Radiation Emergency Medical Preparedness in Japan: A Survey of Nuclear Emergency Core Hospitals.

OBJECTIVE: Based on experiences following the Great East Japan Earthquake and nuclear power plant accident in 2011, Nuclear Emergency Core Hospitals (NECHs) were designated as centers for radiation disaster management in Japan. This study aimed to investigate their current status and identify areas for improvement. METHODS: This cross-sectional study was conducted in October 2018. Demographic data were collected by a questionnaire with free text responses about attitudes toward NECHs. Considerations regarding risk communications during a radiation disaster were analyzed using qualitative text mining analysis. RESULTS: A total of 36 hospitals participated in this study. Only 31% of NECHs anticipated a radiation disaster. The importance of business continuity plans and risk communications was shown. Text analysis identified 7 important categories for health care workers during a radiation disaster, including media response, communications to hospital staff, risk communications, radiation effects on children, planning for a radiation disaster in the region, rumors, and the role in the region. CONCLUSION: The radiation disaster medical system and NECHs in Japan were surveyed. The importance of risk communications, planning for a radiation disaster in each region, and the role in the region are identified as issues that need to be addressed.

RENAL FUNCTION AND PLASMA RENIN ACTIVITY AS POTENTIAL FACTORS CAUSING HYPERKALEMIA IN PATIENTS WITH THYROID CARCINOMA UNDERGOING THYROID HORMONE WITHDRAWAL FOR RADIOACTIVE IODINE THERAPY.

Objective: Hypothyroidism is not commonly considered a cause of hyperkalemia. We previously reported that hyperkalemia was observed mainly in elderly patients treated with renin-angiotensin-aldosterone system (RAS) inhibitors when levothyroxine treatment was withdrawn for the thyroidectomized patients with thyroid carcinoma to undergo radioactive iodine treatment. Here, we investigated whether acute hypothyroidism causes hyperkalemia in patients who were not treated with RAS inhibitors. We also investigated factors influencing potassium metabolism in hypothyroid patients. Methods: We conducted a single-center, prospective cohort study of 46 Japanese patients with thyroid carcinoma undergoing levothyroxine withdrawal prior to radioiodine therapy. All patients were normokalemic before levothyroxine withdrawal. Blood samples were analyzed 3 times: before, and at 3 and 4 weeks after levothyroxine withdrawal. We investigated factors that may be associated with the elevation of serum potassium levels from a euthyroid state to a hypothyroid state. Results: None of the patients developed symptomatic hyperkalemia. The mean serum potassium level was significantly higher at 4 weeks after levothyroxine withdrawal compared to baseline. The serum sodium levels, the estimated glomerular filtration rate (eGFR), and the plasma renin activity (PRA) decreased significantly as hypothyroidism advanced. In contrast, the plasma levels of adrenocorticotropic hormone, cortisol, aldosterone, and antidiuretic hormone were not changed, while serum thyroid hormone decreased. At 4 weeks after their levothyroxine withdrawal, the patients' serum potassium values were significantly correlated with the eGFR and the PRA. Conclusion: Acute hypothyroidism can cause a significant increase in the serum potassium level, which may be associated with a decreased eGFR and decreased circulating RAS. Abbreviations: ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ATPase = adenosine triphosphatase; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; K+ = potassium; Na+ = sodium; PRA = plasma renin activity; RAS = renin-angiotensin-aldosterone system; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

Context: The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. Objective: To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Design, Setting, and Participants: Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Main Outcome and Measures: Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Results: Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Conclusions: Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study.

Quality of life in the patients with central diabetes insipidus assessed by Nagasaki Diabetes Insipidus Questionnaire.

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.

Hyperkalemia develops in some thyroidectomized patients undergoing thyroid hormone withdrawal in preparation for radioactive iodine ablation for thyroid carcinoma.

