subclinical thyroid disorders

Subclinical thyroid Subclinical thyroid disordersdisordersMario Skugor M.D. FACEMario Skugor M.D. FACEAssociate Professor of MedicineAssociate Professor of MedicineCCLCM of CWRUCCLCM of CWRUCleveland ClinicCleveland Clinic

Definitions:Definitions:

Individuals with elevation of TSH but Individuals with elevation of TSH but normal thyroid hormone levels have sub-normal thyroid hormone levels have sub-clinical hypothyroidism*.clinical hypothyroidism*.

*Some authors consider patients with high-normal TSH *Some authors consider patients with high-normal TSH

and abnormal response to TRH as having SCH.and abnormal response to TRH as having SCH.

Gharib H. et al. J Clin Endocrinol Metab 2005;90:581-585

Definitions:Definitions:

Individuals with TSH lower than normal Individuals with TSH lower than normal but with normal thyroid hormone levels but with normal thyroid hormone levels have sub-clinical hyperthyroidism.have sub-clinical hyperthyroidism.

Gharib H. et al. J Clin Endocrinol Metab 2005;90:581-585

Normal TSH???Normal TSH???

Normal TSH rangeNormal TSH range Most common assays in U.S.A.Most common assays in U.S.A.

0.4-5.5 uU/mL0.4-5.5 uU/mL 0.27-4.2 uU/mL0.27-4.2 uU/mL


Lower limit of the normal range is Lower limit of the normal range is somewhat variable but relatively well somewhat variable but relatively well established.established.


Upper level of normal range is Upper level of normal range is controversial.controversial.


0.4 5.5

NHANES IIINHANES III

0.45 4.121.39

median

N = 13,344Healthy, antibody negative subjects


Consensus conference (ATA, AACE, Endo Consensus conference (ATA, AACE, Endo Soc) accepted NHANES III derived normal Soc) accepted NHANES III derived normal range.range.

National Academy of Clinical Biochemistry National Academy of Clinical Biochemistry proposed 0.4-2.5 uU/mL for normal range.proposed 0.4-2.5 uU/mL for normal range.

AACE proposed 0.3-3.0 uU/mLAACE proposed 0.3-3.0 uU/mL

Practical considerationsPractical considerations

Results of lowering upper limit of normal Results of lowering upper limit of normal range from 5 to 2.5 uU/mL changes range from 5 to 2.5 uU/mL changes prevalence of sub-clinical hypothyroidism:prevalence of sub-clinical hypothyroidism:

4.6% to 20%4.6% to 20%

Fatourechi V. et al. JAMA 2003;290:3195-3196


TSH varies with time.TSH varies with time. Mildly abnormal TSH should be rechecked in Mildly abnormal TSH should be rechecked in

3-4 months to confirm persistent elevation.3-4 months to confirm persistent elevation. Transient elevations are not uncommon.Transient elevations are not uncommon.


TSH elevations NOT associated with SC TSH elevations NOT associated with SC hypothyroidism:hypothyroidism: Recovery from non-thyroidal illness.Recovery from non-thyroidal illness. Adrenal insufficiency.Adrenal insufficiency. Treatment with metoclopramide and domperidoneTreatment with metoclopramide and domperidone TSH secreting adenomasTSH secreting adenomas Thyroid hormone resistanceThyroid hormone resistance Assay variabilityAssay variability Late evening pulse in TSH secretionLate evening pulse in TSH secretion


Decreased TSH also could be seen with Decreased TSH also could be seen with conditions that are not associated with conditions that are not associated with hyperthyroidism.hyperthyroidism.


Decreased TSH NOT associated with SC Decreased TSH NOT associated with SC hyperthyroidism:hyperthyroidism:

Central hypothyroidismCentral hypothyroidism Non-thyroidal IllnessNon-thyroidal Illness Glucocorticoid and dopamine useGlucocorticoid and dopamine use Recovery from hyperthyroidismRecovery from hyperthyroidism Early pregnancyEarly pregnancy


Even TSH over 20 uU/mL can be Even TSH over 20 uU/mL can be associated with normal TH levels.associated with normal TH levels.


