Outpatient management of patients with large multinodular goitres treated with fractionated radioiodine

The efficacy of fractionated out-patient radioiodine therapy in 38 patients with compressive symptoms due to long-standing large multinodular goitres was assessed. The diagnosis was established by clinical assessment in addition to technetium-99m pertechnetate thyroid scan or computed tomography scan of the thyroid and mediastinum. Oral iodine-131 therapy was administered as a 2.22 GBq (60 mCi) cumulative dose over 4 months (555 MBq per month). All patients were monitored with serum thyroid-stimulating hormone and free thyroxine (+/- free tri-iodothyronine) assays before the treatment and after each dose fraction. Clinical and biochemical follow-up was performed on all patients and ranged from 6 to 45 months after therapy. The patients consisted of 35 female and three male patients with a median age of 59 years (range 37-87 years). Prior to treatment 20 patients were biochemically hyperthyroid and 18 were euthyroid. Overall, 71% of patients reported a subjective improvement in compressive symptoms and 29% reported no change. Clinically assessed reduction in goitre size occurred in 92% of patients while there was no change in 8%. At 3 months of follow-up, 31% of patients had become hypothyroid and at 18 months 66% were hypothyroid. Seven hyperthyroid patients (35%) became euthyroid and 13 hyperthyroid patients (65%) became hypothyroid. Three patients who became hypothyroid experienced neck soreness (transient in one patient, persistent in two patients). There were no differences in outcome between patients who were hyperthyroid and those who were euthyroid prior to treatment. Fractionated out-patient radioiodine therapy showed excellent short- and medium-term safety, was very well tolerated and offered a satisfactory alternative treatment to surgery.     

High dosage thyroxine treatment in therapy and prevention refractory patients with affective psychoses

Natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) against k562 human tumor cell targets was studied in patients with Graves' disease and Hashimoto's thyroiditis. NK activity was measured in a standard 4-hour 51chromium (Cr) release assay. Cytotoxicity was expressed as lytic units (LU)/10(6) PBL. Significantly decreased NK cell activity was demonstrated in both groups of patients, with mean (+/- SE) lytic units of 10.3 (+/- 9.1) and 13.3 (+/- 10.3) for patients with Graves' disease and Hashimoto's thyroiditis, respectively, compared with 36.0 (+/- 26.3) for age- and sex-matched normal subjects. When patients with Graves' disease were analyzed according to their thyroid status; NK activity was significantly depressed in (1) hyperthyroid patients before treatment; (2) hyperthyroid patients receiving antithyroid therapy; and (3) euthyroid patients receiving antithyroid therapy, compared with normal subjects. Graves' disease patients who were hypothyroid after radioactive iodine therapy or thyroidectomy had normal NK activity. No significant differences between hyperthyroid and euthyroid patients or between hypothyroid patients and normal subjects were demonstrated. NK activity in patients with Graves' disease did not correlate with serum levels of thyroxine, the presence or severity of ophthalmopathy, or titers of serum thyroid antibodies. In patients with Hashimoto's thyroiditis there was no correlation between NK activity and goiter size, titers of antithyroid antibodies, or thyroid status. These findings suggest that depression of NK activity in both disorders is secondary to abnormalities of thyroid hormone secretion, although an effect of the underlying autoimmune reactions has not been excluded.     

