Thyroid diseases

Steven T. Nguy M.D.

Assistant professor of Medicine
Cooper University Hospitalist
 TFT – A practical review
 The hypothalamus-pituitary-thyroid
function and thyroid physiology
 Usefulness and limitation of blood
work studies in thyroid disorder
 Clinical cases
 Hypothalamic-Pituitary-
Thyroid Axis
Physiology
Hypothalamus TRH
–

Pituitary
–

T4 TS
Target Tissues
H
T3 Heart
Thyroid Gland
Liver

TR
T4 T3
Bone

T4  T3
Liver CNS

Adapted from Merck Manual of Medical Information. ed. R

Thyroid Physiology
 Thyroid gland releases T4 and
T3 in molar ratio of 16:1
 >99% of the circulating
thyroid hormones are bound to
proteins (TBG, thyroxine-
binding prealbumin, albumin)
 The vast majority of circulating
T3 is derived from deiodination
of T4 outside the thyroid gland
 Unbound (free) hormones T4
(0.03%) and T3 (0.3%) are
biological active and are not
influenced by TBG protein
 In NTI, T4 conversion to T3 is
reduced and conversion to rT3
is enhanced
 Thyroid Funtion Tests
 TSH
 FT4, (T4)
 T3, FT3
 Thyroglobulin
 Thyroid stimulating immunoglobulin (TSI)
or TSHR antibody
 Antithyroid peroxidase antibodies (Anti
TPO)
 Serum TSH

 Single best or initial test of the thyroid function.

 Central to the negative-feedback system.

 Inverse, log-linear relationship with thyroid hormone.

Small changes in FT4 result in large changes in TSH level

 Normal range 0.5 – 5.0 mU/L

 Third generation TSH chemiluminometric assays have

detection limits of about 0.01mU/L.

 A normal TSH is sufficed to halt further testing unless

suspect of possible hypothalamic pituitary disease.
 Screening:

Recommendations
Various societies and authors disagree about population-based screening
 The USPSTF - insufficient evidences to recommend for or against routine
screening for thyroid disease in adults.
 The AAFP recommends screening high-risk populations:
- women with a family hx of thyroid disease
- women >35 y.o.
- pregnant women
- abnormal physical exam
- diabetic patients
- Hx of autoimmune disorder
 The American Thyroid Association recommends screening start at age 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:
 Serum T4
 measured by radioimmunoassay (RIA), chemiluminometric
assay, or similar immunometric technique.

 99.97% of serum T4 is bound to TBG (thyroxine binding

globulin), transthyretin or TBPA (thyroxine-binding
prealbumin), or albumin.

 Serum total T4 assays measure both bound and unbound

(“free”) T4

 Levels are high in approximately 90% of hyperthyroid

patients and low in approximately 85% of hypothyroid
patients.
 Serum Free T4
 FT4 is measured by equilibrium dialysis
techniques or estimated indirectly by
calculation of free-thyroxine index (FTI)
 FTI = T4 x T3 resin uptake (T3RU)%
(T7, thyroid hormone-binding ratios)
 FT4 assay is preferred test with tsh.
 T3, Free T3, and rT3
T3 - binding protein dependent.
- Levels can be misleading in patients with
acute illness, cirrhosis, uremia, or malnutrition.

 FT3
- Useful to distinguish T3 toxicosis from
subclinical thyrotoxicosis.

 Reverse T3 (rT3)
- increased in NTI.
- inactive.
- helpful to exclude central hypothyroidism
 Other Ancillary Tests
 Serum thyroglobulin – produced and released by thyroid
gland.
- marker for recurrent thyroid cancer
- differentiate Graves disease from factitious thyrotoxicosis

 Serum thyroid-stimulating immunoglobulin

(TSI) or TSHR-Ab - Expensive test
- Graves’ disease.

 Antithyroid peroxidase antibodies (Anti TPO) –

organ-specific and sensitive.
- Hashimoto’s thyroiditis
- predict overt hypothyroidism
 Case 1
TSH 9.0 (0.5 – 5.5 mU/L)
FT4 1.1 (0.8-1.8 ng/dL)

What are your differential diagnoses?

