Kiichiro Higashi

Development of Primary Thyroid Lymphoma during an Ultrasonographic Follow-up of Hashimoto's Thyroiditis: A Report of 9 Cases.

We herein experienced 9 patients with primary thyroid lymphoma that developed during 3-18 years of ultrasonographic follow-up of Hashimotos thyroiditis. All nine patients had localized mucosa-associated lymphoid tissue (MALT) lymphoma. Two patients had diffuse type, one had mixed type, and six had nodular type according to the ultrasonographic classification. A clearly enlarging goiter was observed before the diagnosis of lymphoma in 3 patients. An enlarging goiter was not apparent in the remaining 6 patients with nodular type lymphoma, however, the emergence or enlargement of a hypoechoic nodular lesion was observed. Thyroid MALT lymphoma may be diagnosed early by an ultrasonographic follow-up of Hashimotos thyroiditis.

Iodide Transport Defect and Breast Milk Iodine.

Background: Iodide transport defect (ITD) is a dyshormonogenetic congenital hypothyroidism caused by sodium/iodide symporter (NIS) gene mutations. In the lactating mammary gland, iodide is concentrated by NIS, and iodine for thyroid hormone synthesis is thereby supplied to the infant in the breast milk. Case Description: A 34-year-old Japanese woman was diagnosed with ITD caused by a homozygous NIS gene mutation T354P. She had begun treatment of primary hypothyroidism with levothyroxine at the age of 5. She delivered a baby at the age of 36. The iodine concentration in her breast milk was 54 µg/l. She took a 50-mg potassium iodide tablet daily to supply iodine in the breast milk, starting on the 5th day postpartum. Her breast milk iodine concentration increased to 90 µg/l (slightly above the minimum requirement level). The patient weaned her baby and stopped taking the daily potassium iodide tablet 6 weeks postpartum, and the baby began to be fed with relatively iodine-rich formula milk. The babys thyroid function remained normal from birth until 6 months of age. Conclusion: Possible iodine deficiency in the infant breast-fed by an ITD patient should be kept in mind. Prophylactic iodine supplementation is essential for such infants in order to prevent severe iodine deficiency.

Graves’ disease and Gitelman syndrome

Dear Editor, We read with great interest the letter to the editor entitled ‘Coexistence of Graves’ disease in a 14-year-old young girl with Gitelman syndrome’ by Zha et al. in a recent issue of Clinical Endocrinology. We have cared for three Japanese patients with genetically confirmed Gitelman syndrome (GS) complicated by Graves’ disease (GD). The clinical characteristics at diagnosis of GS and GD as well as the genetic analysis results for SLC12A3 of these patients are listed in Table 1. SLC12A3 codes thiazide-sensitive sodium chloride cotransporter in the early distal tubule in the kidney and is the gene most commonly responsible for Gitelman syndrome. All 3 of our patients were women, and the age at diagnosis of GD ranged from 17 to 56 years. Sustained and unexplained hypokalaemia without hypertension was the initial feature raising clinical suspicion of GS. They had normoor hypomagnesaemia and hypocalciuria and underwent genetic analysis of SLC12A3. Patient 1 had visited another hospital for evaluation of diffuse goitre and palpitations and was diagnosed with GD. She began treatment with methimazole, but was switched to propylthiouracil because of skin eruption. After moving, she transferred to our clinic at the age of 18. Patient 2 had initially visited our clinic because of palpitations. She was diagnosed with GD and began treatment with methimazole. Patient 3 had presented with finger tremor.She was diagnosed with GD and underwent I-131 therapy followed by replacement of LT4 for postablative hypothyroidism. Hypokalaemia persisted during more than 2 years of follow-up even after the treatment of hyperthyroidism in all three patients. The prevalence of GS is estimated to be 1 in 40 000, and the estimated prevalence of heterozygous subjects with one of the genetic mutations that cause GS is at least one per cent in Caucasian populations. The actual prevalence of GS might be much higher in the Japanese population. There are large variations in the severity of clinical manifestations among patients with GS. Correlations between the position or nature of SLC12A3 mutations and the severity of clinical manifestations are not apparent. Some patients are asymptomatic or develop only mild weakness, whereas others show severe neuromuscular symptoms such as generalized weakness. Considerable numbers of GS patients with mild symptoms are presumably not diagnosed precisely because genetic testing is not widespread and renal clearance studies using furosemide and thiazide are cumbersome. Hypokalaemia is the characteristic abnormality of GS on routine clinical laboratory tests. Although hypokalaemia is generally mild in patients with GS, some develop severe manifestations, such as hypokalaemic periodic paralysis. On the other hand, thyrotoxicosis is the most common cause of hypokalaemic periodic paralysis in GD, especially in Asian men. As the prevalence of GS is not necessarily low, clinicians need to be aware of GS as one of the possible causes of hypokalaemia in patients with GD.

S-2-(3-Aminopropylamino) Ethyl Phosphorothioic Acid (WR-2721) in Primary Hyperparathyroidism

Excerpt To the editor: Glover and coworkers (1) have reported previously that a radioprotective agent, WR-2721 [S-2-(3-aminopropylamino) ethyl phosphorothioic acid; amifostine] lowered serum calciu...

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.

