Biomedical subjects
M Safran
Publications and source records attributed to M Safran.
Serum sex hormone-binding globulin in amiodarone-treated patients. A marker for tissue thyrotoxicosis.
The lodinated antiarrhythmic drug amiodarone frequently causes an elevation of the serum thyroxine (T4) level in patients who remain clinically euthyroid. Less frequently, true iodine-induced hyperthyroidism may occur. The clinical and laboratory distinction between these two conditions is often difficult. Since the serum sex hormone-binding globulin (SHBG) concentration is elevated in hyperthyroidism, this study was carried out to evaluate the serum SHBG concentration as a possible marker of hyperthyroidism in patients receiving amiodarone. Patients treated with amiodarone were divided into three groups: clinically euthyroid with normal serum T4 and triiodothyronine (T3) concentrations, clinically euthyroid with elevated serum T4 and normal T3 concentrations, and clinically hyperthyroid with elevated serum T4 and T3 concentrations. The mean serum SHBG concentration was significantly elevated in amiodarone-induced hyperthyroid patients, while it was normal in euthyroid patients treated with amiodarone who had normal or elevated serum T4 concentrations. The results suggest that the hyperthyroxinemia induced by amiodarone is not associated with excess thyroid hormone action in the liver unless the serum T3 concentration is also elevated.
Environmental factors affecting autoimmune thyroid disease.
A number of environmental factors affect the incidence and progression of autoimmune thyroid disease. Exposure to excess iodine, certain drugs, infectious agents and pollutants, and stress have all been implicated.
Effects of amiodarone and desethylamiodarone on pituitary deiodinase activity and thyrotropin secretion in the rat.
The effect of acute administration of amiodarone, its major metabolite desethylamiodarone and iodine in an amount equal to that contained in amiodarone on serum thyroid hormone and thyrotropin (TSH) concentrations and hepatic and pituitary 5' deiodination of thyroxine (T4) in the euthyroid and hypothyroid rat was evaluated. Amiodarone, desethylamiodarone and iodine all caused a decrease in serum T4 and triiodothyronine (T3) concentrations in euthyroid rats, while serum TSH concentrations and pituitary and hepatic 5' deiodinase activities were decreased only in the amiodarone and desethylamiodarone-treated animals. Serum TSH was increased in the iodine treated rats. Amiodarone, but not iodine, decreased serum T3 and TSH concentrations and pituitary and hepatic 5' deiodinase activities in hypothyroid rats. Inhibition of hepatic 5' deiodinase activity was also observed by the addition of amiodarone in vitro in the absence of dithiothreitol (DTT) but not in the presence of DTT. The decrease in the serum T4 concentration observed with amiodarone and desethylamiodarone administration is probably secondary to the inhibitory effect of iodine released from the drugs on thyroidal T4 synthesis and secretion. Iodine inhibition of thyroidal T3 synthesis and secretion, decreased T4 substrate for a peripheral generation of T3 and inhibition of T4 to T3 conversion all contribute to the decrease in serum T3 observed. The decrease in the serum TSH concentration, despite low serum T4 and T3 concentrations and inhibition of pituitary 5' deiodinase, suggest that amiodarone may function as a thyroid hormone agonist in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
Short term administration of potassium perchlorate restores euthyroidism in amiodarone iodine-induced hypothyroidism.
We studied the effect of potassium perchlorate (KClO4) in patients with hypothyroidism due to amiodarone. The short term administration of KClO4 to six such patients led to prompt restoration of euthyroidism, while the three untreated patients remained hypothyroid for 2-6 months. Since KClO4 inhibits thyroid iodide transport, thereby blocking further entrance of iodide into the thyroid and decreasing intrathyroidal iodide content, amiodarone-associated hypothyroidism is probably secondary to the inhibitory effect of excess intrathyroidal iodine on thyroid hormone synthesis.
Thyrotoxicosis and Graves disease.
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The ocular dose of ultraviolet radiation from sunlight exposure.
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Twenty-four hour radioactive iodine uptake in 35 patients with amiodarone associated thyrotoxicosis.
Amiodarone associated thyrotoxicosis (AAT) occurs in approximately 10% of patients treated with this iodine rich drug in areas of mild iodine deficiency. The thyroid radioactive iodine uptake (RAIU) is usually undetectable or very low in iodine-induced thyrotoxicosis. In the present study, 35 patients with AAT were evaluated. Twelve patients had no thyroid abnormalities by physical exam and all had 24-hr RAIU less than or equal to 4%. In contrast, nine of 11 patients with AAT and diffuse goiters and eight of 12 patients with AAT and nodular goiters had RAIU values greater than 8%. In patients with AAT and goiter it appears possible that the thyroid fails to adapt normally to the excess iodide load, resulting in an inappropriately high RAIU in the presence of excess plasma iodine.
Five patients with iodine-induced hyperthyroidism.
Iodine-induced hyperthyroidism has been frequently described when iodine is introduced into an iodine-deficient area. However, it may also occur in patients with and without previous thyroid disease residing in iodine-sufficient areas. Five patients with iodine-induced hyperthyroidism seen in a 12-month period are described. All were exposed to iodine in the form of commonly used drugs (Betadine, Iodo-Niacin, amiodarone, and radiographic contrast dyes). The cause of iodine-induced hyperthyroidism is unclear, but it is probably more common in patients with goiters containing previously existing areas of autonomous function or iodine-poor thyroglobulin. Iodine-induced hyperthyroidism usually abates after iodine withdrawal in patients with multinodular goiters or normal thyroid glands. The hyperthyroidism is usually treated with beta-blockers and antithyroid thionamide drugs, although reinstitution of iodine to block thyroid hormone release or corticosteroids occasionally may be necessary. Iodine-containing drugs should be given with caution to patients with underlying thyroid disease.