Attempts to identify individuals with mild Attempts to identify individuals with mild thyroid disorders based on search for thyroid disorders based on search for thyroid specific symptoms have not been thyroid specific symptoms have not been successful.successful.

Sub-clinical Sub-clinical hypothyroidismhypothyroidism

Should be diagnosed in patients who do Should be diagnosed in patients who do NOT complain of symptoms associated NOT complain of symptoms associated with hypothyroidism.with hypothyroidism.

In patients who are screened for In patients who are screened for presence of thyroid disorder because of presence of thyroid disorder because of increased risk.increased risk.

Elevated TSH normal THElevated TSH normal TH

If patient complains of symptoms and If patient complains of symptoms and elevated TSH with normal TH is found, elevated TSH with normal TH is found, than disorder cannot be considered to be than disorder cannot be considered to be sub-clinical.sub-clinical.

Mild hypothyroidism Mild hypothyroidism

In my opinion, after rechecking to confirm In my opinion, after rechecking to confirm TSH elevation, treatment should be TSH elevation, treatment should be seriously considered in such patients.seriously considered in such patients.

TSH should be corrected to below 2.0 TSH should be corrected to below 2.0 uU/mL and therapeutic effects assessed uU/mL and therapeutic effects assessed after 2-3 months.after 2-3 months.

If benefit is derived treatment should be If benefit is derived treatment should be continued.continued.

Sub-clinical Sub-clinical hypothyroidismhypothyroidism

Individuals with TSH from upper limit of Individuals with TSH from upper limit of normal to 10 uU/mLnormal to 10 uU/mL With normal TH levelsWith normal TH levels With no symptoms that could be explained With no symptoms that could be explained

by hypothyroidismby hypothyroidism

Have “Sub-clinical hypothyroidism”Have “Sub-clinical hypothyroidism”

EpidemiologyEpidemiology

Whickham surveyWhickham survey PrevalencePrevalence

MenMen 2.8%2.8% WomenWomen 7.5%7.5% Women >60 yWomen >60 y 11.6%11.6%

Vanderpump MP. Et al. Clin endocrinol (Oxf) 1991;43:55-69


NHANES IIINHANES III Prevalence in 16,533 individualsPrevalence in 16,533 individuals

Patients with known thyroid disease were Patients with known thyroid disease were excluded.excluded.

SCH found in 4.3%SCH found in 4.3%

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


Colorado Thyroid Disease Prevalence Colorado Thyroid Disease Prevalence StudyStudy

N – 25,862N – 25,862 PrevalencePrevalence

OverallOverall 9.5%9.5% 18-24 y18-24 y 4.0%4.0% Women >74Women >74 22%22% Men >74 yMen >74 y 16%16%

Canaris GJ. Et al. Arch Intern Med 2000:160:526-534/


Increased prevalence is reported in Increased prevalence is reported in patients with:patients with: Diabetes mellitus type 1 Diabetes mellitus type 1 (1)(1) Schmidt’s syndromeSchmidt’s syndrome (2)(2) Celiac diseaseCeliac disease (3)(3)

Due to presence of Hashimoto’s thyroiditisDue to presence of Hashimoto’s thyroiditis

1. Vondra K. et al. J Endocrinol Invest 2004: 27:728-732.2. Betterie C. et al. Endocr rev 2002;23:327-364.3. Sategna-Guidetti C. et al. Am J Gastroenterol 2001:96:751-757.