Plasma cholesteryl ester transfer protein activity in hyper- and hypothyroidism

Thyroid dysfunction is associated with multiple changes in lipoprotein metabolism, and we have determined the effects of thyroid dysfunction on plasma cholesteryl ester transfer protein (CETP) activity. CETP is a plasma protein that mediates the exchange of cholesteryl ester and triglyceride between plasma lipoproteins and plays an important role in high-density lipoprotein metabolism and in the reverse cholesterol transport pathway. Plasma CETP activity was assayed in 18 hyperthyroid and in 17 hypothyroid patients, before and after treatment, by measuring the transfer of cholesteryl esters from exogenous radiolabeled high-density lipoprotein to apolipoprotein B-containing lipoproteins. Plasma CETP activity was increased in hyperthyroid patients, compared with their matched controls (22.11 +/- 8.92% transferred/5 microL.4 h vs. 16.75 +/- 6.48, P < 0.05), whereas in hypothyroid patients, plasma CETP activity was decreased (11.14 +/- 4.84% transferred/5 microL.4 h vs. 17.26 +/- 7.13, P < 0.01). Plasma CETP activity decreased after treatment of thyrotoxicosis, although a significant change was observed, mainly in the severely thyrotoxic patients with free T4 > 100 pmol/L (n = 11, 25.61 +/- 8.12% transferred/5 microL.4 h vs. 21.71 +/- 7.84, P < 0.05). In the hypothyroid patients, there was a significant increase in plasma CETP activity after thyroxine replacement (11.14 +/- 4.84% transferred/5 microL.4 h vs. 15.46 +/- 6.71, P < 0.01). There was a strong positive correlation between log(free T4) and plasma CETP activity (r = 0.51, P < 0.001). In summary, both hyper- and hypothyroidism are associated with significant changes in plasma CETP activity, and these changes are corrected when the patients have been rendered euthyroid.     

The correlation of the vasopressin- and oxytocin-producing activities of different nuclei in the hypothalamo-hypophyseal neurosecretory system]

Radioiodine long has proven to be a safe and effective treatment for thyroid disease. Nonetheless, persisting concerns regarding radiogenic stochastic risks (e.g., carcinogenesis) to patients, their families, and the general public have led regulators to establish criteria for release of 131I-containing patients from medical confinement, with limits ranging from as low as 2 mCi in some parts of Europe to as high as 30 mCi in the United States. To optimize clinical efficacy and cost-effectiveness of 131I therapy, such regulations should be based on logical dosimetric considerations. The thyroidal absorbed dose, proportional to maximum uptake and effective half-life and inversely proportional to mass, is typically approximately 1,500 rad/mCi of 131I administered to a euthyroid adult (based on a thyroid maximum uptake of 25%, effective half-life equivalent to the physical half-life of 131I (8.04 days), and mass of 20 g). As thyroid uptake increases from 0% to 100%, extrathyroidal absorbed doses range from a minimum of 0.15 to 0.5 rad/mCi for breast and gonads to a maximum of 1.5 to 2 rad/mCi for stomach and salivary glands; the absorbed doses of the urinary bladder wall, in contrast, decrease with increasing thyroid uptake, from 2 to 0.6 rad/mCi. In hyperthyroid patients (approximately 15%) with a small iodine pool (so-called small patients), the short effective half-life of radioiodine in the thyroid and high serum concentrations of long-lived protein-bound 131I result in a standard 7,000-rad absorbed dose for treatment of Graves' disease requiring an administered activity of 28 mCi of 131I and yielding a prohibitively high blood absorbed dose of 150 rad. Importantly, once the fetal thyroid begins to function and accumulate radioiodine at a gestational age of 10-12 weeks, fetal thyroid absorbed doses as large as 5,000 rad/mCi of 131I administered to the mother can result. Thus, pregnancy is an absolute contraindication to administration of 131I because of the risk of radiogenic cretinism. Based on actual measurements of thyroid activity and of external absorbed dose, the total thyroid and mean extrathyroidal absorbed doses to adult family members from immediately released 131I-treated patients are approximately 0.01 and approximately 0.02 rad/mCi administered, respectively, yielding an effective dose of approximately 0.02 rem/mCi. A maximum permissible effective dose of 0.5 rem for adults therefore is consistent with a release criterion of 30 mCi of retained 131I. Lower-activity release criteria therefore may be unnecessarily restrictive.     

