Graves' disease and mental disorders.

Mental disorders merge highly with thyroid diseases. Because of its regulatory effects on serotonin and noradrenalin, T3 has been linked closely to depression and anxiety. It has known that in many cases, the mental symptoms persist even after normalization of thyroid function by treatment. Psychosocial factors including stress have been associated with mental symptoms even after thyroid function normalization in Graves' disease and a combination of mental disorders have been related to the exacerbation of hyperthyroidism. These findings suggest that psychosomatic approaches based on the bio-psycho-social medical model are important for the treatment of mental disorders associated with Graves' disease.

Effect of L-thyroxine replacement on apolipoprotein B-48 in overt and subclinical hypothyroid patients.

Apolipoprotein B-48 (ApoB-48) is a constituent of chylomicrons and chylomicron remnants, and is thought to be one of the risk factors for atherosclerosis. We evaluated the effect of L-thyroxine (L-T(4)) replacement on serum ApoB-48 levels in patients with primary hypothyroidism. Eighteen patients with overt hypothyroidism (OH) and 18 patients with subclinical hypothyroidism (SH) participated in the study. The lipid profiles, including ApoB-48, were measured in patients with hypothyroidism before and 3 months after L-T(4) replacement. After L-T(4) replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein(a) (Lp(a)), were significantly decreased in patients with OH. In patents with SH, the serum levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), remnant-like particle cholesterol (RLP-C), apolipoprotein B (ApoB), and ApoB-48 decreased significantly after L-T(4) replacement. The serum levels of triglycerides (TG), HDL-C, low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA-1), and Lp(a) did not change significantly. In all 36 patients, the reduction in the ApoB-48 levels correlated significantly with the reduction in TSH levels (r = 0.39, P<0.05). This study showed clearly that L-T(4) replacement might reduce serum levels of ApoB-48 in both OH and SH patients. Such altered serum levels of ApoB-48 in patients with OH and SH may be related to the disturbed metabolism of chylomicron remnants in patients with hypothyroidism.

Exacerbation of thyroid associated ophthalmopathy after arterial embolization therapy in a patient with Graves' disease.

A novel treatment approach to Graves' disease (GD), embolization of the thyroid gland arteries, is evaluated with respect to its indications and adverse effects. We describe an exacerbation of thyroid associated ophthalmopathy (TAO) following thyroid artery embolization in a woman with GD and mild stable TAO (NOSPECS classification, class I grade a). A 45-year-old woman with GD and inactive TAO, in whom thyroid function was stable following blockade of hormone release combined with replacement therapy, underwent embolization of three thyroid arteries. Initially, there were neither adverse effects nor complications; however, the patient developed severe TAO (NOSPECS classification, class IV grade b) 3 months after the arterial embolization. Steroid pulse treatments followed by total thyroidectomy resulted in improvement of the eye signs and symptoms. The clinical course and the serial changes of the thyroglobulin and thyroglobulin-antibody titers suggested that the destruction of thyroid follicles, induced by the arterial embolization, triggered the exacerbation of her TAO. Our experience argues for the use of caution when arterial embolization is considered for GD patients with even the mildest TAO (NOSPECS classification, class I).

Clinical characteristics of 852 patients with subacute thyroiditis before treatment.

OBJECTIVE: Subacute thyroiditis (SAT) is a transient inflammatory disease of the thyroid. We evaluated the clinical characteristics based on laboratory and imaging studies in patients with SAT before treatment. PATIENTS: We reviewed the medical records of 852 patients (107 men and 745 women) with SAT who visited our thyroid clinic at Kuma Hospital from 1996 through 2004. RESULTS: SAT developed most often in female patients aged 40 to 50 years, with significant seasonal clusters during summer to early autumn. While the rates of any virus infections and diseases did not differ from those in the general population, recurrent episodes of SAT at intervals of 13.6+/-5.6 years accounted for 1.6% of all cases. At the onset of SAT, 28.2% of patients had temperatures greater than 38 degrees C and typical symptoms associated with thyrotoxicosis developed in more than 60% of patients. Before treatment, most of the abnormal laboratory findings associated with thyrotoxicosis, inflammation, and liver dysfunction reached peak levels within 1 week after onset. Ultrasound examination showed that half of the patients with unilateral thyroid pain presented with bilateral hypoechogenic area in the thyroid and the rate of bilateral hypoechogenic area tended to increase 2 months after onset. CONCLUSION: Laboratory studies of thyroid dysfunction and inflammation related to SAT presented peak levels within 1 week after onset.

The prevalence of transient thyrotoxicosis after antithyroid drug therapy in patients with Graves' disease.

