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Mild Hyperthyroidism, Questionable Cause

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Question

F 40+yrs, history of hypothyroidism on variable combination of T4 and T3 replacement (prescribed by GP, not seen by us or any endocrine specialist) for >10 years. The only retrievable TFT around that time (5/1999) : fT4 10.1 pmol/L (10-24), TSH 5.62 mU/L(0.4-4). Early 2005, given herbal treatment for tiredness for 1-2mths then stopped. Mid 2005, started to have mild hyperthyroid symptoms and T3 related hyperthyroid state on TFT: In the past 15months, TFT picture remain very stable with fT4 16-19, fT3 6.2-11 (2.5-5.5pmol/L), TSH <0.08. Thyroid just bearly palpable, no goitre. Thyroglobulin <1ug/L (<55)(DPC Immulite 2000) with antithyroglobulin antibody 259 IU/ml (EIA) (<100), antithyroid peroxidase 300 IU/ml (EIA) (<100). Thyroid 99m Tc pertechnetate scan – Asymmetry R > L, right large hot nodule with left lobe diffusely warm, i.e. no suppressionm. At 20mins – increased uptake at 3.4%. Deny ongoing use of T4 or T3 replacement since mid 2005. Despite tremor and tachycardia found and explanation of cardiac/osteoporosis risk – patient feels good in hyperthyroid state and refuse any kinds of treatment offer. Questions: 1. The differential at the top of the list is toxic adenoma with predominant T3 secretion. However, is it unusual to see toxic adenoma arising from a previously hypothyroid state for some many years ( from whatever reason like Hashimoto thyroiditis to start off with ) ? 2. Is it true that I should expect thyroglobulin to be raised (even if it is mild ) in most patients with toxic adenoma ? 3. Can the undetectable level of thyroglobulin as measured on the Immulite platform be explainable by this relatively low titre of raised antithyroglobulin antibody ?4. Another differential raised was factitious hyperthyroidism – esp with the undetectable thyroglobulin and patient’s apparent comfort in the hyperthyroid state and refusal of any kind of treatment but very willling for regular biochemical monitoring. However, the thyroid scintiscan finding seems to be not typical of factitious hyperthyroidism ( expect reduced uptake ). Thus, does this finding from thyroid scintiscan totally refute this diagnosis ?

Dr. Weldon Chiu FRACP, FRCPA

Response

I think a more likely diagnosis is autoimmune thyroid disease, which began with hypothyroidism, but now manifests itself as very mild hyperthyroidism. The low TG is unreliable in the presence of the antibodies. A toxic nodule should be obvious on physical or US, since it typically would need to be 3 cm in size to produce hyperthyroidism. Having both AITD and a toxic nodule is possible, but a unitary diagnosis is usually better than two. The elevated T3 and normal T4 fits with the output of an auto-immune-damaged gland, and could not easily be duplicated by a pill unless the patient took a special mixture of T4 and T3. (This last statement is conditioned on what would happen to T4 and T3 when taking such pills in the presence of a normal gland, and I can not be sure what would occur in the presence of a nodule or thyroiditis.) The scan and uptake also argue against a toxic nodule, and fit with AITD (Hashitoxicosis?)

L De Groot, MD