 Differential diagnoses for
elevated TSH with normal
FT4
TSH 9.0 (0.5-5.5 mU/L), T4 1.1 (0.8-1.8 ng/dL)
 Transitional thyroid state or recovery from
hypothyroidism (Hashimoto’s thyroiditis)
 TSH receptor inactivating mutation

 Patient with hypothyroidism who is on or recently

started on treatment and the TSH hasn’t enough
time to adjust.
 Subclinical hypothyroidism
 Case 1
A 75 yo woman with no prior medical problem presents for
her annual physical examination. She says that she is
slowing down a bit and has become more forgetful. She
also mentions that she feels cold and is constipated.
Physical examination is essentially within 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.
Which of the following actions would be most appropriate?
A. She should be treated with levothyroxine 0.1 mg/day.
B. Check lipid profile and start her on treatment if her HDL
is low.
C. Check anti TPO level. If it shows high titer, she would be
less likely become overt hypothyroidism in the future.
D. Repeat TSH and FT4 in 2 – 12 weeks.
 Subclinical Thyroid Dysfunction
Clinical Guidelines By USPSTF
Ann Intern Med. 2004;140:125-127,128-141
JAMA, 2004;291:228-238,239-243

 Subclinical hypothyroidism is an elevation of serum TSH

level with a FT4 in (low) normal range.
 Upper limit of normal TSH should remain 4.5 or 5 mU/L
 There was insufficient evidence linking subclinical
hypothyroidism to systemic symptoms, cardiac dysfunction,
adverse cardiac endpoints, LDL elevation and
neuropsychiatric symptoms for TSH values ranging from
4.5 to 10 mU/L
 The evidence for an association with dyslipidemia was rate
as ‘‘fair’’, and only in individuals with TSH >10.
 The decision to begin levothyroxine therapy in patient with
persistent TSH but normal FT4 should be individualized.
 If treatment is given, be cautious not to overtreat. Goal
TSH 2.5-3.5
 Other Ancillary Tests
 Serum thyroglobulin – produced and released by thyroid gland.
Level is elevated in conditions that increase thyroid gland function
or destruction. It can be used as a tumor marker for recurrent of
thyroid cancer or to differentiate Graves’disease from factitious
thyrotoxicosis.
 Serum thyroid-stimulating immunoglobulin (TSI) or TSHR-Ab –
Expensive. Highly specific for Graves disease Generally not
needed, but can be helpful in suspected cases of Graves’ disease
in pregnancy or euthyroid ophthalmopathy.
 Antithyroid peroxidase antibodies (Anti TPO) – useful in suspected
case of Hashimoto’s thyroiditis, and in predicting for the
development of overt hypothyroidism. It is highly organ-specific
and sensitive.
 Case 1 answer
A 75 yo woman with no prior medical problem presents for
her annual physical examination. She says that she is
slowing down a bit and has become more forgetful. She
also mentions that she feels cold and is constipated.
Physical examination is essentially within 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.
Which of the following actions would be most appropriate?
A. She should be treated with levothyroxine 0.1 mg/day.
B. Check lipid profile and start her on treatment if her HDL
is low.
C. Check anti TPO level. If it shows high titers, she would be
less likely to become overt hypothyroidism in the near
future
D. Repeat TSH and FT4 in 2 – 12 weeks.
 Case 1 Answer
 This patient has subclinical hypothyroidism. Her
symptom is nonspecific. It is recommended to
recheck TSH and FT4 in 2 – 12 weeks. If it is still
elevated then consider start treatment with low
dose levothyroxine and to recheck TSH again in 6
– 8 weeks. Goal is to get TSH down to normal
range 2.5 – 3.5. The starting dose in choice A is
too high and patient would likely become
symptomatic from thyrotoxicosis. There is
insufficient evidence to link subclinical
hypothyroidism with elevated LDL for TSH 5.5 –
10. It has no effect on HDL. Patient with high titer
anti TPO are more likely to become overt
hypothyroidism (annualize rate is about 4.5%)
but the current consensus didn’t advise the use of
antiTPO antibodies in the decision making
process.
 Case 2

TSH 0.18 (0.45 – 5.0 mU/L)

FT4 1.6 (0.8 – 1.8 ng/dL)

What are your differential diagnoses?

Causes of low TSH and normal
FT4
 Subclinical thyrotoxicosis (toxic multinodular goiter, toxic
adenomas, mild Graves’disease, excessive replacement
therapy)
 Total triiodothyronine thyrotoxicosis (Early
Graves’disease, autonomous thyroid nodules)
 Drug effect (corticosteroids, octreotide, dopamine)
 Non-thyroidal illness (euthyroid sick)
 Transitional thyroid state (recovery from thyroiditis)
 Excessive thyroid hormone therapy
 Central hypothyroidism
 Case 2
A 60 yo male with history htn, dm type 2, and hypercholesterolemia who
has been doing well with medications including lisinopril 5mg 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 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 – 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 limit
Which of the following statements would be appropriate?
A. He has subclinical hypothyroidism and very likely to develop
osteosporosis and atrial fibrillation so he should be treated.
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, so he should
be treated.
C. He should have thyroid ultrasound, RAIU, and Echocardiogram.
D. He should have a repeat TSH and FT4 in 4 – 6 weeks
E. Start low dose PTU and recheck TSH and FT4 in 3 – 6 weeks
 Subclinical Thyroid Dysfunction
Clinical Guidelines By USPSTF
Ann Intern Med. 2004;140:125-127,128-141
JAMA, 2004;291:228-238,239-243