Parameters of linear-quadratic radiation dose-effect relationships: dependence on LET and mechanisms of reproductive cell death

Nitric oxide mediates a wide array of cellular functions in many tissues. It is generated by three known isoforms of nitric oxide synthases (NOS). Recently, the endothelial isoform, NOSIII, was shown to be abundantly expressed in the rat thyroid gland and its expression increased in goitrous glands. In this study, we analyzed whether NOSIII is expressed in human thyroid tissue and whether levels of expression vary in different states of thyroid gland function. Semiquantitative RT-PCR was used to assess variations in NOSIII gene expression in seven patients with Graves' disease, one with a TSH-receptor germline mutation and six hypothyroid patients (Hashimoto's thyroiditis). Protein expression and subcellular localization were determined by immunohistochemistry (two normal thyroids, five multinodular goiters, ten hyperthyroid patients and two hypothyroid patients). NOSIII mRNA was detected in all samples: the levels were significantly higher in tissues from hyperthyroid patients compared with euthyroid and hypothyroid patients. NOSIII immunoreactivity was detected in vascular endothelial cells, but was also found in thyroid follicular cells. In patients with Graves' disease, the immunostaining was diffusely enhanced in all follicular cells. A more intense signal was observed in toxic adenomas and in samples obtained from a patient with severe hyperthyroidism due to an activating mutation in the TSH receptor. In multinodular goiters, large follicles displayed a weak signal whereas small proliferative follicles showed intense immunoreactivity near the apical plasma membrane. In hypothyroid patients, NOSIII immunoreactivity was barely detectable. In summary, NOSIII is expressed both in endothelial cells and thyroid follicular cells. The endothelial localization of NOSIII is consistent with a role for nitric oxide in the vascular control of the thyroid. NOSIII expression in thyroid follicular cells and the variations in its immunoreactivity suggest a possible role for nitric oxide in thyrocyte function and/or growth.     

Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation

Hypothyroidism is frequently associated with hypercholesterolemia and an increased risk for atherosclerosis, whereas hyperthyroidism is known to precipitate angina or myocardial infarction in patients with underlying coronary heart disease. We have shown previously that L-T4 functions as an antioxidant in vitro and inhibits low density lipoprotein (LDL) oxidation in a dose-dependent fashion. The present study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism and hyperthyroidism. Fasting blood samples for LDL oxidation analyses, lipoprotein determinations, and thyroid function tests were collected at baseline and after the patients were rendered euthyroid. The lag phase (mean +/- SEM hours) of the Cu+2-catalyzed LDL oxidation in the hypothyroid state and the subsequent euthyroid states were 4 +/- 0.0.65 and 14 +/- 0.68 h, respectively (P < 0.05). The lag phase during the hyperthyroid phase was 6 +/- 0.55 h, and that during the euthyroid phase was 12 +/- 0.66 h (P < 0.05). The total and LDL cholesterol levels were higher in hypothyroidism than in euthyroidism and were lower in hyperthyroidism than in the euthyroid state. We conclude that LDL has more susceptibility to oxidation in both the hypothyroid and hyperthyroid states. Thus, the enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.     

Determination of factors affecting the therapeutic outcome of radioiodine therapy in patients with Graves' disease

