Utility of outpatient fractionated radioiodine therapy for Graves disease involving a large goiter measuring more than 100 mL in volume.

Contrary to large multinodular goiters, reports on 131I radioiodine therapy (RIT) for Graves disease (GD) involving a large goiter are scarce. We retrospectively reviewed a total of 71 consecutive patients (25 males, 46 females) with GD involving a large goiter (>100 mL) who had received RIT in our clinic. Patients with a history of thyroid surgery or with large thyroid nodules and those who had dropped out less than one year after the initial RIT session were excluded. A fixed 131I activity of 481 MBq was administered in most cases. RIT was repeated at intervals of 1-47 months, typically 3-6 months. The follow-up duration after the initial RIT session was 13-233 (median: 81) months. The thyroid volume was estimated using ultrasound. The number of 131I doses were 1 dose in 13 patients, 2 doses in 29, 3 doses in 17, 4 doses in 5, 5 doses in 5, 6 doses in 1, and 8 doses in 1. Sixty-six patients had remission from overt hyperthyroidism after RIT: overt hypothyroidism in 45 patients, subclinical hypothyroidism or euthyroidism in 13, and subclinical hyperthyroidism in 8. Their thyroid volume decreased from 101-481 (median: 126) mL to 1.4-37 (8.2) mL. Three patients still had overt hyperthyroidism under treatment with methimazole after one to three doses, and two dropped out less than six months after the third or sixth dose. Even in GD patients with a large goiter (>100 mL), repeated RIT with an activity of 481 MBq could sufficiently shrink goiters and remit overt hyperthyroidism.

Long-Term Outcomes of Radioiodine Therapy for Juvenile Graves Disease with Emphasis on Subsequently Detected Thyroid Nodules: A Single Institution Experience from Japan.

OBJECTIVE: To investigate the long-term outcomes of radioiodine therapy (RIT) for juvenile Graves disease (GD) and the ultrasonographic changes of the thyroid gland. METHODS: All of 117 juvenile patients (25 males and 92 females, aged 10 to 18 [median 16] years) who had undergone RIT for GD at our clinic between 1999 and 2018 were retrospectively reviewed. Each RIT session was delivered on an outpatient basis. The maximum 131I dose per treatment was 13.0 mCi, and the total 131I dose per patient was 3.6 to 29.8 mCi (median, 13.0 mCi). 131I administration was performed once in 89 patients, twice in 26, and three times in 2 patients. Ultrasonography of the thyroid gland was regularly performed after RIT. The duration of follow-up after the initial RIT ranged from 4 to 226 (median 95) months. RESULTS: At the latest follow-up more than 12 months after RIT (n = 111), the patients' thyroid functions were overt hypothyroidism (91%), subclinical hypothyroidism (2%), normal (5%), or subclinical hyperthyroidism (2%). New thyroid nodules were detected in 9 patients, 4 to 17 years after initial RIT. Patients with newly detected thyroid nodules underwent RIT with lower doses of 131I and had larger residual thyroid volumes than those without nodules. None of the patients were diagnosed with thyroid cancer or other malignancies during the follow-up period. CONCLUSION: Over a median follow-up period of 95 months (range, 4 to 226 months), RIT was found to be effective and safe in juvenile GD. However, cumulative evidence from further studies is required to confirm the long-term safety of RIT for juvenile GD. ABBREVIATIONS: ATD = antithyroid drug; GD = Graves disease; KI = potassium iodide; LT4 = levothyroxine; MMI = methimazole; PTU = propylthiouracil; RAIU = radio-active iodine uptake; RIT = radioiodine therapy; 99mTc = technetium-99m; TSH = thyrotropin.

FREQUENCY OF FLAME SENSOR ACTIVATION IN PUBLIC PLACES AFTER ADMINISTRATION OF RADIOACTIVE IODINE TO TREAT GRAVES DISEASE: A RECENT SURVEY.

