during first

trimester of pregnancy

  • American College of Physicians – women
  • ver 50
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SLIDE 9

What Group of Patients Should Always Be Treated For Subclinical Hypothyroidism?

  • Neonates
  • Teenagers who have not closed

their epiphyses

  • Pregnant women
  • Elderly patients over the age of 70
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SLIDE 10

Thyroid Medication in Pregnancy

  • 85% of women with thyroid

dysfunction require a substantial increase in their usual dose

  • Dose requirements often increase 30 –

50%

  • Median time of dose increase is 6 – 8

weeks and plateaus at 16 – 20 weeks

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SLIDE 11

Pregnancy Outcomes – Subclinical Hypothyroidism

  • Increase pre-eclampsia
  • Increase placental abruption
  • Increase pre-term delivery
  • Low birth weight
  • Questionable effect on IQ
  • Increase respiratory distress
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SLIDE 12

Miscarriage Rate with Subclinical Hypothyroidism

  • TSH .4 – 2.5 vs 2.6 – 4.0

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SLIDE 13
  • TSH >6 mU/L in 2.2% of mothers with singleton pregnancies

(n=9,403)

  • Fetal death rate 4x greater with high TSH
  • Other pregnancy complications were equivalent

Rate of Fetal Death and Thyroid Deficiency

Maternal TSH >6 mU/L

.9%

1 2 3 4 5

Maternal TSH <6 mU/L

(P<0.001)

3.8%

Allan WC, et al. J Med Screen. 2000;7:127-130.

Consequences of Mild Hypothyroidism

Fetal Death

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SLIDE 14

Example:

  • 85 y.o. woman who lives by herself. She

had recently lost her husband. She was tired, somnolent and forgetful. No goiter.

  • TSH screen: 7.8 mU/L ( n: 0.4-5 )
  • Free T4: 1.0 ng/dL ( n: 0.8-1.8)
  • Treatment?
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SLIDE 15

85 Year Old Woman

  • Treat with thyroxine
  • Treat with Armour thyroid
  • Do not treat
  • Refer to endocrinology
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SLIDE 16

Subclinical Hypothyroidism

  • She was given 50 mcg of Levothyroxine

daily.

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SLIDE 17

Subclinical Hypothyroidism

  • The patient was admitted 6 weeks later

with severe dyspnea. She was in A-Fib and congestive heart failure.

  • Serum TSH<0.01 mU/L (n: 0.4-5)
  • Serum free T4 high at 2.3 ng/dL (0.8-1.8)
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SLIDE 18

Subclinical Hypothyroidism

  • Three months later on no thyroid

hormone: TSH: 2.3 uU/ml, normal Free T4: 1.3 ng/dL, normal

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SLIDE 19

Subclinical Hypothyroidism

  • 10% of the population in the sixth decade have

subclinical hypothyroidism. Of Those:

  • 5% per year progress to overt hypothyroidism
  • In 20-50%, the TSH returns to normal
  • The rest stay the same
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SLIDE 20

Should we have an age adjusted TSH? Some data support a TSH of 7.0 in healthy elderly population.

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SLIDE 21

Why Treat Subclinical Hypothyroidism?

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SLIDE 22

GPRD – World’s Largest Data Base 2001 - 2009

  • Age greater than 40
  • TSH 5 – 10
  • Normal free T-4
  • Excluded patients with cerebrovascular
  • r IHD
  • Age 40 – 70 or over 70
  • Thyroxine vs placebo
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SLIDE 23

GPRD Findings

  • 38.4% of untreated patients reverted to

a euthyroid state

  • 2.5% developed subclinical

hyperthyroidism

  • 1.3% became overtly hypothyroid
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SLIDE 24

Depression, Anxiety and Cognitive Function and Subclinical Hypo and Hyperthyriodism

  • 5,868 patients age 65 – 98
  • No increased depression with subclinical

hypothyriodism

  • No increased anxiety with subclinical

hypothyriodism

  • No decreased cognitive function
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SLIDE 25

Increased Left Ventricular Mass With Mild Thyroid Failure

10 20 30 40 50 60 70 80 90 100 Left Ventricular Mass Index, g/m2 Patients With Mild Thyroid Failure Control Group

Di Bello V, et al. J Am Soc Echocardiogr. 2000;13:832-840.

