1

Bryan R. Haugen, MDBryan R. Haugen, MD

Associate Professor of MedicineAssociate Professor of Medicine

University of Colorado Health Sciences CenterUniversity of Colorado Health Sciences Center

Past consulting: Abbott LaboratoriesPast consulting: Abbott Laboratories

2

A 62 year-old woman presented with classic A 62 year-old woman presented with classic symptoms of hypothyroidismsymptoms of hypothyroidism

• Fatigue, weight gain, constipationFatigue, weight gain, constipation

TSH 28 mU/L (0.5-5), T4 8 TSH 28 mU/L (0.5-5), T4 8 g/dl (4-12)g/dl (4-12)

She was started on 0.1 mg levothyroxine once a dayShe was started on 0.1 mg levothyroxine once a day

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62 year-old hypothyroid woman (TSH 28 mU/L)62 year-old hypothyroid woman (TSH 28 mU/L)

Eight weeks laterEight weeks later: Symptoms improved, but still has : Symptoms improved, but still has significant fatiguesignificant fatigue– TSH 7 mU/L (0.5-5), T4 9 TSH 7 mU/L (0.5-5), T4 9 g/dl (4-12)g/dl (4-12)– Levothyroxine increased to 0.125 mg a day ( 25%)Levothyroxine increased to 0.125 mg a day ( 25%)

Eight weeks laterEight weeks later: Minimal fatigue, new insomina: Minimal fatigue, new insomina– TSH 0.08 mU/LTSH 0.08 mU/L

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Sensitivity of TSH to Change in Dosage of Sensitivity of TSH to Change in Dosage of LevothyroxineLevothyroxine

TS

H (

TS

H ( I

U/m

L)

IU/m

L)

1010

88

66

44

22

0.20.211

-50-50 -25-25 +25+25 +50+50 +75+75OptimumOptimumTT4 4 (mcg)(mcg)

Carr D, et al. Carr D, et al. Clin EndocrinolClin Endocrinol. 1988;28:325.. 1988;28:325.

Upper limit of normalUpper limit of normal

Lower limit of normalLower limit of normal

5

Undetectable

ng/dL

TSHReferenceInterval

HyperthyroidHypo-Thyroid

FT4 ReferenceInterval

0 .7 1 .8

0.01

0.1

4.0

10

100

1,000

TSHmIU/L

Free T49 2 3 pmol/L{

0.4>100x

2x

TSH - Free T4 Relationships inAmbulatory Patients with Stable Thyroid Status

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Long-term effects of a low TSHLong-term effects of a low TSH

• Increased risk of atrial fibrillation (3-fold)Increased risk of atrial fibrillation (3-fold)– Sawin, New Engl J Med 331:1249, 1994Sawin, New Engl J Med 331:1249, 1994

• Reduced exercise capacity and cardiac functionReduced exercise capacity and cardiac function– Mercuro, J Clin Endo Metab 85:159, 2000Mercuro, J Clin Endo Metab 85:159, 2000

• Decreased BMD and increased fracture risk (3-4x)Decreased BMD and increased fracture risk (3-4x)– DeRosa, Clin Endo 47:529, 1997DeRosa, Clin Endo 47:529, 1997– Bauer, Ann Int Med 134:561, 2001Bauer, Ann Int Med 134:561, 2001

• Increased all cause mortality (2-fold), CV mortalityIncreased all cause mortality (2-fold), CV mortality– Parle, Lancet 358:861, 2001Parle, Lancet 358:861, 2001

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IncidenceIncidenceof Atrialof Atrial

Fibrillation Fibrillation (%)(%)

3030

2525

2020

1515

1010

55

00

Low Thyrotropin

YearsYears

00 11 22 33 44 55 66 77 88 99 1010

HighThyrotropin

NormalThyrotropin

Slightly LowThyrotropin

Serum Thyrotropin Values at BaselineSerum Thyrotropin Values at Baseline

Sawin CT et al. New Engl J Med. 1994;331:1249.

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62 year-old hypothyroid woman62 year-old hypothyroid woman– TSH 0.08 mU/L on 0.125 mg LT4TSH 0.08 mU/L on 0.125 mg LT4

LT4 decreased to 0.112 mg a day ( 10%)LT4 decreased to 0.112 mg a day ( 10%)

Seven weeks laterSeven weeks later: She felt well with no complaints: She felt well with no complaints– TSH 1.6 mU/LTSH 1.6 mU/L

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SummarySummary

• Serum TSH and patient symptoms, not serum T4, Serum TSH and patient symptoms, not serum T4, are therapeutic endpointsare therapeutic endpoints

• True normal range for TSH is quite narrow (0.5 – 2 True normal range for TSH is quite narrow (0.5 – 2 mU/L)mU/L)

• Small changes in administered levothyroxine (10-Small changes in administered levothyroxine (10-20%) result in significant changes in TSH20%) result in significant changes in TSH

• Abnormal TSH has consequencesAbnormal TSH has consequences– Burden on the patientBurden on the patient– Burden on the healthcare systemBurden on the healthcare system