Thyroid diseasesThyroid diseases

Steven T. Nguy M.D.Steven T. Nguy M.D.Assistant professor of MedicineAssistant professor of MedicineCooper University HospitalistCooper University Hospitalist

TFT – A practical reviewTFT – A practical review

The hypothalamus-pituitary-thyroid The hypothalamus-pituitary-thyroid function and thyroid physiologyfunction and thyroid physiology

Usefulness and limitation of blood Usefulness and limitation of blood work studies in thyroid disorderwork studies in thyroid disorder

Clinical casesClinical cases

T4

T3

Hypothalamic-Pituitary-Hypothalamic-Pituitary-Thyroid AxisThyroid AxisPhysiologyPhysiology

Pituitary

Thyroid Gland

Hypothalamus TRH

T4 T3 Liver

T4 T3

Heart

Liver

Bone

CNS

TR

Target Tissues

–

–

TSH

Adapted from Merck Manual of Medical Information. ed. R Berkow. 704:1997.

Thyroid PhysiologyThyroid Physiology

Thyroid gland releases T4 Thyroid gland releases T4 and T3 in molar ratio of 16:1and T3 in molar ratio of 16:1

>99% of the circulating >99% of the circulating thyroid hormones are bound thyroid hormones are bound to proteins (TBG, thyroxine-to proteins (TBG, thyroxine-binding prealbumin, albumin)binding prealbumin, albumin)

The vast majority of The vast majority of circulating T3 is derived from circulating T3 is derived from deiodination of T4 outside the deiodination of T4 outside the thyroid glandthyroid gland

Unbound (free) hormones T4 Unbound (free) hormones T4 (0.03%) and T3 (0.3%) are (0.03%) and T3 (0.3%) are biological active and are not biological active and are not influenced by TBG proteininfluenced by TBG protein

In NTI, T4 conversion to T3 is In NTI, T4 conversion to T3 is reduced and conversion to reduced and conversion to rT3 is enhancedrT3 is enhanced

Thyroid Funtion TestsThyroid Funtion Tests

TSHTSH FT4, (T4)FT4, (T4) T3, FT3T3, FT3 ThyroglobulinThyroglobulin Thyroid stimulating immunoglobulin Thyroid stimulating immunoglobulin

(TSI) or TSHR antibody(TSI) or TSHR antibody Antithyroid peroxidase antibodies Antithyroid peroxidase antibodies

(Anti TPO)(Anti TPO)

Serum TSHSerum TSH

Single best or initial test of the thyroid function. Single best or initial test of the thyroid function.

Central to the negative-feedback system.Central to the negative-feedback system.

Inverse, log-linear relationship with thyroid hormone. Inverse, log-linear relationship with thyroid hormone. Small changes in FT4 result in large changes in TSH Small changes in FT4 result in large changes in TSH levellevel

Normal range 0.5 – 5.0 mU/LNormal range 0.5 – 5.0 mU/L

Third generation TSH chemiluminometric assays have Third generation TSH chemiluminometric assays have detection limits of about 0.01mU/L.detection limits of about 0.01mU/L.

A normal TSH is sufficed to halt further testing unless A normal TSH is sufficed to halt further testing unless suspect of possible hypothalamic pituitary disease.suspect of possible hypothalamic pituitary disease.

Screening: Screening: RecommendationsRecommendations Various societies and authors disagree about population-based Various societies and authors disagree about population-based

screeningscreening The USPSTF - insufficient evidences to recommend for or against The USPSTF - insufficient evidences to recommend for or against

routine screening for thyroid disease in adults.routine screening for thyroid disease in adults. The AAFP recommends screening high-risk populations:The AAFP recommends screening high-risk populations:

- women with a family hx of thyroid disease women with a family hx of thyroid disease - women >35 y.o.women >35 y.o.- pregnant womenpregnant women- abnormal physical examabnormal physical exam- diabetic patientsdiabetic patients- Hx of autoimmune disorderHx of autoimmune disorder

The American Thyroid Association recommends screening start at age The American Thyroid Association recommends screening start at age 35 (and q 5 years after that)35 (and q 5 years after that)

Surks. JAMA. 2004 Jan 14;291(2):228-38.American Academy of Family Physicians. Subclinical Thyroid Disease. Available at: http://www.aafp.org/afp/20051015/1517.pdf Accessed February 16, 2006. The American Thyroid Association Web site. American Thyroid Association Guidelines for Detection of Thyroid Dysfunction. Available at: http://thyroid.org/professionals/publications/documents/GuidelinesdetectionThyDysfunc_2000.pdf. Accessed February 16, 2006.

Serum T4 Serum T4 measured by radioimmunoassay (RIA), measured by radioimmunoassay (RIA),

chemiluminometric assay, or similar chemiluminometric assay, or similar immunometric technique.immunometric technique.

99.97% of serum T4 is bound to TBG (thyroxine 99.97% of serum T4 is bound to TBG (thyroxine binding globulin), transthyretin or TBPA binding globulin), transthyretin or TBPA (thyroxine-binding prealbumin), or albumin.(thyroxine-binding prealbumin), or albumin.

Serum total T4 assays measure both bound and Serum total T4 assays measure both bound and unbound (“free”) T4unbound (“free”) T4

Levels are high in approximately 90% of Levels are high in approximately 90% of hyperthyroid patients and low in approximately hyperthyroid patients and low in approximately 85% of hypothyroid patients. 85% of hypothyroid patients.

Serum Free T4Serum Free T4

FT4 is measured by equilibrium FT4 is measured by equilibrium dialysis techniques or estimated dialysis techniques or estimated indirectly by calculation of free-indirectly by calculation of free-thyroxine index (FTI)thyroxine index (FTI)

FTI = T4 x T3 resin uptake (T3RU)%FTI = T4 x T3 resin uptake (T3RU)%

(T7, thyroid hormone-binding ratios)(T7, thyroid hormone-binding ratios) FT4 assay is preferred test FT4 assay is preferred test with with

tsh.tsh.

T3, Free T3, and rT3T3, Free T3, and rT3 T3T3 - - binding binding protein dependentprotein dependent. . - Levels can be misleading in patients with - Levels can be misleading in patients with

acute illness, cirrhosis, uremia, or acute illness, cirrhosis, uremia, or malnutrition.malnutrition.

FT3FT3 - Useful to - Useful to distinguish T3 toxicosisdistinguish T3 toxicosis from from

subclinical thyrotoxicosissubclinical thyrotoxicosis..

Reverse T3 Reverse T3 (rT3)(rT3) - increased in - increased in NTINTI. . - inactive. - inactive. - helpful to exclude central hypothyroidism- helpful to exclude central hypothyroidism

Other Ancillary TestsOther Ancillary Tests Serum thyroglobulinSerum thyroglobulin – – produced and produced and

released by thyroid gland.released by thyroid gland. - marker for recurrent thyroid cancer - marker for recurrent thyroid cancer - differentiate Graves disease from factitious - differentiate Graves disease from factitious

thyrotoxicosisthyrotoxicosis

Serum thyroid-stimulating Serum thyroid-stimulating immunoglobulin (TSI) or TSHR-immunoglobulin (TSI) or TSHR-AbAb - - Expensive testExpensive test

- Graves’ disease.- Graves’ disease.

Antithyroid peroxidase Antithyroid peroxidase antibodies (Anti TPO)antibodies (Anti TPO) – – organ-specific organ-specific and sensitive.and sensitive.

- Hashimoto’s thyroiditis- Hashimoto’s thyroiditis - predict overt hypothyroidism- predict overt hypothyroidism

Case 1Case 1

TSH 9.0 (0.5 – 5.5 mU/L)TSH 9.0 (0.5 – 5.5 mU/L)

FT4 1.1 (0.8-1.8 ng/dL)FT4 1.1 (0.8-1.8 ng/dL)

What are your differential diagnoses?What are your differential diagnoses?

Differential diagnoses for Differential diagnoses for elevated TSH with normal elevated TSH with normal

FT4FT4TSH 9.0 (0.5-5.5 mU/L), T4 1.1 (0.8-1.8 TSH 9.0 (0.5-5.5 mU/L), T4 1.1 (0.8-1.8

ng/dL)ng/dL) Transitional thyroid state or recovery from Transitional thyroid state or recovery from

hypothyroidism (Hashimoto’s thyroiditis)hypothyroidism (Hashimoto’s thyroiditis) TSH receptor inactivating mutationTSH receptor inactivating mutation Patient with hypothyroidism who is on or Patient with hypothyroidism who is on or

recently started on treatment and the TSH recently started on treatment and the TSH hasn’t enough time to adjust.hasn’t enough time to adjust.

Subclinical hypothyroidismSubclinical hypothyroidism

Case 1 Case 1 A 75 yo woman with no prior medical problem presents A 75 yo woman with no prior medical problem presents

for her annual physical examination. She says that for her annual physical examination. She says that she is slowing down a bit and has become more she is slowing down a bit and has become more forgetful. She also mentions that she feels cold and is forgetful. She also mentions that she feels cold and is constipated. Physical examination is essentially within constipated. Physical examination is essentially within normal. Her blood work shows TSH 9.5 (0.5-4.5 normal. Her blood work shows TSH 9.5 (0.5-4.5 mU/L) FT4 1.1 (0.8-1.8 ng/dL), normal C7, and CBCD.mU/L) FT4 1.1 (0.8-1.8 ng/dL), normal C7, and CBCD.

Which of the following actions would be most Which of the following actions would be most appropriate?appropriate?

A.A. She should be treated with levothyroxine 0.1 mg/day.She should be treated with levothyroxine 0.1 mg/day.B.B. Check lipid profile and start her on treatment if her Check lipid profile and start her on treatment if her

HDL is low.HDL is low.C.C. Check anti TPO level. If it shows high titer, she would Check anti TPO level. If it shows high titer, she would

be less likely become overt hypothyroidism in the be less likely become overt hypothyroidism in the future.future.

D.D. Repeat TSH and FT4 in 2 – 12 weeks.Repeat TSH and FT4 in 2 – 12 weeks.

