A 66-year-old woman with a history of Hashimoto's thyroiditis and thyroid nodules initially presented for fine needle biopsy (FNB). Patient had no symptoms of hypothyroidism or hyperthyroidism. Her initial TSH was 5.9 IU/L (ref 0.27–4.20) with FT4 1.2 ng/dL (ref 0.89–1.76) (Fig. ) and thyroperoxidase (TPO Ab) and thyroglobulin (TG Ab) antibodies were 18,290 IU/mL (ref 0–34) and >2,250.0 IU/mL (ref 0.0–0.9) (Fig. ), respectively. Additionally serum thyroid stimulating immunoglobulin (TSI) level was 88% (ref 0–139) and thyrotropin receptor blocking antibody (TBRAb) (Fig. ) was also in the normal range (<10%, ref <10). Physical examination revealed normal vital signs and patient had no evidence of thyroid orbitopathy. Examination of the thyroid gland confirmed a 2-cm right lower lobe thyroid nodule and a 6-cm left thyroid nodule almost replacing the left lobe. Thyroid ultrasound showed multiple thyroid nodules bilaterally with a dominant hypervascular left thyroid mass 5.9 × 2.7 × 4.4 cm (Fig. ) and a right lower lobe nodule 2.4 × 2.4 × 2.2 cm. Additionally an ultrasound of the neck confirmed bilateral abnormal cervical lymphadenopathy. FNB of the thyroid nodules revealed a population of large lymphocytes with irregular nuclei (Fig. ). Fluorescence in situ hybridization (FISH) revealed a translocation t(14;18), fusing the immunoglobulin heavy chain gene at chromosome 14q32 with BCL2 gene at chromosome 18q21.3. Positron emission tomography computerized axial scan (PET-CT) of the chest and abdomen revealed a large retroperitoneal and mesenteric soft tissue mass, measuring 16 × 14 cm in greatest trans-axial dimension. The retroperitoneal mass encased the aorta and inferior vena cava as well as mesenteric vessels and both renal arteries. The mass also displaced the kidneys peripherally (Fig. ). She was diagnosed with stage-IVE diffuse large B-cell lymphoma (DLBCL) and underwent six cycles of R-CHOP chemotherapy. Patient also received subdiaphragmatic external radiation directed to the retroperitoneal mass. Following chemotherapy, and radiation therapy, PET-CT scan showed resolution of retroperitoneal mass, resolution of fluorodeoxy-glucose (FDG) avid thyroid nodule (Fig. ) as well as no evidence of thyroid nodules on repeat ultrasound. Following chemotherapy her thyroid functions normalized (serum TSH 3.9 IU/L and free T4 1.4 ng/dL). A moderate decrease in thyroid peroxidase Ab (range 8,432 to 11,288 IU/mL) and thyroglobulin Ab (range 1,268 to 1,600 IU/mL) were noted. Additionally TSI 88% and TBRAb <10% (ref <10) (Fig. ) continue to remain in the normal range. She remained euthyroid without any symptoms of hypo or hyperthyroid and her serum TSH and free T4 remained normal for the next 2 years (Fig. ). Additionally she had no evidence of lymphoma recurrence.\nTwo years later, patient reported significant unintentional weight loss and persistent fatigue over the past couple months. Physical examination revealed a heart rate of 120/min, fine tremors of outstretched fingers, and no thyroid orbitopathy. Thyroid was 40 g in size with no palpable nodules and deep tendon reflexes were brisk. Repeat laboratory testing revealed: TSH 0.005 IU/L, FT4 6.73 ng/dL and TSI 535% (Fig. ). Serum TBRAb was also mildly elevated (28%). TPOAb and TGAb levels were 7,976 and 1,088 IU/mL respectively (Fig. ). Additionally, an HLA DQB1*03 was positive. Further evaluation confirmed the diffuse large B-cell lymphoma (DLBCL) lymphoma was in remission. A thyroid uptake and scan showed diffuse uptake with no photopenic areas and the I131 uptake was elevated (4 h: 61.0%, reference 5–15%, at 24 h 70.3%, reference 10–30%).\nSince patient received CAT scan with iodine load she was treated with methimazole for 3 months and following this, the patient was treated with 19.4 millicuries of radioactive iodine for thyroid ablation. Following radioactive iodine treatment patient developed hypothyroidism and this was treated with levothyroxine (Fig. ). Patient remained euthyroid for the next 4 years and during these 4 years the lymphoma continues to remain in remission.
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.