OBJECTIVE: Ultraviolet (UV)-perception-type flame sensors detect gamma rays emitted from iodine 131 ((131)I). Explaining the possibility of flame sensor activation to patients when they receive (131)I to treat Graves disease or other ablative purposes is important. We investigate the current situation of flame sensor activation after radioactive iodine (RAI) therapy. METHODS: A total of 318 patients (65 males and 253 females) with Graves disease who received RAI therapy at our clinic between November 2007 and June 2014 participated in this study. Patients were given both written and oral explanations regarding the possibility of flame sensor activation. Participants were surveyed with a questionnaire. The following question was asked: "Did the fire alarm (flame sensor) go off when you used a restroom in places like shopping centers within a few days after your isotope therapy?" To those who answered "yes," we asked where the fire alarm had gone off. RESULTS: Of the 318 patients, 19 (6.0%) answered "yes," 2 of whom were male while 17 were female. Of the 299 (94.0%) patients who answered "no," 63 were male and 236 were female. As to the place of restroom sensor activation, shopping centers were reported by 9 patients; supermarkets by 5; airports by 2; and a bookstore, the Kyushu Shinkansen (bullet train), and a hospital by 1 each. CONCLUSION: Explaining to patients the possibility of flame sensor activation after RAI therapy is important to avoid some complications, especially in security-sensitive areas. ABBREVIATIONS: (131)I = iodine 131 RAI = radioactive iodine UV = ultra-violet.

Thyroid Function of Infants Breastfed by Mothers with Graves Disease Treated with Inorganic Iodine: A Study of 100 Cases.

CONTEXT: We previously reported that inorganic iodine therapy in lactating women with Graves disease (GD) did not affect the thyroid function in 25 of 26 infants despite their exposure to excess iodine via breast milk. OBJECTIVE: To further assess thyroid function in infants nursed by mothers with GD treated with inorganic iodine. DESIGN: Case series. SETTING: Tajiri Thyroid Clinic, Japan. PARTICIPANTS: One hundred infants of lactating mothers with GD treated with potassium iodide (KI) for thyrotoxicosis. MAIN OUTCOME MEASURES: Infant blood thyrotropin (TSH) and free thyroxine (FT4) levels were measured by the filter paper method. Subclinical hypothyroidism was defined as TSH ≥10 µIU/mL and ≥5 µIU/mL in infants aged <6 and ≥6 months, respectively. RESULTS: Overall, 210 blood samples were obtained from 100 infants. The median infant age was 5 (range, 0-23) months; median maternal KI dose, 50 (4-100) mg/day; median blood TSH level, 2.7 (0.1-12.3) µIU/mL; and median blood FT4 level, 1.04 (0.58-1.94) ng/dL. Blood TSH level was normal in 88/100 infants. Twelve infants had subclinical hypothyroidism; among them, blood TSH levels normalized after maternal KI withdrawal or stopping breastfeeding in 3 infants. In 7 infants, blood TSH levels normalized during KI administration without stopping breastfeeding. Two infants could not be followed up. CONCLUSION: In Japan, inorganic iodine therapy for lactating women with GD did not affect thyroid function in most of the infants. Approximately 10% of infants had mild subclinical hypothyroidism, but blood TSH level normalized during continued or after discontinuing iodine exposure in all followed up infants.

Congenital Primary Hypothyroidism with the Homozygous Nonsense Mutation P.K1374* in the Thyroglobulin Gene and a Normal-sized Thyroid Gland on Levothyroxine Replacement.

Thyroglobulin (TG) gene mutations cause thyroid dyshormonogenesis, which is typically associated with a congenital goiter. We herein report the case of a 64-year-old man with congenital primary hypothyroidism who had a normal-sized thyroid gland on levothyroxine replacement. He had short stature (-3.1 standard deviations) and mild intellectual impairment. Thyroid autoantibodies were all negative, and the serum TG levels were undetectable. Eventually, he was found to have the novel homozygous nonsense mutation p.K1374* in the TG gene. The possibility of TG mutation should be considered for patients with congenital primary hypothyroidism and a very low serum TG level, regardless of the thyroid size.

Thyroglobulin mRNA expression in peripheral blood lymphocytes of healthy subjects and patients with thyroid disease.

BACKGROUND: Thyroglobulin (Tg) mRNA is expressed focally in thyroid tissue. In recent years, the Tg gene has been detected in other tissues, including lymphocytes, although the significance of its presence has not been elucidated yet. We measured Tg mRNA expression in the lymphocytes of healthy subjects and those with thyroid disease. METHODS: Analysis of the quantification of Tg mRNA from 20 healthy subjects and 47 subjects with thyroid disease was carried out by real-time PCR. Furthermore, in cultured lymphocytes we compared changes in Tg mRNA expression following stimulation with TSH. RESULTS: Tg mRNA was detected in the lymphocytes of all subjects. Tg mRNA in the lymphocyte sequence matched that derived from thyroid tissue, and mRNA levels were higher in subjects with thyroid disease than in healthy subjects. Following lymphocyte stimulation, Tg mRNA levels were observed to be increased 2.7-fold in Graves' disease and 1.6-fold in chronic thyroiditis compared to healthy subjects. CONCLUSIONS: Tg mRNA in the lymphocytes was quantified by real-time PCR. The levels of Tg mRNA in the TSH-stimulated lymphocytes were noticeably increased in subjects with thyroid disease. These results suggest an interesting relationship between production of Tg antigen in peripheral blood and autoimmunity in thyroid disease.