Subclinical Thyroid DysfunctionSubclinical Thyroid DysfunctionClinical Guidelines By USPSTFClinical Guidelines By USPSTF

Ann Intern MedAnn Intern Med. 2004;140:125-127,128-141. 2004;140:125-127,128-141JAMAJAMA, 2004;291:228-238,239-243, 2004;291:228-238,239-243

Subclinical hypothyroidism is an elevation of serum TSH Subclinical hypothyroidism is an elevation of serum TSH level with a FT4 in (low) normal range.level with a FT4 in (low) normal range.

Upper limit of normal TSH should remain 4.5 or 5 mU/LUpper limit of normal TSH should remain 4.5 or 5 mU/L There was insufficient evidence linking subclinical There was insufficient evidence linking subclinical

hypothyroidism to systemic symptoms, cardiac hypothyroidism to systemic symptoms, cardiac dysfunction, adverse cardiac endpoints, LDL elevation and dysfunction, adverse cardiac endpoints, LDL elevation and neuropsychiatric symptoms for neuropsychiatric symptoms for TSH values ranging from TSH values ranging from 4.5 to 10 mU/L4.5 to 10 mU/L

The evidence for an association with dyslipidemia was rate The evidence for an association with dyslipidemia was rate as ‘‘fair’’, and only in individuals with TSH >10.as ‘‘fair’’, and only in individuals with TSH >10.

The decision to begin levothyroxine therapy in patient with The decision to begin levothyroxine therapy in patient with persistent TSH but normal FT4 should be individualized.persistent TSH but normal FT4 should be individualized.

If treatment is given, be cautious not to overtreat. Goal If treatment is given, be cautious not to overtreat. Goal TSH 2.5-3.5TSH 2.5-3.5

Other Ancillary TestsOther Ancillary Tests Serum thyroglobulin – produced and released by thyroid Serum thyroglobulin – produced and released by thyroid

gland. Level is elevated in conditions that increase gland. Level is elevated in conditions that increase thyroid gland function or destruction. It can be used as thyroid gland function or destruction. It can be used as a tumor marker for recurrent of thyroid cancer or to a tumor marker for recurrent of thyroid cancer or to differentiate Graves’disease from factitious differentiate Graves’disease from factitious thyrotoxicosis.thyrotoxicosis.

Serum thyroid-stimulating immunoglobulin (TSI) or Serum thyroid-stimulating immunoglobulin (TSI) or TSHR-Ab – Expensive. Highly specific for Graves disease TSHR-Ab – Expensive. Highly specific for Graves disease Generally not needed, but can be helpful in suspected Generally not needed, but can be helpful in suspected cases of Graves’ disease in pregnancy or euthyroid cases of Graves’ disease in pregnancy or euthyroid ophthalmopathy.ophthalmopathy.

Antithyroid peroxidase antibodies (Anti TPO) – useful in Antithyroid peroxidase antibodies (Anti TPO) – useful in suspected case of Hashimoto’s thyroiditis, and in suspected case of Hashimoto’s thyroiditis, and in predicting for the development of overt hypothyroidism. predicting for the development of overt hypothyroidism. It is highly organ-specific and sensitive.It is highly organ-specific and sensitive.

Case 1 answerCase 1 answerA 75 yo woman with no prior medical problem presents A 75 yo woman with no prior medical problem presents

for her annual physical examination. She says that for her annual physical examination. She says that she is slowing down a bit and has become more she is slowing down a bit and has become more forgetful. She also mentions that she feels cold and is forgetful. She also mentions that she feels cold and is constipated. Physical examination is essentially within constipated. Physical examination is essentially within normal. Her blood work shows TSH 9.0 (0.5-4.5 normal. Her blood work shows TSH 9.0 (0.5-4.5 mU/L) FT4 1.1 (0.8-1.8 ng/dL), normal C7, and CBCD.mU/L) FT4 1.1 (0.8-1.8 ng/dL), normal C7, and CBCD.

Which of the following actions would be most Which of the following actions would be most appropriate?appropriate?

A.A. She should be treated with levothyroxine 0.1 mg/day.She should be treated with levothyroxine 0.1 mg/day.B.B. Check lipid profile and start her on treatment if her Check lipid profile and start her on treatment if her

HDL is low.HDL is low.C.C. Check anti TPO level. If it shows high titers, she would Check anti TPO level. If it shows high titers, she would

be less likely to become overt hypothyroidism in the be less likely to become overt hypothyroidism in the near future near future

D.D. Repeat TSH and FT4 in 2 – 12 weeksRepeat TSH and FT4 in 2 – 12 weeks..

Case 1 AnswerCase 1 Answer This patient has subclinical hypothyroidism. Her This patient has subclinical hypothyroidism. Her

symptom is nonspecific. It is recommended to symptom is nonspecific. It is recommended to recheck TSH and FT4 in 2 – 12 weeks. If it is recheck TSH and FT4 in 2 – 12 weeks. If it is still elevated then consider start treatment with still elevated then consider start treatment with low dose levothyroxine and to recheck TSH again low dose levothyroxine and to recheck TSH again in 6 – 8 weeks. Goal is to get TSH down to in 6 – 8 weeks. Goal is to get TSH down to normal range 2.5 – 3.5. The starting dose in normal range 2.5 – 3.5. The starting dose in choice A is too high and patient would likely choice A is too high and patient would likely become symptomatic from thyrotoxicosis. There become symptomatic from thyrotoxicosis. There is insufficient evidence to link subclinical is insufficient evidence to link subclinical hypothyroidism with elevated LDL for TSH 5.5 – hypothyroidism with elevated LDL for TSH 5.5 – 10. It has no effect on HDL. Patient with high 10. It has no effect on HDL. Patient with high titer anti TPO are more likely to become overt titer anti TPO are more likely to become overt hypothyroidismhypothyroidism (annualize rate is about 4.5%) (annualize rate is about 4.5%) but the current consensus didn’t advise the use but the current consensus didn’t advise the use of antiTPO antibodies in the decision making of antiTPO antibodies in the decision making process.process.

Case 2Case 2

TSH 0.18 (0.45 – 5.0 mU/L)TSH 0.18 (0.45 – 5.0 mU/L)

FT4 1.6 (0.8 – 1.8 ng/dL)FT4 1.6 (0.8 – 1.8 ng/dL)

What are your differential diagnoses?What are your differential diagnoses?

Causes of low TSH and normal Causes of low TSH and normal FT4FT4

Subclinical thyrotoxicosis (toxic multinodular Subclinical thyrotoxicosis (toxic multinodular goiter, toxic adenomas, mild Graves’disease, goiter, toxic adenomas, mild Graves’disease, excessive replacement therapy)excessive replacement therapy)

Total triiodothyronine thyrotoxicosis (Early Total triiodothyronine thyrotoxicosis (Early Graves’disease, autonomous thyroid nodules)Graves’disease, autonomous thyroid nodules)

Drug effect (corticosteroids, octreotide, Drug effect (corticosteroids, octreotide, dopamine)dopamine)

Non-thyroidal illness (euthyroid sick)Non-thyroidal illness (euthyroid sick) Transitional thyroid state (recovery from Transitional thyroid state (recovery from

thyroiditis)thyroiditis) Excessive thyroid hormone therapyExcessive thyroid hormone therapy Central hypothyroidismCentral hypothyroidism

Case 2Case 2A 60 yo male with history htn, dm type 2, and A 60 yo male with history htn, dm type 2, and

hypercholesterolemia who has been doing well with hypercholesterolemia who has been doing well with medications including lisinopril 5mg daily, HCTZ 12.5 mg medications including lisinopril 5mg daily, HCTZ 12.5 mg daily, glipizide XL 5 mg daily, and simvastatin 20 mg daily. daily, glipizide XL 5 mg daily, and simvastatin 20 mg daily. Vital signs show T.98.5, pulse 100, resp rate 18, and pulsox Vital signs show T.98.5, pulse 100, resp rate 18, and pulsox 98% on room air. Phys exam is unremarkable. His routine lab 98% on room air. Phys exam is unremarkable. His routine lab shows TSH 0.18 (0.45 – 5.0 mU/L), FT4 1.6 (0.8 – 1.8 ng/dL), shows TSH 0.18 (0.45 – 5.0 mU/L), FT4 1.6 (0.8 – 1.8 ng/dL), FT3 3.5 (1.5-7.0 pmol/L). The remaining of his labs including FT3 3.5 (1.5-7.0 pmol/L). The remaining of his labs including C7, CBCD, lipid profile, and HbA1C are within normal limitC7, CBCD, lipid profile, and HbA1C are within normal limit

Which of the following statements would be appropriate?Which of the following statements would be appropriate?A.A. He has subclinical hypothyroidism and very likely to develop He has subclinical hypothyroidism and very likely to develop

osteosporosis and atrial fibrillation so he should be treated.osteosporosis and atrial fibrillation so he should be treated.B.B. He should have a level of anti thyroid peroxidase antibody He should have a level of anti thyroid peroxidase antibody

check. If it’s positive he will likely develop Graves’ disease in check. If it’s positive he will likely develop Graves’ disease in the future, so he should be treated.the future, so he should be treated.

C.C. He should have thyroid ultrasound, RAIU, and He should have thyroid ultrasound, RAIU, and Echocardiogram.Echocardiogram.

