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Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo- and hyperthyroidism.

Despite their enhanced endogenous de novo cholesterol synthesis, hyperthyroid patients exhibit decreased total and low-density lipoprotein (LDL) cholesterol levels in the serum because of a concomitant increase in LDL catabolism, cholesterol excretion by bile and a reduced enterohepatic bile acid circulation. Hypothyroidism exhibits a reduction (1) in the synthesis of cholesterol and (2) in LDL catabolism, whereas cholesterol reabsorption is unchanged or even enhanced. In addition, obese hypothyroid patients showed an increased cholesterol synthesis which is independent of thyroid hormones and which contributes to the observed LDL cholesterolaemia. Thyroid hormones per se have only a minor influence on plasma triglyceride (TG) levels, but they induce an acceleration of TG turnover and chylomicron clearance rate. In addition, the hepatic lipogenic capacity is increased in hyperthyroidism and reduced in hypothyroidism. However, hepatic total and very low-density lipoprotein (VLDL) triglyceride output is decreased by thyroid hormones due to a reduced re-esterification and a simultaneously increased oxidation of newly synthesized fatty acids. Hypothyroid livers, by contrast, reveal an increased VLDL secretion. Despite their reduced lipogenesis, obese hypothyroidism is often accompanied by a hypertriglyceridaemia type III. The simultaneous stimulation of the synthesis of fatty acids, which are still in part converted to TG, and the degradation of TG contributes to the enhanced thermogenesis in hyperthyroid patients. The concentration and turnover of free fatty acids (FFA) are increased in hyperthyroidism, resulting from a thyroid hormone-induced increase in: (1) lipolysis, explained by an increased adipose tissue sensitivity for lipolytic hormones; and (2) oxidation of fatty acids to CO2 as well as to ketone bodies (KB).(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗

Influence of experimental hyperthyroidism on blood and myocardial serotonin in rats.

Recent reports suggest a role for serotonin in the pathogenesis of primary hypertension and left ventricular (LV) hypertrophy. In this study, we have induced LV hypertrophy by oral feeding of thyroxine at increasing dosages (150-450 micrograms/kg b.wt.) over a 5-week period. The effects of hyperthyroidism on cardiovascular parameters, blood and myocardial serotonin concentrations were assessed. Water-fed rats and formerly hyperthyroid recovered animals served as controls. Thyroxine caused a significant LV hypertrophy: hyperthyroid rats 2.19 +/- 0.16*; controls 1.65 +/- 0.13 g/kg b.wt. (mean +/- SD; *P less than 0.05). An almost complete regression of LV hypertrophy occurred in the recovery group (1.66 +/- 0.20 g/kg b.wt.) 3 weeks after cessation of thyroid hormone application. Thyroxine-treated animals showed a significant increase of serotonin blood levels (thyroxine rats: 2108 +/- 781*, recovery: 1132 +/- 726, controls: 705 +/- 480 ng/ml; *P less than 0.05). The concentrations of serotonin in left ventricular myocardium were increased after thyroid hormone application, whereas the highest levels were found in the recovery group (thyroxine rats: 139.1 +/- 30.4, recovery: 167.2 +/- 43.1, controls: 68.9 +/- 27.9 mg/ml homogenate). Serotonin-containing cells in the left ventricular myocardium were stained immunohistochemically. They were localized perivascularly and were assumed to represent tissue mast cells. In experimental hyperthyroidism the serotonin levels in blood and heart are increased possibly indicating an interaction of both hormones in thyroxine-induced cardiomyopathy.

Administration, Oral↗

Surgery for hyperthyroidism: hemithyroidectomy plus contralateral resection or bilateral resection? A prospective randomized study of postoperative complications and long-term results.