The pharmacokinetics of thyrotropin-releasing hormone (TRH) and deamido-TRH in the rat.
The pharmacokinetics of TRH and its metabolite deamido-TRH (TRH-OH) were evaluated and compared. After a 60- to 90-min infusion of the appropriate peptide into rats, the MCR, half-life of disappearance (t 1/2), and volume of distribution were calculated. The MCR of TRH averaged 4 ml/min, whereas that of TRH-OH was 6.5 ml/min. The serum concentrations of both TRH and TRH-OH decreased in a biexponential manner after stopping the corresponding peptide infusions. The t 1/2 values were 2.4 and 3.9 min for the initial phase of disappearance and 14.1 and 20.6 min for the later phase of disappearance for TRH and TRH-OH, respectively. The volume of distribution of TRH-OH was twice that of TRH. The fractional conversion rate of TRH to TRH-OH, based on serum TRH-OH concentrations measured during TRH infusions, was 0.7-1.4%. Less than 1 ng TRH-OH was excreted in the urine during the last 30 min of TRH infusion. The rapid clearance of TRH-OH and low fractional conversion of TRH to TRH-OH, as measured in serum, suggest that little TRH secretion will be reflected in serum TRH-OH concentrations.
Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy.
Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.
Thyrotropin-releasing hormone metabolism in visceral organ homogenates of the rat.
TRH, which is found in a number of sites outside the central nervous system, is degraded by serum and homogenates of brain, liver, and kidney. The presence of TRH deamidase activity in the brain is well documented. In view of the widespread distribution of TRH, the present study was undertaken to evaluate whether TRH deamidase activity is present in visceral organs and to determine the extent to which TRH degradation, as observed under broken cell conditions, can be accounted for by deamidation. Organs from Sprague-Dawley rats were homogenized in 150 mM sodium maleate, pH 7, and aliquots of the 700 X g supernatant were incubated separately with equimolar amounts of synthetic TRH or the deamidated form of TRH, pGlu-His-Pro. The amount of peptide remaining and the conversion of TRH to deamindated TRH in tubes incubated with TRH were measured by specific RIAs at multiple time points. TRH deamidase activity was found in rat liver, kidney, heart, lung, pancreas, ileum, and skeletal muscle. It was time and temperature dependent and was not observed in boiled tissues. Under relative high substrate conditions, approximately 56%, 50%, and 24% of TRH degradation was via the TRH deamidase pathway in liver, kidney, and lung, respectively. In other tissues, the presence of nondeamidase pathways, in addition to the deamidase pathway, could not be ruled out. TRH deamidation accounted for little or no TRH degradation in serum.
Effect of chronic douching with polyvinylpyrrolidone-iodine on iodine absorption and thyroid function.
Daily vaginal douching with polyvinylpyrrolidone-iodine in 12 euthyroid volunteers for 14 days resulted in a significant increase in serum total iodine concentration and urine iodine excretion. The increase in serum total iodine was associated with a marked decrease in 24-hour iodine 123 uptake by the thyroid and a small but significant increase in serum thyrotropin (TSH) concentration. However, values for serum TSH never rose above the normal range. No significant changes in serum thyroxine (T4), free T4 index (FTI), or triiodothyronine concentrations were observed, although serum T4 and FTI did decrease slightly during treatment. The findings suggest that iodine is absorbed across the vaginal mucosa and that the subsequent increase in serum total iodine does induce subtle increases in serum TSH concentration. There was no evidence, however, of overt hypothyroidism in these euthyroid women.
Follicular variant of papillary thyroid carcinoma: a comparative study of histopathologic features and cytology results in 141 patients.
OBJECTIVE: To characterize the histopathologic features of follicular variant of papillary thyroid carcinoma (FVPC) and its cytology results on fine-needle aspiration (FNA) biopsy and compare them with those of papillary thyroid carcinoma (PC). METHODS: We searched the University of Massachusetts Medical Center pathology database for all surgical specimens associated with a diagnosis of FVPC or PC between January 1992 and February 1998 and reviewed the related pathology reports. In addition, the associated preoperative FNA results were analyzed. RESULTS: On initial assessment, FVPC was associated with a significantly lower incidence of cervical lymph node metastatic involvement in comparison with PC (5.6% versus 35.7%; P<0.001). Even though the mean size of FVPC was larger than that of PC (2.57 cm versus 1.75 cm; P<0.05), FVPC showed a lower incidence of thyroid capsule invasion (5.6% versus 11.4%), infiltrative resection margins (2.8% versus 20.0%; P = 0.01), local soft tissue invasion (7.0% versus 25.7%; P<0.005), and multicentricity (25.4% versus 47.1%; P<0.01). Lymphocytic thyroiditis was a common feature of both FVPC (36.6%) and PC (35.7%). FNA biopsy revealed the presence of malignant cells in 9.8% of patients with FVPC in comparison with 67.5% of patients with PC. Most cytology specimens of FVPC (58.8%) were interpreted as suspicious for a malignant lesion or as a follicular neoplasm. CONCLUSION: FVPC is associated with a significantly lower incidence of cervical lymph node metastatic lesions and invasive histologic features than is PC. Long-term prospective clinical studies are needed to determine whether these findings translate into a more benign natural history for this variant of PC. Results of FNA biopsy in FVPC are more commonly interpreted as suspicious rather than malignant; this factor has major implications for preoperative planning.
[Thyroid uptake of 131I in different forms of hyperthyroidism caused by amiodarone].
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