AIM: Of this study was to determine whether success of radioiodine therapy (RIT) in Graves' disease depends on thyroid volume, function, thyroideal receptor antibodies (TRAK), thyreostasis, therapeutic dosage, 131I uptake, or effective half-life. METHOD: 78 patients received an average of 626 +/- 251 MBq of iodine-131 orally for thyroid ablation. 60 were assessed for successful therapy 3 months after RIT. RESULTS: In patients showing hyperthyreosis or a TRAK value > 11 U/l at the beginning of RIT, a significantly lower therapeutic dosage and effective iodine half-life were found than in non-hyperthyreotic patients or patients with TRAK < or = 11 U/l. Patients with a thyroid volume < or = 25 ml showed a significantly lower 131I uptake, but a significantly higher relative uptake (131I uptake/ volume) than patients with a thyroid volume > 25 ml. All failures were treated thyreostatically during RIT and showed a significantly lower therapeutic iodine dosage and relative uptake, as well as a significantly higher thyroid volume than patients with a successful therapy. RIT caused a thyroid volume reduction of 44%, with therapy failures showing a significantly lower volume reduction. Patients who received a therapeutic dosage of < or = 250 Gy showed significantly worse results than did those who had received > 250 Gy. Only one case of therapy failure received a dosage > 250 Gy, while 50% of failures received dosages > 200 Gy but < 250 Gy. Multivariate analyses (MANOVA, factor analyses) showed thyreostasis as the decisive negative factor for a successful course of therapy. CONCLUSIONS: Since most treatment failures occurred in patients under thyreostatic medication we recommend raising the target dosage to 250 Gy for these cases.     

Elevated plasma adrenomedullin level in hyperthyroidism

Adrenomedullin is a recently discovered peptide that was first purified from phaeochromocytoma tissue and has marked vasodilatory activity, causing hypotension. In thyrotoxicosis, various haemodynamic changes are observed, including an increase in cardiac output and heart rate with a concomitant decrease in peripheral vascular resistance. To evaluate the mechanism underlying these haemodynamic changes in thyrotoxicosis, we measured the plasma adrenomedullin concentration in thyrotoxic patients with Graves' disease. The plasma concentration of adrenomedullin was elevated in hyperthyroid patients (14.7 +/- 5.7 pmol L-1) compared with euthyroid control subjects (5.6 +/- 1.3 pmol L-1) (P < 0.001). The correlation between the plasma adrenomedullin concentration and serum free thyroid hormone levels was marginally significant. The mean blood pressure was relatively low in the face of an elevated plasma adrenomedullin level. Adrenomedullin may therefore be responsible for the vasodilatation observed in thyrotoxicosis.     

Outcome of differentiated thyroid cancer in Graves' patients

The clinical behavior and outcome was evaluated in 21 nonoccult differentiated thyroid carcinomas occurring in Graves' patients during the period 1982-94 and compared with that of matched tumors occurring in euthyroid controls (n = 70). At surgery, patients with Graves' disease showed distant metastases more frequently than euthyroid patients (3/21 = 14.3% vs. 1/70 = 1.4%, P = 0.0556). Graves' patients also showed a significantly higher cumulative risk of recurrent/progressive distant metastases or total adverse events (odd ratios = 3.14 and 2.07, respectively) as compared with euthyroid patients. At the last follow-up visit, persistence of distant metastases was also more frequent in the Graves' group (P = 0.007), although the cumulative individual dose of radioiodine administered was higher than in the control group (median dose = 805 mCi vs. 350 mCi). Two patients died in the Graves' group vs. none in the control group. Circulating thyroid stimulating antibodies were present in all patients but one and persisted as long as signs of disease were evident. These findings indicate that differentiated thyroid carcinomas in patients with Graves' disease are more aggressive than those occurring in matched euthyroid controls and should, therefore, be managed accordingly.     

Hashimoto's thyroiditis and insulin-dependent diabetes mellitus: differences among individuals with and without abnormal thyroid function

