A 27-year old female presented with clinical and biochemical thyrotoxicosis (TSH - 0.01 μIU/mL (ref. range: 0.27–4.2 μIU/mL); free thyroxine (FT4) - 1.58 ng/dL (ref. range 0.98–1.63 ng/dL); free triiodothyronine (FT3) - 4.56 pg/mL (ref. range 2.6–4.4 pg/mL). Clinical examination revealed tachycardia about 100 beats/min and no obvious goitre. Autoimmune profile was suggestive of Graves’ disease [anti-TSH-receptor antibodies (aTSHR) - 16.69 IU/L (ref. 0–1.75), anti-thyroid peroxidase antibodies (aTPO) - 1780 IU/mL (ref.: 0–34 IU/mL)]. The patient had a history of Hodgkin’s lymphoma, diagnosed and treated with chemo- and radiotherapy (including the neck) at the age of 18. At the age of 20 she developed severe hypothyroidism (TSH > 100 μIU/ml), though with high titres of both aTPO (150 IU/mL) and aTSHR (37.56 IU/mL) antibodies. Thyroid function tests normalised after treatment with L-thyroxine (100 μg o.d.). At the age of 26 she became “anxious” and experienced “heart palpitations”. She was found to have suppressed TSH, that remained suppressed even when the dose of L-thyroxine was reduced and then discontinued. After further four months she was found to have raised FT3 (see above). Thyroid scintigraphy revealed a normal and homogenous iodine uptake (41 %). The patient responded very well to treatment with low dose thiamazole (10 mg od, later 5 mg o.d.) that was discontinued after about 12 months. About a year later (while 16-week pregnant) she was off medication and had mild subclinical thyrotoxicosis (TSH - 0.035 μIU/mL, FT4 - 1.04 ng/dL, FT3 - 3.09 pg/mL) and raised aTSHR antibodies, albeit at lower titre than before (7.87 IU/L).\nAccording to the literature data thyroid dysfunction is one of the most common abnormalities seen after radiotherapy for Hodgkin's disease that includes the neck []. Primary hypothyroidism, the most common radiation-induced thyroid dysfunction, appears in 20–30 % patients who had therapeutic radiotherapy administered to the neck region, and this usually occurs within the first 5 years after therapy (peak 2–3 years after treatment) []. Irradiation of the thyroid may also increase the risk of Graves' disease (relative risk 7.2–20.4), or Graves' ophthalmopathy, thyroiditis, benign adenomas and thyroid cancer. The aetiology of radiation-induced thyroid dysfunction includes vascular damage, parenchymal cell damage and auto-immune reactions []. There are reports, that after neck irradiation Graves’ disease may develop in patients previously receiving thyroxine, and indeed 33 % of the patients with Graves’ hyperthyroidism had received thyroxine before its onset []. Therefore thyroid hormone-replacement therapy in patients with hypothyroidism after irradiation of the neck does not eliminate risk of other thyroid abnormalities at a later date. According to some authors, thyroiditis observed in Hodgkin’s disease may be the result of immune regulation disorders in Hodgkin’s disease []. Furthermore, a possibility of a change from hypo- to hyperthyroidism typical for Graves’ disease is has been known for some time [, ], and was also confirmed in more recent publications [, ].\nTakeda et al. [] demonstrated, by measuring changes in cyclic AMP, that thyroid stimulating and thyroid blocking antibodies may coexist within the same patient and their relative activities may change over the course of the disease. Our case illustrates that after neck irradiation, severe hypothyroidism can be followed by thyrotoxicosis. It should be noted that in our patient, both during hypo and hyperthyroidism, aTSHR were elevated. There are two types of aTSHR: thyroid stimulating antibodies (TSAb) and TSH-stimulation blocking antibodies (TBAb). TBAb block TSH-stimulation of the thyroid and cause hypothyroidism. On the other hand, TSAb stimulate the thyroid and result in Graves’ hyperthyroidism. In our opinion, in this case there was a gradual switch from TBAb into TSAb.\nIn some patients, TSAb and hyperthyroidism develop unexpectedly after hypothyroidism that is caused by TBAb []. Fan et al. [] described a case with documented cycles of hypothyroidism alternating with hyperthyroidism. Also, as mentioned above, some hypothyroid patients after irradiation of the neck, while treated for the Hodgkin's disease, developed hyperthyroidism []. A number of mechanisms may be involved in switching from TBAb to TSAb. Significantly, thyroxine treatment in some patients is associated with increase TSAb that - in extreme cases - might lead to development of hyperthyroidism in hypothyroid patients [], though whether this was a case in our patient is speculative as neck irradiation per se is considered to be capable of influencing changes in patients’ immune status.
46 years old female, mother of 3 children diagnosed as having primary hypothyroidism on the basis of clinical symptoms of easy fatigability, weight gain and increase sleep and a serum TSH level of >75 uIU/ml, FT4: 0.25 ng/dl and strongly positive thyroid antibodies in December 2002. Thyroxine 50 mcg/day was started which she continued. After 2 years she presented to us with complain of weight loss. Her serum TSH level was 0.035 uIU/ml and a T4: 7.84 ng/dl so thyroxine was stopped. She came for follow up after 5 months with serum TSH: 0.010 uIU/ml off thyroxine. After another 6 months her serum TSH remained suppressed with a value of 0.018 uIU/ml and an FT4 of 1.18 ng/dl and she remained off thyroxine. After further 2 years her TSH was 0.837 uIU/ml, FT4 0.922 ng/dl and FT3 3.06. And after 1 year she presented with a TSH level of <0.005 uIU/ml, raised FT4 and positive thyroid microsomal antibodies (1: 1600). Techniteum 99 thyroid scan showed diffusely increased homogenous tracer uptake. Neomercazole was started at the dose of 5 mg/day which was gradually increased to 10 mg/day. She followed up after 4 months with TSH: 0.01 uIU/ml, T4: 5.84 ng/dl, T3: 1.99 ng/dl. Neomercazole was continued. Then she came for follow up after 1 year, at this time she was clinically euthyroid but biochemically hypothyroid with serum TSH: 14.89 uIU/ml, FT4:0.65 ng/dl. Neomercazole was stopped and advised to repeat TFT’s after 8 weeks. She came after 4 months with TSH: 3.98 uIU/ml, so no treatment was advised. After a period of 1 year she again came with complains of weight loss and palpitations. At this time her TSH: < 0.005 uIU/ml, FT4: 2.25 ng/dl. Neomercazole was restarted and Radioactive iodine 131 ablation planned.