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Exchange of free cholesterol between plasma and erythrocytes from hyperthyroid and hypothyroid rats in vitro.

In our previous studies, we found that circulating thyroid hormone levels alter cholesterol partition between plasma and erythrocytes by changing the phospholipid content of erythrocytes (Ruggiero, F. M., et al. (1984) Horm. Metabol. Res. 16, 37-40; Ruggiero, F. M., et al. (1987) Lipids 22, 148-151). As an extension of this work, we now followed the exchange of free cholesterol between plasma and erythrocytes in control, hyperthyroid and hypothyroid rats under various experimental conditions in vitro. In control rats, erythrocytes incubated with plasma at 37 degrees C for 4 hr lose 10% of cholesterol which was esterified by lecithin:cholesterol acyltransferase (LCAT) present in the plasma. In hyperthyroid rats, erythrocytes incubated with plasma lose 30% of cholesterol within the same time. By contrast, in the case of hypothyroid rats incubation for 4 hr was necessary to transfer 24% of free cholesterol from plasma to erythrocytes. Inhibition of cholesterol esterification did not affect the loss of erythrocyte cholesterol in control and in hyperthyroid rats. Ca2+ increased the LCAT activity in the plasma of these rats. The findings shed light on the role of thyroid hormones in regulating cholesterol levels in plasma through active cholesterol transfer between plasma and erythrocytes.

Animals↗

Calcium, magnesium, and zinc status in experimental hyperthyroidism.

In this study, experimental hyperthyroidism was established and used to investigate possible alterations in the calcium (Ca), magnesium (Mg), and zinc (Zn) homeostasis by assessing their concentrations in plasma and erythrocytes. In the L-thyroxine-induced hyperthyroidism condition, the experimental animals show a significant decrease in erythrocyte Ca, Mg, and Zn concentrations, and a significant decrease in plasma Mg concentration. Significant positive correlations were found for Mg and Zn both in plasma and in erythrocytes. The results suggest that the homeostasis of Ca, Mg, and Zn is altered during experimental hyperthyroidism.

Animals↗

Is it safe to treat hyperthyroid patients with I-131 without fear of thyroid storm?

OBJECTIVES: Thyroid storm is extremely rare. However, hyperthyroid patients with severe thyrotoxicosis are frequently not treated immediately with I-131 for fear of thyroid storm but are placed on thiouracil drugs for varying periods of time. We demonstrate herein that it is safe to treat these patients with 1-131, without pretreatment with thiouracil drugs, provided they do not have complicating intercurrent disease. Our definition of severe hyperthyroidism includes marked signs and symptoms of thyrotoxicosis, suppressed TSH, markedly elevated free T4 and/or free T3 and elevated radioactive iodine uptake (RAIU) (>30%) at 4 or 24 hours. Our diagnostic criteria for thyroid storm include two or more findings of fever (>38 degrees C, 100 degrees F), severe tachycardia, high pulse pressure, agitation with tremors, flushing, sweating, heart failure, nausea, vomiting, diarrhea, jaundice associated with high free T4 and/or free T3. METHODS: Patients were selected retrospectively for the period between August 2003 and December 2004. One hundred and twenty-two patient visits were identified. These patients were treated with 370-740 MBq (10-20 mCi) of I-131 and were evaluated for any evidence of thyroid storm. Most of the patients were placed on beta blocker drugs at the time of initial I-131 therapy; these were continued for at least two months, when the first follow-up visit occurred. At the time of I-131 therapy, it is our policy to educate the patients to seek immediate medical attention for exacerbation of symptoms of thyrotoxicosis. RESULTS: Not one of these patients developed thyroid storm. A subset of 25% of these cases with higher potential for thyroid storm (RAIU more than 65%, very marked signs and symptoms, and very markedly elevated free T4 and/or free T3) also tolerated the I-131 therapy well with marked clinical improvement and no exacerbation of the thyrotoxic state. CONCLUSION: It is safe to administer I-131 to patients who are severely hyperthyroid without fear of thyroid storm, provided beta blockade drugs are used to control the signs and symptoms; patient education is also important. With these steps, 4-6 weeks of prior medical treatment may not be necessary.

Adolescent↗

[Occurrence of immune hyperthyroidism after radioiodine therapy of autonomous goiter].