OBJECTIVE: Hyponatremia is observed in hypothyroidism, but it is not known if hypo- or hyperkalemia is associated with hypothyroidism. To study these questions, we determined serum potassium (K(+)) levels in thyroidectomized patients undergoing levothyroxine withdrawal before radioactive iodine (RAI) therapy for thyroid carcinoma. METHODS: We retrospectively studied the records of 108 patients who had undergone total thyroidectomy for thyroid carcinoma followed by levothyroxine withdrawal and then ablation with RAI at Nagasaki University Hospital from 2009-2013. Blood samples were analyzed for serum K(+) concentrations when patients were euthyroid just before levothyroxine withdrawal and hypothyroid 21 days after levothyroxine withdrawal. We determined the proportion of patients who developed hyperkalemia (K(+) ≥5 mEq/L) and hypokalemia (K(+) ≤3.5 mEq/L). RESULTS: Five (4.6%) patients developed hyperkalemia and 2 (1.9%) patients developed hypokalemia after levothyroxine withdrawal. The mean serum K(+) level after levothyroxine withdrawal was significantly higher than before levothyroxine withdrawal (4.23 ± 0.50 mEq/L vs. 4.09 ± 0.34 mEq/L; P<.001). After levothyroxine withdrawal, serum K(+) values were significantly correlated with age, serum sodium and creatinine levels, and the estimated glomerular filtration rate but not with serum free thyroxine or thyroid-stimulating hormone concentrations. The finding of an elevated serum K(+) of >0.5 mEq/L after levothyroxine withdrawal was more prevalent with age >60 years (odds ratio [OR], 4.66; P = .026) and with the use of angiotensin-II receptor blockers or angiotensin-converting enzyme inhibitors (OR, 3.53; P = .033) in a multivariate analysis. CONCLUSION: Hyperkalemia develops in a small percentage of hypothyroid patients after thyroid hormone withdrawal, especially in patients over 60 years of age who are using antihypertensive agents that inhibit the reninangiotensin-aldosterone system.

Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007-2011).

IMPORTANCE: Few studies have evaluated the association of radiation dose with thyroid nodules among adults exposed to radiation in childhood. OBJECTIVE: To evaluate radiation dose responses on the prevalence of thyroid nodules in atomic bomb survivors exposed in childhood. DESIGN, SETTING, AND PARTICIPANTS: This survey study investigated 3087 Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years at exposure and participated in the thyroid study of the Adult Health Study at the Radiation Effects Research Foundation. Thyroid examinations including thyroid ultrasonography were conducted between October 2007 and October 2011, and solid nodules underwent fine-needle aspiration biopsy. Data from 2668 participants (86.4% of the total participants; mean age, 68.2 years; 1213 men; and 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; median dose, 0.018 Gy; dose range, 0-4.040 Gy) were analyzed. MAIN OUTCOMES AND MEASURES: The prevalence of all thyroid nodules having a diameter of 10 mm or more (consisting of solid nodules [malignant and benign] and cysts), prevalence of small thyroid nodules that were less than 10 mm in diameter detected by ultrasonography, and atomic bomb radiation dose-responses. RESULTS: Thyroid nodules with a diameter of 10 mm or more were identified in 470 participants (17.6%): solid nodules (427 cases [16.0%]), malignant tumors (47 cases [1.8%]), benign nodules (186 cases [7.0%]), and cysts (49 cases [1.8%]), and all were significantly associated with thyroid radiation dose. Excess odds ratios per gray unit were 1.65 (95% CI, 0.89-2.64) for all nodules, 1.72 (95% CI, 0.93-2.75) for solid nodules, 4.40 (95% CI, 1.75-9.97) for malignant tumors, 2.07 (95% CI, 1.16-3.39) for benign nodules, and 1.11 (95% CI, 0.15-3.12) for cysts. The interaction between age at exposure and the dose was significant for the prevalence of all nodules (P = .003) and solid nodules (P < .001), indicating that dose effects were significantly higher with earlier childhood exposure. No interactions were seen for sex, family history of thyroid disease, antithyroid antibodies, or seaweed intake. No dose-response relationships were observed for small (<10-mm diameter) thyroid nodules. CONCLUSIONS AND RELEVANCE: Radiation effects on thyroid nodules exist in atomic bomb survivors 62 to 66 years after their exposure in childhood. However, radiation exposure is not associated with small thyroid nodules.

Liraglutide as a potentially useful agent for regulating appetite in diabetic patients with hypothalamic hyperphagia and obesity.