D.D. He should have a repeat TSH and FT4 in 4 – 6 weeksHe should have a repeat TSH and FT4 in 4 – 6 weeksE.E. Start low dose PTU and recheck TSH and FT4 in 3 – 6 weeksStart low dose PTU and recheck TSH and FT4 in 3 – 6 weeks

Subclinical Thyroid DysfunctionSubclinical Thyroid DysfunctionClinical Guidelines By USPSTFClinical Guidelines By USPSTF

Ann Intern MedAnn Intern Med. 2004;140:125-127,128-141. 2004;140:125-127,128-141JAMAJAMA, 2004;291:228-238,239-243, 2004;291:228-238,239-243

Subclinical hyperthyroidism is a suppressed serum Subclinical hyperthyroidism is a suppressed serum TSH value resulting from an increase in serum T4 TSH value resulting from an increase in serum T4 and/or T3 within the confines of the normal rangeand/or T3 within the confines of the normal range

Evidence for adverse effects on the skeleton and the Evidence for adverse effects on the skeleton and the heart was “fair” to “good”, but only in patients with heart was “fair” to “good”, but only in patients with serum TSH levels serum TSH levels < 0.1 mU/L< 0.1 mU/L

It is recommended that treatment “be considered” in It is recommended that treatment “be considered” in patients with TSH levels < 0.1 mU/L even though patients with TSH levels < 0.1 mU/L even though there is a “paucity of intervention trials” showing there is a “paucity of intervention trials” showing benefitbenefit

For patients with the serum TSH levels between 0.1 For patients with the serum TSH levels between 0.1 and 0.45 mU/L, the evidence for adverse health and 0.45 mU/L, the evidence for adverse health consequences was insufficient or absent, and consequences was insufficient or absent, and therefore therapy was not recommended. therefore therapy was not recommended.

Case 2Case 2

A 60 yo male with history htn, dm type 2, and hypercholesterolemia A 60 yo male with history htn, dm type 2, and hypercholesterolemia who has been doing well with medications including lisinopril 5mg who has been doing well with medications including lisinopril 5mg daily, HCTZ 12.5 mg daily, glipizide XL 5 mg daily, and daily, HCTZ 12.5 mg daily, glipizide XL 5 mg daily, and simvastatin 20 mg daily. Vital signs show T.98.5, pulse 100, resp simvastatin 20 mg daily. Vital signs show T.98.5, pulse 100, resp rate 18, and pulsox 98% on room air. Phys exam is unremarkable. rate 18, and pulsox 98% on room air. Phys exam is unremarkable. His routine lab shows TSH 0.18 (0.45 – 5.0 mU/L), FT4 1.6 (0.8 – His routine lab shows TSH 0.18 (0.45 – 5.0 mU/L), FT4 1.6 (0.8 – 1.8 ng/dL), FT3 3.5 (1.5-7.0 pmol/L). The remaining of his labs 1.8 ng/dL), FT3 3.5 (1.5-7.0 pmol/L). The remaining of his labs including C7, CBCD, lipid profile, and HbA1C are within normal including C7, CBCD, lipid profile, and HbA1C are within normal limit. EKG is also normallimit. EKG is also normal

Which of the following statements would be appropriate?Which of the following statements would be appropriate?A. He has subclinical hypothyroidism and very likely to develop A. He has subclinical hypothyroidism and very likely to develop

osteosporosis and atrial fibrillation so he should be treated.osteosporosis and atrial fibrillation so he should be treated.B. He should have a level of anti thyroid peroxidase antibody check. B. He should have a level of anti thyroid peroxidase antibody check.

If it’s positive he will likely develop Graves’ disease in the future.If it’s positive he will likely develop Graves’ disease in the future.C. He should have thyroid ultrasound, RAIU, and Echocardiogram.C. He should have thyroid ultrasound, RAIU, and Echocardiogram.D. He should have a repeat TSH and FT4 in 3 – 6 weeks.D. He should have a repeat TSH and FT4 in 3 – 6 weeks.E. Start low dose PTU and recheck TSH and FT4 in 3 – 6 weeks.E. Start low dose PTU and recheck TSH and FT4 in 3 – 6 weeks.

Case 2 AnswerCase 2 Answer

This patient has subclinical hypertyroidism and is This patient has subclinical hypertyroidism and is doing well. Current evidences suggest that risks of doing well. Current evidences suggest that risks of having osteosporosis and atrial fibrillation are “fair” to having osteosporosis and atrial fibrillation are “fair” to “good” but only in patients with TSH <0.1 mU/L. In “good” but only in patients with TSH <0.1 mU/L. In patients with thyrotoxicosis, the presence of patients with thyrotoxicosis, the presence of thyroglobulin-receptor antibodies, not anti TPO thyroglobulin-receptor antibodies, not anti TPO antibodies, in the serum is diagnostic of Graves’ antibodies, in the serum is diagnostic of Graves’ disease, but the antibodies are absent in approximately disease, but the antibodies are absent in approximately 5 to 20 percent of patients with hyperthyroid Graves’ 5 to 20 percent of patients with hyperthyroid Graves’ disease and almost certainly in a greater proportion of disease and almost certainly in a greater proportion of those with subclinical hyperthyroidism. Additional those with subclinical hyperthyroidism. Additional imaging or radioiodine uptake studies are not indicate imaging or radioiodine uptake studies are not indicate as patient has no abnormal finding on exam. So at this as patient has no abnormal finding on exam. So at this time no treatment is needed and patient should have a time no treatment is needed and patient should have a repeat TFT in 4-6 weeks.repeat TFT in 4-6 weeks.

Case 3Case 3A 60 year old woman with hx afib, HTN, and DM type 2 presents to ED A 60 year old woman with hx afib, HTN, and DM type 2 presents to ED

complaining of feeling nervous and difficulty with sleep. She admits to have complaining of feeling nervous and difficulty with sleep. She admits to have only mild palpitation but no CP or diaphoresis and the remaining of ROS are only mild palpitation but no CP or diaphoresis and the remaining of ROS are negative. Her medication includes amiodarone 200mg daily, metoprolol XL negative. Her medication includes amiodarone 200mg daily, metoprolol XL 50mg daily, metformin 500mg BID, and simvastatin 20mg bedtime. 50mg daily, metformin 500mg BID, and simvastatin 20mg bedtime.

She appears mild anxious but no distress. She appears mild anxious but no distress. VS. BP 134/78, T. 98.7, P.108, R.22VS. BP 134/78, T. 98.7, P.108, R.22 Neck exam shows slight tenderness and mild enlarged thyroid, heart exam is Neck exam shows slight tenderness and mild enlarged thyroid, heart exam is

tachycardia with regular rhythm and a soft systolic murmur. The remaining of tachycardia with regular rhythm and a soft systolic murmur. The remaining of exam is within normal. exam is within normal.

Lab shows TSH is 0.01 (0.5-5.0 mU/L), FT4 50.3 (10.3-30.6 pmol/L). Remaining Lab shows TSH is 0.01 (0.5-5.0 mU/L), FT4 50.3 (10.3-30.6 pmol/L). Remaining labs are within normal including C7, CBCD, CK, and TnT.labs are within normal including C7, CBCD, CK, and TnT.

Which of the following statements are true?Which of the following statements are true?A.A. Patient has amiodarone induced thyroiditis so amiodarone must be stopped Patient has amiodarone induced thyroiditis so amiodarone must be stopped

immediately and start on PTU or methimazole low dose.immediately and start on PTU or methimazole low dose.B.B. Order color flow Doppler of thyroid gland, RAUI, and IL6 to determine the type Order color flow Doppler of thyroid gland, RAUI, and IL6 to determine the type

of thyrotoxicosisof thyrotoxicosisC.C. Treat patient with both a thionamide and prednisone, continue amiodarone, Treat patient with both a thionamide and prednisone, continue amiodarone,

and recheck TSH and FT4 in 2-4 weeksand recheck TSH and FT4 in 2-4 weeksD.D. Stop amiodarone and recheck TSH, FT4 in 4-6 weeks.Stop amiodarone and recheck TSH, FT4 in 4-6 weeks.E.E. She should be start on ASA and prednisone if the RAIU is highShe should be start on ASA and prednisone if the RAIU is high

Amiodarone induced Amiodarone induced thyrotoxicosisthyrotoxicosis

About 3% of amiodarone-treated patients in the About 3% of amiodarone-treated patients in the United States become hyperthyroid. United States become hyperthyroid. (Hypothyroidism is more common than (Hypothyroidism is more common than hyperthyroidism)hyperthyroidism)

Two basic mechanisms in AITTwo basic mechanisms in AIT Type I – Type I – Increase synthesisIncrease synthesis of T4 and T3 of T4 and T3 - Pre-existing multinodular goiter or latent Graves’ - Pre-existing multinodular goiter or latent Graves’

disease. More commonly seen in iodine-deficient disease. More commonly seen in iodine-deficient areas of the worldareas of the world

Type II – Type II – Direct toxic effectDirect toxic effect of amiodarone of amiodarone causing thyroiditis and hence release of T4 and T3 causing thyroiditis and hence release of T4 and T3 without increased hormone synthesis. More without increased hormone synthesis. More commonly seen in iodine-sufficient countriescommonly seen in iodine-sufficient countries

Amiodarone induced Amiodarone induced thyrotoxicosisthyrotoxicosis

Distinction between the two types is critical because Distinction between the two types is critical because the treatment is different.the treatment is different.

Criteria used to attempt to distinguish type I from type Criteria used to attempt to distinguish type I from type II areII are

24-hour radioiodine uptake24-hour radioiodine uptake – if detectable, it suggest – if detectable, it suggest type I AITtype I AIT

GoitersGoiters – if has multinodular or diffuse goiter, it is – if has multinodular or diffuse goiter, it is more likely type I AIT. more likely type I AIT.

Serum thyroglobulinSerum thyroglobulin – higher in type I – higher in type I Serum IL-6Serum IL-6 – higher in type II – higher in type II Color-flow Doppler sonographyColor-flow Doppler sonography – may distinguish – may distinguish

type I (increased vascularity) from type II (absent type I (increased vascularity) from type II (absent vascularity) hyperthyroidism. vascularity) hyperthyroidism.

Amiodarone induced Amiodarone induced thyrotoxicosisthyrotoxicosis

Should amiodarone be discontinued?Should amiodarone be discontinued? There are There are no good datano good data that answer this that answer this

question; however, the following should be question; however, the following should be considered:considered:

Amiodarone may be necessary to control a life Amiodarone may be necessary to control a life threatening arrythmia.threatening arrythmia.

It has a It has a very long half-lifevery long half-life so stopping it would so stopping it would not give any immediate benefit.not give any immediate benefit.