Fifty consecutive patients undergoing surgical treatment for hyperthyroidism were randomized to have either bilateral subtotal resection (n = 23) or hemithyroidectomy plus contralateral resection (n = 27). No significant differences in operating time or intra-operative bleeding were found. No postoperative bleeding and no temporary or persistent recurrent laryngeal nerve paralysis occurred. Four patients who underwent bilateral resection and 2 patients who had hemithyroidectomy resection needed temporary calcium supplementation, and the serum calcium concentrations were slightly lower during the first few postoperative days in the patient undergoing hemithyroidectomy/resection. No persistent hypocalcemia occurred in either of the groups. At follow-up 3-4 years (mean 3.6 years) postoperatively, 1 patient in the bilateral resection group developed recurrent hyperthyroidism; no patients in the hemithyroidectomy/resection group developed recurrent hyperthyroidism. Twelve (44%) patients in the hemithyroidectomy/resection group and 8 (35%) patients in the bilateral resection group needed thyroxine supplementation because of a rise in thyroid stimulating hormone concentration combined with clinical signs of hypothyroidism that developed during follow-up. Hyperthyroidism can be treated by hemithyroidectomy plus contralateral resection without increasing the risk of complications. The results also suggest that when using this method, a slightly larger thyroid remnant should be left to avoid an increase in the incidence of hypothyroidism postoperatively.

Adult↗

Influence of hypo- and hyperthyroidism on rat liver glycerophospholipid metabolism.

The effects of hyper- and hypothyroidism on enzyme activities involved in phospholipid metabolism in the rat liver were studied. Hyperthyroidism significantly decreases activities of both microsomal acyl-CoA:glycero-3-phosphate acyltransferase (GPAT) (34%, p less than 0.01) and microsomal acyl-CoA:1-acylglycero-3-phosphocholine acyltransferase (GPCAT) (28-33%, p less than 0.01). This may contribute to the decreased proportions of certain unsaturated fatty acids found in microsomal phosphoglycerides in hyperthyroidism. Mitochondrial GPAT, phospholipase A2 and cytosol lysophospholipase are unaffected by hyperthyroidism. In contrast, hypothyroidism stimulates mitochondrial GPAT (38%, p less than 0.01) and microsomal GPCAT (14-19%) activities but decreases both mitochondrial phospholipase A2 (36%, p less than 0.01) and cytosol lysophospholipase (56%, p less than 0.01) activities. The increased GPCAT activity may contribute to the increased proportions of certain unsaturated fatty acids found in microsomal phosphoglycerides in hypothyroidism. Triiodothyronine (T3) treatment of the hypothyroid rat (25 micrograms/100 g body weight/day for four days) corrected phospholipase A2 and lysophospholipase activities to the level of the control rat, but failed to correct the increased mitochondrial GPAT activity and not only corrected but lowered GPCAT activity to the level of the hyperthyroid rat.

1-Acylglycerophosphocholine O-Acyltransferase↗

Hyperthyroidism in children.

This study was done to characterize the clinical features, laboratory parameters and response to therapy and outcome of childhood hyperthyroidism. The evaluation included history, examination, laboratory investigations: serum T3, T4, TSH, free T3, free T4 by RIA or immunochemiluminescence (IC), antithyroid antibodies by standard techniques, bone age (BA) by Greulich and Pyle's method, clinical and laboratory response to treatment, and follow-up of 15 children with hyperthyroidism seen in past eight years. Age of onset, presentation, nature and duration of symptoms, family history, anthropometry and signs of hyperthyroidism were recorded. There were 10 girls and 5 boys (2:1). Three families had a history of thyroid disorders. Mean ages of onset and presentation were 8.25 +/- 3.4 and 9.27 +/- 3.2 years respectively. Clinical features included weight loss, heat intolerance and sweating, diarrhoea, behavioral problems, ophthalmopathy and tachycardia. BA was advanced. Serum T3 (mean = 4.29 +/- 1.77 ng/mL), T4 (18.75 +/- 5.64 micrograms/dL), FT3 (7.11 +/- 4.58 pg/mL) and FT4 (2.93 +/- 0.29 ng/mL) were markedly elevated. TSH was suppressed. Anti-microsomal antibodies (AMA) and anti-thyroglobulin antibodies (ATG) were positive in five. They were started on standard treatment with carbimazole 0.5-0.7 mg kg-1. Clinical and biochemical euthyroidism was achieved within 2.5 to 6 months in all, after which the drug was tapered, however, they required treatment for 2 years to 7.5 years. Four children were retreated for relapse and are now euthyroid and off treatment. Childhood hyperthyroidism requires long term treatment and careful monitoring. This study shows a remission rate of 67%.