 Subclinical hyperthyroidism is a suppressed serum TSH

value resulting from an increase in serum T4 and/or T3
within the confines of the normal range
 Evidence for adverse effects on the skeleton and the
heart was “fair” to “good”, but only in patients with
serum TSH levels < 0.1 mU/L
 It is recommended that treatment “be considered” in
patients with TSH levels < 0.1 mU/L even though there is
a “paucity of intervention trials” showing benefit
 For patients with the serum TSH levels between 0.1 and
0.45 mU/L, the evidence for adverse health consequences
was insufficient or absent, and therefore therapy was not
recommended.
 Case 2
A 60 yo male with history htn, dm type 2, and hypercholesterolemia who has been
doing well with medications including lisinopril 5mg 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 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 –
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 limit. EKG is also normal
Which of the following statements would be appropriate?
A. He has subclinical hypothyroidism and very likely to develop osteosporosis and
atrial fibrillation so he should be treated.
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.
C. He should have thyroid ultrasound, RAIU, and Echocardiogram.
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.
 Case 2 Answer
 This patient has subclinical hypertyroidism and is doing
well. Current evidences suggest that risks of having
osteosporosis and atrial fibrillation are “fair” to “good” but
only in patients with TSH <0.1 mU/L. In patients with
thyrotoxicosis, the presence of thyroglobulin-receptor
antibodies, not anti TPO antibodies, in the serum is
diagnostic of Graves’ disease, but the antibodies are absent
in approximately 5 to 20 percent of patients with
hyperthyroid Graves’ disease and almost certainly in a
greater proportion of those with subclinical
hyperthyroidism. Additional imaging or radioiodine uptake
studies are not indicate as patient has no abnormal finding
on exam. So at this time no treatment is needed and
patient should have a repeat TFT in 4-6 weeks.
 Case 3
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 of ROS are negative. Her medication includes amiodarone
200mg daily, metoprolol XL 50mg daily, metformin 500mg BID, and simvastatin 20mg
bedtime.
She appears mild anxious but no distress.
VS. 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 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 including C7, CBCD, CK, and TnT.

Which of the following statements are true?

A. Patient has amiodarone induced thyroiditis so amiodarone must be stopped immediately
and start on PTU or methimazole low dose.
B. Order color flow Doppler of thyroid gland, RAUI, and IL6 to determine the type of
thyrotoxicosis
C. Treat patient with both a thionamide and prednisone, continue amiodarone, and recheck
TSH and FT4 in 2-4 weeks
D. Stop amiodarone and recheck TSH, FT4 in 4-6 weeks.
E. She should be start on ASA and prednisone if the RAIU is high
 Amiodarone induced
thyrotoxicosis
 About 3% of amiodarone-treated patients in the
United States become hyperthyroid. (Hypothyroidism
is more common than hyperthyroidism)

 Two basic mechanisms in AIT

Type I – Increase synthesis of T4 and T3
- Pre-existing multinodular goiter or latent Graves’
disease. More commonly seen in iodine-deficient
areas of the world

Type II – Direct toxic effect of amiodarone causing

thyroiditis and hence release of T4 and T3 without
increased hormone synthesis. More commonly seen
in iodine-sufficient countries
 Amiodarone induced
thyrotoxicosis
 Distinction between the two types is critical because the
treatment is different.
 Criteria used to attempt to distinguish type I from type II are
24-hour radioiodine uptake – if detectable, it suggest type I
AIT
Goiters – if has multinodular or diffuse goiter, it is more likely
type I AIT.
Serum thyroglobulin – higher in type I
Serum IL-6 – higher in type II
Color-flow Doppler sonography – may distinguish type I
(increased vascularity) from type II (absent vascularity)
hyperthyroidism.
 Amiodarone induced
thyrotoxicosis
Should amiodarone be discontinued?
 There are no good data that answer this question;
however, the following should be considered:
 Amiodarone may be necessary to control a life
threatening arrythmia.
 It has a very long half-life so stopping it would
not give any immediate benefit.
 Amiodarone appears ameliorate hyperthyroidism
by blocking T4 to T3 conversion, beta-
adrenergic receptors, and possibly T3
receptors. Stopping amiodarone might actually
exacerbate hyperthyroid symptoms and signs.
 Amiodarone induced
thyrotoxicosis treatment
 Type I AIT
. Drugs-Thionamide (PTU or methimazole) is the first line therapy (whether
amiodarone is continued or discontinued). Higher than average doses
are often needed
. Radioiodine ablation – if the RAIU is high enough.
. Surgery – only if refractory to antithyroid drug therapy.

