A 55-year-old man presented for a regular follow-up to your office 6 months ago ago at which time a palpable nodule of 1.7 cm was noted in the left thyroid lobe. A TSH level was normal. Subsequently, he underwent an FNAC which revealed Papillary Carcinoma of thyroid. Staging work-up revealed no evidence of distant metastases and a neck CT scan did not reveal any lymphadenopathy. He underwent total thyroidectomy combined with RAIU therapy and was started on levothyroxine. The patient arrives for follow up visit at 6 months. His TSH level at 6 month is less than 0.1. He denies any symptoms such as palpitations or chest pain or heat intolerance. His weight is unchanged. Most appropriate next step in management?
a) Reduce levothyroxine dose
b) Discontinue levothyroxine
c) Obtain serum thyroglobulin level
d) Obtain anti-thyroglobulin antibodies and serum thyroglobulin levels.
e) Radio-iodine scan
Archer USMLE Step 3 Blog 
A
a
A. TSH suggesting excessive T3 – T4 level in blood
C Both TSH & thyroglobulin are follow up markers, TSH matters less as it is a stimulant to thyroid so having less TSH is fine till pt c/o palpitation or other hyperthyroid s/s. Thyroglobulin measures the activity of thyroid.
C
and keep TSH undetectable
A, There is no point to measure thyroglobulin since the thyroid already removed. Reduce levothyroxine
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I think its best to reduce the levo thyroxine dose.
Dr Red, what is the answer pls.
a
Answer E
Low TSH levels in the bloodstream reduce tumoral growth rates and reduce recurrence rates of well-differentiated thyroid carcinomas. The extent to which TSH should be suppressed is controversial. Most authors recommend reducing TSH levels to 0.1 mU/L. This level provides adequate thyroid suppression while avoiding deleterious cardiac and bone effects of profound thyroid suppression.
Patients are regularly monitored every 6-12 months with serial radioiodine scanning and serum thyroglobulin measurements after surgery and radioiodine therapy. Thyroglobulin is a useful marker of tumor recurrence because well-differentiated thyroid cancers synthesize thyroglobulin. However, it is useful only after total thyroid ablation. Serum thyroglobulin is measured at the time of follow-up thyroid scanning, during the withdrawal of thyroid hormone or the administration of recombinant TSH. Serum antithyroglobulin antibodies are measured in addition to thyroglobulin because their presence invalidates the assay. Thyroglobulin antibody levels should be obtained with each thyroglobulin measurement. Rising thyroglobulin level after thyroid ablation suggests recurrence.
Because we do not know the status of thyroglobulin and anti thyroglobulin antibodies before treatment, the best answer is thyroide scan.
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I guess it makes sence to investigate any remenance of further thyroid tissue still existing after thyroidectomy and ablation with RAIU.
a) Reduce levothyroxine dose
A
A
1.this drug induse
e, fu because you dont have tyroglobulina level and ab
this pt has total throidectomy done and hence on levothyroxine that is y tsh is decreased and t4 increased now we lower the levothyroxine dose to normalise the level
so,ans is a
small amount of tg can produce the thyroid hormone —–ans is D
the answer is D. Check out the most recent NCCN guidelines. Both Tg+anti-Tg Ab and TSH should be checked q6 and 12m in addition to PExam and neck US. TSH level should be kept below 0.1 (in come cases can keep between 0.1-0.5).
Serum thyroglobulin (Option C) is produced by functional thyroid tissue. This tissue includes normal tissue, or tissue affected by Grave’s disease, thyroiditis, or differentiated thyroid cancer like papillary thyroid cancer. If levels are higher than 100ng/ml, it usually suggests cancer. After removing or destroying functional thyroid tissue, the levels are expected to drop. So during the follow up of this patient, if thyroglobin level begins to rise or it is found to exceed 100ng/ml, it is a cause for concern and raises the probability of recurrence of cancer.
It’s our approach that I believe the question is testing.