Insulin-dependent diabetes mellitus probands from the Familial Autoimmune and Diabetes Study were evaluated for autoimmune thyroid disease (n = 265). The prevalence of Hashimoto's thyroiditis was 26.6%; 42.0% of these individuals were euthyroid, and 58.0% were hypothyroid. There was a female predominance among hypothyroid and euthyroid Hashimoto's cases compared to those with no thyroid disease (75% vs. 72.4% vs. 41.6%; P < 0.001). Insulin-dependent diabetes mellitus patients with hypothyroid Hashimoto's thyroiditis were more likely to report another autoimmune disease compared to euthyroid Hashimoto's patients or individuals with no thyroid disease (30.8% vs. 17.2% vs. 13.9%; P < 0.01). Sex-specific analysis revealed that this difference was significant for men but not for women. Both euthyroid and hypothyroid Hashimoto's cases were more likely to have a family history of the disease (66.7% vs. 69.2% vs. 47.7%; P < 0.05). No differences were observed in the prevalence of DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302 across the three groups. Body mass index, lipid levels, glycemic control, and diabetes complications were also similar. However, euthyroid Hashimoto's women were more likely to report spontaneous abortions than those with hypothyroid Hashimoto's thyroiditis or no thyroid disease (23.8% vs. 61.5% vs. 29.1%; P < 0.05). These data suggest that gender-specific risk factors may be primary determinants of Hashimoto's thyroiditis and other autoimmune diseases among women. However, disease-specific determinants may also increase susceptibility to other autoimmune diseases.     

Behavior of soluble intercellular adhesion molecule-1 and endothelial-leukocyte adhesion molecule-1 concentrations in patients with Graves' disease with or without ophthalmopathy and in patients with toxic adenoma

Expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1) on endothelium can be considered a critical early step for leukocyte migration from blood to tissues during inflammatory processes. Increased circulating soluble ICAM-1 (sICAM-1) levels have been found in sera from patients with Graves' disease (GD) with or without ophthalmopathy. Serum soluble ELAM-1 (sELAM-1) levels have not been measured in these patients. The aim of this study was to clarify the behavior of sICAM-1 and sELAM-1 levels in patients with hyperthyroidism due to GD with or with or without ophthalmopathy and in hyperthyroid patients with toxic thyroid adenoma. We studied sICAM-1 and sELAM-1 levels in 130 subjects (age 23-54 yr), grouped as follows: group 1, 30 untreated hyperthyroid GD patients (21 females and 9 males) with active ophthalmopathy; group 2, 26 euthyroid GD patients (16 females and 10 males) with active ophthalmopathy; group 3, 33 hyperthyroid GD patients (22 females and 11 males) without ophthalmopathy; group 4, 11 untreated hyperthyroid patients (7 females and 4 males) with single toxic adenoma; and a control group of 30 healthy subjects (21 females and 9 males). sICAM-1 and sELAM-1 concentrations were measured by a sandwich enzyme linked immunosorbent assay (ELISA) method. Groups 1, 2, and 3 (P < 0.001 for all 3 groups) but not group 4 showed increased sICAM-1 levels compared with the control group. However, groups 1 and 2 (P < 0.001 for both) showed higher values of sICAM-1 than group 3, and group 1 showed higher sICAM-1 levels than group 2 (P < 0.002). Groups 1 and 2 (P < 0.001 for both) but not groups 3 and 4 showed sELAM-1 levels significantly higher than the control group and positively correlated to the severity score of Graves' ophthalmopathy (GO) (P < 0.002 for group 1 and < 0.01 for group 2). Our results confirm that increased sICAM levels in GD patients with or without ophthalmopathy (with higher levels in patients with GO) but not in hyperthyroid nonautoimmune patients may be the consequence of orbital and thyroid inflammation, and they also suggest that sICAM concentrations could reflect the degree of inflammatory activity. Increased sELAM-1 concentrations only, in patients with ophthalmopathy with or without hyperthyroidism significantly correlated to severity score of GO, suggest the measurement of sELAM-1 levels as a specific marker of endothelium activation in GO.     

