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 44-year-old woman with 5-year history of Basedow’s disease had a total thyroidectomy. She had no past and family history and had no drug allergy. She was diagnosed as Basedow’s disease at 39 years old and after then she started taking 30 mg of thiamazole (MMI). In physical examination, she had no remarkable symptom such as palpitation, general fatigue and insomnia and did not have a goiter. Her height and body weight were 158.0 cm and 63.6 kg. Her vital signs were: heart rate 112 beats/min, blood pressure 132/86 mmHg. Laboratory data were as follows: white blood cell count, 4580 /μL (neutrophil 57.7%); red blood cell count, 476 × 104 /μL; hemoglobin, 12.7 g/dL; platelet, 26.5 × 104 /μL; Na, 142 mmol/L; K, 5.2 mmol/L. Renal and liver function was within normal range (creatinine (CRE), 0.38 mg/dL; blood urea nitrogen (BUN), asparate aminotransferase (AST), 25 U/L; alanine transaminase (ALT), 26 U/L; alkaline phosphatase (ALP), 231 U/L; γ-glutamyltranspeptidase (γ-GTP), 17 U/L; lactate dehydrogenase (LDH), 174 U/L). Thyroid-associated data were as follows: thyroid-stimulating hormone (TSH), < 0.010 μIU/mL; free triiodothyronine (FT3), 19.05 pg/mL; free thyroxine (FT4) 4.88 ng/dL; TRAb, 10.6 IU/L (electro chemiluminescence immunoassay (ECLIA), SRL Inc., Tokyo); TPOAb, 216.9 IU/mL (ECLIA, SRL Inc., Tokyo); TgAb antibody, 428.9 IU/mL (ECLIA, SRL Inc., Tokyo). Ultrasound examination revealed that the thyroid gland was hypervascular although it was not enlarged (Fig. ). Based on such findings, we finally diagnosed her as Basedow’s disease. Two weeks after starting MMI therapy, she had liver dysfunction (AST, 420 U/L; ALT, 368 U/L; ALP, 565 U/L; γ-GTP, 178 U/L; LDH, 337 U/L), and we changed the treatment of MMI to 300 mg of propylthiouracil (PTU) although her thyroid hormone levels were decreased (TSH, < 0.010 μIU/mL; FT3, 7.2 4 pg/mL; F T4 1.97 ng/dL). After then, her liver function was improved, and we tapered PTU. About 2 years later, her thyroid hormone levels were within normal range with 50 mg of PTU every other day, and her TRAb became negative. After then, we stopped PTU therapy.\nAbout 1.5 years later, she had low grade fever and palpitation and visited our office again. Her body weight was 70.9 kg. Her vital signs were: heart rate 116 beats/min, blood pressure 140/98 mmHg. Laboratory data were as follows: white blood cell count, 3710 /μL (neutrophil 58.3%); red blood cell count, 535 × 104 /μL; hemoglobin, 12.2 g/dL; platelet, 22.4 × 104 /μL; Na, 142 mmol/L; K, 4.2 mmol/L. Renal and liver function was within normal range (CRE, 0.52 mg/dL; BUN 9 mg/dL; AST, 25 U/L; ALT, 17 U/L; ALP, 218 U/L; γ-GTP, 19 U/L; LDH, 206 U/L). Thyroid-associated data were as follows: TSH, < 0.010 μIU/mL; FT3, 5.22 pg/mL; FT4, 1.85 ng/dL; TRAb, 4.6 IU/L; TPOAb, 147.4 IU/mL; TgAb, 591.2 IU/mL. Ultrasound examination revealed that the thyroid gland was not hypervascular compared to that at the onset of Basedow’s disease (Fig. ). Based on such findings, we finally diagnosed her as the relapse of Basedow’s disease. We started again 300 mg of PTU and tapered PTU dose. About 4 months later, her thyroid hormone levels became within normal range by taking 50 mg of PTU every other day. During the PTU therapy, her WBC levels were slightly lower and CRP levels were slightly higher, although she had no symptom in the whole body including in skin. We checked various autoimmune antibodies. Anti-double stranded DNA IgG antibody, anti-SS-A/Ro antibody and anti-SS-B/La antibody were all negative. However, anti-nuclear antibody (ANA), myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) and proteinase3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) were all positive (ANA, 37.8 (+); MPO-ANCA, 35.0 U/mL; PR3-ANCA, 36.9 U/mL).\nWe performed a total thyroidectomy. Table shows laboratory data before a total thyroidectomy in this subject taking 50 mg of PTU every other day. In general, the thyroid gland in subjects with Basedow’s disease shows diffuse goiter due to chronic stimulation. However, her thyroid was flat and atrophic although diffuse hyperplasia of the thyroid gland was observed in histopathological macroscopic findings (Fig. ). Furthermore, hyperplasia of the thyroid gland was shown in part and hyperplastic thyroid follicles with papillary infoldings was observed in histopathological microscopic examination. Tall follicular cells with papillae usually lacked fibrovascular cores and peripheral scalloping was present (Fig. ). On the other hand, a part of the thyroid area showed a dense lymphoplasmacytic infiltrate, accompanied by follicles containing germinal centers. In addition, a destroyed pattern of lymphoid follicle was observed (Fig. ).\nOne year later, thyroid-associated autoimmune antibodies were all decreased (TRAb, 2.2 IU/L; TSAb, 130% (enzyme immunoassay, SRL Inc., Tokyo); TPOAb, 98. 3 IU/mL; TgAb, 151.0 IU/mL), and 2 years later thyroid-associated autoimmune antibodies were further improved (TRAb, 1.1 IU/L; TSAb, 90%; TPOAb, 24.0 IU/mL; TgAb, 12.8 IU/mL). White blood cell count became within normal range (about 5000–7000 /μL (neutrophil 58–68%) and CRP level became almost normal (0.15–0.20 mg/dL).