Tetsuya Mizokami

Reversible primary hypothyroidism with blocking or stimulating type TSH binding inhibitor immunoglobulin following recombinant interferon‐α therapy in patients with pre‐existing thyroid disorders

OBJECTIVE Treatment with recombinant interferon‐α (rIFN‐α) may induce autoimmunity. We have evaluated the effect of rIFN‐α on pre‐existing thyroid disease with special reference to changes in TSH receptor antibody.

Immunological and chemical types of reversible hypothyroidism; clinical characteristics and long‐term prognosis

OBJECTIVE Spontaneous improvement occurs in about one‐half of patients with primary hypothyroidism who reside in an iodine‐sufficient area of Japan, but the pathogenetic factors related to reversible hypothyroidism are still not fully understood. We therefore investigated the clinical features and prognosis of patients with reversible hypothyroidism with or without iodine excess and antithyroid antibodies.

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.

Risk factors for brain infarction in patients with Cushing's disease. Case reports.

Two women aged 51 and 52 years old, respectively, developed a brain infarction before and after undergoing treatment for Cushings disease. A biochemical remission was obtained more than ten years after the onset of signs or symptoms of Cushings disease. The arteriosclerotic changes of the cerebral vessels progressed even during replacement therapy for posttreatment hypopituitarism after they underwent either ablative surgery or radiotherapy. One patient, who showed the signs of Nelsons syndrome, demonstrated severe progressive cerebrovascular sclerotic changes, especially around the irradiated site. It is thus suggested that hypercortisolemia, external pituitary irradiation, and post treatment hypopituitarism may be risk factors for brain infarction. The early diagnosis and adequate treatment are therefore important to prevent cerebrovascular complica tions in patients with Cushings disease.

Multiple intracranial recurrent tumors with hyperprolactinemia combined with a parasellar malignant fibrous histiocytoma long after transfrontal surgery and irradiation to a pituitary adenoma

We herein describe a 40-year-old woman with hyperprolactinemia, an empty sella and two extrasellar intracranial recurrent tumors which were revealed 23 years after the first transfrontal craniotomy and 18 years after the second transfrontal surgery and irradiation to a provable prolactin-producing pituitary macroadenoma. One recurrent tumor was in the right orbital apex causing right oculomotor nerve palsy, and the other tumor was in the right apex partispetrosae and foramen jugulare. Although her serum prolactin level decreased after the administration of bromocriptine mesilate, and the size of the two tumors remained unchanged, a malignant fibrous histiocytoma, which might have been induced by the irradiation 18 years before, grew rapidly in the right suprasellar-prepontine cistern to the right pedunculus cerebralis, leading to a poor prognosis. This case confirmed the importance of the life-lasting follow-up of pituitary adenomas treated with surgery and/or irradiation therapy. Not only ectopic recurrence of the primary tumor but also post-irradiation tumors may become apparent long after the removal of the primary tumor.

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.

Localized painful giant-cell thyroiditis without inflammatory signs in a euthyroid patient followed by serial sonography

We describe a patient with localized painful giant‐cell thyroiditis. A 45‐year‐old woman noticed a tender lump in the left side of the neck. Sonography of the thyroid revealed diffuse swelling of the left lobe with irregular hypoechoic areas. Three months later, the tender swelling subsided, and the hypoechoic areas disappeared without any treatment. There were never any systemic signs of inflammation or thyroid dysfunction. Atypical localized subacute thyroiditis was considered to be the most probable diagnosis based on fine‐needle aspiration cytology and serial sonography. Serial sonographic evaluations are useful to avoid unnecessary surgery.

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...