Subclincal Thyroid Disease and the Work-up of a Thyroid Nodule Jared Bunevich MS IV LECOM.

Subclincal Thyroid Subclincal Thyroid Disease and the Disease and the

Work-up of a Work-up of a Thyroid NoduleThyroid NoduleJared Bunevich MS IVJared Bunevich MS IV

LECOMLECOM

ObjectivesObjectives Discuss the diagnosis and clinical Discuss the diagnosis and clinical

presentation of subclincal hypothyroidismpresentation of subclincal hypothyroidism Discuss the controversies surrounding Discuss the controversies surrounding

treatment of subclincal hypothyroidismtreatment of subclincal hypothyroidism Discuss the diagnosis and clinical Discuss the diagnosis and clinical

presentation of subclincal presentation of subclincal hyperthyroidismhyperthyroidism

Discuss the controversies surrounding the Discuss the controversies surrounding the treatment of subclincal hyperthyroidismtreatment of subclincal hyperthyroidism

Discuss cost-effective and clinically based Discuss cost-effective and clinically based work-up of a Thyroid Nodulework-up of a Thyroid Nodule

Subclinical Subclinical HypothyroidismHypothyroidism

Definition: Definition: Increased TSH Increased TSH levels in the face of levels in the face of normal free normal free thyroxin (T4)thyroxin (T4)

Even though Even though referred to as referred to as subclinical, patients subclinical, patients still may have still may have symptoms (fatigue, symptoms (fatigue, weight gain, muscle weight gain, muscle loss)loss)


DiagnosisDiagnosis Increase serum TSH and free T4 within the Increase serum TSH and free T4 within the

normal rangenormal range Measurement of TSH is sensitive and specific, even Measurement of TSH is sensitive and specific, even

though free T4 levels maybe within normal limits the though free T4 levels maybe within normal limits the actual levels of T4 maybe less than that patient actual levels of T4 maybe less than that patient previously hadpreviously had

7% of women and 3% of men aged 60-89 were 7% of women and 3% of men aged 60-89 were found to have TSH greater than 10 uU per mL found to have TSH greater than 10 uU per mL without obvious hypothyroidism clinical findingswithout obvious hypothyroidism clinical findings

Risk Factors for Diagnosis: family history of Risk Factors for Diagnosis: family history of thyroid disease, autoimmune disease, previous thyroid disease, autoimmune disease, previous head and neck radiation, drugs (lithium, head and neck radiation, drugs (lithium, amiodarone)amiodarone)

Subclincal Subclincal HypothyroidismHypothyroidism

Guidelines:Guidelines: U.S. Preventive task force recommends U.S. Preventive task force recommends

routine universal screening NOT be routine universal screening NOT be carried out on asymptomatic patients carried out on asymptomatic patients because clinical benefit is insufficientbecause clinical benefit is insufficient

American Thyroid Association American Thyroid Association recommends screening in men and recommends screening in men and women every five years beginning at women every five years beginning at age 35age 35

Subclincal Subclincal HypothyroidismHypothyroidism


Course:Course: TSH may return to normal after several TSH may return to normal after several

month reassessment and can be attributed month reassessment and can be attributed to:to: Lab errorLab error Silent thyroiditis Silent thyroiditis

Sub clinical hypothyroidism with detectable Sub clinical hypothyroidism with detectable antithyroid antibodies progesses to overt antithyroid antibodies progesses to overt hypothyroidism at about 5% per year, and hypothyroidism at about 5% per year, and maybe as high as 20% in the elderly and maybe as high as 20% in the elderly and patients with high antithyroid antibodiespatients with high antithyroid antibodies


Symptoms:Symptoms: In studies comparing euthyroid individuals In studies comparing euthyroid individuals

and subclinical hypothyroid easy fatigability, and subclinical hypothyroid easy fatigability, cold intolerance and dry skin were more cold intolerance and dry skin were more common in the subclincal hypothyroid groupcommon in the subclincal hypothyroid group