Adolescent↗

Relapses of hyperthyroidism in patients treated with radioiodine for nodular toxic goiter: relation to thyroid autoimmunity.

Relapses of hyperthyroidism after treatment with radioiodine for uni- or multi-nodular goiter may be accompanied by the appearance of TSAb. However, this phenomenon has only emerged from one retrospective study on Northern European patients, in which it was not possible to determine whether TSAb also appeared in treated patients who did not relapse. The present study aimed to assess the appearance, immunogenic nature and clinical characteristics of hyperthyroidism relapse after treatment with 131I for nodular toxic goiter in patients from the Mediterranean area. A retrospective study was performed on 76 consecutive patients, born and resident in Sicily and aged 56-80 yr at diagnosis, who were treated with radioiodine. Serum aliquots obtained from the patients before 131I treatment and during a follow-up of 36-144 months were assayed for TSAb and TPOAb. The clinical charts of the patients were also re-examined. Twenty-six out of 76 patients (36.8%) had a hyperthyroidism relapse after a first treatment with 131I. Eight of the 26 (30.7%) also relapsed after the second treatment. Three out of 26 (11.5%) relapsed after a third treatment. The 50 patients who required only one treatment and the 18 who relapsed only once were all TSAb-negative at baseline, while 3/8 (37.5%) who relapsed also after the second treatment were already TSAb-positive at baseline. TSAb became positive in 3/18 patients (16.7%) who relapsed once, and in 4/8 (50.0%) of those who relapsed after a second treatment. One of these 7 TSAb-positive relapsers was also already TPOAb-positive at baseline and another became TPOAb-positive after treatment. The presence of circulating TSAb in 3/76 (3.9%) patients before treatment for toxic goiter more probably points to a diagnosis of Marine-Lenhart's syndrome. In contrast, the de novo appearance of TSAb in the presence of hyperthyroidism relapse in 4/76 (5.3%) patients suggests the development of a Graves'-like disease after radioiodine treatment. This occurrence does not seem to have precise ethnic grounds, since the incidence we observed in Mediterranean patients was similar to that previously reported in Northern European patients.

Aged↗

Visual evoked potentials in hypothyroid and hyperthyroid patients before and after achievement of euthyroidism.

Thyroid hormone deficiency is frequently associated with central nervous system (CNS) disturbances such as mental retardation, convulsions, coma etc. Studies of quantitative changes in CNS in hypo- or hyperthyroidism are scarce. Evoked potentials is a good method of assessing the electrical response of the brain to different (visual, acoustic, somatosensory) stimuli and has been used extensively in the study of brain disturbances and to a lesser degree in metabolic diseases. We studied the visual evoked potentials (latency and amplitude) in 12 patients with hyperthyroidism and 15 patients with hypothyroidism, before treatment and after they became euthyroid. Four of the hyperthyroids (33%) had abnormally prolonged (> 104 msec) latencies before therapy. Two of them had clinical exophthalmos. No change was observed after euthyroidism was achieved. On the contrary 7 out of 15 (47%) hypothyroids had abnormally prolonged latencies which became normal in 4 when euthyroidism was achieved. Amplitude was lower than normal in 6 and became normal only in one of them after treatment. None of the hyperthyroid patients had amplitude changes. In conclusion, hypothyroid patients may have changes in the amplitude and/or the latency of visual evoked potentials which are reversible to a great extent with thyroxine. Evoked potentials is another method of studying in humans the metabolic effects of thyroxine deficiency in CNS.

Adult↗

Serum soluble interleukin-2 receptors as an index of the biological activity of thyroid hormones in hyperthyroidism.