AIM: The goal of the study was to examine the prevalence of Graves' disease following I-131 treatment of autonomous goiter with special regard to pretreatment scintigraphic patterns. PATIENTS AND METHOD: Pre- and posttreatment in-vitro and in-vivo parameters were studied in 375 consecutive patients treated with I-131 therapy for nodular or diffuse autonomous goiter. All patients included were within ambulant control for at least 2.5 months following treatment. According to the pretreatment Tc-99m pertechnetate scan 59% (220/375) had multifocal (MF), 23% (86/375) unifocal (UF), 10% (38/375) mixed focal-disseminated (FD) and 8% (31/375) disseminated (D) scintigraphic patterns. RESULTS: In 93.9% (352/375), the autonomous tissue was totally, in 2.1% (8/375) partially and in 1.6% (6/375) insufficiently eliminated. In 2.4% (9/375) a relapse of hyperthyroidism was observed 2 to 10 months following I-131 therapy. In 8 patients a relapse of hyperthyroidism was accompanied or followed by an elevation of the previously non-elevated TSH-receptor antibody (TRAb) level and in 1 patient by an TRAb increase to the upper borderline range implicating Graves' disease. With the prevalence of Graves' disease following I-131 therapy a statistically significant difference in pretreatment Tc-99m pertechnetate scintigraphic patterns was found: 0% of unifocal (0/86) or multifocal (0/220), however 18% (7/38) of focal-disseminated and 7% (2/31) of disseminated scintigraphic patterns. From the 366 patients without relapse of hyperthyroidism 2 (MF) had elevated pre- and posttreatment TRAb levels and 3 (D) had elevated TRAb levels for the first time after I-131 therapy. CONCLUSION: There is a low overall prevalence (2.4%) of Graves' disease following I-131 therapy for nodular or diffuse autonomous goiter. However, the prevalence of posttreatment Graves' disease is highly dependent upon pretreatment scintigraphic patterns exhibiting focal-disseminated or disseminated patterns.

Adult↗

Bone turnover in hyperthyroidism before and after thyrostatic management.

Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary-hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered.

Adult↗

Thyroid cancer in hyperthyroidism: incidence rates and value of ultrasound-guided fine-needle aspiration biopsy in this patient group.

Three hundred and thirty-three hyperthyroidism cases were retrospectively investigated to provide information about the association between hyperthyroidism and thyroid cancer. There were 112 cases of toxic multinodular goiter (TMNG), 77 cases of toxic nodular goiter (TNG) and 144 cases of Graves' disease (GD). All nodules detected in GD patients, all nodules greater than 1 cm diameter in nodular goiter patients, nodules 5-10 mm size diameter if they had calcification were fine-needle biopsied (FNAB) under ultrasound guidance (US-guided), and a total of 612 such biopsies were performed. The biopsy samples were cytologically assessed as benign (no.=552; 90.2%), suspicious (no.=6; 1.1%), malignant (no.=13; 2.1%), or inadequate for diagnosis (no.=41; 6.7%). All patients with a biopsy diagnosis of malignant or suspicious nodules underwent surgery. Histological examination confirmed the diagnosis of thyroid cancer in all 13 (2.1%) patients with malignant FNAB findings. Papillary thyroid carcinoma (PTC) was identified in 2 patients with TMNG (%1.8), 5 with TNG (%6.5) and 5 with GD (%3.5). Metastatic follicular thyroid carcinoma (FTC) was identified in a patient with TNG. Thyroid malignancy (micro- or macrocarcinoma) was diagnosed pre-operatively in all 13 cases by US-guided FNAB. Thyroid cancer was diagnosed in 6 (5.5%) of the 109 nodules detected in the TNG group, 2 (0.44%) of the 452 nodules detected in the TMNG group, and 5 (9.8%) of the 51 nodules detected in the GD group. Two (2.6%) of the 77 functioning nodules in the TNG patients were malignant, but none of the 402 functioning nodules in the TMNG patients was malignant. In patients with hyperthyroidism, US-guided FNAB is useful for detecting thyroid cancer in nodules greater than 5 mm diameter before radioiodine therapy or surgery.

Adult↗

Circulating soluble interleukin 2 receptor concentration is increased in both immunogenic and nonimmunogenic hyperthyroidism.