P<.01

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SLIDE 26

Endothelial Function in Patients With Mild Thyroid Failure and CAD Risk

Lekakis J, et al. Thyroid. 1997;7:411-414.

Flow-mediated vasodilatation is impaired in patients with mild thyroid failure, which could contribute to the development of CAD. 2 4 6 8 10 12 14 <2 >10

TSH Levels, mIU/ML Flow-Mediated Endothelium- Dependent Vasodilatation, %

2-4 >4-10

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SLIDE 27

Slowed Left Ventricular Relaxation in Mild Thyroid Failure

Biondi B, et al. Thyroid. 2002;12:505-510.

Mild Thyroid Failure

Heart Vascular Smooth Muscle Slowed LV Relaxation at Rest Impaired LV Diastolic Filling on Exercise Increased Vascular Tone at Rest Impaired Peripheral Vasodilation on Exercise LV Systolic Dysfunction on Effort Cardiovascular Abnormalities Leading to LV Dysfunction on Effort in Mild Thyroid Failure

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SLIDE 28

Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.

7.2 7.0 6.8 6.6 6.4 6.2 6.0 5.8 5.6 5.4 5.2 Mean Total Cholesterol Level, mmol/L 280 270 260 250 240 230 220 210 200 (mg/dL) >10-15 <0.3 0.3-5.1 >5.1-10 >15-20 >20-40 >40-60 >60-80 >80 TSH, mlU/L Abnormal TSH Level Euthyroid

5.41 (209) 5.59 (216) 5.78 (223) 5.85 (226) 5.93 (229) 6.16 (238) 6.19 (239) 6.99 (270) 6.92 (267)

Consequences of Hypothyroidism

Cholesterol - Mild & Overt

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SLIDE 29

Elevated Lipoprotein(a) Levels Increase CAD Risk

50 100 150 200 250 300 Lipoprotein(a) Levels, U/L Patients With Mild Thyroid Failure Control Group*

  • PROCAM. Lipoprotein(a) and cardiovascular risk.

Available at: http://www.chd-taskforce.de/pdf/sk_procam_03.pdf. Accessed April 17, 2003. Kung AW, et al. Clin Endocrinol. 1995;43:445-449.

  • Elevated lipoprotein(a)

levels are associated with an increased risk of CAD development and MI

  • ccurrence
  • Patients with mild thyroid

failure have higher lipoprotein(a) levels, which increases their risk of CAD

P<.005

*Control group consisted of age- and gender-matched healthy patients.

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SLIDE 30

Levothyroxine Treatment Reduces Lipoprotein(a) Levels in Patients With Mild Thyroid Failure

  • Lipoprotein(a) levels in

patients with mild thyroid failure had a statistically significant (P<.001) mean decrease after treatment with levothyroxine

  • Levothyroxine therapy is

effective in lowering lipoprotein(a) levels and had beneficial effects on lipid profiles

100 110 120 130 140 150 160 170 Lipoprotein(a) Levels, mg/L

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h y r

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i n e T r e a t m e n t After Levothyroxine Treatment

Yildirimkaya M, et al. Endocrin J. 1996;43:731-736.

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SLIDE 31

Odds Ratio† 0.5 1 1.5 2 2.5 3 3.5

Aortic Atherosclerosis Myocardial Infarction Euthyroid

1.0* 1.0*

Mild Hypothyroidism (TSH >4.0)

1.7 2.3

Hak AE, et al. Ann Intern Med. 2000;132:270-278.