In order to examine whether serum soluble Interleukin-2 Receptors (sIL-2R) could be used as a marker of the biological effects of the thyroid hormones, we measured the sIL-2R, sex hormone binding globulin and beta-2 microglobulin levels in thirty-three hyperthyroid patients (14 with Graves' disease, 17 with Toxic Nodular Goiter and 2 with toxic adenoma) before and during treatment with antithyroid drugs. We found that serum sIL-2R concentrations of the patients, at diagnosis, were significantly higher compared with normal controls (2424 +/- 1447 vs 459 +/- 184 U/ml). All hyperthyroid patients had sIL-2R levels > mean + 2SD of normal controls, with 28 of the 33 patients having sIL-2R concentrations higher than 1011 U/ml (mean + 3SD of normal controls). Only 15 patients had SHBG levels higher than 3SD above the mean for the normal controls and 28 had SHBG levels 2SD above the mean for the normal controls. Three of the 5 hyperthyroid patients with normal SHBG levels at presentation had abnormally high sIL-2R levels. In all patients sIL-2R levels decreased gradually during therapy down to normal levels when euthyroidism was achieved. A strong positive correlation was found between sIL-2R, SHBG and T3 and T4 concentrations. Serum B2-microglobulin (B2-m) levels were higher than the upper normal limit only in 9 patients, but a significant decrement was observed in all patients when euthyroidism was achieved. The above results indicate that serum sIL-2R levels could be a useful marker of the in vivo biological effects of the thyroid hormones on lymphocytes in hyperthyroid patients.

Adult↗

Development of hyperthyroidism in nodular goiter and thyroid malignancies in an area of relatively low iodine intake.

A high incidence of toxic nodular goiter has recently been described in areas of relatively low iodine intake. We studied the development of hyperthyroidism in nodular goiter and thyroid malignancies in an area of relatively low iodine intake (median 87 micrograms/h). The material comprised a total of 557 patients admitted to our department in the period 1978-88. The follow-up material consisted of 214 patients with a median age of 55 yr (19-86). Eighty-eight percent were females. The period of observation was 33 months (1-205). All patients had technetium thyroid scans, serum T3, serum T4, T3 uptake test and serum TSH performed. TRH tests were performed in 58 patients. During the follow-up period 45 initially euthyroid patients became hyperthyroid (18%). The incidence increased with age, and the median age in the group, who developed hyperthyroidism, was 65 yr. An estimated minimal incidence of toxic nodular goiter was 23/100,000/yr. Contrary to previous assumption, hyperthyroidism developed frequently in elderly patients with nodular goiter in a low iodine intake area. Thyroid cancer was found in 13 patients corresponding an estimated incidence of 1.5/100,000/yr. The cancer incidence was very low compared to other nordic countries with high iodine intake. This finding may suggest a possible influence of iodine intake on the incidence of thyroid cancer.

Adult↗

Na+, K+ ATPase activity in red cells predicts the recurrence of hyperthyroidism in patients with Graves' disease.

Graves' disease is an autoimmune disorder characterized by a course of remission and relapse. Several parameters have been evaluated for their abilities to predict the clinical course of Graves' disease in patients treated with antithyroid drugs. We recently demonstrated in patients with hyperthyroidism dependent by Graves' disease, an impaired Na+, K+ ATPase activity in red cells and a correlation between ATPase and free T3. With the aim to clarify the relationship between the course of hyperthyroidism and the Na+, K+ ATPase activity during and after discontinuing the antithyroid therapy, we followed up 24 patients for two years. In our previous work by restoring a normal level of free T3, we obtained a normalization of Na+, K+ ATPase activity in the red cells of all the patients. However, in eight subjects after a period of 150 days following the suspension of therapy, we observed a new reduction of ATPase activity in a clinical condition of euthyroidism. The same subjects, newly evaluated after 150 days, developed a clinical and biochemical relapse of hyperthyroidism. We believe that the determination of Na+, K+ ATPase activity is able to predict the recurrence of hyperthyroidism in patients with Graves' disease.

Adult↗

Severe hyperthyroidism due to neoplastic TSH hypersecretion in an old man.