Contraction of extracellular matrix by transdifferentiated retinal pigment epithelial cells, inducers and inhibitors

Adhesion molecules relate to cell invasion of autoimmune thyroid disease. We studied plasma soluble P-Selectin (platelet activation-dependent granule-external membrane protein), E-Selectin (endothelial leukocyte adhesion molecule) and L-Selectin (leukocyte endothelial cell adhesion molecule-1) levels in patients with Graves' disease before and during methimazole treatment. Plasma P-, E- and L-Selectin levels in patients with untreated Graves' disease were significantly higher than those in normal subjects. Plasma P-Selectin levels decreased when their thyroid functions were normal for more than 6 months after the start of methimazole treatment. No significant change in plasma E- and L-Selectin levels in patients with Graves' disease was found between hyperthyroid state and euthyroid state after the start of methimazole treatment, but plasma L-Selectin levels in patients with untreated Graves' disease were significantly lower than those in the patients in the first euthyroid state. There was no significant correlation between plasma P-Selectin levels and serum FT4 levels, nor between plasma P-Selectin levels and serum FT3 levels. These results suggested that thyroid hormones might reflect expression of P-, L- and E-Selectin from endothelial cells, or lymphocytes, or platelets in patients with Graves' disease.     

Changes in thyroid state affect pHi and Nai+ homeostasis in rat ventricular myocytes

We have tested the hypothesis that thyroid state may influence both the flow of cellular Ca2+ and the myofilament response to Ca2+ by effects on intracellular pH (pHi) and Na+ (Nai+). Single cardiac myocytes isolated from hypothyroid, euthyroid and hyperthyroid animals were loaded with fura-2/AM (Cai2+ probe), BCECF/AM (pHi probe) or SBFI/AM (Nai+ probe). Compared with hypothyroid animals, myocytes isolated from hyperthyroid rat hearts demonstrated a significant: (1) increase in extent of shortening; (2) decrease in the time to peak contraction; (3) increase in the peak amplitude of the fura-2 fluorescence ratio; (4) decrease in pHi (DeltapHi=0. 19+/-0.05); and (5) increase in Nai+ (DeltaNai+=2.88+/-0.55 mM). We have also compared pHi in Langendorff perfused hypo- and hyperthyroid rat hearts using NMR. We have found that hyperthyroid hearts are 0.15+/-0.03 pH units more acidic than hypothyroid hearts. Analysis of mRNA levels demonstrated that hyperthyroidism increased expression of both the Na+/Ca2+ exchanger and Na+/H+ antiporter, and decreased expression of Na+ channel mRNAs. These changes appear partially responsible for the observed changes in Nai+ and pHi. Our results provide the first evidence that changes in cardiac contractility associated with altered thyroid state not only involve effects on Ca2+, but may also involve changes in the response of the myofilaments to Cai2+mediated by altered pHi and Nai+.     

Large, compressive goiters treated with radioiodine

OBJECTIVE: To evaluate the effectiveness of radioiodine therapy as an alternative for surgery in elderly patients with a large, compressive goiter using objective methods for measuring thyroid volume and tracheal compression. DESIGN: Prospective study. SETTING: University hospital in the Netherlands. PATIENTS: 19 patients (mean age +/- SD, 66 +/- 14 years) with a large, compressive multinodular goiter who had a high operative risk or refused to have thyroid surgery. INTERVENTION: A single intravenous dose of 131I at 2.6 +/- 1.0 GBq (70 +/- 28 mCi) (3.7 MBq or 100 microCi/g of thyroid tissue), followed by daily administration of L-thyroxine in doses that did not suppress thyroid-stimulating hormone. MEASUREMENTS: Clinical evaluation and measurements of thyroid volume, maximal tracheal deviation, and the smallest cross-sectional area of the tracheal lumen with magnetic resonance imaging before and 1 year after 131I treatment. RESULTS: No exacerbation of compressive symptoms after 131I therapy was observed. Thyroid volume was 269 +/- 153 mL before treatment and 154 +/- 73 mL 1 year after treatment (P < 0.001). Thyroid volume was reduced 40% +/- 15% (range, 19% to 68%). Maximal tracheal deviation (1.9 +/- 0.8 cm before and 1.5 +/- 0.7 cm 1 year after therapy) had decreased by 20% +/- 20% (range, -4% to 73%; P < 0.001), and the smallest cross-sectional area of tracheal lumen (0.78 +/- 0.38 cm2 before and 1.04 +/- 0.48 cm2 1 year after therapy) had increased by 36% +/- 38% (range, -3% to 125%; P < 0.001). Clinical signs and symptoms improved in 8 of 12 patients with dyspnea and inspiratory stridor and in both patients with compression of the superior vena cava. CONCLUSIONS: Therapy with 131I is an effective alternative to surgery for elderly patients with a large, compressive multinodular goiter.     