Amiodarone appears ameliorate hyperthyroidism Amiodarone appears ameliorate hyperthyroidism by by blocking T4 to T3 conversion, beta-blocking T4 to T3 conversion, beta-adrenergic receptors, and possibly T3 adrenergic receptors, and possibly T3 receptorsreceptors. Stopping amiodarone might actually . Stopping amiodarone might actually exacerbate hyperthyroid symptoms and signs.exacerbate hyperthyroid symptoms and signs.

Amiodarone induced Amiodarone induced thyrotoxicosis treatmentthyrotoxicosis treatment

Type I AITType I AIT . Drugs-Thionamide (PTU or methimazole) is the first line therapy . Drugs-Thionamide (PTU or methimazole) is the first line therapy

(whether amiodarone is continued or discontinued). Higher than (whether amiodarone is continued or discontinued). Higher than average doses are often neededaverage doses are often needed

. Radioiodine ablation – if the RAIU is high enough.. Radioiodine ablation – if the RAIU is high enough. . Surgery – only if refractory to antithyroid drug therapy.. Surgery – only if refractory to antithyroid drug therapy.

Type II AIT Type II AIT . Glucocorticoids – Prednisone 40-60 mg/day. Continue therapy for . Glucocorticoids – Prednisone 40-60 mg/day. Continue therapy for

one to two months before taperingone to two months before tapering

““Mixed” type I and type II AITMixed” type I and type II AIT . Combination of glucocorticoid and thionamine initially. . Combination of glucocorticoid and thionamine initially. A rapid response suggests type II, the thionamide can then be A rapid response suggests type II, the thionamide can then be

tapered or stopped. tapered or stopped. A poor or slow initial response argues for type I AITA poor or slow initial response argues for type I AIT

Case 3Case 3A 60 year old woman with hx afib, HTN, and DM type 2 presents to ED complaining of feeling nervous and A 60 year old woman with hx afib, HTN, and DM type 2 presents to ED complaining of feeling nervous and

difficulty with sleep. She admits to have only mild palpitation but no CP or diaphoresis and the remaining difficulty with sleep. She admits to have only mild palpitation but no CP or diaphoresis and the remaining of ROS are negative. Her medication includes amiodarone 200mg daily, metoprolol XL 50mg daily, of ROS are negative. Her medication includes amiodarone 200mg daily, metoprolol XL 50mg daily, metformin 500mg BID, and simvastatin 20mg bedtime. metformin 500mg BID, and simvastatin 20mg bedtime.

She Appears mild anxious but no distress. She Appears mild anxious but no distress. VS. BP 134/78, T. 98.7, P.108, R.22VS. BP 134/78, T. 98.7, P.108, R.22 Neck exam shows slight tenderness and mild enlarged thyroid, heart exam is tachycardia with regular Neck exam shows slight tenderness and mild enlarged thyroid, heart exam is tachycardia with regular

rhythm and a soft systolic murmur. The remaining of exam is within normal. rhythm and a soft systolic murmur. The remaining of exam is within normal. Lab shows TSH is 0.01 (0.5-5.0 mU/L), FT4 50.3 (10.3-30.6 pmol/L). Remaining labs are within normal Lab shows TSH is 0.01 (0.5-5.0 mU/L), FT4 50.3 (10.3-30.6 pmol/L). Remaining labs are within normal

including C7, CBCD, CK, and TnT.including C7, CBCD, CK, and TnT.

Which of the following statements are true?Which of the following statements are true?A.A. Patient has amiodarone induced thyroditis so amiodarone Patient has amiodarone induced thyroditis so amiodarone

must be stopped immediately and start on PTU or must be stopped immediately and start on PTU or methimazole low dose.methimazole low dose.

B.B. The color flow Doppler of thyroid gland, RAUI, and IL6 may The color flow Doppler of thyroid gland, RAUI, and IL6 may help to determine the type of thyrotoxicosishelp to determine the type of thyrotoxicosis

C.C. Treat patient with both a thionamide and prednisone, Treat patient with both a thionamide and prednisone, continue amiodarone, and recheck TSH and FT4 in 2-4 weekscontinue amiodarone, and recheck TSH and FT4 in 2-4 weeks

D.D. Stop amiodarone and recheck TSH, FT4 in 4-6 weeks.Stop amiodarone and recheck TSH, FT4 in 4-6 weeks.E.E. She should be start on ASA and prednisone if the RAIU is highShe should be start on ASA and prednisone if the RAIU is high

Case 3 answerCase 3 answer

B and C are the correct statement.B and C are the correct statement.

A is false because amiodarone has a very long A is false because amiodarone has a very long half-life so stopping it would not have any half-life so stopping it would not have any immediate benefit and potentially can cause immediate benefit and potentially can cause arrhythmia.arrhythmia.

D is false because patient needs treatment for D is false because patient needs treatment for thyrotoxicosisthyrotoxicosis

E is false because in acute thyrotoxicosis state E is false because in acute thyrotoxicosis state aspirin can exacerbate the condition because aspirin can exacerbate the condition because it binds to TBG and causing more available it binds to TBG and causing more available unbound thyroxine.unbound thyroxine.

Case 4Case 4A 70 yo male patient was admitted to ICU 3 days ago for A 70 yo male patient was admitted to ICU 3 days ago for

pneumonia, COPD exacerbation which required intubation. pneumonia, COPD exacerbation which required intubation. He was successfully extubated and transferred to telemetry He was successfully extubated and transferred to telemetry floor yesterday. Overnight the telemetry shows sinus rhythm floor yesterday. Overnight the telemetry shows sinus rhythm 80 to sinus tachycardia 105 with few atrial ectopy and a 80 to sinus tachycardia 105 with few atrial ectopy and a normal EKG. He is on Levaquin 750mg daily, duoneb Q4H, normal EKG. He is on Levaquin 750mg daily, duoneb Q4H, and hydrocortisone 60mg Q6H.and hydrocortisone 60mg Q6H.

He appears frail, weak and complains only of no appetite. The BP He appears frail, weak and complains only of no appetite. The BP 98/70 T.99, P.100, RR. 20, pulsox 96% on 2L. On exam, he has 98/70 T.99, P.100, RR. 20, pulsox 96% on 2L. On exam, he has RLL rhonchi but no crackles, heart rate is slightly fast but no RLL rhonchi but no crackles, heart rate is slightly fast but no murmur or rub. The remaining of his exam was murmur or rub. The remaining of his exam was unremarkable.unremarkable.

AM lab shows WBC 13.0 Hb 12 Plt 200K, band 6%, seg. neutrophil AM lab shows WBC 13.0 Hb 12 Plt 200K, band 6%, seg. neutrophil 80%, normal C7, TSH 0.15 (0.45-4.5), T4 normal and T3 low.80%, normal C7, TSH 0.15 (0.45-4.5), T4 normal and T3 low.

Which of the following would be appropriate to do next?Which of the following would be appropriate to do next?A.A. This patient has lab result suggestive of central This patient has lab result suggestive of central

hypothyroidism so MRI of the head should be done first.hypothyroidism so MRI of the head should be done first.B.B. Order a baseline cortisol level and do a cosyntropin test to Order a baseline cortisol level and do a cosyntropin test to

rule out adrenal insufficiency.rule out adrenal insufficiency.C.C. Order a serum rT3 level and if the level is high no other test is Order a serum rT3 level and if the level is high no other test is

necessary.necessary.D.D. Start patient on levothyroxine 0.025mg daily for Start patient on levothyroxine 0.025mg daily for

hypothyroidismhypothyroidism

Nonthyroidal illness Nonthyroidal illness (Euthyroid Sick Syndrome)(Euthyroid Sick Syndrome)

Abnormal findings on TFT that occur in the setting of a NTI without Abnormal findings on TFT that occur in the setting of a NTI without preexisting hypothalamic-pituitary and thyroid gland dysfunction.preexisting hypothalamic-pituitary and thyroid gland dysfunction.

The most prominent alterations are low serum T3 and elevated reverse The most prominent alterations are low serum T3 and elevated reverse T3 (rT3).T3 (rT3).

Serum TSH, T4, and FT4 are also affected in variable degrees based on Serum TSH, T4, and FT4 are also affected in variable degrees based on the severity and duration of the NTI. the severity and duration of the NTI.

Probable mechanism: Probable mechanism: - - Decreased or inhibition of 5’-monodeiodinationDecreased or inhibition of 5’-monodeiodination (endogenous (endogenous

cortisol or exogenous glucocorticoid therapy, non-esterified fatty acids, cortisol or exogenous glucocorticoid therapy, non-esterified fatty acids, cytokines TNF, IF, IL6.)cytokines TNF, IF, IL6.)

- The peripheral production of T3 is decrease, but its clearance is - The peripheral production of T3 is decrease, but its clearance is unchanged; whereas, the production of rT3 is unchanged, while its unchanged; whereas, the production of rT3 is unchanged, while its clearance is diminishedclearance is diminished

Treatment is not needed. After recovery from an NTI, these thyroid Treatment is not needed. After recovery from an NTI, these thyroid function test result abnormalities should be completely reversiblefunction test result abnormalities should be completely reversible

Case 4Case 4A 70 yo male patient was admitted to ICU 3 days ago for A 70 yo male patient was admitted to ICU 3 days ago for

pneumonia, COPD exacerbation which required intubation. pneumonia, COPD exacerbation which required intubation. He was successfully extubated and transferred to telemetry He was successfully extubated and transferred to telemetry floor yesterday. Overnight the telemetry shows sinus rhythm floor yesterday. Overnight the telemetry shows sinus rhythm 80 to sinus tachycardia 105 with few atrial ectopy and a 80 to sinus tachycardia 105 with few atrial ectopy and a normal EKG. He is on Levaquin 750mg daily, duoneb Q4H, normal EKG. He is on Levaquin 750mg daily, duoneb Q4H, and hydrocortisone 60mg Q6H.and hydrocortisone 60mg Q6H.

He appears frail, weak and complains only of no appetite. The BP He appears frail, weak and complains only of no appetite. The BP 98/70 T.99, P.100, RR. 20, pulsox 96% on 2L. On exam, he has 98/70 T.99, P.100, RR. 20, pulsox 96% on 2L. On exam, he has RLL rhonchi but no crackles, heart rate is slightly fast but no RLL rhonchi but no crackles, heart rate is slightly fast but no murmur or rub. The remaining of his exam was murmur or rub. The remaining of his exam was unremarkable.unremarkable.