Here is my protocol,
Most appropriate next step in mgmt? Option C, thyroglobulin level.
Then, the following sequence;
Serial quantitative thyroglobulin assay – positive? Yes,
Radiiodine Whole Body Scan – to localize tumor cells – negative? Yes,
PET/CT scans – to localize tumor cells.
Why am I not measuring the anti thyroglobulin antibodies?
1. If these are present, thyroglobulin will still be detected in serial thyroglobulin testing.
2. Anti thyroid antibodies decrease over time with successful treatment unless the thyroid is inflamed or injured. It still says nothing about actual thyroglobulin level and after serial thyroglobulin assay will still be required.
3. Serial thyroglobulin is more informative than antithyroglobulin antibody testing.
Re: most appropriate next step is Option C, measurement of thyroglobin
I’m sorry if I sounded unclear towards the end of my previous (above) post.
It’s true National Comprehensive Community Network (NCCN) 2007 guideline recommended testing for antithyroglobulin antibodies along with TSH & Thyroglobulin level at 6 months and 12 months and then annually. But I have serious reservations about this test.
1. It is highly non-specific for cancer.
2. It is highly inconclusive.
The argument of protagonists is based on 2 facts which I shall refute now;
1. ‘If antithyroglobulin antibodies are present then thyroglobulin readings are unreliable.’ Serial testing of thyroglobulin levels makes this test more sensitive and reliable. There is also a set value (100ng/ml) that makes cancer much more likely.
Normal people, plus those who have injury or inflammation of the thyroid may have elevated antithyroglobulin antibodies. Rising antibody title is not conclusive of cancer and it may suggest autoimmune disease.
Accepting ‘thyroglobin level as ‘unreliable’ does not provide any alternative solution for monitoring thyroid cancer,
On the contrary, autonomous thyroglobulin production from cancer cells is reliably bound to rise at every reading – typically to much greater than 100ng/ml mark. The thyroglobulin level will fall if antithyroglobulin antibody titres rise and thyroid tissue is destroyed. So what’s the sense in checking antithyroglobulin when thyroglobulin level will eventually fall in serial measurements?
2. ‘Persistent anti thyroglobulin antibodies may suggest possible residual tissue and increased risk of recurrence of thyroid cancer.’
Again, there is no proof that it may be thyroid cancer and not an autoimmune disease process. Serial anti globulin antibodies testing is not helpful in making this distinction. Both thyroid cancer and autoimmune disease process can cause elevated antithyroglobulin titres. But on the contrary, eventually, (when the thyroid tissue is significant and wishfully destroyed by autoimmune process, falling serial thyroglobulin level may suggest an autoimmune process), and rising levels of thyroglobulin may suggest thyroid cancer. Steady low probability readings may also suggest inconsequential residual thyroid tissue that may warrant continued surveillance.
Thyroglobulin measurements alone is sufficient to distinguish cancer from autoimmune process. If levels are indeterminate, another thyroglobulin test can be repeated in 6 months.
C. 6 months after TT + RAIU. Check levels of Tg.
I am getting confused by two concepts related to this question which would lead to answers A & C.
1) thyroglobulin f/u 6mo after cancer resection.
f/u Thyroglobulin level must be carefully monitored q6 months in patients with history of thyroid cancer to detect recurrence or persistent or metastatic disease.
2) overtreatment w/ thyroxine
treatment started → monitor TSH q6 to 8 wks (do not Δ dose if asymptomatic – let reach steady state) → adjust LT4 dose → TSH desired range → recheck TSH level 3 to 6 months later
→ if normal → recheck annually
→ If ↑ TSH → hypo treating → ↑ LT4 dose by 12.5 to 25 ng/d and recheck in 6 to 8 weeks.