Etiology–SC Etiology–SC hypothyroidismhypothyroidism

Common causesCommon causes Iatrogenic Iatrogenic

In patients with coexisting heart diseaseIn patients with coexisting heart disease In patients with malignant diseasesIn patients with malignant diseases In patients with poor complianceIn patients with poor compliance In patients taking medications inappropriatelyIn patients taking medications inappropriately


Common causesCommon causes IatrogenicIatrogenic Hashimoto’s thyroiditisHashimoto’s thyroiditis

Most common causeMost common cause 54% of SCH patients in U.S. are abs positive (1)54% of SCH patients in U.S. are abs positive (1) UK study found abs in 67% of women and 40% UK study found abs in 67% of women and 40%

of men with SCH (2)of men with SCH (2)

1. Hamburger JI, et al. NEJM 1985;313:267.2. Tonbridge WM. Et al. Br Med J 1974;3:89.


Common causesCommon causes IatrogenicIatrogenic Hashimoto’s thyroiditisHashimoto’s thyroiditis Postpartum thyroiditisPostpartum thyroiditis


Common causesCommon causes IatrogenicIatrogenic Hashimoto’s thyroiditisHashimoto’s thyroiditis Postpartum thyroiditisPostpartum thyroiditis MedicationsMedications

AmiodaroneAmiodarone LithiumLithium InterferonInterferon SunitinibSunitinib SorafenibSorafenib


Common causesCommon causes IatrogenicIatrogenic Hashimoto’s thyroiditisHashimoto’s thyroiditis Postpartum thyroiditisPostpartum thyroiditis MedicationsMedications Partial thyroidectomyPartial thyroidectomy


Common causesCommon causes IatrogenicIatrogenic Hashimoto’s thyroiditisHashimoto’s thyroiditis Postpartum thyroiditisPostpartum thyroiditis MedicationsMedications Partial thyroidectomyPartial thyroidectomy Head and neck radiationHead and neck radiation


Common causesCommon causes IatrogenicIatrogenic Hashimoto’s thyroiditisHashimoto’s thyroiditis Postpartum thyroiditisPostpartum thyroiditis MedicationsMedications Partial thyroidectomyPartial thyroidectomy Head and neck radiationHead and neck radiation RAI ablation of Graves’ diseaseRAI ablation of Graves’ disease

Clinical consequencesClinical consequences

Progression to overt hypothyroidismProgression to overt hypothyroidism 2-5% yearly2-5% yearly 10% may eventually normalize10% may eventually normalize Higher initial TSH – higher the risk of Higher initial TSH – higher the risk of

progressionprogression Positive AMA-s – higher risk of progressionPositive AMA-s – higher risk of progression

Huber G. et al. J Clin Endocrinol Metab 2002;87:3221-3226.Diez JJ. et al. J Clin Endocrinol Metab 1991:72:209-213.


Development of hypothyroidism, 20 year Development of hypothyroidism, 20 year follow up – Whickham survey follow up – Whickham survey 27% if abs positive27% if abs positive 33% if TSH higher than normal 33% if TSH higher than normal 55% if TSH higher and abs positive55% if TSH higher and abs positive 4% if TSH was normal and abs negative4% if TSH was normal and abs negative



Risk of CV diseaseRisk of CV disease Diastolic dysfunctionDiastolic dysfunction Diastolic hypertensionDiastolic hypertension Increase in LDL-CIncrease in LDL-C Increased hsCRPIncreased hsCRP Alteration in coagulation parametersAlteration in coagulation parameters Endothelial dysfunctionEndothelial dysfunction

Alber CP. et al. Am Heart J 1964Diez JJ. et al. J Clin Endocrinol Metab 1991:72:209-213.


Risk of CV diseaseRisk of CV disease Whickham survey showed no association Whickham survey showed no association

over 20 years with:over 20 years with: Coronary heart diseaseCoronary heart disease DyslipidemiaDyslipidemia MortalityMortality

Vanderpump MP, et al. Clin Endocrinol (Oxf) 1991:43:55-69.


Risk of CV diseaseRisk of CV disease Rotterdam study showed increased Rotterdam study showed increased

prevalence of atherosclerosis (odds ratio prevalence of atherosclerosis (odds ratio 1.7) and MI (odds ratio 2.3) in women with 1.7) and MI (odds ratio 2.3) in women with SCH.SCH.