 Type II AIT
. Glucocorticoids – Prednisone 40-60 mg/day. Continue therapy for one to
two months before tapering

 “Mixed” type I and type II AIT

. Combination of glucocorticoid and thionamine initially.
A rapid response suggests type II, the thionamide can then be tapered or
stopped.
A poor or slow initial response argues for type I AIT
 Case 3
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 of ROS are negative.
Her medication includes amiodarone 200mg daily, metoprolol XL 50mg daily, metformin 500mg BID, and
simvastatin 20mg bedtime.
She Appears mild anxious but no distress.
VS. 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 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 including C7,
CBCD, CK, and TnT.

Which of the following statements are true?

A. Patient has amiodarone induced thyroditis so amiodarone must be
stopped immediately and start on PTU or methimazole low dose.
B. The color flow Doppler of thyroid gland, RAUI, and IL6 may help to
determine the type of thyrotoxicosis
C. Treat patient with both a thionamide and prednisone, continue
amiodarone, and recheck TSH and FT4 in 2-4 weeks
D. Stop amiodarone and recheck TSH, FT4 in 4-6 weeks.
E. She should be start on ASA and prednisone if the RAIU is high
 Case 3 answer
B and C are the correct statement.
A is false because amiodarone has a very long
half-life so stopping it would not have any
immediate benefit and potentially can cause
arrhythmia.
D is false because patient needs treatment for
thyrotoxicosis
E is false because in acute thyrotoxicosis state
aspirin can exacerbate the condition because it
binds to TBG and causing more available
unbound thyroxine.
 Case 4
A 70 yo male patient was admitted to ICU 3 days ago for pneumonia,
COPD exacerbation which required intubation. He was successfully
extubated and transferred to telemetry floor yesterday. Overnight
the telemetry shows sinus rhythm 80 to sinus tachycardia 105 with
few atrial ectopy and a normal EKG. He is on Levaquin 750mg daily,
duoneb Q4H, and hydrocortisone 60mg Q6H.
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 RLL rhonchi
but no crackles, heart rate is slightly fast but no murmur or rub. The
remaining of his exam was unremarkable.
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.
Which of the following would be appropriate to do next?
A. This patient has lab result suggestive of central hypothyroidism so
MRI of the head should be done first.
B. Order a baseline cortisol level and do a cosyntropin test to rule out
adrenal insufficiency.
C. Order a serum rT3 level and if the level is high no other test is
necessary.
D. Start patient on levothyroxine 0.025mg daily for hypothyroidism
 Nonthyroidal illness
(Euthyroid Sick Syndrome)
 Abnormal findings on TFT that occur in the setting of a NTI without
preexisting hypothalamic-pituitary and thyroid gland dysfunction.

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

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

 Probable mechanism:
- Decreased or inhibition of 5’-monodeiodination (endogenous cortisol
or exogenous glucocorticoid therapy, non-esterified fatty acids, cytokines
TNF, IF, IL6.)
- The peripheral production of T3 is decrease, but its clearance is
unchanged; whereas, the production of rT3 is unchanged, while its
clearance is diminished

 Treatment is not needed. After recovery from an NTI, these thyroid function
test result abnormalities should be completely reversible
 Case 4
A 70 yo male patient was admitted to ICU 3 days ago for pneumonia,
COPD exacerbation which required intubation. He was successfully
extubated and transferred to telemetry floor yesterday. Overnight
the telemetry shows sinus rhythm 80 to sinus tachycardia 105 with
few atrial ectopy and a normal EKG. He is on Levaquin 750mg daily,
duoneb Q4H, and hydrocortisone 60mg Q6H.
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 RLL rhonchi
but no crackles, heart rate is slightly fast but no murmur or rub. The
remaining of his exam was unremarkable.
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.
Which of the following would be appropriate to do next?
A. This patient has lab result suggestive of central hypothyroidism so
MRI of the head should be done first.
B. Order a baseline cortisol level and do a cosyntropin test to rule out
adrenal insufficiency.
C. Order a serum rT3 level and if the level is high no other test is
necessary.
D. Start patient on levothyroxine 0.025mg daily for hypothyroidism
 Case 4 answer
 This patient has low TSH, low T3 and normal T4. The differential
diagnoses includes central hypothyroidism, euthyroid sick syndrome
(NTI), or patient with hyperthyroidism undergoing treatment with
antithyroid medication. Base on the information given (the patient
recently went through physiological stressful event, and is on
corticosteroid and no history of hyperthyroidism) the patient most
likely has euthyroid sick syndrome. In NTI the activities of 5’-
monodeiodinase is decreased or inhibited so the peripheral
conversion of T3 diminishes and the clearance of rT3 is reduced
causing low serum T3 and high rT3. There are no abnormal finding on
neuro exam and so MRI would not be the first test. Cotrosyn test on
this patient would be inappropriate because he is on exogenous
glucocorticoid therapy (except dexamethasone) which interfere with
the test and aside from that his C7 is normal so adrenal insufficiency
is unlikely. In NTI no treatment is necessary.
 Case 5
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.
Physical exam reveals a solitary, mobile thyroid nodule, 2 x 3 cm,
without lymphadenopathy. The patient has no family history of
thyroid disease and no history of external radiation. A blood drawn
was sent for serum TSH and FT4.

