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QUESTION-Could I have your input on this case. Thank you in advance.

He is a 27 year old Psychologist who presented in September 2011 with 18 months history of poor concentration, fatigue, headaches, bloating, weight gain, constipation and dull pain at the back of his eyes. He had gained 10kg over last 4 months with both heat and cold intolerance. There were no tremors. He had small smooth goitre, no nodules or bruit.

Initial investigations: TSH<0.04mIU/L (0.5-4.5), FT4 42pmol/L (10-20). Technitium 99m Pertechnetate scan showed diffuse increase uptake consistent with Grave's disease. TPO and TRAB were negative. Coeliac disease antibodies negative. I do not know if he was commenced on thionamide medications at that time.

A repeat TFT in November 2011: TSH 100 mIU/L (0.5-4.5), FT4 7.3pmol/L(10-20), FT3 2.1pmol/L(3.5-6). He was commenced on thyroxine 100mcg daily. Unfortunately he felt so unwell and was admitted to hospital. He also had bradycardia. His symptoms were slow to improve and he was also given Tertroxin (Liothyronin) for 3 weeks.

He has been maintained on variable doses of thyroxine since then. 200mcg daily, then 200/100 mcg on alternate days.

Nov 2012: TSH 0.87 mIU/L (0.5-4.5), FT4 22pmol/L (10-20), FT3 5.5pmol/L (3.5-6). According to him his thyroxine dose was reduced to 100 mcg daily and TFT in Jan 2013 were normal (TSH 1.8, FT4 20).

I saw him for the first time in June 2013 as he has noticed 7 kg of weight gain over past months despite being active. He also describes memory disturbance and decrease concentration (symptoms that he had initially). TFTs in June 2013 TSH 0.64 (0.5-4.5), FT4 25 (10-20). FT3 not available. He takes thyroxine regularly on an empty stomach half an hour before breakfast. He is not taking any other medications. I asked him if he overdosed but he denied.

1) After I saw him I requested a repeat TFTs along with FT3. If he has normal TSH and FT3 but elevated FT4 (he had such a result in Nov 2012) then do you think he has adequate thyroxine replacement even though his FT4 is elevated. Or is there a T4 to T3 conversion disorder.

2) If his FT3 is also elevated along with FT4 and normal TSH would you then reduce the dose of thyroxine.

3) If repeat TFTs are normal then considering his current symptoms would you give a trial of liothyronine along with thyroxine. If yes then may I know what is your preferred method of giving liothyronine (frequency, dose).

4) In general, If you see such a patient who has clinical and biochemical hyperthyroidism with negative antibodies but elevated or normal thyroid uptake scan then would you start them on thionamides.

Thank you for your precious time. Dr S. Irfan A

RESPONSE- To me the case sounds more like a variety of thyroiditis rather than Graves’ disease, in view of the episodic hyperthyroidism, then hypothyroidism, and negative antibodies. The Positive Pertechnetate scan is confusing, but I believe this could happen in a gland able to take up isotope, but not bind it, which is the situation with technetium. It might also be seen in the recovery phase of silent thyroiditis, but typically when TSH has rebounded.. It would have been interesting to have an ESR or CRP At the time of the first thyroid tests.
There are some issues in current T4 treatment, in that his own thyroid remains in place and presumably could be making hormone at times, and in variable amounts. You do not mention the thyroid exam, or an US, so we can only guess about possible thyroid function.

Regarding the questions---
1-It is absolutely NORMAL to have a high normal or moderately elevated T4 when on  T4 replacement, and with TSH in the normal range. With T4 levels in the normal rang e on T4 replacement,  T3 levels tend to be too low.
2-That is not a combination of tests Iwould expect, except in thyroid hormone resistance syndrome, a congenital disease not present here. The TSH is the best guide for treatment in almost every instance.
3-First I would establish a consistent dose of T4 that kept TSH about 1uU/ml. If on that program he still feels bad, there is nothing against adding 25ug T3 qd.  Checking TSH in 6 weeks, and considering holding course or even increasing if TSH remains around 1uU.
4-Not unless the situation was desperate, since I would be little surprised by the tests. Before we did antibodies, that history would have been typical of Graves. But since 90-95% of Graves patients have positive antibodies, a negative test now rings a small alarm, I would get a family history of thyroid disease,  I would examine the thyroid (enlarged? Tender? Small?), do an 125-I uptake and scan, perhaps US, ESR or CRP, TRAb, check antibodies in a different lab, and reconsider.
Good luck, LeslieJ  De Groot,  MD