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


Risk of CV diseaseRisk of CV disease Studies show mixed results but population Studies show mixed results but population

studied are different and number of patients studied are different and number of patients are usually small (total number of subjects is are usually small (total number of subjects is high but patients with SCH are not many).high but patients with SCH are not many).

Example – 4331 subjects but 281 with SCH (1)Example – 4331 subjects but 281 with SCH (1)

Pearce EN, et al. Endo Soc, Boston MA abstract 42-1.

ControversyControversy

McDermott MT, Ridgway EC 2001 McDermott MT, Ridgway EC 2001 Subclinical hypothyroidism is mild thyroid Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin failure and should be treated. J Clin Endocrinol Metab 86:4585–4590.Endocrinol Metab 86:4585–4590.

Chu JW, Crapo LM 2001 The treatment of Chu JW, Crapo LM 2001 The treatment of subclinical hypothyroidism is seldom subclinical hypothyroidism is seldom necessary. J Clin Endocrinol Metab 86: necessary. J Clin Endocrinol Metab 86: 4591–4599.4591–4599.

Clinical ConsequencesClinical Consequences

FertilityFertility 17% of Tg and AM antibodies positive had 17% of Tg and AM antibodies positive had

spontaneous miscarriage, compared to 8.4% spontaneous miscarriage, compared to 8.4% of antibody negative women (1)of antibody negative women (1)

2.3% of 25,756 pregnant women had SCH, 2.3% of 25,756 pregnant women had SCH, and their risk for placental abruption and and their risk for placental abruption and preterm delivery was 2 times normal (2)preterm delivery was 2 times normal (2)

1. Stagnaro-Green A, et al. JAMA 1990;264:1422-1425.2. Casey BM, et al.Obstet Gynecol 2005;105:239-245.

Clinical ConsequencesClinical Consequences

FertilityFertility The 16 and 11 recurrent aborters with The 16 and 11 recurrent aborters with

positive TPO-abs were treated with T4 and positive TPO-abs were treated with T4 and IV immunoglobulins respectively.IV immunoglobulins respectively.

T4 treated patients had 81.2% delivery rate T4 treated patients had 81.2% delivery rate and IV Immunoglobulin treated 54.5%.and IV Immunoglobulin treated 54.5%.

Vaquero E, et al. Am J Reprod Immunol 2000;43:204-208

Clinical ConsequencesClinical Consequences Neuropsychiatric disordersNeuropsychiatric disorders

SCH patients with depression have poorer SCH patients with depression have poorer response to antidepressant medications (1)response to antidepressant medications (1)

SCH patient have increased lifetime SCH patient have increased lifetime prevalence of depression (2)prevalence of depression (2)

Women with SCH and goiter have increased Women with SCH and goiter have increased rate of anxiety and depressive features (3)rate of anxiety and depressive features (3)

1. Joffe RT, Levitt AJ. Psychoneuroendocrinology 1992;17:2152. Haggerty JJ, et al. Am J Psychiatry 1993:150:508.3. Monzani F, et al. Clin Invest 1993;71:367.

Clinical ConsequencesClinical Consequences MortalityMortality

CV health study (N = 3,233) showed NO CV health study (N = 3,233) showed NO increase (1)increase (1)

Meta-analysis showed increased risk in Meta-analysis showed increased risk in those older than 65 (2)those older than 65 (2)

Several studies showed increase in CV and Several studies showed increase in CV and all-cause mortality (3-5)all-cause mortality (3-5)

1. Cappola AR, et al. JAMA 2006;295:1033.2. Razvi S, et al. J Clin Endocrinol Metab 2008;93:2998.3. Imaizumi M, at al. J Clin Endocrinol Metab 2004:89:3365.4. Iervasi G, et al. Arch Intern Med 2007;167:1526.5. Walsh JP, et al. Arch Intern Med 2005;165:2467.