→ If ↓ TSH → ↓ LT4 dose by 12.5 to 25 → re check in 6 to 8 weeks
Dr. Red, which concept is this question testing? Thank you for the great question!
i guess i would go w/ thyroglobulin as the pt “denies any symptoms such as palpitations or chest pain or heat intolerance. His weight is unchanged”
doctafizzlemynizzle, greetings,
Here is the explanation:
You wondered, which one it is? Is this result of over-treatment with thyroxine or overactive functional thyroid cancer?
Both conditions will suppress TSH so which is responsible here.
Simple, extraneous thyroxine does not cause elevation of thyroglobulin. Thyroglobulin is produced only by endogenous functional thyroid cells. So when we do thyroglobulin test, if it is an endogenous production from an over-active functional thyroid cell, thyroglobulin will be elevated.
So, what’s the interpretation of elevated thyroglobulin?
Exogenous T4: No
Recurrence of functional thyroid cancer (after surgery): Yes
Guys, The National Comprehensive Cancer Network (NCCN) is an alliance of 25 US cancer centers mostly designated by the US National Cancer Institute. We are talking huge expert minds. Compared to their word, my opinion is like a ridiculously small flying saucer lost in the Milky Way – meaning completely hear-say.
Their summary for surveillance of papillary thyroid cancer 2013 is the working Bible for all exams.
So they say, do physical exam, TSH, Serum Thyroglobin + Antithyroid antibody at 6 mths and 12 mths, then annually if disease free. And if thyroglobulin is negative with significant antibodies, do stimulated TSH thyroglobulin measurement, if this is positive, do radioactive iodine imaging, if this is positive, screening is highly suggestive of recurrence and re-treatment is justified.
So the Answer is D.
But in practice my next step will be C, only serum thyroglobulin.
In exam, my next step will be D.
In practice, I will do only thyroglobulin, if it is high, it is good enough for me to move to the next step, which is, stimulated TSH thyroglobulin assay or radioiodine imaging for further screening. If it is low or normal, then I will do anti-thyroglobulin antibody just to be on the safe side.
In exam, I will do D – i.e follow the guideline, do serum thyroglobulin with anti-thyroglobulin antibody.
You guys must hate me. What I am saying is that when guidelines clash with opinions, follow guidelines in exams.
Please memorize this chart – it’s privy info hacked (not for free stuff)
http://www.pennstatehershey.org/documents/101847/10424174/NCCN+Thyoid+Cancer+V2.2103+.pdf/fa771599-a350-4d52-92d8-6d4772529398
Review the whole list of guidelines for exams if you have the time:
http://www.pennstatehershey.org/documents/101847/10424174/NCCN+Thyoid+Cancer+V2.2103+.pdf/fa771599-a350-4d52-92d8-6d4772529398
other references:
http://jnm.snmjournals.org/content/45/6/988.full
http://emedicine.medscape.com/article/2007769-overview
http://annonc.oxfordjournals.org/content/21/suppl_5/v214.long
http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/84382
SUMMARY:
FROM NCCN 2013 GUIDELINE:
At 6 mth, do physical, do TSH, TG + TG Antibodies (so total 4 things -PTTA),
Step b, if any is positive, then do stimulated TSH TG assay
if periodic neck ultrasound is positive anytime, do step b
Step c, if Step b is positive, then do RAI imaging
Step d, if Step c is positive, then follow treatment protocol, surveillance is highly suggestive of recurrent disease.
Thyroglobulin (TgAb) is a glycoprotein located within the colloid on which thyroid hormones are synthesized and stored. Serum Tg and TgAb measurements are used to monitor patients with thyroid cancer; serum Tg is a highly sensitive and specific marker of residual thyroid tissue. After total thyroidectomy and radioactive iodine ablation, the persistence of a detectable serum Tg is a possible indicator of residual or recurrent disease. Thyroglobulin antibodies are present in up to 30% of patients. Their presence in the serum is only significant in patients with thyroid cancer, as they can falsely lower the serum Tg. Therefore, TgAb titers should always be assessed simultaneously with the Tg; if antibodies are present, the Tg level may not be reliable(will be falsely low)
Source: MKSAP17