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.
A 60-year-old man originally from China with no prior history of thyroid or autoimmune disease received a standard course of 48-week pegylated IFN-α and ribavirin therapy for chronic HCV (genotype 1b) with achievement of sustained virological response. He had compensated chronic liver disease with cirrhosis (Child-Pugh A) without other complications and no other reported medical problems. He denied previous use of amiodarone, lithium, medications, or supplements containing iodine or exposure to contrast. He was a nonsmoker and did not drink alcohol. Six months after commencing treatment, he reported fatigue, weight gain of 3 kg, and slowed cognition at a routine clinical visit. He denied changes to his skin, hair, or bowel habits. On examination, his vital signs were normal. His weight was 78 kg with a body mass index (BMI) of 26.8 kg/m2. There was no goitre and there were no signs of oedema, dermopathy, ophthalmopathy, or lymphadenopathy. Cardiac, respiratory, and gastrointestinal examinations were normal and in particular no stigmata of chronic liver disease was present. A peripheral neurological examination including reflexes was normal.\nSerum biochemistry including electrolytes, renal function, and full blood count were within normal limits, with no biochemical or serological evidence of decompensated liver disease. Alpha-fetoprotein (AFP) was normal at 3.5 kIU/L [normal, 0.0–6.0]. Pretreatment HCV quantitative RNA was >3,000,000 IU/mL and was undetectable 6 months after commencing treatment. A recent abdominal ultrasound revealed a radiologically normal liver with no signs of portal hypertension or hepatic lesions. His serum thyroid stimulating hormone (TSH) prior to therapy was 1.65 mIU/L [normal, 0.27–4.2] with a normal free T4 (fT4) of 14.5 pmol/L [normal, 12–25]. The TSH at the time of review (i.e., 6 months later) was 58.8 mIU/L, free T4 was 11.1 pmol/L, and free T3 was 4.2 pmol/L [normal, 2.5–6.0] (). Anti-TPO (983 IU/mL, normal <35) and anti-TG (733 U/mL, normal <80) antibodies were elevated ().\nGiven his symptoms and biochemical evidence of autoimmune hypothyroidism, the patient was commenced on standard adult thyroxine replacement therapy at 100 mcg daily. His symptoms improved and there was full clinical and biochemical resolution of his hypothyroid state. Fourteen months later, he returned for follow-up reporting symptoms of hyperthyroidism with weight loss, tremor, and palpitations. He had lost 5 kg of weight. At the time of review, serum TSH was suppressed at <0.02 mIU/L with elevated fT4 of 54.3 pmol/L, fT3 of 20.2 pmol/L, and an elevated TRAb of 4.0 U/L (normal <1.0), with anti-TPO (1,163 IU/mL) and anti-TG (114 U/mL) antibodies. Technetium scan revealed bilateral diffuse increased tracer uptake (5.9%, normal 0.5–3.5%), consistent with Graves' Disease ().\nThe patient's thyroxine was ceased and he was placed on antithyroid treatment with carbimazole 5 mg TDS. He self-ceased therapy 6 months later, with serendipitous clinical and biochemical remission. His serum TSH was 3.84 mIU/L, fT4 17 pmol/L, and fT3 4.5 pmol/L, but with persistently elevated anti-TPO at 383 IU/mL. Anti-TG 23 U/mL and TRAb < 1 U/L were normal. At the time of writing, the patient remained clinically and biochemically euthyroid.