Our experienceOur experience We examined cohort of 6,408 patients at HIGH We examined cohort of 6,408 patients at HIGH

RISK for cardiovascular disease.RISK for cardiovascular disease. Patients were enrolled in cardiovascular Patients were enrolled in cardiovascular

disease prevention program of Cleveland disease prevention program of Cleveland Clinic between January 16, 1995 and June 25, Clinic between January 16, 1995 and June 25, 2008.2008.

Data about patients were entered in the Data about patients were entered in the Preventive Cardiology Information System Preventive Cardiology Information System (PreCIS) database.(PreCIS) database.

McQuade C, et al. ATA meeting, Chicago IL, 2008 abstract 311.

MethodsMethods Patients:Patients:

Secondary prevention ~ 50%Secondary prevention ~ 50% Primary prevention ~ 50%Primary prevention ~ 50%

HypercholesterolemiaHypercholesterolemia Strong family history of CVDStrong family history of CVD

The CVD risk factors are aggressively The CVD risk factors are aggressively treated.treated.

Methods (cont)Methods (cont)

Five TSH intervals predefined:Five TSH intervals predefined:

<0.4 µU/ml (hyperthyroid) <0.4 µU/ml (hyperthyroid) 0.4-3.0 µU/ml (normal)0.4-3.0 µU/ml (normal) 3.0-6.0 µU/ml (mild SCH)3.0-6.0 µU/ml (mild SCH) 6.0-10.0 µU/ml ( moderate SCH)6.0-10.0 µU/ml ( moderate SCH) >10.0 µU/ml (hypothyroid)>10.0 µU/ml (hypothyroid)

Methods (cont)Methods (cont) Number of patients:Number of patients:

<0.4 µU/ml<0.4 µU/ml 168 patients168 patients

0.4-3.0 µU/ml0.4-3.0 µU/ml 4,755 patients4,755 patients

3.0-6.0 µU/ml3.0-6.0 µU/ml 1,214 patients1,214 patients

6.0-10.0 µU/ml6.0-10.0 µU/ml 178 patients178 patients

>10.0 µU/ml >10.0 µU/ml 79 patients79 patients

No TSH availableNo TSH available 14 patients14 patients

Patients characteristics:Patients characteristics: There was no difference between groups:There was no difference between groups:

Framingham risk scoreFramingham risk score Diabetes mellitusDiabetes mellitus LDLLDL Lp(a)Lp(a) MicroalbuminuriaMicroalbuminuria Body mass indexBody mass index Diastolic blood pressureDiastolic blood pressure

ResultsResults

Adjustment was made for:Adjustment was made for: AgeAge SexSex SmokingSmoking HDLHDL LDLLDL Systolic blood pressureSystolic blood pressure Diastolic blood pressureDiastolic blood pressure DiabetesDiabetes

ResultsResults

After adjusting for common risk factors After adjusting for common risk factors there were no increased risk for the there were no increased risk for the group of patients with TSH less than group of patients with TSH less than 0.4.0.4.

Source: Arial 9pt, left-aligned with slide title

All cause mortality - All cause mortality - adjustedadjusted

All Patients

Time in Years

876543210

Cum

Sur

viva

l1.0

.9

.8

.7

.6

TSH Category

0.4-3.0

3.0-6.0

6.0-10.0

>10.0

All Patients (n = 6,394)

p<0.001P<0.001

Source: Arial 9pt, left-aligned with slide title

All cause mortality - All cause mortality - adjustedadjusted

All Patients

Time in Years

876543210

Cum

Sur

viva

l1.0

.9

.8

.7

.6

TSH Category

0.4-3.0

3.0-6.0

6.0-10.0

>10.0

All Patients (n = 6,394)

P=0.021

LimitationsLimitations Thyroid status based only on elevated TSH values Thyroid status based only on elevated TSH values

as L-T4 and T3 values are not consistently availableas L-T4 and T3 values are not consistently available The PreCIS database consists of exclusively The PreCIS database consists of exclusively

preventive cardiology patients at the Cleveland preventive cardiology patients at the Cleveland Clinic. The cohort is highly selected for patients Clinic. The cohort is highly selected for patients with or at risk for CHD. Results may not be with or at risk for CHD. Results may not be generalizable generalizable

Cause of death cannot be determined from the SS Cause of death cannot be determined from the SS death index. death index.