BACKGROUND: Although transient thyrotoxicosis occurring after antithyroid drug (ATD) withdrawal in patients with Graves' hyperthyroidism has been reported, the prevalence of transient thyrotoxicosis after ATD therapy is as yet unknown. When patients with transient hyperthyroidism are mistakenly regarded as recurrences, they receive unnecessary therapy. The aim of this study was to investigate the prevalence of transient thyrotoxicosis after ATD withdrawal. METHODS: We selected 110 consecutive patients with Graves' disease whose ATD therapy was stopped from December 2002 to September 2004 prospectively. Patients were observed for more than 1 year after ATD withdrawal, and 12 patients dropped out. Serum levels of free thyroxine (FT(4)), thyrotropin, and thyrotropin-binding inhibitor immunoglobulin were measured at ATD withdrawal, and 3, 6, and 12 months after withdrawal. When the patients showed mild thyrotoxicosis (serum FT(4) level of less than 3.00 ng/dL), we followed them up for 1 month without medication. RESULTS: The remission rate of the study group was 61.8% (68/110). Twenty-eight patients became euthyroid after transient thyrotoxicosis, equivalent to 41.2% of the remission patients. Eight of 28 patients showed overt thyrotoxicosis, and the rest subclinical thyrotoxicosis. Transient thyrotoxicosis occurred mostly 3-6 months after ATD withdrawal. CONCLUSIONS: Transient thyrotoxicosis after ATD withdrawal in patients with Graves' disease is not a rare phenomenon. Clinicians should be aware that the recurrence of Graves' disease after the withdrawal of ATD may be transient.

Sustained fever resolved promptly after total thyroidectomy due to huge Hashimoto's fibrous thyroiditis.

We encountered a 55-year-old female patient with Hashimoto's thyroiditis who showed persistent fever, and could not find any source of fever other than the large nontender goiter. Her fever continued with positive CRP for 6 months. Although we did not assume that the inflammation was related to Hashimoto's thyroiditis, total thyroidectomy was performed for cosmetic reasons; however, fever was resolved immediately after thyroidectomy. Pathological diagnosis was Hashimoto's chronic thyroiditis. Immunohistochemical staining showed that the follicular cells were positive for IL-1alpha, IL-1beta, and TNF-alpha. We believed that fever was induced by inflammatory cytokines produced in thyroid. The case indicated that Hashimoto's thyroiditis with nontender goiter could cause idiopathic fever.

Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients.

CONTEXT: Recently, non-high-density lipoprotein cholesterol (non-HDL-C), a measure of total cholesterol minus HDL-C, has emerged as a predictor of cardiovascular disease. OBJECTIVE: We evaluated the effect of L-T4 replacement on non-HDL-C levels in patients with primary hypothyroidism. METHODS: Thirteen patients with overt hypothyroidism and 26 patients with subclinical hypothyroidism participated in the study. The lipid profiles, including non-HDL-C, were measured in patients with hypothyroidism before and 3 months after L-T4 replacement was started. RESULTS: After L-T4 replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein (a) [Lp(a)], were significantly decreased in patients with overt hypothyroidism. In patients with subclinical hypothyroidism, the serum concentrations of total cholesterol, non-HDL-C, remnant-like particle cholesterol, and apolipoprotein B (Apo B) were significantly decreased, whereas no significant changes in the serum concentrations of low-density lipoprotein cholesterol, HDL-C, triglycerides, apolipoprotein A-I, and Lp(a) were observed. In all 39 patients, the reduction in the non-HDL-C levels correlated with the reduction in the low-density lipoprotein cholesterol, remnant-like particle cholesterol, and Apo B levels. However, the reduction in the non-HDL-C levels did not correlate with the reduction in the HDL-C, Lp(a), and apolipoprotein A-I levels. CONCLUSIONS: This study is the first to show that L-T4 replacement may reduce serum concentrations of non-HDL-C in patients with hypothyroidism. The study also suggests that such altered serum concentrations of non-HDL-C in hypothyroidism may be related to the disturbed metabolism of low-density lipoprotein, remnant lipoprotein, and Apo B.

Serum concentrations of granulocyte colony-stimulating factor (G-CSF) in antithyroid drug-induced agranulocytosis.

Granulocyte colony-stimulating factor (G-CSF) levels in serum were determined by a highly-sensitive chemiluminescent enzyme immunoassay (limit of detection, 0.5 pg/ml) in 54 patients with Graves' disease including 6 patients complicated with methimazole-induced agranulocytosis. Serum G-CSF levels in patients with Graves' disease were not different from normal subjects and did not correlate with serum FT4 level or circulating neutrophil counts. Before the onset of agranulocytosis, there was no difference in serum G-CSF level between the patients complicated with agranulocytosis and the uncomplicated patients. When circulating neutrophil counts decreased to less than 0.5 x 10(9)/L, serum G-CSF level elevated with the mean of 106.8 +/- 82.2 (SD) pg/ml, but the level did not correlate with the duration of agranulocytosis. Interestingly, maximum serum G-CSF level during the treatment with recombinant human G-CSF (100 microg/day) was related to bone marrow finding at the onset of agranulocytosis and correlated with the duration of agranulocytosis (r = 0.824, p < 0.05). In conclusion, measuring serum G-CSF levels with a highly-sensitive chemiluminescent enzyme immunoassay revealed that 1) thyrotoxicosis does not affect serum G-CSF level, 2) serum G-CSF level during antithyroid drug treatment does not play an important role in development of agranulocytosis, 3) the maximum serum G-CSF level in the course of agranulocytosis is related to the responsiveness of bone marrow to G-CSF and the recovery time from agranulocytosis.