AM lab shows WBC 13.0 Hb 12 Plt 200K, band 6%, seg. neutrophil AM lab shows WBC 13.0 Hb 12 Plt 200K, band 6%, seg. neutrophil 80%, normal C7, TSH 0.15 (0.45-4.5), T4 normal and T3 low.80%, normal C7, TSH 0.15 (0.45-4.5), T4 normal and T3 low.

Which of the following would be appropriate to do next?Which of the following would be appropriate to do next?A.A. This patient has lab result suggestive of central This patient has lab result suggestive of central

hypothyroidism so MRI of the head should be done first.hypothyroidism so MRI of the head should be done first.B.B. Order a baseline cortisol level and do a cosyntropin test to Order a baseline cortisol level and do a cosyntropin test to

rule out adrenal insufficiency.rule out adrenal insufficiency.C.C. Order a serum rT3 level and if the level is high no other test is Order a serum rT3 level and if the level is high no other test is

necessary.necessary.D.D. Start patient on levothyroxine 0.025mg daily for Start patient on levothyroxine 0.025mg daily for

hypothyroidismhypothyroidism

Case 4 answerCase 4 answer This patient has low TSH, low T3 and normal T4. The This patient has low TSH, low T3 and normal T4. The

differential diagnoses includes central hypothyroidism, differential diagnoses includes central hypothyroidism, euthyroid sick syndrome (NTI), or patient with euthyroid sick syndrome (NTI), or patient with hyperthyroidism undergoing treatment with antithyroid hyperthyroidism undergoing treatment with antithyroid medication. Base on the information given (the patient medication. Base on the information given (the patient recently went through physiological stressful event, and is recently went through physiological stressful event, and is on corticosteroid and no history of hyperthyroidism) the on corticosteroid and no history of hyperthyroidism) the patient most likely has euthyroid sick syndrome. In NTI patient most likely has euthyroid sick syndrome. In NTI the activities of 5’-monodeiodinase is decreased or the activities of 5’-monodeiodinase is decreased or inhibited so the peripheral conversion of T3 diminishes inhibited so the peripheral conversion of T3 diminishes and the clearance of rT3 is reduced causing low serum T3 and the clearance of rT3 is reduced causing low serum T3 and high rT3. There are no abnormal finding on neuro and high rT3. There are no abnormal finding on neuro exam and so MRI would not be the first test. Cotrosyn exam and so MRI would not be the first test. Cotrosyn test on this patient would be inappropriate because he is test on this patient would be inappropriate because he is on exogenous glucocorticoid therapy (except on exogenous glucocorticoid therapy (except dexamethasone) which interfere with the test and aside dexamethasone) which interfere with the test and aside from that his C7 is normal so adrenal insufficiency is from that his C7 is normal so adrenal insufficiency is unlikely. In NTI no treatment is necessary. unlikely. In NTI no treatment is necessary.

Case 5Case 5

A 28 year-old woman presents with a palpable mass on the left side of A 28 year-old woman presents with a palpable mass on the left side of her neck. She has no neck pain and no symptoms of thyroid her neck. She has no neck pain and no symptoms of thyroid dysfunction. Physical exam reveals a solitary, mobile thyroid dysfunction. Physical exam reveals a solitary, mobile thyroid nodule, 2 x 3 cm, without lymphadenopathy. The patient has no nodule, 2 x 3 cm, without lymphadenopathy. The patient has no family history of thyroid disease and no history of external radiation. family history of thyroid disease and no history of external radiation. A blood drawn was sent for serum TSH and FT4. A blood drawn was sent for serum TSH and FT4.

Which of the following statements are true?Which of the following statements are true?A.A. If TSH is low and FT4 high, she has hyperthyroidism so no further If TSH is low and FT4 high, she has hyperthyroidism so no further

evaluation needed and start treatment with antithyroid medication.evaluation needed and start treatment with antithyroid medication.B.B. If TSH is elevated check anti TPO antibody level. If it is elevated she If TSH is elevated check anti TPO antibody level. If it is elevated she

has Hashimotos thyroiditis and no further testing necessary and has Hashimotos thyroiditis and no further testing necessary and start treatment with thyroid medication.start treatment with thyroid medication.

C.C. Serum calcitonin level should be routinely check in young patient Serum calcitonin level should be routinely check in young patient with thyroid nodule(s).with thyroid nodule(s).

D.D. She would need to have thyroid ultrasound and scintigraphy She would need to have thyroid ultrasound and scintigraphy regardless of the TSH level. regardless of the TSH level.

E.E. If TSH is normal, the next step to evaluate her nodule would be If TSH is normal, the next step to evaluate her nodule would be doing a FNAB (with ultrasound guidance.)doing a FNAB (with ultrasound guidance.)

Thyroid NodulesThyroid Nodules Palpable nodules occur in 4-7% of the population. Palpable nodules occur in 4-7% of the population. Studies suggest about 30% of subjects 19 to 50 Studies suggest about 30% of subjects 19 to 50

years of age had an incidental nodule on years of age had an incidental nodule on ultrasonography.ultrasonography.

Types of nodules Types of nodules Colloid, cysts, and thyroiditis (80%)Colloid, cysts, and thyroiditis (80%) Benign follicular neoplasms (10-15%)Benign follicular neoplasms (10-15%) Thyroid carcinoma (5%)Thyroid carcinoma (5%) History and physical exam remain the diagnostic History and physical exam remain the diagnostic

cornerstones in evaluating the patient with cornerstones in evaluating the patient with thyroid nodule and may be suggestive of thyroid thyroid nodule and may be suggestive of thyroid carcinomacarcinoma

Hegedus L. N Engl J Med 2004;351:1764-1771

Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Case 5Case 5A 28 year-old woman presents with a palpable mass on the left side of her A 28 year-old woman presents with a palpable mass on the left side of her

neck. She has no neck pain and no symptoms of thyroid dysfunction. neck. She has no neck pain and no symptoms of thyroid dysfunction. Physical exam reveals a solitary, mobile thyroid nodule, 2 x 3 cm, Physical exam reveals a solitary, mobile thyroid nodule, 2 x 3 cm, without lymphadenopathy. The patient has no family history of thyroid without lymphadenopathy. The patient has no family history of thyroid disease and no history of external radiation. A blood drawn was sent for disease and no history of external radiation. A blood drawn was sent for serum TSH and FT4.serum TSH and FT4.

Which of the following statements is true?Which of the following statements is true?A.A. If TSH is low and FT4 high, she has hyperthyroidism so no further If TSH is low and FT4 high, she has hyperthyroidism so no further

evaluation needed and start treatment with antithyroid medication.evaluation needed and start treatment with antithyroid medication.B.B. If TSH is elevated check anti TPO antibody level. If it is elevated she If TSH is elevated check anti TPO antibody level. If it is elevated she

has Hashimoto’s thyroiditis and no further testing necessary and start has Hashimoto’s thyroiditis and no further testing necessary and start treatment with thyroid medication.treatment with thyroid medication.

C.C. Serum calcitonin level should be routinely check in young patient with Serum calcitonin level should be routinely check in young patient with thyroid nodule(s).thyroid nodule(s).

D.D. She would need to have thyroid ultrasound and scintigraphy regardless She would need to have thyroid ultrasound and scintigraphy regardless of the TSH level. of the TSH level.

E.E. If TSH is normal, the next step to evaluate her nodule would be doing a If TSH is normal, the next step to evaluate her nodule would be doing a FNAB (with ultrasound guidance.)FNAB (with ultrasound guidance.)

Case 5 answerCase 5 answer A is false because eventhough she has thyrotoxicosis one A is false because eventhough she has thyrotoxicosis one

needs to check whether the nodule is hot or cold. A hot needs to check whether the nodule is hot or cold. A hot nodule is nearly always benign, whereas a nonfunctioning nodule is nearly always benign, whereas a nonfunctioning nodule, constituting approximately 90% of nodules, has a 5% nodule, constituting approximately 90% of nodules, has a 5% risk of being malignant. Thus, in patient with a suppressed risk of being malignant. Thus, in patient with a suppressed TSH and a hot nodule no further evaluation is necessaryTSH and a hot nodule no further evaluation is necessary

B is false because although the elevated anti TPO level B is false because although the elevated anti TPO level confirm Hashimoto’s thyroiditis one must rule out a coexisting confirm Hashimoto’s thyroiditis one must rule out a coexisting cancer, including lymphoma, which accounts for only 5% of cancer, including lymphoma, which accounts for only 5% of thyroid cancers but is associated with Hashimoto’s thyroiditis.thyroid cancers but is associated with Hashimoto’s thyroiditis.

C is false because medullary carcinoma is rare (about 1 of 250 C is false because medullary carcinoma is rare (about 1 of 250 patients with thyroid nodule), it should be check only in patients with thyroid nodule), it should be check only in patient with family history of MEN or medullary thyroid patient with family history of MEN or medullary thyroid carcinomacarcinoma

D is false because if she has normal TSH FNAB (with D is false because if she has normal TSH FNAB (with ultrasound guidance) would be the next step of evaluation.ultrasound guidance) would be the next step of evaluation.

E is the correct statement.E is the correct statement.

Case 6Case 6

A 30 yo woman presents to clinic with a complain of insomnia. She A 30 yo woman presents to clinic with a complain of insomnia. She recently gave birth to a healthy baby boy 3 months ago and is still recently gave birth to a healthy baby boy 3 months ago and is still breastfeeding. ROS is also positive for nervousness, heat intolerance, breastfeeding. ROS is also positive for nervousness, heat intolerance, and weight loss (she now weighs 5 lbs lighter than before her and weight loss (she now weighs 5 lbs lighter than before her pregnancy)pregnancy)

On exam she appears anxious, pulse 104, bp 140/68. Eye has lid lag but no On exam she appears anxious, pulse 104, bp 140/68. Eye has lid lag but no proptosis or soft tissue inflammation. Neck has nontender thyroid proptosis or soft tissue inflammation. Neck has nontender thyroid gland twice the normal size, without bruit or nodules. She has fine gland twice the normal size, without bruit or nodules. She has fine tremor and moist palmar skin. DTR are brisk.tremor and moist palmar skin. DTR are brisk.