Arem et al and Franklin et al found a decrease Arem et al and Franklin et al found a decrease in the LDL of patients with subclincal in the LDL of patients with subclincal hypothyroidism when treated with synthyroidhypothyroidism when treated with synthyroid

Cooper et al found the PEP:LVET was found to Cooper et al found the PEP:LVET was found to significantly improve in subclincal patients significantly improve in subclincal patients when treated with levothyyroxinewhen treated with levothyyroxine

Subclincal HypothyroidismSubclincal Hypothyroidism

When should we treat?When should we treat? When TSH is consistently 10 uU/mL on When TSH is consistently 10 uU/mL on

two or more occasions six months apart two or more occasions six months apart and the patient has increased and the patient has increased antithyroid antibodiesantithyroid antibodies

Persons who have hypothyroid type Persons who have hypothyroid type complaints and elevated TSH should be complaints and elevated TSH should be treated (even if TSH is in the 5-10 treated (even if TSH is in the 5-10 uU/mL range)uU/mL range)



Treatment optionsTreatment options Overt HypothyroidismOvert Hypothyroidism

Typical PatientTypical Patient Start with Levothyroxine 25-50 ug daily and increased Start with Levothyroxine 25-50 ug daily and increased

slowly by 25-50 ug to 75 or 100 ug slowly by 25-50 ug to 75 or 100 ug Elderly and the Patients with heart diseaseElderly and the Patients with heart disease

Start a lower doses and progress at smaller Start a lower doses and progress at smaller increments to 50 or 100 ug or 1.6 ug/kgincrements to 50 or 100 ug or 1.6 ug/kg

Subclinical HypothyroidismSubclinical Hypothyroidism Levothyroxine 25-50 ug with a repeat TSH in 6 Levothyroxine 25-50 ug with a repeat TSH in 6

weeks with the goal of maintaining TSH in the weeks with the goal of maintaining TSH in the normal rangenormal range

Smaller overall dosages are more commonly Smaller overall dosages are more commonly utilizedutilized

Subclinical Subclinical HyperthyroidismHyperthyroidism


DiagnosisDiagnosis Definition: normal serum free thyroxine Definition: normal serum free thyroxine

and free triiodothyronine with a TSH and free triiodothyronine with a TSH suppressed below the normal levelssuppressed below the normal levels

Physical exam will NOT yield an Physical exam will NOT yield an enlarged thyroid glandenlarged thyroid gland


Differential DiagnosisDifferential Diagnosis Silent thyroiditis Silent thyroiditis Steroid useSteroid use Dopamine administrationDopamine administration Pituitary dysfunctionPituitary dysfunction Early Hashimoto’s or Graves diseaseEarly Hashimoto’s or Graves disease Multinodular goiter (particularly in the Multinodular goiter (particularly in the

elderly)elderly)


EtiologyEtiology Vanderpump et al found subclinical Vanderpump et al found subclinical

hyperthyroidism progresses to overt hyperthyroidism progresses to overt hyperthyroidism at 1-3% yearhyperthyroidism at 1-3% year

There is an increased risk of cardiac There is an increased risk of cardiac and bone density abnormalitiesand bone density abnormalities


Cardiac AbnormalitiesCardiac Abnormalities A-fib risk increased 3-5 fold in persons A-fib risk increased 3-5 fold in persons

older than 60 with decreased TSH older than 60 with decreased TSH values (Sawin et al)values (Sawin et al)

A small study showed resting baseline A small study showed resting baseline left ventricular diastolic filling was left ventricular diastolic filling was impaired at maximal exerciseimpaired at maximal exercise In addition patients increased In addition patients increased

interventicualr wall thicknessinterventicualr wall thickness


Bone DensityBone Density Premenopausal women with subclinical Premenopausal women with subclinical

hyperthyroidism do NOT appear to be hyperthyroidism do NOT appear to be at risk for increased bone lossat risk for increased bone loss