Which of the following statements are true?

A. If TSH is low and FT4 high, she has hyperthyroidism so no further
evaluation needed and start treatment with antithyroid medication.
B. If TSH is elevated check anti TPO antibody level. If it is elevated she
has Hashimotos thyroiditis and no further testing necessary and start
treatment with thyroid medication.
C. Serum calcitonin level should be routinely check in young patient with
thyroid nodule(s).
D. She would need to have thyroid ultrasound and scintigraphy
regardless of the TSH level.
E. If TSH is normal, the next step to evaluate her nodule would be doing
a FNAB (with ultrasound guidance.)
 Thyroid Nodules
 Palpable nodules occur in 4-7% of the population.
 Studies suggest about 30% of subjects 19 to 50 years of
age had an incidental nodule on ultrasonography.
 Types of nodules
Colloid, cysts, and thyroiditis (80%)
Benign follicular neoplasms (10-15%)
Thyroid carcinoma (5%)
 History and physical exam remain the diagnostic
cornerstones in evaluating the patient with thyroid nodule
and may be suggestive of thyroid carcinoma
Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary
Thyroid Nodule

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

 Case 5
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.
Physical exam reveals a solitary, mobile thyroid nodule, 2 x 3 cm, without
lymphadenopathy. The patient has no family history of thyroid disease
and no history of external radiation. A blood drawn was sent for serum
TSH and FT4.

Which of the following statements is true?

A. If TSH is low and FT4 high, she has hyperthyroidism so no further
evaluation needed and start treatment with antithyroid medication.
B. 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
treatment with thyroid medication.
C. Serum calcitonin level should be routinely check in young patient with
thyroid nodule(s).
D. She would need to have thyroid ultrasound and scintigraphy regardless of
the TSH level.
E. If TSH is normal, the next step to evaluate her nodule would be doing a
FNAB (with ultrasound guidance.)
 Case 5 answer
 A is false because eventhough she has thyrotoxicosis one needs to
check whether the nodule is hot or cold. A hot nodule is nearly
always benign, whereas a nonfunctioning nodule, constituting
approximately 90% of nodules, has a 5% risk of being malignant.
Thus, in patient with a suppressed TSH and a hot nodule no further
evaluation is necessary
 B is false because although the elevated anti TPO level confirm
Hashimoto’s thyroiditis one must rule out a coexisting cancer,
including lymphoma, which accounts for only 5% of thyroid
cancers but is associated with Hashimoto’s thyroiditis.
 C is false because medullary carcinoma is rare (about 1 of 250
patients with thyroid nodule), it should be check only in patient
with family history of MEN or medullary thyroid carcinoma
 D is false because if she has normal TSH FNAB (with ultrasound
guidance) would be the next step of evaluation.
 E is the correct statement.
 Case 6
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 breastfeeding.
ROS is also positive for nervousness, heat intolerance, and weight loss
(she now weighs 5 lbs lighter than before her pregnancy)
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 gland
twice the normal size, without bruit or nodules. She has fine 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
mU/L), normal C7, CBCD, and LFT.

Which of the following statement would be done next?