Can radioactive iodine be used in the treatment of diffuse non-toxic goiter?

Traditional treatment modalities of diffuse nontoxic goitre are thyroid hormone suppression or surgery. When treating nodular nontoxic goitre with 131I treatment, a reduction in thyroid volume to about 50% is seen. In the present study we evaluated the effect of 131I treatment in 21 patients treated for a diffuse nontoxic goitre and followed by evaluation of thyroid volume measured by ultrasound. Thyroid volume declined in all patients from median of 66 ml (range 27-160 ml) to 21 ml (9-108 ml) over a year, a reduction of 62%. Three patients developed hypothyroidism in the follow-up period (14%), one of these had a temporary hyperthyroid fase. In conclusion, 131I treatment of diffuse nontoxic goitre reduces thyroid volume by approximately 60% within 12 months. Hypothyroidism developed in 14% during a limited follow-up period.     

Glucose transport correlates with GLUT2 abundance in rat liver during altered thyroid status

Glucose transport activity ([3H]D-glucose uptake) in liver sinusoidal membrane vesicles (SMVs) from hyperthyroid rats was significantly higher than that from euthyroid controls (2.1-times increase in V(max) with K(m) unchanged at approximately 18 mM), associated with increased GLUT2 expression. In contrast, glucose transport V(max) into SMVs from hypothyroid rats was reduced to 0.75-times that of euthyroid controls, associated with a reduced GLUT2 abundance. GLUT1 expression in SMVs was unaffected by changes in thyroid status. GLUT2, but not GLUT1 abundance on the blood-facing membrane of liver cells is sensitive to changes in thyroid status and these changes in transporter expression directly correlate (r = 0.96) with altered glucose transport activity.     

Successful treatment of hypothyroid Graves'' disease with a combination of levothyroxine replacement, intravenous high-dose steroid and irradiation to the orbit

A 46-year-old woman with hypothyroid Graves' disease (EMO syndrome) is reported. The patient had bilateral exophthalmos, conjunctival chemosis, periorbital edema and limitation of lateral gaze. Laboratory examination revealed the presence of primary hypothyroidism with positive thyroid-stimulating hormone (TSH) binding inhibitory immunoglobulin and thyroid stimulation antibody. These findings indicated a diagnosis of hypothyroid Graves' disease or EMO syndrome. She received levothyroxine replacement and steroid pulse therapy followed by radiotherapy. Her visual symptoms showed marked improvement and pretibial myxedema disappeared. Although several studies indicate that hypothyroid Graves' disease is a different entity from hyperthyroid Graves' disease, this report suggests that steroid pulse therapy combined with radiotherapy may be effective to treat ophthalmopathy in both diseases.     

Disappearance of the Vicia villosa-positivity from the perineuronal net containing chondroitin proteoglycan after chondroitinase digestion