Hypothalamic hyperphagia and obesity are characterized by a lack of satiety and an abnormally high appetite that is difficult to control. We herein report the cases of two patients with hypothalamic hyperphagia and obesity with MRI-detectable hypothalamic lesions. These patients suffered from diabetes mellitus associated with an abnormal eating behavior and weight gain. Liraglutide was successfully used to treat their diabetes mellitus and suppress their abnormal appetites. Glucagon-like peptide-1 analogues, including liraglutide, are promising treatment options in patients with hypothalamic hyperphagia and obesity, as these agents enhance the hypothalamic input of the satiety signal, which is lacking in such patients.

Moderate to severe nausea in radioactive iodine (RAI) therapy is associated with the RAI dose per body weight and was not prevented by ramosetron.

To retrospectively analyze the individual risk factors for radioactive iodine (RAI)-associated nausea and vomiting, and to examine the anti-emetic effect of ramosetron (5-hydroxytryptamine-3 receptor antagonist) in RAI therapy. Patients with differentiated thyroid carcinoma who underwent first-time RAI therapy at Nagasaki University Hospital between January 2009 and 2013 were included (N = 81). As a routine treatment, all patients were administered 30 mg of domperidone per day. Patients who underwent RAI therapy between April 2011 and January 2013 were also administered 0.1 mg of ramosetron per day in addition to domperidone. Nausea and vomiting were evaluated based on Common Terminology Criteria for Adverse Events version 4.0. RAI-associated nausea and vomiting of any grade were seen in 37.0 and 6.2 % of patients in total, respectively. Moderate to severe nausea (grade 2­3) was seen in 22.2 % of patients and associated with the dose of RAI per body weight (odds ratio = 1.046, p = 0.013), but not with the use of ramosetron, in multivariate logistic regression analysis. We have identified the dose of RAI per body weight to be an individual risk factor associated with moderate to severe RAI-associated nausea. This study failed to show that the combined use of ramosetron and domperidone reduced the frequency of RAI-associated nausea and vomiting.

Spatiotemporal characteristics of internal radiation exposure in evacuees and first responders after the radiological accident in fukushima.

After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident on March 11, 2011, the reconstruction of early internal radiation doses in residents of Fukushima plays a major role in evaluating their future heath risk, including thyroid cancer by internal radioiodine. Internal radioactivity was measured using a whole body counter (WBC) at the Nagasaki University Medical School to evaluate the health risks of residents and short term visitors in Fukushima. Measurable (131)I, (134)Cs and (137)Cs were detected altogether in 49 out of 196 people who were in Fukushima prefecture at any time during March 11 and April 20, 2011. In 49 people, the 90 percentile of the thyroid equivalent dose by (131)I and the committed effective dose (total effective dose over a lifetime) by the sum of (134)Cs and (137)Cs was 3 mSv and 0.06 mSv, respectively. The radionuclide intakes in early evacuees who left Fukushima before March 16 were more than five times as high as in the responders who moved to Fukushima later. The intake ratio of (131)I/(137)Cs of the earlier evacuees was approximately three. The spatial analysis of 16 evacuees to the south indicated a reduction of internal radioactivity depending on the distance from the nuclear power plant. Among them, high internal (131)I radioactivity in 6 people in a particular evacuation route could be explained by the arrival of a radioactive cloud with a high airborne (131)I/(137)Cs ratio to the environment, as predicted by atmospheric dispersion simulations. Overall, the actual internal radioactivity assessed by a WBC examination comparatively agreed with the predicted airborne radioactivity. These results suggest that the accurate estimation of internal doses in the first week after the radiological accident is critical for the dose reconstruction. The evaluation of internal doses of residents based on their evacuation routes and the advanced estimation of airborne radioactivity from the atmospheric dispersion model should continue to be assessed.

A case of nonfunctioning pituitary carcinoma that responded to temozolomide treatment.