A. Check EKG, UDAS, and RAIU.
B. Check anti TPO antibody.
C. Start on B blocker for post partum thyroiditis
D. Check serum anti TSI (thyroid-stimulating immunoglobulin) or anti TSHR..
E. Start on SSRI for post partum depression.
 Case 6 Answer
Two common form of thyrotoxicosis developed shortly after pregnancy (1-4
months) are postpartum thyroiditis and Graves’ disease. It’s important to
determine the cause of thyrotoxicosis in post partum because the course of
treatment would be different. RAIU would be helpful to differentiate
hyperthyroidism (Graves’ disease, autonomous thyroid nodules, and toxic
mutlinodular goiter) from thyroiditis (subacute thyroiditis, postpartum
thyroiditis) or exogenous thyroid hormone but it’s contraindicated in
breasfeeding patient. Both postpartum thyroiditis and Graves’ disease are
considered autoimmune diseases so a positive anti TPO antibody testing is
not helpful. Serum TSI is more specific and is diagnostic for Graves’
disease. The treatment for Graves’ disease in postpartum include
antithyroid drugs, radioactive iodine (if patient is not breastfeeding), and
surgery. Postpartum thyroiditis is treated with observation, with or without
B-Blocker during the thyrotoxic stage. Caution is indicated, however,
because B-Blockers are secreted into breast milk. Starting SSRI treatment
for depression or anxiety is inappropriate at this time because this patient
has true abnormal thyroid function studies and medication may interfere
with her alertness to care for an infant.
 Case 7
An elderly woman comes to your clinic complaining of weakness,
fatigue, and having no interest in life. On questioning, she reports
cold intolerance, one bowel movement every 4-5 days, and some
hair loss, but denies any weight gain. She is depressed and
doesn’t care about herself or her home.
BP 98/62 and HR 57
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 – 5.0mU/L)

What should you do next?

A. Begin oral thyroxine 100 mcg daily
B. Give one dose of IV thyroxine 500 mcg in One Day Stay and begin
oral thyroxine 150 mcg daily
C. Begin oral thyroxine 300 mcg daily
D. Begin oral thyroxine 50 mcg daily
E. Begin oral dexamethasone 0.5 mg q a.m. first then oral thyroxine
100 mcg per day and perform an ACTH (cosyntropin) stimulation
test
 Case 7 Answer
E is the correct answer – This patient has both hypothyroidism and
adrenal insufficiency (Schmidt’s syndrome)
Of course the thyroid function test confirm hypothyroidism but don’t miss
other possible issue. She has several clues that raise the possibility of
adrenal insufficiency: not gaining weight despite being hypothyroid,
low blood pressure, and a hint of hyperkalemic metabolic acidosis.
The blood pressure is not unusual for a woman, but hypothyroidism
usually raises diastolic blood pressure. The bp alone is not diagnostic
of adrenal insufficiency, but it highly suggestive when taken in context
with other findings. The glucose is also low normal. It is imperative to
recognize a possible case of Schmidt’s syndrome because the patients
die soon after starting thyroid hormone replacement unless they begin
glucocorticoid replacement. If you ever suspect that a patient may
have adrenal insufficiency, you must begin steroids and work up the
patient. The standard test is an ACTH1-24 (cosyntropin) stimulation
test. Because dexamethasone is the only available glucocorticoid that
doesn’t interfere with cortisol assay, the patient must be started on
dexamethasone until the results of the tests are available. If she truly
has adrenal insufficiency, it should be treated with hydrocortisone
because it also has some mineralcorticoid activity. Once she takes her
first steroid pill, she can begin thyroxine.
 Case 8
A 60 year-old woman with hx multinodular goiter and CAD presents
to hospital with c/o palpitation and nervous. She is found to
have atrial fibrillation with a rapid ventricular response. One
month ago when she was admitted for anginal chest pain and
had an abnormal stress test. A follow up coronary arteriogram
showed non-significant coronary artery disease. The thyroid
function test at that time was within normal limit (TSH 0.8 mU/L).
Thyroid function testing is repeated
TSH <0.01 mU/L (0.5-4.5 mU/L)
FT4 40.5 pmol/L (10.3-30.6 pmol/L)
What is the most likely diagnosis?
A. Graves’ disease
B. Stress-induced hyperthyroidism
C. Iodine-induced hyperthyroidism
D. Silent thyroiditis
E. Euthyroid sick syndrome
 Case 8 answer
The natural history of multinodular goiter is slow growth and gradual decrease in the TSH
level that reflects increasing production of thyroid hormone. This progression occurs over
years to decades. Many patients with multinodular goiters have autonomous areas within
the thyroid gland. This patient had normal thyroid function 1 month before admission.
However, his serum TSH level was near the lower limits of normal, suggesting
autonomous thyroid function.
When patients with multinodular goiters are exposed to excess iodine, severe
hyperthyroidism, known as iodine-induced hyperthyroidism or Jod-Basedow phenomenon,
may occur. When iodine supplement is introduced into areas of iodine deficiency, iodine-
induced hyperthyroidism may occur in patients with multinodular goiters. Iodine-induced
hyperthyroidism also may occur in areas in which goiter is uncommon, often with
devastating consequences.
The high iodine content of the dye used for cardiac catherization undoubtedly precipitated
this patient’s hyperthyroidism. The onset of hyperthyroidism may be delayed for several
weeks to months after iodine exposure.
Although other causes of hyperthyroidism are possible, none is as likely as this scenario.
When patients with multinodular goiter must be exposed to excess iodine (for example,
during cardiac cath, CT contrast, or amiodarone therapy), premedication with antithyroid
drugs (methimazole or proylthiouracil) shoud be considered.
 General Summary In
Evaluating TFT
 TSH would be the first test to do assess thyroid disorder. If suspect a
thyroid disorder or hypothalamic-pituitary disorder get FT4 ( and in some
case also T3 or FT3)
 The TSH is very sensitive to the change of FT4.
 If both TSH and FT4 are changed in the same direction – the disorder is
secondary (central) causes
 If the TSH and FT4 are changed in the opposite direction – the disorder is
primary (thyroid) causes.
 Always check the amount of change in TSH reflects the appropriate
change in the FT4.
 Pay attention to other clues on physical exam and blood works that may
suggest secondary thyroid diseases or other conditions coexist (If FT4 is
very low but TSH is only mildly elevated think central hypothyroidism)
 Other ancillary blood works are expensive and rarely use, but in certain
cases TSI, Anti TPO, thyroglobulin may be helpful in making diagnosis
and provide prognosis.
 Total T4, TBG, T3resin uptake, Free Thyroid Index (FTI) are available but
not commonly used anymore
 Case 9
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 losing
weight. He has been smoking for 35 years and doesn’t drink alcohol.
He takes propranolol for mild hypertension. He 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 kg/m2.
The physical exam is unremarkable. You order a routine metabolic
profile, CBD, and a CXR. He comes back for the results in two weeks,
and you tell him the labs and xray were normal.