41 studies including 1200 41 studies including 1200 postmenopausal patients found patients postmenopausal patients found patients with suppressed TSH values were with suppressed TSH values were associated with significant bone loss in associated with significant bone loss in the lumbar spine and femurthe lumbar spine and femur


Neuropsychiatic: Boomer et alNeuropsychiatic: Boomer et al Reduced feelings of well beingReduced feelings of well being Inability to concentrateInability to concentrate Feelings of fearFeelings of fear


Diagnostic AssessmentDiagnostic Assessment TSH, T3, T4 evaluationTSH, T3, T4 evaluation

Monitor for three months if indicative of Monitor for three months if indicative of subclinical hyperthyroidismsubclinical hyperthyroidism

If TSH concentration remains suppressed a RAIU If TSH concentration remains suppressed a RAIU is indicated with possible sonographyis indicated with possible sonography

Also, in elderly patients consider ECG, bone Also, in elderly patients consider ECG, bone mineral density exams mineral density exams


Treatment optionsTreatment options Antithyroid medicationsAntithyroid medications

PTU 50-100 mg /dayPTU 50-100 mg /day Mehtimazole 5 mg /day if not pregnantMehtimazole 5 mg /day if not pregnant

Initiate if RAIU is positive or if patient is Initiate if RAIU is positive or if patient is symptomatic for 6-12 monthssymptomatic for 6-12 months

SurgerySurgery Non-complaint or patients who develop Non-complaint or patients who develop

Garves, Hashimoto’sGarves, Hashimoto’s Radioactive iodineRadioactive iodine

Only cost-effective if medical therapy fails x2Only cost-effective if medical therapy fails x2

Thyroid Nodule Work-upThyroid Nodule Work-up

Clinical HxClinical Hx ConsiderConsider

AgeAge Malignancy is higher in youth with nodulesMalignancy is higher in youth with nodules

SexSex Less common in men but more likely to be Less common in men but more likely to be

malignantmalignant Family historyFamily history History of neck radiationHistory of neck radiation

0.5 Gy increases risk of thyroid cancer 1-7% up 0.5 Gy increases risk of thyroid cancer 1-7% up to 30 years laterto 30 years later

Thyroid NoduleThyroid Nodule

Tests:Tests: Calcitonin: Small reports suggest Calcitonin: Small reports suggest

meduallry CA mets can be prevented meduallry CA mets can be prevented Cost effectiveness unclearCost effectiveness unclear

FNA: Gold standard to evaluate thyroid FNA: Gold standard to evaluate thyroid nodulenodule Adequate specimen can be obtained in 90% Adequate specimen can be obtained in 90%

of patientsof patients False negative and false positive are reported to False negative and false positive are reported to

be as low as 5%be as low as 5%


FNAFNA 5-8% of aspirates are diagnostic of 5-8% of aspirates are diagnostic of

malignancymalignancy 10-20% considered suspicious for 10-20% considered suspicious for

malignancymalignancy 2-5% fail to provide adequate samples2-5% fail to provide adequate samples

With suspicious findings 25% of patients are With suspicious findings 25% of patients are found to have malignancyfound to have malignancy

If patients chooses, questionable biopsy can If patients chooses, questionable biopsy can be followed with sonography every 6 months be followed with sonography every 6 months


Thyroid SonographyThyroid Sonography Sensitive to 3 mm nodulesSensitive to 3 mm nodules 3-20% of nodules are found to be cystic3-20% of nodules are found to be cystic

Cystic lesions have lower incidence of Cystic lesions have lower incidence of malignancy than solid masses (3% vs. 10%)malignancy than solid masses (3% vs. 10%)

Thyroid Nodule Thyroid Nodule

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Subclincal Thyroid Disease and the Work-up of a Thyroid Nodule Jared Bunevich MS IV LECOM.

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