High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves' disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves' disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significant increased concentrations of sIL-2R were found in 46 patients with untreated hyperthyroid GD (mean +/- SD: 1,683 +/- 1016 U/ml, vs 461 +/- 186 U/ml in normal controls, p less than 0.0001) and in 21 with untreated TA (1,111 +/- 617 U/ml, p less than 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or 131I administration was associated with a normalization of sIL-2R (516 +/- 174 U/ml in 38 patients with GD and 365 +/- 90 U/ml in 12 with TA; p = NS vs normals and p less than 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT3) (r = 0.724, p less than 0.0001) or free thyroxine (FT4) (r = 0.698, p less than 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Hyperthyroidism due to Graves' disease and due to autonomous goiter.

An attempt was made to classify 326 patients with hyperthyroidism due to Graves' disease and due to autonomous goiter in an area of endemic iodine deficient goiter using the following two sets of criteria: Primary criteria: the presence of endocrine ophthalmopathy (Graves' disease) and the absence of endocrine ophthalmopathy and the absence of microsomal antibodies greater than or equal to 1:1600 (autonomous goiter). Sixty-nine percent of the patients could be divided in the two groups with the aid of these criteria. Secondary criteria: age greater than 50 years, presence of a goiter, presence of thyroid nodules, activity distribution in the scan, iodine intake determined by iodine excretion in the urine. These criteria had to be applied in the 31% of the patients who could not be divided into one of the two groups using the primary criteria. The secondary criteria were accumulative. Using these criteria 55% of the 326 patients were classified as having Graves' disease and 45% as having autonomous goiter. The probability of correct grouping when both primary and secondary criteria were applied was estimated to be 90% compared to 54% when we used only the classical terms, i.e. endocrine ophthalmopathy and diffuse goiter on the one hand and multinodular goiter without endocrine ophthalmopathy on the other hand. In a second group of 120 hyperthyroid patients classified in this way, thyrotropin displacing activity was determined independently. Its prevalence was 79% in patients classified as having Graves' disease but only 3% in those classified as having autonomous goiter. The prevalence of TDA observed in patients who presumably had autonomous goiter was in the same range as in the following groups: 45 normal individuals; 126 patients with euthyroid goiter; and in 112 patients with euthyroid and hyperthyroid autonomous adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Anti-iodothyronine autoantibodies in a girl with hyperthyroidism due to pituitary resistance to thyroid hormones.

In the present study, we report the uncommon case of a 9.6-yr-old girl with circulating anti-T3 autoantibodies (T3-Ab) and hyperthyroidism due to inappropriate secretion of TSH (IST). The diagnosis of IST was based on the findings of normal TSH levels (2.4 mU/L) in the presence of high free T4 (28.2 pmol/L) and free T3 (FT3) levels, as measured by direct measurement methods based on "one-step" analog tracer (28.0 pmol/L) and "two-step" Lisophase (13.3 pmol/L) techniques. The discrepancy between the two measurements suggested a methodological interference due to T3-Ab in "one-step" technique, being the "two-step" methodology unaffected by the presence of such autoantibodies. T3-Ab were documented by high nonspecific binding of serum to labeled T3 (38.0% vs 4.3 +/- 2.1% in controls). The clinical picture of hyperthyroidism, the qualitatively normal TSH responses to TRH and T3 suppression tests, the normal pituitary imaging and the values of some parameters of peripheral thyroid hormone action compatible with hyperthyroidism indicated that the patient was affected by pituitary resistance to thyroid hormones (PRTH). Chronic treatment with dopaminergic agent bromocriptine (7.5 mg/day) did not cause TSH secretion to be suppressed, while the administration of thyroid hormone analog TRIAC (1.4 mg/day) inhibited TSH release (from 2.4 to 0.2 mU/L). As a consequence, circulating thyroid hormone levels normalized and euthyroidism was restored. During TRIAC administration, FT3 levels, measured by "one-step" analog tracer technique, gave spuriously high values due to the methodological interference of T3-Ab (15.2 vs 4.3 pmol/L as measured by "two-step" Lisophase technique).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Thyroid blood flow rate in man. Electromagnetic flowmetry during operation in euthyroid normal gland, nontoxic goiter, and hyperthyroidism.