Which of the following would you do next?

A. Begin low-dose fluoxetine for his depression
B. Order a total body CT scan
C. Discontinue propranolol and begin treating his HTN with a thiazide
diuretic
D. Check TSH and FT4
E. Order a CT scan of the chest.
 Case 9 answer
D is the correct answer. This question requires you to recognize
apathetic hyperthyroidism. He has clues for hyperthyroidism,
but they can easily be missed. He has been losing weight
(which could also be due to depression or cancer, but the initial
work up is negative). He has been depressed and could be
worsen by side effect of B-blocker. His heart rate is not as slow
as you might expect in someone taking B-blockers. Weight
loss, depression, and higher than expected heart rate should
lead you to at consider hyperthyroidism. Checking his TSH and
FT4 would be the next step if not already checked. It is
inappropriate to begin fluoxetine or any other drug for
depression until you are sure of the diagnosis. It is also
premature to order CT scans at this time. Finally, changing his
blood pressure drug is okay, but you should first check his
thyroid status.
 Case 10
A 40 year-old woman has anxiety, tremors, excessively
sweating, palpitations, and insomnia of approximately 1
month’s duration. Her medical history is unremarkable.
She has had no recent pregnancies or miscarriage. She
has a modest, nontender goiter and no exophthalmos.
She takes no medications and has had no recent radiologic
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,
thyroglobulin 35 ng/ml (normal, 2-20ng/mL), Anti TPO 26
(normal, <2)
What is the most likely diagnosis?
A. Surreptitious use of thyroid hormones
B. Recent ingestion of iodine-containing foods or medications
C. Subacute thyroiditis
D. Struma ovarii
E. Painless (silent) thyroiditis
 Case 10 answer
This patient has clinical and biochemical evidence of
thyrotoxicosis, but the 24 hr RAIU is low. The differential diagnosis
includes postpartum thyroiditis, silent thyroiditis, subacute
thyroiditis, factitious thyrotoxicosis, and iodine-induced
thyrotoxicosis. She has not been pregnant recently and denies
medication use and recent iodine exposure. Subacute thyroiditis
typically causes thyroid pain and tenderness and a very high ESR.
This condition is characterized by granulomatous inflammation
and often follows a recent viral infection. The nontender gland,
elevated thyroglobulin level, and normal ESR are most consistent
with diagnosis of silent thyroiditis, which is caused by lymphocytic
inflammation within the thyroid. A transient (1 to 3-month)
thyrotoxic phase, followed by a transient (1 to 3-month)
hypothyroid phase, usually occurs before the condition resolves;
however, 20% of patients remain hypothyroid. In symptomatic
patients, the thyrotoxic phase is best treated with B-blocker, and
the hypothyroid phase can be managed with levothyroxine, if
necessary.
 Case 11
An elderly man with BPH is scheduled for a TURP. He has complete obstruction
and required a suprapubic catheter. He now has post-obstruction diuresis a
concentrating defect. The surgeon is having difficulty managing the patient’s
fluid and electrolytes. He wants to perform the TURP as soon as possible and
has consulted you for medical clearance. During your examination you find a
small goiter, tachycardia, and afib as well as prostate hypertrophy, a
suprapubic catheter, and a large volume of dilute urine, but the urine
osmolality is improving. 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
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 health care.
Your consult includes multiple recommendations, but which of the following is not
included?
A. Begin a beta-blocker
B. Postpone surgery until his FT4 is within normal limits
C. Begin anticoagulants
D. Avoid contrast dye and anything else that contains iodine so he can be referred
for radioactive iodine ablation after surgery
E. Begin PTU 200 mcg every 8 hours