Consequences of Mild Hypothyroidism

Atherosclerosis

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SLIDE 32

Cardiac Benefits of Thyroxine Treatment in SCH

Decrease LDL Decrease total cholesterol Improve endothelial function Decrease carotid intimal medial thickness Improved left ventricular diastolic function

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SLIDE 33

Subclinical Thyroid Disease – Risk of CHF

  • 7 – 9.9 1.01
  • Over 10 1.86
  • .1 - .4 1.31
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SLIDE 34

Subclinical Hypothyroidism – Cardiovascular Health Study

  • Retrospective, age over 65 years, 4863

patients

  • TSH
  • No increase in CHD, CVD death or heart

failure in any of the groups

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SLIDE 35

Subclinical Hypothyroidism – Cardiovascular Health Study

  • Retrospective, age over 65 years, 4863

patients

  • TSH
  • No increase in CHD, CVD death or heart

failure in any of the groups

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SLIDE 36

Subclnical Hypothyroidism

  • Increase TSH with normal T4/T3
  • 10% of elderly population
  • Recent Meta-analysis confirms

increased CV events in young to middle age adults

  • We lack proof that treatment of

SCH is efficacious

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SLIDE 37

Subclinical Hypothyroidism – Development of Ischemic Heart Disease

  • 68 of 1634 patients treated with thyroxine
  • 97 of 1459 untreated patients
  • 104 of 819 patients treated with thyroxine
  • 88 of 823 untreated patients

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SLIDE 38

Subclinical Hypothyroidism- Development of Ischemic Heart Disease

  • 46% decrease circulatory disorders
  • 41% decrease malignant neoplasms
  • Non-significant 24% decrease A-fib

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SLIDE 39

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SLIDE 40

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SLIDE 41

Subclinical Hypothyroidism – Effects of Treatment on GFR

  • Decrease in GFR 50% or progression to

ESRD

  • 180 patients treated with thyroxine and

129 patients without thyroxine

  • Follow-up 34 +/- 24 months

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SLIDE 42

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SLIDE 43

Prevalence of Elevated Serum TSH by Decade of Age and Gender

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

  • At <40 years of

age, prevalence is relatively low and similar between males and females

  • At ≥40 years of

age, a higher percentage of female patients have elevated TSH levels

Males Females Females NHANES III Study (N=17 353)

Hollowell JG, et al. J Clin Endocrinol Metab. 2002;87:489-499.

Participants With Elevated TSH, %

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SLIDE 44

Subclinical Hypothyroidism In The Elderly

  • May not have any adverse effects
  • One study of a healthy population
  • ver 85 years showed SCH

associated with increased longevity

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SLIDE 45

“One of the reasons that treating

  • lder patients with subclinical

hypothyroidism might not help them is because there is nothing wrong with them in the first place.”

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SLIDE 46

What Percent of Patients on Thyroxine have a Suppressed TSH?

  • 15%
  • 20%
  • 40%
  • 45%
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SLIDE 47

Thyroid Status of Treated Patients

Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.

20 40 60 80 100

Euthyroid

60.1 Participants, %

Hyperthyroid Subclinical Hyperthyroid

0.9 20.7

Overtreated >20%

Subclinical Hypothyroid Hypothyroid

17.6 0.7

Undertreated >18%

Colorado Thyroid Disease Prevalence Study

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SLIDE 48

Consequences of Subclinical Hypothyroidism

  • 3 – 20% will develop overt

hypothyroidism

  • Risk is especially high in those

with a goiter or thyroid antibodies

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SLIDE 49

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SLIDE 50

Subclinical Hypothyroidism- Who To Treat?

  • TSH >10
  • Positive thyroid antibodies
  • Goiter
  • Age <70 years
  • Pregnant patients
  • Renal insufficency
  • ? Children/ adolescents
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SLIDE 51

Example:

  • 85 y.o. woman who lives by herself. She

had recently lost her husband. She was tired, somnolent and forgetful. No goiter.

  • TSH screen: 7.8 mU/L ( n: 0.4-5 )
  • Free T4: 1.0 ng/dL ( n: 0.8-1.8)
  • Treatment?
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SLIDE 52

????Questions????