Effect of treatmentEffect of treatment

Psychometric outcomes and hypothyroid Psychometric outcomes and hypothyroid symptoms scores in double blind symptoms scores in double blind randomized trials:randomized trials: Improvement is seen consistently in those Improvement is seen consistently in those

with TSH >10 uU/mL.with TSH >10 uU/mL.

Cooper DS, et al. Ann Intern Med 1984;101:18.Nystrom E, et al. Clin Endocrinol 1988;29:63.Jaeschke R, et al. J Gen Intern Med 1996;11:744.Meier C, et al. J Clin Endocrinol Metab 2001;86:4860.


CholesterolCholesterol T4 treatment decreases:T4 treatment decreases:

Total Cholesterol in those with initial level over Total Cholesterol in those with initial level over 240 mmol/L (meta-analysis)240 mmol/L (meta-analysis)

LDL – CLDL – C Apolipoprotein B-100Apolipoprotein B-100

Danese MD, et al. J Clin Endocrinol Metab 2000;85:2993.Mikhail GS, et al. Endocr Pract 2008;14:570.Iqbal A, et al. J Intern Med 2006;260:53.


Cardiac function, blood pressureCardiac function, blood pressure Cardiac output increases (1)Cardiac output increases (1) Vascular resistance decreases (1)Vascular resistance decreases (1) Mean arterial pressure decreases (1)Mean arterial pressure decreases (1) Carotid intimal-media thickness decreases Carotid intimal-media thickness decreases

(2)(2) Diastolic and systolic function improve (3)Diastolic and systolic function improve (3)

1. Faber J, et al. Thyroid 2002;12:319.2. Adress M, et al. Clin Endocrinol 2008.3. Turhan S, et al. J CLin Endocrinol Metab. 2006;91:3490.

Bottom line:Bottom line:

I treat individuals with SCH if there are I treat individuals with SCH if there are associated clinical symptoms or positive associated clinical symptoms or positive thyroid autoantibodies.thyroid autoantibodies. A 2-6 months later clinical and laboratory A 2-6 months later clinical and laboratory

response is assessed.response is assessed. Decision to treat or not to treat further is Decision to treat or not to treat further is

made in discussion with patient.made in discussion with patient.

SC hyperthyroidismSC hyperthyroidism

EtiologyEtiology IatrogenicIatrogenic

25% of patients taking T4 may have low TSH.25% of patients taking T4 may have low TSH.

Some of these are intentionalSome of these are intentional Thyroid carcinomaThyroid carcinoma History of head and neck radiationHistory of head and neck radiation Presence of nodules and goitersPresence of nodules and goiters

De Whalley P. Br J Gen Pract 1995;45:93.


EtiologyEtiology IatrogenicIatrogenic Autonomous nodules (solitary and in MNG)Autonomous nodules (solitary and in MNG)

A 22% of patient with MNG found to have SC A 22% of patient with MNG found to have SC hyperthyroidism (1)hyperthyroidism (1)

In hyperthyroid patients over 55 years of age with In hyperthyroid patients over 55 years of age with MNG 57% were sub-clinical (2)MNG 57% were sub-clinical (2)

Diaz JJ. Gerontology 2003;49:316Rieu M, et al. Clin Endocrinol 1993;39:67


EtiologyEtiology IatrogenicIatrogenic Autonomous nodules (solitary and in MNG)Autonomous nodules (solitary and in MNG) Graves’ diseaseGraves’ disease

About 6% of patients with Graves’ disease are About 6% of patients with Graves’ disease are sub-clinical.sub-clinical.