RADIOIODINE TREATMENT FOR HYPERTHYROIDISM IN A PATIENT WITH PENDRED SYNDROME

ABSTRACT Objective: To report a case of Pendred syndrome accompanied by hyperthyroidism that was treated with radioiodine. Pendred syndrome is an autosomal recessive disorder characterized by bilateral sensorineural hearing impairment, goiter, and impaired iodide organification. The majority of patients with Pendred syndrome are euthyroid or hypothyroid, and hyperthyroidism is rare. Thus far, there are no reported cases of Pendred syndrome with 131I-treated hyperthyroidism. Methods: A 39-year-old woman with congenital hearing impairment visited our clinic because of easy fatigability and body weight loss. Results: She had a diffuse goiter (estimated thyroid weight, 65 g) and subclinical thyrotoxicosis. 99mTechnetium pertechnetate scintigraphy revealed diffuse thyroidal uptake, but thyroid autoantibodies were absent. Since the therapeutic response to a single 131I dose was poor, the patient underwent a second 131I dose (13 mCi each) for hyperthyroidism. Seven years after the second 131I dose, she was euthy...

ACUTE AND TRANSIENT THYROID SWELLING FOLLOWING FINE-NEEDLE ASPIRATION BIOPSY: ITS PREVALENCE, CLINICAL FEATURES AND ULTRASONOGRAPHIC FINDINGS

ABSTRACT Objective: Acute diffuse swelling of the thyroid gland in the absence of hematoma formation is a rare complication following fine-needle aspiration biopsy (FNAB) that often resolves spontaneously. This complication has not been investigated in a large number of cases. Therefore, this study investigated the prevalence, clinical features, and ultrasonographic findings of acute and transient thyroid swelling after FNAB. Methods: We performed 16,817 FNABs for 9,596 thyroid nodules between 2011 and 2015. Results: We identified 10 patients (8 women and 2 men) with acute and transient thyroid swelling without significant hematoma. The biopsied nodules were multi-nodular goiter (likely adenomatous goiter; n = 7), solitary thyroid nodule (including one follicular adenoma; n = 2), and papillary carcinoma (n = 1). The thyroid glands enlarged by 1.3- to 4.7-fold, accompanied with anterior neck pain and/or swelling immediately after FNAB in five cases, 5 to 15 minutes after FNAB in two, and 1 to 2 hours after...

Radioiodine for patients with autonomously functioning thyroid nodules with a normal TSH level.

Dear Editor, We read with interest the recent article entitled ‘Prevalence of normal TSH value among patients with autonomously functioning thyroid nodule’ by Treglia et al. [1]. Their meta-analysis showed approximately half of patients with autonomously functioning thyroid nodules (AFTN) demonstrated by thyroid scintigraphy to have TSH values within normal range. Herein, we report our investigation of AFTN cases with normal TSH levels treated with radioiodine therapy (RIT). The subjects were 13 patients (one man and 12 women) diagnosed as having AFTN with a normal TSH level and treated with RIT. The median age was 69 [interquartile range (IQR): 58–72] years. Of these 13 patients, nine had a solitary nodule and four had multinodular goitres. All but one patient received radioiodine at a fixed dose of 481 MBq once, the exception being one given this treatment twice. The TSH and free thyroxine (FT4) levels before RIT and at hypothyroidism onset, and the AFTN volumes before and 2 years after treatment were evaluated. In multinodular goitres, the volume of the largest AFTN was measured. Ultrasonography-guided fine needle aspiration biopsy was performed in all AFTN nodules. None of our patients had malignancies. The AFTN volume was reduced from 9 73 (IQR: 5 48–12 53) mL to 3 28 (IQR: 0 88–6 45) mL (P < 0 05). In 10 of the 13 cases, hot nodules disappeared after treatment. Thyroid function test results before RIT and at hypothyroidism onset were as follows: TSH, 1 25 (IQR: 0 63–1 53) mIU/L and FT4, 1 13 (IQR: 1 05– 1 26) ng/dL (multiply by 12 87 for SI units, pmol/L); and TSH, 19 41 (IQR: 2 6–84 89) mIU/L and FT4, 0 85 (IQR: 0 59–0 94) ng/dL, respectively. Of the 13 patients, nine started taking levothyroxine and one had been on this medication since before treatment. The median daily levothyroxine dosage of medicated patients was 80 35 (IQR: 75–100) lg. Autonomously functioning thyroid nodules with normal TSH levels was recently reported [2,3]. However, there are no reports describing RIT treatment of such cases. This is the first report of RIT performed for AFTN cases with normal TSH levels. RIT significantly reduced nodule volumes in AFTN patients with normal TSH levels. However, as many patients undergoing RIT experience hypothyroidism, sufficient explanation and careful follow-up are required. Our results suggest that the diagnosis of AFTN with a normal TSH level can provide more treatment options to patients with nodular goitre who do not wish to undergo surgery.

Significance of immunological diagnostic methods in primary cancer of the liver

慢性肝炎,肝硬変からの発癌過程追跡例17例を含む188例の原発性肝癌について,癌胎児性蛋白(AFPおよびCEA), B型肝炎ウイルス(HBV)および補体系の変動を長期間経時的に追跡し,これら免疫学的診断法の臨床的意義を検討した.AFPは本症の診断に極めて有用で,診断確定時のAFP値の推移をみても比較的低値例の占める割合が年々増加しており,肝炎,肝硬変に肝癌を併発した例の多くは,他の所見に先がけてAFPの漸増がみられた.CEAの陽性率は比較的低率で,しかもその値も低いものが多く,転移性肝癌との鑑別には有用ではあるが,肝硬変との鑑別や原発性肝癌の早期診断の指標には有用でなかった.HBs抗原陽性例は54.0%で,血清補体価も比較的高値の傾向にあった.慢性肝疾患ことにHBs抗原陽性者で,AFPなどを指標とした定期的な観察は,本症の早期発見に重要であると考えられた.