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.
Our patient is a twenty-four-year-old female with a sixteen-year history of HT-related hypothyroidism on oral levothyroxine 100 mcg once daily. She complained of occasional palpitations, nervousness, weight loss, and irregular menses. Thyrotoxicosis was confirmed with a thyroid function test, and levothyroxine dose was reduced. However, the patient continued to exhibit thyrotoxic symptoms even after completely stopping levothyroxine. On examination, the patient was calm but tachycardic and afebrile, and her blood pressure was 116/90 mmHg, weight was 58 kg, and BMI was 21.8. She was noted to have peripheral tremors. Her thyroid exam revealed the presence of diffuse nontender goiter, with no palpable nodules. Eye examination was only remarkable for mild exophthalmos, and there was no evidence of dermopathy.\nThyroid function revealed depressed TSH <0.01 mIU/L (0.3–4.2) and high T4 26.4 pmol/L (11.6–21.9) (). Based on the persistence of symptoms despite stopping thyroid hormone supplementations and the presence of ophthalmopathy elements, the rare shift to GD was suspected. Autoimmune workup revealed a strong positive Anti-TSH Receptor (Anti-TSHR) titer, in addition to persistent positivity of previously positive thyroid peroxidase antibody (TPO Ab) and an increasing titer of Antithyroglobulin Ab (). Thyroid ultrasound revealed slight enlargement of the right lobe and increased vascularity in both lobes. Radioactive iodine uptake scan (RAIU) showed diffuse radiotracer uptake more prominent in the right thyroid lobe (). Those findings kept with the shift to GD.\nThe patient received suppressive therapy with oral carbimazole 20 mg once daily and propranolol. A subsequent follow-up three months later showed normalization of thyroid function and improvement in clinical status.