Human thyroid blood flow rate (TBF) was measured during operations by electromagnetic flowmetry in 75 euthyroid patients with normal thyroid tissue, nodular goiter, or solitary adenoma, and in 22 hyperthyroid patients with diffuse or nodular goiter. Blood flow rate was measured in one to four of the thyroid arteries. No difference in blood flow rate was seen between the left and right lobes. The slight difference found between the inferior and superior arteries was not significant. In each subject, total TBF was calculated as 4 times the mean of the recorded blood flow in the single arteries. The total TBF was 31 (9-109) ml/min (inner 95 percentile range) in euthyroid patients, similar in all 3 groups. This is less than in most earlier reports. The relative TBF was 1.2 (0.4-3.8) ml/min/g thyroid tissue in normal thyroid tissue and 0.6 (0.1-3.7) ml/min/g in nontoxic nodular goiter (p less than 0.01). Patients with hyperthyroidism had a higher total TBF 54 (15-197) ml/Min (p less than 0.001), despite preoperative treatment giving euthyroidism, Similar TBF rates were found in 3 hyperthyroid patients given propranolol preoperatively. Electromagnetic flowmetry is applicable to study thyroid blood flow rate. Human TBF shows considerable interindividual variations, which must be kept in mind when studying directly the rate of thyroid hormone secretion from arteriovenous gradients.

Adult↗

Iodine contamination as a cause of hyperthyroidism or lack of TSH response to TRH stimulation (results based on a screening investigation).

The sera of all patients with completely suppressed TSH response to TRH obtained during one year (n = 668), and of those with diminished TSH response (n = 153) were screened for total serum iodine content. The ratio between serum iodine and thyroxine iodine below 1.5 indicates none or only a minor degree of iodine contamination, whereas a ratio above 1.5 is a clear index of exogenous iodine contamination. Eighty-four (21.3%) of 395 patients with overt hyperthyroidism were iodine contaminated. No prevalence of hyperthyroidism with hyperthyroxinemia could be detected as compared to T3-hyperthyroidism in the contaminated groups. Surprisingly, the iodine contamination rate was twice as high in 273 patients with suppressed TSH response to TRH but normal thyroid hormone levels and not fully explained thyroidal diseases. A high incidence of multifocal autonomous adenomas of the thyroid is the most probable explanation for the TSH suppression in iodine contaminated patients with normal thyroid hormone levels.

Angiocardiography↗

Non-autoimmune hyperthyroidism associated with isolated bilateral ocular lymphoma mimicking Graves' disease with ophthalmopathy: a cause of misdiagnosis.

A very rare association of non-autoimmune hyperthyroidism due to nodular goiter with isolated bilateral non-Hodgkin's ocular lymphoma is described. A 66-year-old woman presented with bilateral proptosis, marked periocular swelling, conjunctival hyperemia and chemosis, severe extraocular muscle impairment with diplopia. Thyroid function tests showed normal free thyroid hormone concentrations with undetectable serum thyrotropin levels. Patient was placed on antithyroid drug treatment, ocular conditions deteriorated. More than two years later, when first seen in our institution, orbital CT scan showed the presence of a retro-ocular mass that, at biopsy, proved to be B-cell non-Hodgkin's lymphoma, apparently with no localization in other sites. Thyroid evaluation revealed subclinical hyperthyroidism due to an autonomous thyroid nodule in the left lobe of the gland. Radiotherapy of the orbit was followed by a dramatic regression of lymphoma, but further staging some months later showed involvement of several abdominal lymph node structures. This case underscores the need of a thorough diagnostic work-up of ocular disease resembling Graves' ophthalmopathy, even when it is bilateral and associated with overt or subclinical hyperthyroidism.

Aged↗

Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment.

Plasma concentration of fibrinogen and B beta 15-42, a specific product of fibrinogen metabolism induced by plasmin, were measured in a group of patients with untreated hyperthyroidism and in controls. Significantly increased plasma levels of both parameters were observed in hyperthyroid patients. The restoration of euthyroidism either by antithyroid drug or by radioiodine caused a significant decrease of fibrinogen and B beta 15-42. These data indicate that hyperthyroidism is another clinical condition associated with increased concentration of fibrinogen and B beta 15-42.

Adult↗

Atrial fibrillation with hyperthyroidism in a 14-year-old male.

Atrial fibrillation is an uncommon feature of hyperthyroidism in childhood. We report a 14-year-old male who was referred to our hospital with hyperthyroidism and atrial fibrillation. He had a family history of atrial fibrillation. Spontaneous conversion of atrial fibrillation to sinus rhythm occurred 20 weeks after achieving euthyroid state by an antithyroid agent and a beta-blocker. Atrial fibrillation reoccurred after reduction of antithyroid medication and persisted for 19 weeks. Successful electrical cardioversion was performed resulting in conversion of heart rhythm to sinus. Usually, hyperthyroidism associated atrial fibrillation spontaneously reverts to sinus rhythm several weeks after achieving a euthyroid state. Control of thyroid function and heart rate is the goal of therapy for this type of atrial fibrillation.