Lab studies: serum FT4 49.7 (10.3-30.6pmol/L), serum TSH <0.01 (0.5-5.0 Lab studies: serum FT4 49.7 (10.3-30.6pmol/L), serum TSH <0.01 (0.5-5.0 mU/L), normal C7, CBCD, and LFT.mU/L), normal C7, CBCD, and LFT.

Which of the following statement would be done next?Which of the following statement would be done next?A.A. Check EKG, UDAS, and RAIU.Check EKG, UDAS, and RAIU.B.B. Check anti TPO antibody.Check anti TPO antibody.C.C. Start on B blocker for post partum thyroiditisStart on B blocker for post partum thyroiditisD.D. Check serum anti TSI (thyroid-stimulating immunoglobulin) or anti Check serum anti TSI (thyroid-stimulating immunoglobulin) or anti

TSHR..TSHR..E.E. Start on SSRI for post partum depression.Start on SSRI for post partum depression.

Case 6 AnswerCase 6 Answer

Two common form of thyrotoxicosis developed shortly after Two common form of thyrotoxicosis developed shortly after pregnancy (1-4 months) are postpartum thyroiditis and Graves’ pregnancy (1-4 months) are postpartum thyroiditis and Graves’ disease. It’s important to determine the cause of thyrotoxicosis in disease. It’s important to determine the cause of thyrotoxicosis in post partum because the course of treatment would be different. post partum because the course of treatment would be different. RAIU would be helpful to differentiate hyperthyroidism (Graves’ RAIU would be helpful to differentiate hyperthyroidism (Graves’ disease, autonomous thyroid nodules, and toxic mutlinodular disease, autonomous thyroid nodules, and toxic mutlinodular goiter) from thyroiditis (subacute thyroiditis, postpartum goiter) from thyroiditis (subacute thyroiditis, postpartum thyroiditis) or exogenous thyroid hormone but it’s contraindicated thyroiditis) or exogenous thyroid hormone but it’s contraindicated in breasfeeding patient. Both postpartum thyroiditis and Graves’ in breasfeeding patient. Both postpartum thyroiditis and Graves’ disease are considered autoimmune diseases so a positive anti disease are considered autoimmune diseases so a positive anti TPO antibody testing is not helpful. Serum TSI is more specific TPO antibody testing is not helpful. Serum TSI is more specific and is diagnostic for Graves’ disease. The treatment for Graves’ and is diagnostic for Graves’ disease. The treatment for Graves’ disease in postpartum include antithyroid drugs, radioactive disease in postpartum include antithyroid drugs, radioactive iodine (if patient is not breastfeeding), and surgery. Postpartum iodine (if patient is not breastfeeding), and surgery. Postpartum thyroiditis is treated with observation, with or without B-Blocker thyroiditis is treated with observation, with or without B-Blocker during the thyrotoxic stage. Caution is indicated, however, during the thyrotoxic stage. Caution is indicated, however, because B-Blockers are secreted into breast milk. Starting SSRI because B-Blockers are secreted into breast milk. Starting SSRI treatment for depression or anxiety is inappropriate at this time treatment for depression or anxiety is inappropriate at this time because this patient has true abnormal thyroid function studies because this patient has true abnormal thyroid function studies and medication may interfere with her alertness to care for an and medication may interfere with her alertness to care for an infant.infant.

Case 7Case 7An elderly woman comes to your clinic complaining of weakness, An elderly woman comes to your clinic complaining of weakness,

fatigue, and having no interest in life. On questioning, she fatigue, and having no interest in life. On questioning, she reports cold intolerance, one bowel movement every 4-5 reports cold intolerance, one bowel movement every 4-5 days, and some hair loss, but denies any weight gain. She is days, and some hair loss, but denies any weight gain. She is depressed and doesn’t care about herself or her home.depressed and doesn’t care about herself or her home.

BP 98/62 and HR 57BP 98/62 and HR 57Labs show Na 140, K 5.2, Cl 109, HCO3 18, BUN 9, Cr 0.9, Labs show Na 140, K 5.2, Cl 109, HCO3 18, BUN 9, Cr 0.9,

Glucose 70, FT4 0.3 (0.8-1.5ng/dL), and TSH 24.5 (0.5 – Glucose 70, FT4 0.3 (0.8-1.5ng/dL), and TSH 24.5 (0.5 – 5.0mU/L)5.0mU/L)

What should you do next?What should you do next?A.A. Begin oral thyroxine 100 mcg dailyBegin oral thyroxine 100 mcg dailyB.B. Give one dose of IV thyroxine 500 mcg in One Day Stay and Give one dose of IV thyroxine 500 mcg in One Day Stay and

begin oral thyroxine 150 mcg dailybegin oral thyroxine 150 mcg dailyC.C. Begin oral thyroxine 300 mcg dailyBegin oral thyroxine 300 mcg dailyD.D. Begin oral thyroxine 50 mcg dailyBegin oral thyroxine 50 mcg dailyE.E. Begin oral dexamethasone 0.5 mg q a.m. first then oral Begin oral dexamethasone 0.5 mg q a.m. first then oral

thyroxine 100 mcg per day and perform an ACTH thyroxine 100 mcg per day and perform an ACTH (cosyntropin) stimulation test(cosyntropin) stimulation test

Case 7 AnswerCase 7 AnswerE is the correct answer – This patient has both hypothyroidism and E is the correct answer – This patient has both hypothyroidism and

adrenal insufficiency (Schmidt’s syndrome)adrenal insufficiency (Schmidt’s syndrome)Of course the thyroid function test confirm hypothyroidism but don’t Of course the thyroid function test confirm hypothyroidism but don’t

miss other possible issue. She has several clues that raise the miss other possible issue. She has several clues that raise the possibility of adrenal insufficiency: not gaining weight despite possibility of adrenal insufficiency: not gaining weight despite being hypothyroid, low blood pressure, and a hint of hyperkalemic being hypothyroid, low blood pressure, and a hint of hyperkalemic metabolic acidosis. The blood pressure is not unusual for a metabolic acidosis. The blood pressure is not unusual for a woman, but hypothyroidism usually raises diastolic blood woman, but hypothyroidism usually raises diastolic blood pressure. The bp alone is not diagnostic of adrenal insufficiency, pressure. The bp alone is not diagnostic of adrenal insufficiency, but it highly suggestive when taken in context with other findings. but it highly suggestive when taken in context with other findings. The glucose is also low normal. It is imperative to recognize a The glucose is also low normal. It is imperative to recognize a possible case of Schmidt’s syndrome because the patients die possible case of Schmidt’s syndrome because the patients die soon after starting thyroid hormone replacement unless they soon after starting thyroid hormone replacement unless they begin glucocorticoid replacement. If you ever suspect that a begin glucocorticoid replacement. If you ever suspect that a patient may have adrenal insufficiency, you must begin steroids patient may have adrenal insufficiency, you must begin steroids and work up the patient. The standard test is an ACTH1-24 and work up the patient. The standard test is an ACTH1-24 (cosyntropin) stimulation test. Because dexamethasone is the (cosyntropin) stimulation test. Because dexamethasone is the only available glucocorticoid that doesn’t interfere with cortisol only available glucocorticoid that doesn’t interfere with cortisol assay, the patient must be started on dexamethasone until the assay, the patient must be started on dexamethasone until the results of the tests are available. If she truly has adrenal results of the tests are available. If she truly has adrenal insufficiency, it should be treated with hydrocortisone because it insufficiency, it should be treated with hydrocortisone because it also has some mineralcorticoid activity. Once she takes her first also has some mineralcorticoid activity. Once she takes her first steroid pill, she can begin thyroxine.steroid pill, she can begin thyroxine.

Case 8Case 8A 60 year-old woman with hx multinodular goiter and CAD A 60 year-old woman with hx multinodular goiter and CAD

presents to hospital with c/o palpitation and nervous. She is presents to hospital with c/o palpitation and nervous. She is found to have atrial fibrillation with a rapid ventricular found to have atrial fibrillation with a rapid ventricular response. One month ago when she was admitted for response. One month ago when she was admitted for anginal chest pain and had an abnormal stress test. A follow anginal chest pain and had an abnormal stress test. A follow up coronary arteriogram showed non-significant coronary up coronary arteriogram showed non-significant coronary artery disease. The thyroid function test at that time was artery disease. The thyroid function test at that time was within normal limit (TSH 0.8 mU/L).within normal limit (TSH 0.8 mU/L).

Thyroid function testing is repeatedThyroid function testing is repeated TSH <0.01 mU/L (0.5-4.5 mU/L)TSH <0.01 mU/L (0.5-4.5 mU/L) FT4 40.5 pmol/L (10.3-30.6 pmol/L)FT4 40.5 pmol/L (10.3-30.6 pmol/L)What is the most likely diagnosis?What is the most likely diagnosis?A.A. Graves’ diseaseGraves’ diseaseB.B. Stress-induced hyperthyroidismStress-induced hyperthyroidismC.C. Iodine-induced hyperthyroidismIodine-induced hyperthyroidismD.D. Silent thyroiditisSilent thyroiditisE.E. Euthyroid sick syndromeEuthyroid sick syndrome

Case 8 answerCase 8 answerThe natural history of multinodular goiter is slow growth and gradual The natural history of multinodular goiter is slow growth and gradual

decrease in the TSH level that reflects increasing production of thyroid decrease in the TSH level that reflects increasing production of thyroid hormone. This progression occurs over years to decades. Many patients hormone. This progression occurs over years to decades. Many patients with multinodular goiters have autonomous areas within the thyroid with multinodular goiters have autonomous areas within the thyroid gland. This patient had normal thyroid function 1 month before gland. This patient had normal thyroid function 1 month before admission. However, his serum TSH level was near the lower limits of admission. However, his serum TSH level was near the lower limits of normal, suggesting autonomous thyroid function.normal, suggesting autonomous thyroid function.