The clinical utility of Lens culinaris agglutinin-reactive thyroglobulin ratio in serum for distinguishing benign from malignant conditions of the thyroid.

BACKGROUND: Traditionally, the follow-up of differentiated thyroid carcinoma consists of periodic withdrawal from L-T4-suppressive therapy to allow performance of a highly sensitive serum Tg measurement to detect recurrences. We investigated Lens culinaris agglutinin-reactive thyroglobulin ratios in serum to evaluate in usefulness for detection of thyroid carcinoma. METHODS: The study was conducted on 93 serum sample from 23 healthy volunteers, 32 patients with benign thyroid tumor, 28 patients with thyroid carcinoma without metastasis, and 10 patients with thyroid carcinoma with lymph node metastasis. RESULTS: The Lens culinaris Agglutinin reactive thyroglobulin ratio in patients with thyroid carcinoma was significantly lower than in patients with benign thyroid tumor with serum thyroglobulin concentration >200 ng/ml. Among cases of thyroid carcinoma with lymph node metastasis, Lens culinaris Agglutinin reactive thyroglobulin ratios were significantly lower than in patient with thyroid carcinoma without metastasis and those with benign tumor regardless of serum thyroglobulin concentration. CONCLUSION: Measurement of Lens culinaris Agglutinin reactive thyroglobulin ratio in serum may be useful for distinguishing between thyroid carcinoma and benign thyroid tumor.

Discrimination of thyroglobulin from thyroid carcinoma tissue and that from benign thyroid tissues with use of competitive assay between lectin and anti-thyroglobulin antibody.

Thyroglobulin is produced only by thyroid follicular cells, and has a molecular weight of 660,000 and carbohydrate content of approximately 10%. The composition of carbohydrate chains on thyroglobulin from thyroid carcinoma has been reported to differ from that in normal thyroid tissue. In this study, heterogeneities of carbohydrate chains on thyroglobulin obtained from thyroid tissues were investigated by competitive reaction between lectin and anti-thyroglobulin monoclonal antibody. Concanavalin A, Lens culinaris agglutinin, Ricinus communis agglutinin-120 and Datura stramonium agglutinin were compared. The ratio of Lens culinaris agglutinin-reactive thyroglobulin to thyroglobulin was significantly lower in thyroid carcinoma than in normal thyroid tissue, Graves' disease and benign thyroid tumor. However, no differences between malignant and benign tissues were observed with the other lectins tested. Differences in carbohydrate chain on thyroglobulin were observed between malignant and benign thyroid tissues.

[Approach to thyroid incidentaloma and follicular adenoma].

Recently, people are interested in health and many hospitals perform medical examinations flourishingly. They can choose the thyroid ultrasound optionally, too. Accordingly, a lot of thyroid incidentaloma are found. The leaving is not possible if thyroid incidentaloma is found. At first, I describe how we handle thyroid incidentalomas. Secondly, I describe the differential diagnosis of follicular adenoma and follicular carcinoma that we should call the last fort of thyroid medical practice. The latter is in particular a very difficult issue. I examined important articles closely from an enormous article and want to describe the management of these two disorders based on evidence by the present.

Effects of Inorganic Iodine Therapy Administered to Lactating Mothers With Graves Disease on Infant Thyroid Function.