Diaz JJ. Gerontology 2003;49:316.


EtiologyEtiology IatrogenicIatrogenic Autonomous nodules (solitary and in MNG)Autonomous nodules (solitary and in MNG) Graves’ diseaseGraves’ disease ThyroiditisThyroiditis Graves’ disease in remissionGraves’ disease in remission High hCG High hCG


EpidemiologyEpidemiology Reports vary from 0.7% to 12.4%Reports vary from 0.7% to 12.4%

NHANES III showed 0.7% (1)NHANES III showed 0.7% (1) Smokers two times higher prevalence.Smokers two times higher prevalence.

Another study found 1.8% with TSH <0.1 uU/mL Another study found 1.8% with TSH <0.1 uU/mL in U.S. (2)in U.S. (2)

In England 6% had TSH <0.5 uU/mL (3)In England 6% had TSH <0.5 uU/mL (3)

1. Hollowell JG, et al. J Clin endocrinol Metab 2002;87:4892. Sawin CT, et al. Arch Intern Med 1991;151:165.3. Parle JV, et al. Clin Endocrinol (Oxf) 1991;34:77.


Natural courseNatural course 40-60% normalize (1-3)40-60% normalize (1-3) About 4% progresses to overt About 4% progresses to overt

hyperthyroidism (4,5)hyperthyroidism (4,5)

1. Eggersten R, et al. BMJ 1988;297:15862. Parle JV, et al. Clin Endocrinol (Oxf) 1991;34:77.3. Meyerovitch J et al. Arch Intern Med 2007;167:1533.4. Sawin Ct, et al. Arch Intern Med 1991;151:1655. Sandrock D, et al. Acta endocrinol (Copenh) 1993;128:51

Clinical consequencesClinical consequences Bone metabolismBone metabolism

No good data on fracture rates.No good data on fracture rates. A meta-analysis found decreased BMD, but A meta-analysis found decreased BMD, but

only in postmenopausal women (1).only in postmenopausal women (1). In those taking T4 low BMD was found only In those taking T4 low BMD was found only

if dose was higher than 1.6 mcg/kg/d (2).if dose was higher than 1.6 mcg/kg/d (2). Markers of bone turnover have been Markers of bone turnover have been

reported to be increased (3)reported to be increased (3)

Faber J, Galloe AM. Eur J Endocrinol 1994;130:350Schneider DL, et al. JAMA 1994;271:1245Loviselli A, etr al. Thyroid 1997;7:561

Clinical consequencesClinical consequences CV effectsCV effects

Atrial fibrillationAtrial fibrillation Prospective study- 2,000 adults over 60 followed Prospective study- 2,000 adults over 60 followed

for 10 yearsfor 10 years TSH <0.1 uU/mL TSH <0.1 uU/mL - 28% cumulative - 28% cumulative

incidenceincidence TSH 0.1-0.4 uU/mL TSH 0.1-0.4 uU/mL - 16% cumulative incidence- 16% cumulative incidence TSH >0.4 uU/mLTSH >0.4 uU/mL - 11% cumulative - 11% cumulative

incidenceincidence

Cappola AR, et al. JAMA 2006;295:1033.


Atrial fibrillationAtrial fibrillation A cross-sectional study, 24,000 hospitalized A cross-sectional study, 24,000 hospitalized

patients.patients. 14% prevalence if overtly hyperthyroid14% prevalence if overtly hyperthyroid 13% prevalence in SC hyperthyroidism13% prevalence in SC hyperthyroidism 2% prevalence in euthyroid controls2% prevalence in euthyroid controls

Auer J, et al. Am Heart J 2001;142:838


Other described effectsOther described effects Increased heart rate and atrial premature beatsIncreased heart rate and atrial premature beats Reduced exercise toleranceReduced exercise tolerance Increased cardiac contractilityIncreased cardiac contractility Increase in LV mass indexIncrease in LV mass index Lower LDL-C and total cholesterolLower LDL-C and total cholesterol Systolic hypertensionSystolic hypertension