 Case 11 answer
B is the answer – Even though surgery is more risky in patients with hyperthyroidism compared
to euthyroidism, his condition is in need of surgical correction. Though his surgery can be
postponed for a short period of time to give the thyroid treatments a chance to start working,
he needs the surgery soon. Sending him home with a suprapubic catheter until he is euthyroid
is not a good option in this case. Therefore, your best strategy is to address his
hyperthyroidism in anticipation of surgery. PTU will cause the thyroid to decrease its synthesis
of new thyroid hormone. A beta-blocker will help control his symptoms of hyperthyroidism. A
good choice would be a beta-blocker 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 should
be anticoagulated because he may revert to a normal rhythm once he becomes euthyroid.
This can be done with a heparin product before surgery because it can be stopped
preoperatively and with coumadin after surgery. His ultimate treatment will be 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 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 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 few days.
 General Summary In
Evaluating TFT
 TSH would be the first test to do assess thyroid disorder. If suspect a
thyroid disorder or hypothalamic-pituitary disorder get FT4 ( and in some
case also T3 or FT3)
 The TSH is very sensitive to the change of FT4.
 If both TSH and FT4 are changed in the same direction – the disorder is
secondary (central) causes
 If the TSH and FT4 are changed in the opposite direction – the disorder is
primary (thyroid) causes.
 Always check the amount of change in TSH reflects the appropriate
change in the FT4.
 Pay attention to other clues on physical exam and blood works that may
suggest secondary thyroid diseases or other conditions coexist (If FT4 is
very low but TSH is only mildly elevated think central hypothyroidism)
 Other ancillary blood works are expensive and rarely use, but in certain
cases TSI, Anti TPO, thyroglobulin may be helpful in making diagnosis
and provide prognosis.
 Total T4, TBG, T3resin uptake, Free Thyroid Index (FTI) are available but
not commonly used anymore
 Radioiodine Uptake
 Useful to differentiate the type of
thyrotoxicosis
 A set dose of I123 is given and 24 hr later a
radiation detector is placed over the thyroid to
determine the percentage of the dose that was
taken up by the thyroid
 RAIU is high in : Graves disease, TSH-secreting
pituitary tumor, hot nodules, hCG secreting
tumor, iodine deficiency
 RAIU is low in : thyroiditis, thyroiditis factitia,
iodine excess (contrast dye, amiodarone-
induced thyrotoxicosis type 2)
 Thyroid Scans
 Scintiscan, or radionuclide scan
 A radioidine or Tc99m is given, and a
scintillation scanner produces a rough
picture indicating how these isotopes
localize in the thyroid.
 Useful in nodular disease to determine
whether a nodule is hot or cold.
 A “hot” functioning nodule is nearly
always benign.
 A “cold” nodule has 5% chance of being
malignant and should be further evaluate
 Thyroid Ultrasound
 determine the size and the content of nodules
(cystic or solid, or mixed.)
 Select site for biopsy FNA
 Provide assistance in therapeutic procedure
(cyst aspiration, ETOH injection, laser therapy)
and facilitate the monitoring of the effects of
treatment.
 Worrisome characteristics: hypoechogenicity,
microcalcification, irregular margins, increased
nodular blood flow and evidence of margin or
regional lymphadenopathy
 Fine Needle Aspiration
 First test of choice in euthyroid patient with
a (palpable) nodule.
 False negative rate is 1-11%, and false
positive rate of 1-8%
 About 69-74% of specimens are benign, 22-
27% are indeterminate or suspicious, and
about 4% are positive for cancer
 Cannot differentitiate microfollicular from
follicular carcinoma.
 Sampling errors can be minimize by using
ultrasound-guided biopsy.