Adolescent↗

Enhancement of radioiodine uptake in hyperthyroidism with hydrochlorothiazide: a prospective randomised control study.

The aim of this study was to determine whether hydrochlorothiazide (HCTZ) could improve radioiodine uptake in low-uptake hyperthyroid patients. Eighteen hyperthyroid patients with low 3-h and 24-h iodine-131 uptake were recruited to the study. Eleven patients were assigned to the HCTZ group, and seven to the control group. Two weeks after the first, baseline uptake study, a second uptake study was performed. Patients in both groups had a low-iodine diet after the first uptake study. In the HCTZ group, 50 mg of HCTZ was administered twice a day for 5 days prior to the second uptake study. Improvement in uptake at 3 and 24 h in the second uptake study, as compared with the baseline study, was assessed within and between groups. In the control group, compared with the baseline study there was a significant improvement in uptake at 3 h ( P=0.03) but a non-significant improvement at 24 h ( P=0.07). In the HCTZ group, significant improvements were observed at both 3 h ( P=0.0005) and 24 h ( P=2.28 x 10(-5)). Patients in the HCTZ group had statistically greater improvement in uptake at both 3 h and 24 h compared with the control group ( P=0.003 and 0.0008, respectively). There was a 7.18-fold average improvement in uptake in the HCTZ group at 24 h, compared with only a 1.33-fold improvement in the control group. Administration of HCTZ significantly improves 24-h radioiodine uptake in high-iodide pool, low-uptake hyperthyroid patients compared with patients who have received a low-iodine diet alone.

Adult↗

Inflammation of the cardiac conduction system in a case of hyperthyroidism.

A 37-year-old female showed signs of hyperthyroidism 2 weeks before death after a partial thyroidectomy was carried out 15 years previously. An examination 3 days before death revealed a normal blood cell count, an increased level of thyroidal hormones, sinus tachycardia and a high blood pressure of 170/90 mm Hg. A hyperthyroidism was diagnosed and therapy with carbimazol (2 x 10 mg) was started but 2 days later fever and chill occurred and before death short phases of unconsciousness and dyspnoea. The autopsy findings showed an interstitial inflammation of the AV-node, the His-bundle and its branches which can correlate with typical ECG changes in hyperthyroidism.

Adult↗

The use of LigaSure in patients with hyperthyroidism.

BACKGROUND: Thyroidectomies of hyperthyroidic patients are known to be more blood-spattered than the operations performed for euthyroid nodular diseases and require careful hemostasis. Our purpose was to evaluate the efficacy of the use of LigaSure in patients with hyperthyroidism. MATERIALS AND METHODS: Between January 2004 and October 2005, 100 patients underwent total or near-total thyroidectomy. Bipolar vessel ligation system (LigaSure) was the choice of modality for hemostasis in half of these patients, and the conventional suture ligation technique was used for the rest. The following data were evaluated non-randomized and prospectively in this study: patients demographics, thyroid pathology, operative duration, presence of complications, and the duration of the hospital stay. Comparisons of the data were evaluated by the Wilcoxon and chi-square tests. RESULTS: Among the patients of the LigaSure group, 14 patients were detected to have hyperthyroidism (seven patients with Graves' disease and another seven patients with multinodular toxic goiter), while 36 patients were found to be euthyroidic. The durations of the operation time and of the hospital stay of the patients in the LigaSure group were significantly lower than the conventional thyroidectomy group (p<0.05). The complication rates of the LigaSure and conventional thyroidectomy groups were 4 and 6%, respectively (p>0.05). CONCLUSIONS: The use of LigaSure as an operative technique in the treatment of Graves' disease and toxic goiter is a safe and effective modality that provides a shorter hospital stay and a shorter operation time as well.

Adolescent↗

Thyroid lymphoma in a patient with hyperthyroidism.

A patient presenting with hyperthyroidism had a rapidly enlarging thyroid mass that histopathologically was a diffuse histiocytic lymphoma arising in a gland with Hashimoto's thyroiditis. The concurrent development of both hyperthyroidism and lymphoma may have resulted from similar immunologic abnormalities. Appreciation of the relationship between thyroid lymphoma and Hashimoto's thyroiditis, and their presentation with either hypothyroidism or hyperthyroidism should lead to an earlier diagnosis of lymphoma and improved survival.

Body Weight↗