Pituitary carcinoma is a rare malignancy and is difficult to manage. Pituitary carcinomas commonly produce either PRL or ACTH, but some do not produce pituitary hormones. The alkylating reagent temozolomide (TMZ) was recently shown to be effective as a treatment for pituitary carcinoma. Most of the published reports of TMZ use in pituitary carcinoma cases were against hormone-producing carcinomas. Only a few patients with a nonfunctioning pituitary carcinoma treated with TMZ have been reported. Here we describe our treatment of a patient with nonfunctioning pituitary carcinoma and a background of multiple endocrine neoplasia type 1. The pituitary carcinoma was accompanied by meningeal dissemination with cerebral and L1 spinal bone metastasis. The patient received continuous dosing of TMZ along with external radiation, followed by standard dosing of TMZ. There was an apparent antitumor response seen in MRI. MGMT, an enzyme antagonized by TMZ, was negative in the tumor. The therapeutic efficacy of TMZ and dosing schedules of TMZ in pituitary carcinoma are discussed.

Clinical and genetic characteristics of autoimmune polyglandular syndrome type 3 variant in the Japanese population.

OBJECTIVE: Type 1 diabetes (T1D) is commonly associated with autoimmune thyroid disease (AITD), and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(-)] in the Japanese population. DESIGN/PATIENTS: Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the present. RESULTS: A remarkable female predominance, a slow and older age onset of T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age of T1D in APS3v patients was associated with a higher proportion of slow-onset T1D. Among the two major susceptible human leukocyte antigen (HLA) class II haplotypes in Japanese T1D, DRB1*0405-DQB1*0401, but not DRB1*0901-DQB1*0303, was associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not protective in patients with APS3v. The frequencies of the GG genotype in +49G>A and +6230G>A polymorphism in the CTLA4 gene were significantly higher in T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects. CONCLUSIONS: In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms.

Risk for progression to overt hypothyroidism in an elderly Japanese population with subclinical hypothyroidism.

BACKGROUND: Few population-based studies report the changes with time in thyroid function tests in patients with subclinical hypothyroidism. We compared the risk for developing overt hypothyroidism in patients with subclinical hypothyroidism and euthyroid controls from the same population of elderly Japanese. We also sought associations of selected parameters with the development of overt hypothyroidism in the subclinical hypothyroid and euthyroid groups. METHODS: We measured thyrotropin (TSH) and free thyroxine (T4) levels at baseline examinations performed from 2000 to 2003 in the cohort of Japanese atomic-bomb survivors and identified 71 patients with spontaneous subclinical hypothyroidism (normal free T4 and TSH >4.5 mIU/L without a history of thyroid treatment, mean age 70 year) and 562 euthyroid controls. We re-examined TSH and free T4 levels an average of 4.2 years later (range, 1.9-6.9). RESULTS: The risk for progression to overt hypothyroidism was significantly increased in subclinical hypothyroid patients (7.0%) compared with control subjects (1.6%) after adjusting for age and sex (odds ratio, 4.56; p=0.009). Higher baseline TSH levels were associated with progression from subclinical to overt hypothyroidism (p=0.02) in the multivariate analysis, including age, sex, antithyroid peroxidase antibody, and ultrasonography (US) findings. The analysis using binary TSH data suggested that a TSH level >8 mIU/L was a predictive value for development of overt hypothyroidism (p=0.005). On the other hand, serum TSH levels spontaneously normalized in 38 (53.5%) of the patients with subclinical hypothyroidism. In the multivariate analysis, normalization of TSH levels was associated with lower baseline TSH levels (p=0.004) and normal and homogenous thyroid US findings (p=0.04). Atomic-bomb radiation dose was not associated with subclinical hypothyroidism or its course. CONCLUSIONS: Subclinical hypothyroidism was four times more likely to be associated with development of overt hypothyroidism than euthyroid controls in the sample population of Japanese elderly. TSH levels in half of the patients normalized spontaneously when assessed after an average follow-up period of 4.2 years. Baseline TSH level and thyroid US findings are potential predictors of future thyroid function in subclinical hypothyroidism.

Graves' disease complicated by ventricular fibrillation in three men who were smokers.