Clinical consequencesClinical consequences MortalityMortality

In 3,121 cardiac patients SC In 3,121 cardiac patients SC hyperthyroidism was associated with 2.32 hyperthyroidism was associated with 2.32 increased risk for cardiac death (1)increased risk for cardiac death (1)

Meta-analysis of 290 subjects over 60 found Meta-analysis of 290 subjects over 60 found 41% increase in all cause mortality (2)41% increase in all cause mortality (2)

Cardiovascular Health Study (3,233 subjects Cardiovascular Health Study (3,233 subjects over 65 y) found no increase in mortality (3)over 65 y) found no increase in mortality (3)

1. Iervasi G, et al. Arch Intern Med 2007;167:15262. Haentjens P, et al. Eur J Endocrinol 2008;159:329.3. Cappola AR, et al. JAMA2006;295:1033

SC HyperthyroidismSC Hyperthyroidism

Most individuals with TSH of 0.1 um/mL Most individuals with TSH of 0.1 um/mL or higher do not experience any or higher do not experience any symptoms.symptoms.

ManagementManagement

High risk patientsHigh risk patients TSH <0.1 uU/mL evaluate and treat.TSH <0.1 uU/mL evaluate and treat. TSH 0.1-0.4 uU/mL evaluate and treat if TSH 0.1-0.4 uU/mL evaluate and treat if

BMD low, a-fibb or symptoms of BMD low, a-fibb or symptoms of hyperthyroidism are present.hyperthyroidism are present.

Low risk patientsLow risk patients TSH <0.1 uU/mL evaluate and treat if BMD TSH <0.1 uU/mL evaluate and treat if BMD

low or symptoms present.low or symptoms present. TSH 0.1-0.4 uU/mL observe.TSH 0.1-0.4 uU/mL observe.

QuestionsQuestions

What is the appropriate normal range for What is the appropriate normal range for TSH?TSH? Answer will require more studies that will Answer will require more studies that will

need to include antibody determination and need to include antibody determination and more than one determination of TSH over more than one determination of TSH over period of time to avoid transient elevations to period of time to avoid transient elevations to creep into the normal ranges.creep into the normal ranges.

QuestionsQuestions Should we screen for SC thyroid Should we screen for SC thyroid

dysfunction?dysfunction? Population screening is probably not cost Population screening is probably not cost

effective.effective. Testing patients with mild symptoms Testing patients with mild symptoms

suggestive of hypothyroidism is NOT suggestive of hypothyroidism is NOT screening.screening.

QuestionsQuestions Who should we screen for SC thyroid Who should we screen for SC thyroid

dysfunction?dysfunction? High risk groups should be screened.High risk groups should be screened.

History of neck irradiationHistory of neck irradiation Pituitary surgery or irradiationPituitary surgery or irradiation Use of medications known to affect thyroidUse of medications known to affect thyroid Presence of thyroid nodule or MNGPresence of thyroid nodule or MNG

QuestionsQuestions Should we screen for SC thyroid Should we screen for SC thyroid

dysfunction?dysfunction? Studies needed aboutStudies needed about

Patients with autoimmune disordersPatients with autoimmune disorders Unexplained infertilityUnexplained infertility Previous postpartum thyroiditisPrevious postpartum thyroiditis Refractory depressionRefractory depression Turner’s and Down’s syndromeTurner’s and Down’s syndrome ObesityObesity

QuestionsQuestions

Is there a treatment benefit?Is there a treatment benefit? Studies are inconclusive.Studies are inconclusive. Patients with mild laboratory abnormalities Patients with mild laboratory abnormalities

should not be treated automatically.should not be treated automatically. These should be followed in 3-6 months and These should be followed in 3-6 months and

reassessed.reassessed. If even mild symptoms are present treatment If even mild symptoms are present treatment

should be offered.should be offered. Long term outcomes need studiesLong term outcomes need studies

subclinical thyroid disorders

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