A case is reported of neoplastic TSH hypersecretion in a 62-year-old man with severe hyperthyroidism and cardiovascular disease. He had been known to be hyperthyroid for 14 yr, and had been treated by thyreostatic drugs and subtotal thyroidectomy without satisfactory results. When he was referred to our Center, he was frankly hyperthyroid with both TSH (14 microU/ml) and thyroid hormone serum levels (TT4 24 micrograms/dl, TT3 370 ng/dl, FT41 7.9) above the normal range. alpha-subunit serum level was markedly increased (7.2 ng/ml), while beta-subunit was only 0.3 ng/ml. Skull X-ray showed an enlarged sella turcica with destruction of the dorsum and an intrasellar tumor was visualized on conventional and computer tomography. TSH response was absent after TRH and domperidone, while TSH serum levels decreased by 25% after bromocriptine. Methimazole therapy temporarily decreased serum thyroid hormones to normal levels, while TSH levels rose to 34 microU/ml, thus indicating that pituitary-thyroid feed-back was maintained at a higher set point. Surgical attempt failed because of cardiac problems during anesthesia. Radiotherapy plus methimazole was begun and TSH serum levels first increased markedly, up to 140 microU/ml, and then progressively decreased without reaching normal values. After methimazole withdrawal hyperthyroidism recurred.

Bromocriptine↗

Dose selection for radioiodine therapy of borderline hyperthyroid patients with multifocal and disseminated autonomy on the basis of 99mTc-pertechnetate thyroid uptake.

The aim of this study was to optimise radioiodine therapy of diffuse and nodular toxic goitre by calculation of the radiation dose delivered to the thyroid on the basis of the pretreatment technetium-99m pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)). The TcTU(s) value serves as a substitute for the non-suppressible iodine turnover and the functional autonomous mass. Marinelli's formula was used to calculate tissue absorbed doses of 150 Gy, 200 Gy, 250 Gy and 300 Gy to the thyroids of 438 patients with multifocal and disseminated autonomy. The mean age of patients was 70+/-9 years, and the mean thyroid volume was 54+/-26 ml. Two hundred and sixty-one of the patients had at least one documented previous episode of overt hyperthyroidism. Tissue absorbed doses were adapted to the pretreatment TcTU(s): 150 Gy for a TcTU(s) of 1.5%-2.49%, 200 Gy for a TcTU(s) of 2.5%-3.49%, 250 Gy for a TcTU(s) of 3.5%-4.49% and 300 Gy for a TcTU(s) of > or =4.5%. Normalisation of TcTU(s) and thyrotropin (TSH), thyroid volume reduction and frequency of hypothyroidism and recurrent hyperthyroidism were evaluated 1 year after a single radioiodine therapy. The presented dose strategy resulted in normalisation of TcTU(s) in 96% and an increase in TSH to the normal range in 92%. Recurrent hyperthyroidism was observed in only five patients. Thyroid volume decreased from 54+/-26 before treatment to 34+/-20 ml, a mean reduction of 37%. The frequency of hypothyroidism, at 0.9%, was encouragingly low. Dose selection in accordance with pretreatment TcTU(s) can be recommended for elimination of functional autonomous tissue with a single radioiodine therapy in patients of advanced age with enlarged thyroid glands and relevant autonomous masses who are at risk of developing iodine-induced hyperthyroidism.

Adult↗

Safety and efficacy of surgical management of hyperthyroidism: 15-year experience from a tertiary care center in a developing country.

BACKGROUND: Ideal management of toxic goiter still remains elusive. Though surgical management of toxic multinodular goiter (MNG) is well accepted, surgical treatment of Graves' disease (GD) is still controversial in view of the presumed increased incidence of complications. In this paper, we discuss the experience of the surgical management of hyperthyroidism at a specialized tertiary care endocrine center in a developing country, highlighting the minimal morbidity and satisfactory outcome in experienced hands. MATERIALS AND METHODS: We retrospectively reviewed 325 consecutive patients with hyperthyroidism managed surgically from 1990 to 2005. The etiologic diagnoses were Graves' disease (185), toxic MNG (105), and autonomously functioning thyroid nodules (AFTN) (n = 35). The indications for surgery in Graves' patients were large goiter, relapse after antithyroid drug therapy (ATD), Graves' ophthalmopathy, and presence of nodule. The indications for surgery in toxic MNG were retrosternal extension (n = 15), compressive symptoms (n = 20), and large size (grade II). Among the AFTN nodule size, those greater than 4 cm (85%) formed the major indication for surgery. Subjects with GD and toxic MNG were subjected to subtotal thyroidectomy (n = 93 prior to 1995) or total thyroidectomy (n = 205 post-1995). Hemithyroidectomy was the procedure of choice in patients with AFTN. RESULTS: Patients with Graves' disease were younger in age, with shorter mean duration of goiter when compared with the other 2 groups. Eight percent of patients with Graves' disease without a clinically palpable nodule and 25% of those with nodules had associated differentiated carcinoma, including papillary, follicular, and medullary thyroid cancer. Four percent of patients with toxic MNG had malignancy. Complications included temporary hypocalcemia (24%), permanent hypocalcemia (3%), and permanent vocal-cord palsy (1%). CONCLUSIONS: Surgery for hyperthyroidism has negligible mortality and acceptable morbidity in experienced hands. It is a definite option in selected cases. Immediate and permanent cure of hyperthyroidism is achieved, with no recurrences, after total thyroidectomy. The cosmetic outcome is good, with excellent patient satisfaction and acceptance.