BACKGROUND: Thyrotoxicosis is known to be associated with sinus tachycardia and supraventricular tachyarrhythmias, but rarely with ventricular fibrillation (Vf), which has only occurred in some patients with hypokalemic periodic paralysis or ischemic heart disease. PATIENT FINDINGS: We present three men who were transferred to our hospital with Graves' disease who developed idiopathic Vf. None of them had hypokalemic periodic paralysis or ischemic heart disease but all were smokers. None of other patients with thyrotoxicosis (587 females and 155 males) who were seen at our hospital, in the period during which the three men were seen, had idiopathic Vf. In our three men with thyrotoxicosis and idiopathic Vf, there was no identifiable underlying heart disease. One of the three patients died of hypoxic encephalopathy. The other two men did not have recurrent Vf after their thyroid function normalized. SUMMARY: These cases and a review of similar cases in the literature imply that improving thyrotoxicosis seems to be effective for treating idiopathic Vf in some patients. CONCLUSIONS: Our findings suggest that thyroid hormone excess might play a direct role in the development of Vf in susceptible individuals. Our experience with these three patients suggests that smoking men with thyrotoxicosis likely have an increased risk for Vf, even if they do not have other predisposing factors.

A case of mixed medullary and follicular cell carcinoma of the thyroid.

A medullary thyroid carcinoma is a malignant tumor derived from the C-cells of the thyroid. Despite their distinct embryological origin, medullary thyroid carcinomas are exceptionally accompanied by a tumor derived from the follicular cells; this is defined as mixed medullary and follicular cell carcinoma. There have been controversies regarding the origin of this rare mixed thyroid carcinoma questioning whether or not a mixed carcinoma originates from a common cancer stem cell. We present a case of mixed medullary and follicular cell carcinoma in which two thyroid carcinomas were found intermingled in the thyroid as well as in the metastatic cervical lymph nodes. We examined the tumor by immunostaining with thyroglobulin, calcitonin, and thyroid transcription factor-1, and also reviewed the literature and discuss the origin of this rare mixed thyroid carcinoma.

Emergence of anti-islet autoantibodies in Japanese patients with type 1 diabetes.

Circulating anti-islet autoantibodies in sera are used as a predictive marker for type 1 diabetes (T1D). We here report two Japanese patients with autoimmune thyroid disease complicated with T1D in whom the time course of anti-islet autoantibodies were observed before the clinical onset of diabetes. Case 1: A woman who had developed Graves' disease at age 25 was diagnosed with type 2 diabetes at age 31; six months later, insulin therapy was started. At age 36 she was diagnosed with T1D due to glutamic acid decarboxylase 65 autoantibodies (GAD65Ab)-positive status and decreased C-peptide levels. With stored sera we retrospectively followed her anti-islet autoantibodies. GAD65Ab, zinc transporter 8 autoantibodies (ZnT8Ab) and insulin autoantibodies (IAA) were found to be positive at age 25. IAA soon turned negative, but GAD65Ab and ZnT8Ab remained positive with high levels. Insulinoma-associated antigen-2 autoantibodies (IA-2Ab) emerged 2 years before the initiation of insulin therapy. She has T1D-susceptible HLA-DRB1-DQB1 haplotypes, (*)0405- (*)0401/(*)0802-(*)0302. Case 2: A 49-year-old woman with hypothyroidism due to 19 years' history of atrophic thyroiditis noticed marked thirst, polyuria and weight loss. On admission she was diagnosed as T1D due to GAD65Ab-positive findings and poor C-peptide response to i.v. glucagon. Retrospective serology revealed the emergence of GAD65Ab and IAA just after the clinical onset. IA-2Ab and ZnT8Ab never developed. She has T1D-susceptible and -resistant HLADRB1- DQB1 haplotypes, (*)0901-(*)0303/(*)1502-(*)0601. The autoantibody profile and the mode of diabetes onset in the two cases were remarkably different. These cases imply that anti-islet autoantibodies do not always precede the onset of T1D.

Putative IgG4-related pituitary disease with hypopituitarism and/or diabetes insipidus accompanied with elevated serum levels of IgG4.

