Naoko Momotani

Management of atrial fibrillation in the post-thyrotoxic state

This study was designed to investigate the appropriate timing for cardioversion in patients with chronic atrial fibrillation who had been rendered euthyroid from a thyrotoxic state. We carried out a retrospective study of 163 patients with thyrotoxic atrial fibrillation, with a mean follow-up of 34 months. With control of thyroid function alone, 101 patients had spontaneous reversion of atrial fibrillation to sinus rhythm and 62 patients had persistent atrial fibrillation. In those with spontaneous reversion, the longest duration of atrial fibrillation prior to the euthyroid state was 13 months. In those with persistent fibrillation, the shortest duration of atrial fibrillation prior to the euthyroid state was eight months. Almost three-quarters of those with spontaneous reversion had conversion to sinus rhythm within three weeks of becoming euthyroid. No spontaneous reversion occurred if atrial fibrillation was still present after the patients had been in a euthyroid state for four months. This study suggests that spontaneous reversion of atrial fibrillation to sinus rhythm is highly unlikely if the duration of atrial fibrillation before the euthyroid state is achieved exceeds 13 months, or if it is still present after the patient has been in a euthyroid state for four months, Cardioversion should be performed at about the 16th week after the euthyroid state is achieved.

Serum leptin concentrations in patients with thyroid disorders

Leptin, the obese gene product, is secreted exclusively by adipocytes and is thought to act as a lipostatic signal that regulates body weight homeostasis. We previously reported that thyroid hormone is one of the up‐regulating factors of leptin in vitro. T3, at physiological concentrations, stimulates leptin mRNA expression and leptin secretion by 3T3‐L1 adipocytes. The aim of this study was to explore the role of thyroid hormone in the regulation of leptin in humans.

Neurodevelopment in Children Born to Hypothyroid Mothers Restored to Normal Thyroxine (T4) Concentration by Late Pregnancy in Japan: No Apparent Influence of Maternal T4 Deficiency

CONTEXT The importance of maternal T₄ for brain development prior to the onset of fetal thyroid function has been suggested in basic studies, and a correlation between mild maternal T₄ deficiency in early gestation and disturbance of neurodevelopment in progenies has been shown in large case-control studies. These findings suggest that maternal T₄ deficiency in early pregnancy potentially affects neurointellectual development. On the other hand, no apparent adverse effect in children born to mothers with overt hypothyroidism in Japan has been reported where maternal T₄ had been restored to normal by late pregnancy. OBJECTIVE We report five cases in Japan showing no apparent effect of maternal T₄ deficiency on neurodevelopment in progenies where low T₄ levels had been corrected by late pregnancy. METHODS Five women with overt hypothyroidism detected at 6-16 wk gestation initiated T₄ treatment. Four women restored euthyroidism by the 20th week. One remained in a subclinical hypothyroid state. Developmental scores of their children were evaluated between 25 months and 11 yr of age by either the Tsumori-Inage Infants Developmental Test or the Wechsler Intelligence Scale for Children-Third Edition and compared to those of corresponding siblings with no exposure to maternal hypothyroidism. RESULTS The development scores of all the children turned out to be either normal or advanced. CONCLUSIONS In iodine-sufficient areas, maternal T₄ deficiency in early pregnancy does not necessarily affect neurodevelopment. Therefore, other potential factors altering neurodevelopment, such as iodine deficiency, must be investigated.

Toxic multinodular goitre in a patient with generalized resistance to thyroid hormone who harbours the R429Q mutation in the thyroid hormone receptor β gene

The association of resistance to thyroid hormone (RTH) due to a receptor defect with toxic multinodular goitre or with carcinoma of the thyroid has not been previously reported. Previous histopathological studies of the thyroid gland in patients with RTH have revealed changes similar to multinodular goitre, probably due to continuous stimulation by TSH. We report here a case of generalized resistance to thyroid hormone associated with a multinodular goitre, which became toxic. The patient was a 46‐year‐old Japanese woman who noticed a goitre although she had no symptoms of thyrotoxicosis. Initial examination revealed elevated serum thyroid hormone levels and a normal TSH level. Ultrasonography disclosed a multinodular goitre with cystic lesions. Three years later, the patient complained that the goitre had become larger and that she had developed symptoms of thyrotoxicosis such as palpitation and hyperhydrosis. Progressive hyperthyroxinaemia with relatively suppressed TSH, increased radioiodine uptake and negative anti‐TSH receptor antibodies led to the diagnosis of toxic multinodular goitre. Subtotal thyroidectomy was performed, and pathological examination revealed a micropapillary carcinoma within the multinodular goitre. Occurrence of thyroid carcinoma should be considered in RTH because its incidence is high in multinodular goitre. Molecular examination revealed the R429Q mutation in the thyroid hormone receptor β gene, which is one of the mutations usually manifesting as the pituitary resistance phenotype. That thyrotoxic manifestations appeared only during toxic stage of multinodular goitre in this case suggests that the phenotype of this type of mutation can be dependent on the amount of thyroid hormone.

Stimulation of thyroid‐stimulating hormone (TSH) receptor antibody production following painless thyroiditis

objective  Development or recurrence of Graves’ disease (GD) following painless thyroiditis (PT) has been documented. Therefore, we measured titres of TSH receptor antibodies (TSHR Ab) using a novel sensitive TSHR Ab assay in patients with PT to determine whether PT enhances TSHR Ab production, possibly triggering the development or recurrence of GD.

The Incidence of Hyperthyroidism in Patients with Adenomatous Goiter

It has been reported that the occurrence of hyperthyroidism from large adenomatous goiter is high in America. Furthermore, many studies in recent years have demonstrated that the Thyrotropin (TSH) response to Thyrotropin Releasing Hormone (TRH) in clinical euthyroid patients with adenomatous goiter resulted in failure. However, there has been no data on the incidence of hyperthyroidism in patients with adenomatous goiter in Japan. The present paper reports the incidence of hyperthyroidism in a large number of patients with adenomatous goiter in Japan. Three hundred and fourteen patients (29 males and 285 females, aged 12-74) with adenomatous goiter are included in this study. The diagnosis of adenomatous goiter depends on the microscopic criteria described by Meissner and Warren, regardless of the nodularity of goiter. The resected goiter weight of these patients ranged from 2.8 to 280.5 gm. Serum concentrations of T3 T4 and TSH were measured in these patients. Furthermore, a TRH test was performed on 51 (3 males and 48 females, aged 13-64) out of 314 patients, who were supposed to be euthyroid from T3 T4 and clinical findings. 500 big TRH were injected intravenously. Blood samples for TSH determination were taken before and 15, 30 and 60 min. after injection. Serum T3 T4 and TSH were measured by using commercial kits (T3 RIA kit, T4 RIA kit and TSH RIA kit, Dainabot Japan). One hundred and sixty-four subjects (54 males and 110 females, aged 10-74), who had no clinical suspicion of thyroid disease and were apparently healthy, served as normal controls. Serum T3 , T4 and TSH values in the control subjects were 117.1 ± 18.4 ng/dl