Adult↗

Preoperative change of thyroid stimulating hormone receptor antibody level: possible marker for predicting recurrent hyperthyroidism in patients with Graves' disease after subtotal thyroidectomy.

To make the surgical treatment for Graves' disease more ideal, it is important to elucidate factors related to postoperative thyroid dysfunction in addition to thyroid remnant. Because TSH receptor antibody (TRAb) is thought to be one of the essential causes of Graves' disease, we investigated whether preoperative changes in serum TRAb levels are related to postoperative recurrent hyperthyroidism. Between 1987 and 1992 a total of 1520 patients with Graves' disease were treated by subtotal thyroidectomy. Of these patients 335 visited Ito Hospital with no history of drug treatment of their disease and were treated surgically after several courses of antithyroid drug (ATD) therapy. There were 68 males and 267 females with a mean age of 25.8 years. The mean follow-up period was 48 months (range 12-84 months). Factors analyzed by univariate and multivariate analysis were as follows: age, sex, duration of ATD treatment, weight of resected thyroid, weight of thyroid remnant, preoperative titer of MCHA, TRAb at the time of initial examination (TRAb1), TRAb at the time of surgery (TRAb2), and DeltaTRAb, the difference between TRAb1 and TRAb2 (DeltaTRAb = TRAb1 - TRAb2). The chi-square test was used for univariate analysis and a logistic model for multivariate analysis. Of this group, 119 patients were euthyroid (35.5%), 50 were hyperthyroid (14.9%), and 166 were hypothyroid (49.3%). Significant factors related to recurrent hyperthyroidism were weight of thyroid remnant and DeltaTRAb in both univariate and multivariate analyses. DeltaTRAb is a possible new marker for predicting postoperative recurrent hyperthyroidism. If the preoperative TRAb level is not improved by ATDs in patients with Graves' disease, the thyroid remnant should be made smaller.

Adolescent↗

Prevalence of thyroid cancer in hyperthyroid patients treated by surgery.

A retrospective study has been carried out to evaluate the prevalence of malignant thyroid tumors in 202 patients submitted to surgery for hyperthyroidism. Thyroid cancer was diagnosed in 12 cases (5.9%); the final histologic examination revealed nine papillary carcinomas, one follicular carcinoma, and two Hürthle cell carcinomas. Concurrence of hyperthyroidism and thyroid cancer was more frequent in patients with single toxic adenomas than in those with toxic diffuse or multinodular goiters. In five cases thyroid malignancy was detected in the context of the hyperthyroid lesion (three toxic adenomas and two diffuse goiters). In eight patients the malignant lesion showed a maximum diameter of less than 1 cm, although in five of these cases unfavorable histologic features, such as minimal capsular invasion or multifocality, were present. All patients presenting with thyroid cancer are currently alive and apparently free of residual disease. It is concluded that hyperthyroid patients, particularly those with single toxic adenomas, should be carefully evaluated to exclude the presence of an associated malignancy and to plan the most appropriate therapeutic options.

Adult↗

Outcome of patients surgically treated for various forms of hyperthyroidism with differentiated thyroid cancer: experience at an endocrine center in Italy.