IgG4-positive plasma cell infiltration into multiple organs or tissues, such as the pancreas and salivary glands, associated with increased serum levels of IgG4 is a characteristic finding seen in IgG4-related disease. Affected organs may appear tumorous as a result of chronic inflammatory processes accompanied with progressive fibrosis. Recent cases of this disorder in which the pituitary gland was affected include cases of diffuse enlargement of the pituitary and/or its stalk associated with central diabetes insipidus and/or impaired anterior hormone production. Here we report two such cases, as well as two additional previously undiagnosed cases found in our database. In order to make a correct diagnosis of pituitary lesion involvement with IgG4-related disease, the clinical background and concomitant disorders should be carefully taken into consideration and the measurement of serum levels of IgG4 seems to be useful.

Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism.

OBJECTIVE: A possible association between subclinical hypothyroidism and cardiovascular disease (CVD) has been reported. Monitoring of atomic-bomb survivors for late effects of radiation exposure at the Radiation Effects Research Foundation has provided the opportunity to examine associations between subclinical hypothyroidism and metabolic CVD risk factors. The objective of the study was to evaluate associations between subclinical hypothyroidism and metabolic CVD risk factors, and a cluster of these factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study of 3549 subjects (mean age 70 years; 1221 men and 2328 women) between 2000 and 2003 comprising 306 subjects with subclinical hypothyroidism and 3243 control euthyroid subjects in Japan. MEASUREMENTS: We investigated associations between subclinical hypothyroidism and metabolic CVD risk factors such as hypertension, diabetes mellitus, dyslipidaemia and hyperuricaemia, and a cluster of these factors. RESULTS: Subclinical hypothyroidism was not significantly associated with either hypertension, diabetes mellitus or hyperuricaemia defined by taking into account the use of medications in both men and women, but in men it was associated with dyslipidaemia (P = 0.02). We observed a significantly increased odds ratio (OR) for the presence of three or more metabolic CVD risk factors in men with subclinical hypothyroidism after adjusting for age, body mass index (BMI), and smoking status [OR: 1.83, 95% confidence interval (CI): 1.13-2.94, P = 0.01]. The significant associations remained after an additional adjustment for atomic-bomb radiation dose. CONCLUSIONS: There appears to be a significant increase in a cluster of metabolic CVD risk factors among people with subclinical hypothyroidism.

First Japanese patient treated with parathyroid hormone peptide immunization for refractory hypercalcemia caused by metastatic parathyroid carcinoma.

Patients with unresectable parathyroid carcinoma develop severe hypercalcemia, bone fractures and renal failure, and become unresponsive to conventional treatments. It has been shown that successful induction of anti-parathyroid hormone (PTH) antibodies, using PTH peptide fragments for immunisation, normalized serum levels of calcium as well as improved clinical symptoms. Here, we report our experience of PTH immunization in a Japanese female suffering from refractory hypercalcemia and renal failure caused by unresectable metastatic parathyroid carcinoma. Upon immunization, there were apparent clinical responses including reduction of serum levels of Ca along with anti-PTH antibodies induction. Therefore, we concluded that PTH immunization was an effective treatment against hypercalcemia caused by metastatic parathyroid carcinomas that are unresponsive to conventional treatments.

A long-term follow-up of serum myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves disease treated with propylthiouracil.

Propylthiouracil (PTU) is known to induce myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves disease (GD). Previously, we showed that serum MPO-ANCA were frequently seen in patients with GD treated with PTU. In this study, we analyzed 13 patients with positive MPO-ANCA examining a long-term clinical consequence of these patients as well as antibody titers during 5.6 +/- 3.0 years. PTU therapy was continued in 8 patients and discontinued in 5 patients. Antibody titers decreased in 7 of 8 patients who discontinued PTU therapy but remained positive in 5 patients 5 years after PTU withdrawal. The initial MPO-ANCA levels were significantly higher in those antibody titers remained positive for longer than 5 years (n=5) than in those titers turned to be negative within 5 years after PTU withdrawal (n=3) (203 +/- 256 EU and 22 +/- 2 EU, respectively, P=0.04), but there were no significant differences in age, gender, duration of PTU therapy or dosage of PTU. Among 5 patients who continued PTU therapy, 2 patients with initially low MPO-ANCA titers turned to having negative antibody. No patients had new symptoms or signs of vasculitis throughout the follow-up periods. The long-term follow-up study suggests that higher MPO-ANCA levels remain positive for years after PTU withdrawal but are rarely associated with vasculitis.