The effects of thyroid status on glycolysis using 10, 20, and 40 mM glucose have been examined in hepatocytes derived from hypothyroid, euthyroid, and hyperthyroid rats. For any given concentration of added glucose, total glycolytic rates, as measured by the release of tritium from [6-3H]glucose, were similar in all thyroid states. The aerobic component of glycolysis, where cytoplasmically generated reducing equivalents are transferred to the mitochondria for oxidation, was the major component in the hyperthyroid state, at all concentrations of glucose. In contrast, the aerobic proportion of glycolysis in the hypothyroid and euthyroid states decreased with increasing concentration of added glucose and the anaerobic component became dominant above 20 mM glucose. Cytoplasmic reducing equivalents generated during aerobic glycolysis were transferred to the mitochondria via both the glycerol 1-phosphate and malate/aspartate shuttles in each thyroid state, even though the former shuttle was considerably depressed in the livers of hypothyroid rats. Both asparagine and aminooxyacetate had only minor effects on the rate of glycolysis, but aminooxyacetate depressed the contribution of aerobic glycolysis whereas asparagine had relatively little influence. The respiration rate in the presence of 40 mM glucose was twice as high in hepatocytes from hyperthyroid rats as in cells from hypothyroid animals, and 1.4 times as high as in hepatocytes from euthyroid rats. Smaller stimulations were observed with lower concentrations of added glucose. Furthermore, the increase in respiratory rate over the endogenous value, induced by 10 mM glucose, was six times higher in cells from hyperthyroid rats than in hepatocytes from hypothyroid animals and 2.7 times higher than that observed with cells from euthyroid rats. The insensitivity of glycolysis to thyroid status in contrast to the marked response of respiration provides additional support for the view that the stimulation of metabolism by thyroid hormone is mediated primarily by its action on mitochondrial processes.     

Evidence for the effect of antibodies to TSH receptors on the thyroid ultrasonographic volume in patients with Graves' disease

OBJECTIVE: It has been demonstrated that antibodies (Ab) to thyroid-stimulating hormone receptors (R), which stimulate the thyroid gland, induce hyperthyroidism in patients with Graves' disease. Furthermore, it has been shown in thyroid cells in culture that thyroid-stimulating hormone receptor Ab acts through the adenosine 3', 5'-monophosphate pathway which stimulates both thyroid hormonogenesis and growth. We investigated the relations between thyroid autoimmunity expression and thyroid ultrasonographic parameters or thyroid hormonal status in patients with Graves' disease. PATIENTS: A prospective study of 53 consecutive patients referred with untreated Graves' disease. MEASUREMENTS: Measurements were made of serum TSH-R, peroxidase (TPO) and thyroglobulin (Tg) Ab and basal plasma free T4 (FT4), free T3 (FT3) and TSH. Thyroid morphological characteristics (number and total volume of nodule(s), total volume of lobes and total thyroid volume) were determined by ultrasonography. RESULTS: There were significant correlations (P < 0.001) between TSH-RAb levels and FT4 values (r = 0.48) or FT3 levels (r = 0.46). Likewise, significant correlations were found between TSH-RAb levels and total lobe volume values (r = 0.56, P < 0.001), total nodular volume values (r = 0.59, P < 0.01) or total thyroid volume values (r = 0.63, P < 0.001). By contrast, no correlation was found between TSH-RAb levels and the number of nodules or between any of the ultrasonographic parameters and TPOAb levels or TgAB values. CONCLUSIONS: This study demonstrates, in vivo, that TSH receptor antibodies modulate the thyroid ultrasonographic extranodular and nodular volumes in patients with Graves' disease.     

Surgical treatment of hyperthyroidism in children

During the past ten years, subtotal thyroidectomy for hyperthyroidism was performed upon 43 children at Childrens Hospital of Los Angeles. There were no deaths, no recurrent laryngeal nerve injuries and no permanent hypoparathyroidism. During the one to ten year follow-up period, one patient had recurrent hyperthyroidism develop and was treated with 131I. Twenty-five patients are hypothyroid and require thyroid supplement; 14 are euthyroid and receiv no medication. Postoperative thyroid function did not correlate well with gland remnant size, degree of fibrosis or the extent of lymphoid follicle formation. Lymphocytic infiltration was more severe in patients who had hypothyroidism develop postoperatively. Transient hypocalcemia developed in 22 patients. The effectiveness and safety of the surgical treatment for hyperthyroidism in children is reaffirmed, and it is advocated for consideration over 131I or prolonged medical therapy.