PURPOSE: The incidence and aggressiveness of thyroid cancer associated with hyperthyroidism remains a subject of much controversy. The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid cancer, and to determine whether cancer becomes more aggressive with different forms of hyperthyroidism. METHODS: We retrospectively studied 2,449 patients assessed for hyperthyroidism between 1985 and 2001. All patients with a "cold" nodule on scintigraphy, such as those with Graves' disease and a concomitant solid nodule, underwent fine-needle aspiration biopsy (FNAB). Criteria for surgery were cytological findings indicative of malignancy, goiter with signs of tracheal or esophageal compression, side effects of antithyroid drug therapy, or Graves' disease with multiple relapses after therapy withdrawal or responsiveness to antithyroid drugs. RESULTS: Thyroid cancer was diagnosed more frequently in patients with Graves' disease (6.5%) than in those with uninodular toxic goiter (UTG) (4.4%) or multinodular toxic goiter (MTG) (3.9%). Lymph node involvement was found in 56% of the patients with Graves' disease, in 23% of those with MTG, and in none of those with UTG. Distant metastases were found in one patient with Graves' disease. CONCLUSIONS: Cancers associated with Graves' disease seems to be more aggressive than those associated with MTG or UTG. Thus, we suggest that patients with Graves' disease be carefully monitored for the detection of thyroid nodules. Ultrasonography seems to be the best modality to detect such nodules.

Adult↗

Effects of triiodothyronine-induced hyperthyroidism on lipid peroxidation, erythrocyte resistance and iron-binding and iron-oxidizing antioxidant properties of plasma in the rabbit.

The effect of hyperthyroidism on some oxidative stress parameters is reported. The hyperthyroid state was induced by intraperitoneal injection of triiodothyronine (T3)(10 microg/kg body weight) for 14 days in two groups of female rabbits (3 and 12 months old). The T3 injection caused increase by 1.5-fold to 1.7-fold in T3 serum level, and 2-fold to 3-fold decrease (age-dependent) in body weight gain at the end of experimental period. The induced hyperthyroidism caused a significant increase in the serum concentration of the lipid peroxidation end-product malondialdehyde and lowered erythrocyte resistance to oxidative stress when subjected to the free radical generator 2,2'-azobis(2-amidinopropane) hydrochloride in vitro. The half maximum haemolysis time (HT50) decreased in the both experimental groups of rabbits, by about 12 min in the 3-month-old animals and 27 min in the 12-month-old animals. The study showed for the first time that hyperthyroidism enhances the ability of plasma to protect against iron-binding and iron oxidizing organic radicals. The scavenging property and antioxidant capacity of plasma against iron-binding inorganic radicals also increased. Measurement of erythrocyte resistance to oxidative stress and the protective ability of plasma against oxygen radicals discriminates the thyroid hormone modulatory effects in defence mechanisms against lipid peroxidation.

Animals↗

Circulating atrial natriuretic peptides in hyperthyroidism and hypothyroidism.

Plasma concentrations of atrial natriuretic peptides were measured in 32 normal control subjects, 25 patients with hyperthyroidism, and 18 patients with hypothyroidism. Atrial natriuretic peptide values were measured before and after successful therapy with methimazole or 1-thyroxine. Plasma atrial natriuretic peptide concentration was increased in patients with hyperthyroidism (48.0 +/- 19.5 pg/ml) but was decreased in patients with severe hypothyroidism (16.3 +/- 5.7 pg/ml) compared with values in normal control subjects (31.2 +/- 9.5 pg/ml). There was no significant difference between values in normal control subjects and mildly hypothyroid patients (35.0 +/- 12.2 pg/ml). The plasma atrial natriuretic peptide concentration was correlated with the serum thyroxine level and heart rate. The elevated atrial natriuretic peptide concentration in hyperthyroidism decreased, whereas the reduced atrial natriuretic peptide concentration in severe hypothyroidism increased, compared with the initial value after successful therapy. These results suggest that plasma atrial natriuretic peptide concentration is frequently increased in hyperthyroidism and is frequently decreased in severe hypothyroidism, and that thyroid hormone is one of the regulatory factors for circulating atrial natriuretic peptides.

Adult↗