Junichi Tajiri

Successful treatment of thyrotoxic crisis with plasma exchange

A 36-yr-old woman with thyroid storm was successfully treated with plasma exchange. After the first plasma exchange, free serum thyroxine (T4) was decreased and serum thyroxine-binding globulin (TBG) was significantly increased. The decrease in the patients free T4 level after plasma exchange can perhaps be attributed to T4s increased binding capacity. Plasma exchange may be an effective therapy for thyrotoxic crisis and should be performed immediately if conventional therapy fails to improve the patients condition.

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.

Acute transient thyroid swelling after fine-needle aspiration biopsy: three cases during only 6 weeks - a rare complication?

We read, with great interest, the article recently published in Clinical Endocrinology regarding acute transient thyroid swelling after fine-needle aspiration biopsy (FNAB). It has been thought that this complication is quite rare. However, surprisingly, we experienced three cases with this complication during only 6 weeks. The first case was a 58-year-old woman referred to the clinic because of a multinodular goitre. On physical examination, her thyroid gland was not palpable. There was no relevant family medical history or known allergies or use of specific medication. Thyroid function test and antithyroid antibody levels were normal. Estimated thyroid volume was 16Æ3 ml, and there were multiple nodules in the thyroid gland on ultrasound. Subsequently, FNA of the heterogeneous solid nodule (9 · 6 · 8 mm) in the left lobe was performed once using a 22-gauge needle with negative pressure. After 1 h, the patient developed mild anterior neck pain and visible swelling of the entire thyroid gland. On physical examination, there was mild tenderness and a palpable diffuse goitre. No local swelling or ecchymosis was observed at the site of needle insertion. Signs of airway obstruction were absent. Repeat ultrasound revealed an obvious increase in thyroid volume from 16Æ3 to 48Æ5 ml (nearly three-fold increase). The ultrasound pattern of the bilateral lobes was patchy with hypoechoic areas, which contrasted to the homogeneous pattern before FNA. No signs of haemorrhage were noted along the needle tract. The swelling gradually improved within a few hours. Cytological diagnosis was benign. The second case was a 31-year-old man referred to the clinic because of a multinodular goitre. He presented with a visible, palpable, slightly firm, diffuse goitre. He had a history of mechanical valve replacement surgery for valvular heart disease at 13-year-old and was receiving warfarin and aspirin. There was no relevant family medical history or reported allergies. Thyroid function test and antithyroid antibody levels were normal. Estimated thyroid volume was 37Æ7 ml, and there were multiple nodules in the thyroid gland on ultrasound. FNA of the slightly heterogeneous solid nodule with an irregular margin (15 · 14 · 14 mm) in the right lobe was performed twice using a 22-gauge needle with negative pressure. One and a half hours after the second aspiration, the patient experienced acute neck pain. No local swelling or ecchymosis was observed at the site of needle insertion. Signs of airway obstruction were absent. Ultrasound revealed diffuse swelling of the gland, with an increase in thyroid volume from 37Æ7 to 73Æ7 ml (nearly twofold increase). The ultrasound pattern was similar to that of the previous case. The swelling gradually improved within a few hours. Cytological diagnosis was benign. The third case was a 45-year-old woman referred to the clinic because of a multinodular goitre. She presented with a visible, palpable, diffuse goitre. There was no relevant family medical history or known allergies or use of specific medication. Thyroid function test and antithyroid antibody levels were normal. Ultrasound revealed multiple nodules, and estimated thyroid volume was 29Æ9 ml (Fig. 1a). FNA of the heterogeneous solid nodule (Fig. 1b) measuring 12 · 23 · 24 mm in the left lobe was performed twice using a 22-gauge needle with negative pressure. Two hours after the second aspiration, the patient developed visible swelling of the entire thyroid gland (Fig. 1c). No local swelling or ecchymosis was observed at the site of needle insertion. Signs of airway obstruction were absent. Repeat ultrasound revealed an obvious increase in thyroid volume from 29Æ9 to 71Æ8 ml (nearly 2Æ5-fold increase). The ultrasound pattern was similar to that of the previous case. There was no excess blood flow in the thyroid on Doppler ultrasound (Fig. 1d). The swelling gradually improved within a few hours. Cytological diagnosis was benign. In our clinic, about 2000 cases of FNA are performed a year. We routinely confirm that there is no swelling of the thyroid at 5–10 min after FNA. Currently, only six cases with acute transient thyroid swelling after FNA have been reported in the literature. We experienced three cases with this complication during only 6 weeks. All patients developed diffuse enlargement of both thyroid lobes at 1–2 h after FNA. The thyroid volume increased twoto three-fold compared with the original volume and neither bleeding nor airway obstruction developed. Ultrasound images of the swollen thyroid gland showed a characteristic patchy and heterogeneous appearance in all cases, so that the entire thyroid gland looked cracked. There was no blood flow in the cracks on Doppler ultrasound. Although there may have been fluid (blood or exudate) accumulation in the cracks, this was unclear. The thyroid swelling returned to the original volume within a few hours in all cases. All cytological diagnoses were benign. We have not changed the technique of FNA recently. No clear trigger or underlying pathology has been identified. We have absolutely no idea why three cases with this complication were observed during such a short period. Our experience could suggest that this complication is more frequent than that previously thought.