When patients with multinodular goiters are exposed to excess iodine, severe When patients with multinodular goiters are exposed to excess iodine, severe hyperthyroidism, known as iodine-induced hyperthyroidism or Jod-hyperthyroidism, known as iodine-induced hyperthyroidism or Jod-Basedow phenomenon, may occur. When iodine supplement is introduced Basedow phenomenon, may occur. When iodine supplement is introduced into areas of iodine deficiency, iodine-induced hyperthyroidism may occur into areas of iodine deficiency, iodine-induced hyperthyroidism may occur in patients with multinodular goiters. Iodine-induced hyperthyroidism in patients with multinodular goiters. Iodine-induced hyperthyroidism also may occur in areas in which goiter is uncommon, often with also may occur in areas in which goiter is uncommon, often with devastating consequences.devastating consequences.

The high iodine content of the dye used for cardiac catherization undoubtedly The high iodine content of the dye used for cardiac catherization undoubtedly precipitated this patient’s hyperthyroidism. The onset of hyperthyroidism precipitated this patient’s hyperthyroidism. The onset of hyperthyroidism may be delayed for several weeks to months after iodine exposure.may be delayed for several weeks to months after iodine exposure.

Although other causes of hyperthyroidism are possible, none is as likely as Although other causes of hyperthyroidism are possible, none is as likely as this scenario. When patients with multinodular goiter must be exposed to this scenario. When patients with multinodular goiter must be exposed to excess iodine (for example, during cardiac cath, CT contrast, or excess iodine (for example, during cardiac cath, CT contrast, or amiodarone therapy), premedication with antithyroid drugs (methimazole amiodarone therapy), premedication with antithyroid drugs (methimazole or proylthiouracil) shoud be considered.or proylthiouracil) shoud be considered.

General Summary In General Summary In Evaluating TFTEvaluating TFT

TSH would be the first test to do assess thyroid disorder. If TSH would be the first test to do assess thyroid disorder. If suspect a thyroid disorder or hypothalamic-pituitary disorder get suspect a thyroid disorder or hypothalamic-pituitary disorder get FT4 ( and in some case also T3 or FT3)FT4 ( and in some case also T3 or FT3)

The TSH is very sensitive to the change of FT4. The TSH is very sensitive to the change of FT4. If both TSH and FT4 are changed in the same direction – the If both TSH and FT4 are changed in the same direction – the

disorder is secondary (central) causesdisorder is secondary (central) causes If the TSH and FT4 are changed in the opposite direction – the If the TSH and FT4 are changed in the opposite direction – the

disorder is primary (thyroid) causes.disorder is primary (thyroid) causes. Always check the amount of change in TSH reflects the Always check the amount of change in TSH reflects the

appropriate change in the FT4. appropriate change in the FT4. Pay attention to other clues on physical exam and blood works Pay attention to other clues on physical exam and blood works

that may suggest secondary thyroid diseases or other conditions that may suggest secondary thyroid diseases or other conditions coexist (If FT4 is very low but TSH is only mildly elevated think coexist (If FT4 is very low but TSH is only mildly elevated think central hypothyroidism)central hypothyroidism)

Other ancillary blood works are expensive and rarely use, but in Other ancillary blood works are expensive and rarely use, but in certain cases TSI, Anti TPO, thyroglobulin may be helpful in certain cases TSI, Anti TPO, thyroglobulin may be helpful in making diagnosis and provide prognosis.making diagnosis and provide prognosis.

Total T4, TBG, T3resin uptake, Free Thyroid Index (FTI) are Total T4, TBG, T3resin uptake, Free Thyroid Index (FTI) are available but not commonly used anymoreavailable but not commonly used anymore

Case 9Case 9An elderly man comes to your clinic at the insistence of his children. An elderly man comes to your clinic at the insistence of his children.

Ever since his wife died last year, he has been depressed and Ever since his wife died last year, he has been depressed and losing weight. He has been smoking for 35 years and doesn’t losing weight. He has been smoking for 35 years and doesn’t drink alcohol. He takes propranolol for mild hypertension. He drink alcohol. He takes propranolol for mild hypertension. He talks to you easily but doesn’t seem very interested.talks to you easily but doesn’t seem very interested.

His vital signs: BP 128/80, P.96, T. 98.9, wt. 160 lbs, and BMI 23 His vital signs: BP 128/80, P.96, T. 98.9, wt. 160 lbs, and BMI 23 kg/m2. The physical exam is unremarkable. You order a routine kg/m2. The physical exam is unremarkable. You order a routine metabolic profile, CBD, and a CXR. He comes back for the metabolic profile, CBD, and a CXR. He comes back for the results in two weeks, and you tell him the labs and xray were results in two weeks, and you tell him the labs and xray were normal.normal.

Which of the following would you do next?Which of the following would you do next?A.A. Begin low-dose fluoxetine for his depressionBegin low-dose fluoxetine for his depressionB.B. Order a total body CT scanOrder a total body CT scanC.C. Discontinue propranolol and begin treating his HTN with a Discontinue propranolol and begin treating his HTN with a

thiazide diureticthiazide diureticD.D. Check TSH and FT4Check TSH and FT4E.E. Order a CT scan of the chest.Order a CT scan of the chest.

Case 9 answerCase 9 answerD is the correct answer. This question requires you to D is the correct answer. This question requires you to

recognize apathetic hyperthyroidism. He has clues for recognize apathetic hyperthyroidism. He has clues for hyperthyroidism, but they can easily be missed. He hyperthyroidism, but they can easily be missed. He has been losing weight (which could also be due to has been losing weight (which could also be due to depression or cancer, but the initial work up is depression or cancer, but the initial work up is negative). He has been depressed and could be negative). He has been depressed and could be worsen by side effect of B-blocker. His heart rate is worsen by side effect of B-blocker. His heart rate is not as slow as you might expect in someone taking B-not as slow as you might expect in someone taking B-blockers. Weight loss, depression, and higher than blockers. Weight loss, depression, and higher than expected heart rate should lead you to at consider expected heart rate should lead you to at consider hyperthyroidism. Checking his TSH and FT4 would be hyperthyroidism. Checking his TSH and FT4 would be the next step if not already checked. It is the next step if not already checked. It is inappropriate to begin fluoxetine or any other drug for inappropriate to begin fluoxetine or any other drug for depression until you are sure of the diagnosis. It is depression until you are sure of the diagnosis. It is also premature to order CT scans at this time. Finally, also premature to order CT scans at this time. Finally, changing his blood pressure drug is okay, but you changing his blood pressure drug is okay, but you should first check his thyroid status.should first check his thyroid status.

Case 10Case 10A 40 year-old woman has anxiety, tremors, excessively A 40 year-old woman has anxiety, tremors, excessively

sweating, palpitations, and insomnia of approximately 1 sweating, palpitations, and insomnia of approximately 1 month’s duration. Her medical history is unremarkable. month’s duration. Her medical history is unremarkable. She has had no recent pregnancies or miscarriage. She She has had no recent pregnancies or miscarriage. She has a modest, nontender goiter and no exophthalmos. She has a modest, nontender goiter and no exophthalmos. She takes no medications and has had no recent radiologic takes no medications and has had no recent radiologic procedures. The 24-hour RAIU is 1% (normal, 20%-35%)procedures. The 24-hour RAIU is 1% (normal, 20%-35%)

Lab studies ESR 10 mm/h, FT4 3.5 ng/dL, TSH <0.01 mU/L, Lab studies ESR 10 mm/h, FT4 3.5 ng/dL, TSH <0.01 mU/L, thyroglobulin 35 ng/ml (normal, 2-20ng/mL), Anti TPO 26 thyroglobulin 35 ng/ml (normal, 2-20ng/mL), Anti TPO 26 (normal, <2)(normal, <2)

What is the most likely diagnosis?What is the most likely diagnosis?A.A. Surreptitious use of thyroid hormonesSurreptitious use of thyroid hormonesB.B. Recent ingestion of iodine-containing foods or medicationsRecent ingestion of iodine-containing foods or medicationsC.C. Subacute thyroiditisSubacute thyroiditisD.D. Struma ovariiStruma ovariiE.E. Painless (silent) thyroiditisPainless (silent) thyroiditis

Case 10 answerCase 10 answer This patient has clinical and biochemical evidence of This patient has clinical and biochemical evidence of

thyrotoxicosis, but the 24 hr RAIU is low. The differential thyrotoxicosis, but the 24 hr RAIU is low. The differential diagnosis includes postpartum thyroiditis, silent thyroiditis, diagnosis includes postpartum thyroiditis, silent thyroiditis, subacute thyroiditis, factitious thyrotoxicosis, and iodine-subacute thyroiditis, factitious thyrotoxicosis, and iodine-induced thyrotoxicosis. She has not been pregnant recently induced thyrotoxicosis. She has not been pregnant recently and denies medication use and recent iodine exposure. and denies medication use and recent iodine exposure. Subacute thyroiditis typically causes thyroid pain and Subacute thyroiditis typically causes thyroid pain and tenderness and a very high ESR. This condition is tenderness and a very high ESR. This condition is characterized by granulomatous inflammation and often characterized by granulomatous inflammation and often follows a recent viral infection. The nontender gland, follows a recent viral infection. The nontender gland, elevated thyroglobulin level, and normal ESR are most elevated thyroglobulin level, and normal ESR are most consistent with diagnosis of silent thyroiditis, which is caused consistent with diagnosis of silent thyroiditis, which is caused by lymphocytic inflammation within the thyroid. A transient by lymphocytic inflammation within the thyroid. A transient (1 to 3-month) thyrotoxic phase, followed by a transient (1 to (1 to 3-month) thyrotoxic phase, followed by a transient (1 to 3-month) hypothyroid phase, usually occurs before the 3-month) hypothyroid phase, usually occurs before the condition resolves; however, 20% of patients remain condition resolves; however, 20% of patients remain hypothyroid. In symptomatic patients, the thyrotoxic phase is hypothyroid. In symptomatic patients, the thyrotoxic phase is best treated with best treated with B-blocker, B-blocker, and the hypothyroid phase can be and the hypothyroid phase can be managed with levothyroxine, if necessary.managed with levothyroxine, if necessary.