CONTEXT: The effects of maternal inorganic iodine therapy on infant thyroid function are not well known. OBJECTIVE: This study investigated the effects on infant thyroid function of maternal inorganic iodine therapy when administered to lactating mothers with Graves disease. DESIGN AND SETTING: This study was a prospective case series performed at the Tajiri Thyroid Clinic, Kumamoto, Japan. PARTICIPANTS: Subjects were 26 infants of lactating mothers with Graves disease treated with potassium iodide (KI) for postpartum thyrotoxicosis. MAIN OUTCOME MEASURES: Infant blood levels of thyroid-stimulating hormone (TSH) and free thyroxine were measured using the dried filter-paper method. Iodine concentrations in breast milk and infant urine were measured on the same day. Subclinical hypothyroidism was defined as a blood TSH level of ≥10 or ≥5 µIU/mL in <6-month-old and 6- to 12-month-old infants, respectively. RESULTS: The median age of the infants was 3 months (range, 0 to 10 months). The median KI dose was 50 mg/d (range, 10 to 100 mg/d). High median iodine concentrations were detected in breast milk (15,050 µg/L; range, 831 to 72,000 µg/L) and infant urine (15,650 µg/L; range, 157 to 250,000 µg/L). Twenty-five of 26 infants had normal thyroid function. Although one infant had subclinical hypothyroidism (blood TSH, 12.3 µIU/mL), the TSH level normalized to 2.3 µIU/mL at 2 months after KI discontinuation. CONCLUSION: In Japan, where iodine intake is sufficient, administration of inorganic iodine to lactating mothers with Graves disease did not affect thyroid function in most infants despite high levels of exposure to iodine via breast milk.

Radioactive iodine therapy for goitrous Hashimoto's thyroiditis.

CONTEXT: Hashimoto's thyroiditis is an autoimmune disease that can produce marked clinical symptoms when patients have large diffuse goiters. DESIGN: This retrospective cohort study was designed to evaluate whether radioactive iodine (RAI) is effective for Hashimoto's thyroiditis with a large goiter. Starting in November 1999, 13 Hashimoto's patients with large goiters, whose thyroiditis was refractory to TSH suppression therapy with thyroid hormone administration [two men and 11 women with a mean age of 61.2 +/- 8.9 yr (50-79 yr)], were recruited for the present study. The duration of symptomatic goiter before undergoing RAI was 12.0 +/- 7.9 yr (4-33 yr). Thirteen millicuries of 131I was administered two to six times, at an interval of 1-6 months on an outpatient basis. Thyroid weight was measured ultrasonographically, or by computed tomography if ultrasound was not possible due to the large size of the goiter. RESULTS: RAI was administered an average of 4.7 +/- 1.4 times (two to six times), with a total dose of 59.8 +/- 17.3 mCi (25.0-78.0 mCi). The observation period was 47.9 +/- 13.4 months (26-66 months) after the first RAI. The average weight of the thyroid gland was 125.3 +/- 57.7 g (42.9-269.4 g) before the first RAI, decreasing significantly to 49.7 +/- 25.8 g (18.3-93.3 g) after the last RAI (P < 0.001, paired Student's t test). The percent reduction from baseline was 58.7 +/- 14.2% (35.7-84.0%). None of the patients showed an increase in goiter size or complained of a pressure sensation after any of the RAI treatments. CONCLUSION: RAI is effective in Hashimoto's thyroiditis with a large goiter.

[Radioiodine treatment of patients with autonomously functioning thyroid nodules at outpatient clinic].

OBJECTIVES: This retrospective study was aimed at evaluating the efficacy of radioiodine (RI) treatment for patients with autonomously functioning thyroid nodules (AFTN). METHODS: The subjects were 38 patients including 26 cases of toxic adenoma (TA) and 12 cases of toxic multinodular goiter (TMNG), who attended our clinic from July 1999 to April 2005. RI treatment was performed in the outpatient clinic. Thirteen mCi (481 MBq) of 131I were administered to all patients, and additional administrations were performed at an interval of 3 to 4 months when not sufficient. Patients with TA were followed for 31.9 +/- 18.7 months (5-68 months) and those with TMNG for 40.5 +/- 18.3 months (10-63 months). A curative effect was defined as absence of TSH suppression. RESULTS: After RI treatment, hyperthyroidism improved, associated with reduction in size of the goiter or nodes in all 38 cases. Hypothyroidism was observed in one of 19 patients with TA in whom RI was performed under a suppressed TSH level, while all 6 patients whose serum TSH levels were not suppressed at the time of the treatment, developed into hypothyroidism (p < 0.001). CONCLUSION: RI treatment was effective in patients with AFTN. RI is an alternative treatment of AFTN. Development of hypothyroidism in patients with TA can be prevented by maintaining a suppressed TSH level when RI is administered.

[Issues of side effects induced by antithyroid drugs].

Antithyroid drugs have been widely used in the treatment of hyperthyroidism. However, these drugs are known to have significant side effects. There are minor side effects such as skin rash or urticaria and major side effects. Especially, agranulocytosis and MPO-ANCA related vasculitis syndrome are the most serious, and although it occurs infrequently, it is clinically important, and clinicians must be alert to it when using antithyroid arugs. The author describes about the issues of side effects induced by antithyroid drugs.