Diagnosis of iodide transport defect: do we need to measure the saliva/serum radioactive iodide ratio to diagnose iodide transport defect?

BACKGROUND Iodide transport defect (ITD) is an infrequent condition associated with congenital dyshormonogenetic goiter due to mutations in the Na(+)/I(-) symporter (NIS) gene transmitted in an autosomal recessive manner. Herein, we describe a patient with ITD and discuss the features important for the diagnosis, focusing on whether or not measuring the saliva/serum radioactive iodide ratio is useful. SUMMARY A 42-year-old Japanese man attended our hospital in 2010. At that time, he had been off L-thyroxine for several months. He had no obvious mental retardation. His parents were cousins and his sister also had a goiter. Since thyroid dyshormonogenesis could not be ruled out, thyroid function tests, scintigraphy, and ultrasonography were performed. The results showed marked hypothyroidism with a high thyroglobulin level of 627 ng/mL. The results for thyroglobulin antibody and thyroid peroxidase antibody were both negative. Ultrasonography showed an enlarged thyroid gland. Neither the thyroid nor the salivary gland was visualized by (99m)TcO(4)(-) scintigraphy. Therefore, we performed genetic testing for the NIS gene without measuring the saliva/serum radioactive iodide ratio. A homozygous mutation, T354P, was identified in the NIS gene. On the basis of this finding, we could make the definitive diagnosis of ITD due to an NIS mutation. CONCLUSIONS We recommend confirming the presence of the thyroid by ultrasonography of the neck first and then performing (99m)TcO(4)(-) scintigraphy. If neither the salivary gland nor the thyroid is visualized, screening for NIS mutations should be undertaken. This approach obviates the need to undertake measurement of the saliva/serum radioactive iodide ratio to diagnose ITD.

Hypercholinesterasemia in patients with hepatocellular carcinoma: A new paraneoplastic syndrome

SummaryTwo cases of hepatocellular carcinoma (HCC) were described, in whom hypercholinesterasemia was found. Histochemical examinations revealed that there was a significantly increase in enzyme activity of cholinesterase in liver tissue slice obtained from the part of carcinoma in case 1. It was found that cholinesterase activity in homogenized liver tissue in part of carcinoma was much higher than that of non-carcinoma, and even in other HCC cases, hepatic cirrhosis and control liver tissues. These results suggested that HCC cells were capable of producing cholinesterase and, therefore, that hypercholinesterasemia was an additional paraneoplastic syndrome in HCC.

A Japanese family with familial nonautoimmune hyperthyroidism with a novel mutation (Asn406Ser) in extracellular domain of thyrotrophin receptor.

Dear Sir, Smoking is dangerous for health. We are sure that an overwhelming majority of the readers agree with this statement based on heavy data that point out to the pathogenic effect of smoking on cardiovascular diseases, cancers, respiratory diseases or periodontal conditions. There are, however, just few autoimmune diseases that are negatively influenced by smoking, for example, rheumatic arthritis and Grave’s ophtalmopathy (GO). Both diseases have a clear genetic influence and have cigarette smoking as the strongest modifiable risk factor. It is still unclear what pathogenic mechanism is activated by cigarette smoking in these autoimmune processes, but a new model has been recently suggested for a subset of rheumatic arthritis patients. According to this model, chronic exposure to cigarette smoking would induce mechanisms that increase citrullination of certain proteins present in the lungs, which is followed by activation of the immune system against citrullinated proteins. This process includes formation of antibodies to citrullinated protein antigen (ACPA) which also are referred to as anti-cyclic citrullinated peptide (CCP) and results in immune complex formation and release of proinflammatory cytokines that represent the driving force in the chronic inflammation characteristic of RA. We have raised the question whether the same pathogenic mechanism contributes to the negative effect of cigarette smoking in GO. We have therefore investigated the presence of ACPA in serum of 38 smokers with Grave’s disease (GD) using the second-generation CCP test with a sensitivity of 70% and a specificity of 99% (Immunoscan CCPPlus test kit from Euro-Diagnostica, Malmö, Sweden). The levels of CCP antibodies are stable in patients with RA and are not influenced by therapy. The patient group included 19 patients with GD with GO and 19 patients without GO. None of these patients exhibited detectable CCP antibodies in serum (<25 U/ml) pointing out that the negative effect of cigarette smoking is mediated by a different pathogenic mechanism in GO than formation of ACPA.

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.