Case 11Case 11An elderly man with BPH is scheduled for a TURP. He has complete An elderly man with BPH is scheduled for a TURP. He has complete

obstruction and required a suprapubic catheter. He now has post-obstruction and required a suprapubic catheter. He now has post-obstruction diuresis a concentrating defect. The surgeon is having obstruction diuresis a concentrating defect. The surgeon is having difficulty managing the patient’s fluid and electrolytes. He wants to difficulty managing the patient’s fluid and electrolytes. He wants to perform the TURP as soon as possible and has consulted you for medical perform the TURP as soon as possible and has consulted you for medical clearance. During your examination you find a small goiter, tachycardia, clearance. During your examination you find a small goiter, tachycardia, and afib as well as prostate hypertrophy, a suprapubic catheter, and a and afib as well as prostate hypertrophy, a suprapubic catheter, and a large volume of dilute urine, but the urine osmolality is improving. large volume of dilute urine, but the urine osmolality is improving. Because of the tachyarrythmia, you check his thyroid function.Because of the tachyarrythmia, you check his thyroid function.

Lab shows TSH <0.01 mU/L (0.5-5.0 mU/L) and FT4 2.4 (0.7-1.5 ng/dL). The Lab shows TSH <0.01 mU/L (0.5-5.0 mU/L) and FT4 2.4 (0.7-1.5 ng/dL). The patient doesn’t have anyone at home to help him and cannot go home with patient doesn’t have anyone at home to help him and cannot go home with a suprapubic catheter. He has no insurance and cannot afford home a suprapubic catheter. He has no insurance and cannot afford home health care.health care.

Your consult includes multiple recommendations, but which of the following is Your consult includes multiple recommendations, but which of the following is not included?not included?

A.A. Begin a beta-blockerBegin a beta-blockerB.B. Postpone surgery until his FT4 is within normal limitsPostpone surgery until his FT4 is within normal limitsC.C. Begin anticoagulantsBegin anticoagulantsD.D. Avoid contrast dye and anything else that contains iodine so he can be Avoid contrast dye and anything else that contains iodine so he can be

referred for radioactive iodine ablation after surgeryreferred for radioactive iodine ablation after surgeryE.E. Begin PTU 200 mcg every 8 hoursBegin PTU 200 mcg every 8 hours

Case 11 answerCase 11 answerB is the answer – Even though surgery is more risky in patients with B is the answer – Even though surgery is more risky in patients with

hyperthyroidism compared to euthyroidism, his condition is in need of hyperthyroidism compared to euthyroidism, his condition is in need of surgical correction. Though his surgery can be postponed for a short surgical correction. Though his surgery can be postponed for a short period of time to give the thyroid treatments a chance to start working, period of time to give the thyroid treatments a chance to start working, he needs the surgery soon. Sending him home with a suprapubic he needs the surgery soon. Sending him home with a suprapubic catheter until he is euthyroid is not a good option in this case. catheter until he is euthyroid is not a good option in this case. Therefore, your best strategy is to address his hyperthyroidism in Therefore, your best strategy is to address his hyperthyroidism in anticipation of surgery. PTU will cause the thyroid to decrease its anticipation of surgery. PTU will cause the thyroid to decrease its synthesis of new thyroid hormone. A beta-blocker will help control his synthesis of new thyroid hormone. A beta-blocker will help control his symptoms of hyperthyroidism. A good choice would be a beta-blocker symptoms of hyperthyroidism. A good choice would be a beta-blocker that can be given IV and rapidly titrated during surgery. Because he has that can be given IV and rapidly titrated during surgery. Because he has afib, he must be suspected of having an atrial thrombus and therefore afib, he must be suspected of having an atrial thrombus and therefore should be anticoagulated because he may revert to a normal rhythm should be anticoagulated because he may revert to a normal rhythm once he becomes euthyroid. This can be done with a heparin product once he becomes euthyroid. This can be done with a heparin product before surgery because it can be stopped preoperatively and with before surgery because it can be stopped preoperatively and with coumadin after surgery. His ultimate treatment will be radioactive coumadin after surgery. His ultimate treatment will be radioactive iodine ablation. This requires his thyroid to take up the radioactive iodine ablation. This requires his thyroid to take up the radioactive iodine, so if at all possible he should not be given iodine. CT contrast dye iodine, so if at all possible he should not be given iodine. CT contrast dye has a large load of iodine. As soon as he is stable after surgery, he can has a large load of iodine. As soon as he is stable after surgery, he can be referred to nuclear medicine for the ablation. If his surgery was not be referred to nuclear medicine for the ablation. If his surgery was not so important, perhaps he could go home and wait until he is euthyroid, so important, perhaps he could go home and wait until he is euthyroid, but this patient should probably not postpone his surgery more than a but this patient should probably not postpone his surgery more than a few days.few days.

General Summary In General Summary In Evaluating TFTEvaluating TFT

TSH would be the first test to do assess thyroid disorder. If TSH would be the first test to do assess thyroid disorder. If suspect a thyroid disorder or hypothalamic-pituitary disorder get suspect a thyroid disorder or hypothalamic-pituitary disorder get FT4 ( and in some case also T3 or FT3)FT4 ( and in some case also T3 or FT3)

The TSH is very sensitive to the change of FT4. The TSH is very sensitive to the change of FT4. If both TSH and FT4 are changed in the same direction – the If both TSH and FT4 are changed in the same direction – the

disorder is secondary (central) causesdisorder is secondary (central) causes If the TSH and FT4 are changed in the opposite direction – the If the TSH and FT4 are changed in the opposite direction – the

disorder is primary (thyroid) causes.disorder is primary (thyroid) causes. Always check the amount of change in TSH reflects the Always check the amount of change in TSH reflects the

appropriate change in the FT4. appropriate change in the FT4. Pay attention to other clues on physical exam and blood works Pay attention to other clues on physical exam and blood works

that may suggest secondary thyroid diseases or other conditions that may suggest secondary thyroid diseases or other conditions coexist (If FT4 is very low but TSH is only mildly elevated think coexist (If FT4 is very low but TSH is only mildly elevated think central hypothyroidism)central hypothyroidism)

Other ancillary blood works are expensive and rarely use, but in Other ancillary blood works are expensive and rarely use, but in certain cases TSI, Anti TPO, thyroglobulin may be helpful in certain cases TSI, Anti TPO, thyroglobulin may be helpful in making diagnosis and provide prognosis.making diagnosis and provide prognosis.

Total T4, TBG, T3resin uptake, Free Thyroid Index (FTI) are Total T4, TBG, T3resin uptake, Free Thyroid Index (FTI) are available but not commonly used anymoreavailable but not commonly used anymore

Radioiodine UptakeRadioiodine Uptake Useful to differentiate the type of Useful to differentiate the type of

thyrotoxicosisthyrotoxicosis A set dose of I123 is given and 24 hr later a A set dose of I123 is given and 24 hr later a

radiation detector is placed over the thyroid radiation detector is placed over the thyroid to determine the percentage of the dose that to determine the percentage of the dose that was taken up by the thyroidwas taken up by the thyroid

RAIU is high in : Graves disease, TSH-RAIU is high in : Graves disease, TSH-secreting pituitary tumor, hot nodules, hCG secreting pituitary tumor, hot nodules, hCG secreting tumor, iodine deficiencysecreting tumor, iodine deficiency

RAIU is low in : thyroiditis, thyroiditis RAIU is low in : thyroiditis, thyroiditis factitia, iodine excess (contrast dye, factitia, iodine excess (contrast dye, amiodarone-induced thyrotoxicosis type 2)amiodarone-induced thyrotoxicosis type 2)

Thyroid ScansThyroid Scans Scintiscan, or radionuclide scan Scintiscan, or radionuclide scan A radioidine or Tc99m is given, and a A radioidine or Tc99m is given, and a

scintillation scanner produces a rough scintillation scanner produces a rough picture indicating how these isotopes picture indicating how these isotopes localize in the thyroid.localize in the thyroid.

Useful in nodular disease to determine Useful in nodular disease to determine whether a nodule is hot or cold.whether a nodule is hot or cold.

A “hot” functioning nodule is nearly A “hot” functioning nodule is nearly always benign.always benign.

A “cold” nodule has 5% chance of being A “cold” nodule has 5% chance of being malignant and should be further evaluatemalignant and should be further evaluate

Thyroid UltrasoundThyroid Ultrasound determine the size and the content of nodules determine the size and the content of nodules

(cystic or solid, or mixed.)(cystic or solid, or mixed.) Select site for biopsy FNASelect site for biopsy FNA Provide assistance in therapeutic procedure Provide assistance in therapeutic procedure

(cyst aspiration, ETOH injection, laser (cyst aspiration, ETOH injection, laser therapy) and facilitate the monitoring of the therapy) and facilitate the monitoring of the effects of treatment.effects of treatment.

Worrisome characteristics: Worrisome characteristics: hypoechogenicity, microcalcification, hypoechogenicity, microcalcification, irregular margins, increased nodular blood irregular margins, increased nodular blood flow and evidence of margin or regional flow and evidence of margin or regional lymphadenopathylymphadenopathy

Fine Needle AspirationFine Needle Aspiration First test of choice in euthyroid patient First test of choice in euthyroid patient

with a (palpable) nodule.with a (palpable) nodule. False negative rate is 1-11%, and false False negative rate is 1-11%, and false

positive rate of 1-8%positive rate of 1-8% About 69-74% of specimens are benign, About 69-74% of specimens are benign,

22-27% are indeterminate or suspicious, 22-27% are indeterminate or suspicious, and about 4% are positive for cancerand about 4% are positive for cancer

Cannot differentitiate microfollicular Cannot differentitiate microfollicular from follicular carcinoma.from follicular carcinoma.

Sampling errors can be minimize by using Sampling errors can be minimize by using ultrasound-guided biopsy.ultrasound-guided biopsy.