A patient-specific treatment model for Graves' hyperthyroidism.

BACKGROUND: Graves' is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of thyroid stimulating hormone (TSH) and stimulates the thyroid hormone receptor (TSHR), which results in hyperthyroidism (overactive thyroid gland) and goiter. Methimazole (MMI) is used for hyperthyroidism treatment for patients with Graves' disease. METHODS: We have developed a model using a system of ordinary differential equations for hyperthyroidism treatment with MMI. The model has four state variables, namely concentration of MMI (in mg/L), concentration of free thyroxine - FT4 (in pg/mL), and concentration of TRAb (in U/mL) and the functional size of the thyroid gland (in mL) with thirteen parameters. With a treatment parameter, we simulate the time-course of patients' progression from hyperthyroidism to euthyroidism (normal condition). We validated the model predictions with data from four patients. RESULTS: When there is no MMI treatment, there is a unique asymptotically stable hyperthyroid state. After the initiation of MMI treatment, the hyperthyroid state moves towards subclinical hyperthyroidism and then euthyroidism. CONCLUSION: We can use the model to describe or test and predict patient treatment schedules. More specifically, we can fit the model to individual patients' data including loading and maintenance doses and describe the mechanism, hyperthyroidism→euthyroidism. The model can be used to predict when to discontinue the treatment based on FT4 levels within the physiological range, which in turn help maintain the remittance of euthyroidism and avoid relapses of hyperthyroidism. Basically, the model can guide with decision-making on oral intake of MMI based on FT4 levels.

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts.

Thyroid hormone as L-thyroxine (T4) stimulates proliferation of glioma cells in vitro and medical induction of hypothyroidism slows clinical growth of glioblastoma multiforme (GBM). The proliferative action of T4 on glioma cells is initiated nongenomically at a cell surface receptor for thyroid hormone on the extracellular domain of integrin αvß3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone derivative that blocks T4 action at αvß3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) that increases the potency of tetrac and broadens the anticancer properties of the drug. In the present studies of human GBM xenografts in immunodeficient mice, NDAT administered daily for 10 days subcutaneously as 1 mg tetrac equivalent/kg reduced tumor xenograft weight at animal sacrifice by 50%, compared to untreated control lesions (p < 0.01). Histopathological analysis of tumors revealed a 95% loss of the vascularity of treated tumors compared to controls at 10 days (p < 0.001), without intratumoral hemorrhage. Up to 80% of tumor cells were necrotic in various microscopic fields (p < 0.001 vs. control tumors), an effect attributable to devascularization. There was substantial evidence of apoptosis in other fields (p < 0.001 vs. control tumors). Induction of apoptosis in cancer cells is a well-described quality of NDAT. In summary, systemic NDAT has been shown to be effective by multiple mechanisms in treatment of GBM xenografts.

Effects of short term mild L-Thyroxine suppression therapy on myocardial functions, and its assessment with tissue Doppler imaging.

BACKGROUND: While adverse effects of overt hyperthyroidism on the cardiovascular system are well-known, the effects of subclinical hyperthyroidism are not clear. The aim of the study was to investigate the effects of short term mild L-thyroxine (LT4) suppression therapy on myocardial functions in a group of premenopausal women with goiter, by using echocardiographic methods and tissue Doppler imaging (TDI). METHODS: Sixteen participants with goiter received LT4 suppression therapy to keep TSH levels between 0.1-0.4 µIU/mL. After baseline and 1st month assessment, 6-weeks follow-up were scheduled until 6th month assessment to adjust the medication dose during study period. All TSH levels decreased below 0.4 µIU/mL by the end of first month and stayed below this level throughout study period. At the beginning of the study and at month 6, the thyroid ultrasonography, Holter monitorization test, stress test, electrocardiograms and echocardiograms of participants were assessed. This was followed by a comparison of baseline and 6th month data. RESULTS: Baseline and 6th month 2-D echocardiography measurements of participants revealed that mean left ventricle diameter in diastole (4.1±0.3 vs 3.8±0.2 mm) and posterior wall thickness in diastole (0.9±0.1 vs. 0.8±0.1 mm) decreased (P<0.05); while stroke volume (41.9±9.9 vs. 48±8.2), stroke volume index (25.6±5.4 vs. 29.4±4.7), cardiac output (3.5±1.4 vs. 3.9±0.9) and cardiac index (2.2±0.8 vs. 2.4±0.5) increased (P<0.05). Other 2D echocardiography parameters did not change significantly. The pulse wave Doppler examination, stress test and Holter monitorization of participants did not reveal any difference between baseline and 6th month measurements. No statistically significant difference was observed in measurements of TDI except decreased septum S velocity. CONCLUSIONS: Short term mild LT4 suppression treatment did not cause systolic or diastolic dysfunction, or conduction defect in the heart; therefore may be safe in premenopausal females with not known cardiac disease.

Effects of phytate on thyroid gland of rats intoxicated with cadmium.

Cadmium (Cd) is one of the most dangerous occupational and environmental toxins. The objective of the present study is to examine the potential prophylactic effects of phytic acid (PA) on thyroid hormones of male rats intoxicated with Cd. The male albino rats were divided into five groups: group I (control) was fed with the basal diet, group II was intoxicated with Cd in drinking water, groups III, IV, and V were intoxicated with Cd in drinking water and fed with the diet containing 3.5, 7, and 10 g of PA/kg, respectively. The results indicated that the serum calcium, iron (Fe), and total Fe binding capacity levels and serum T3 and T4 in Cd-treated rats of group II were decreased when compared with the control group, while PA-administered groups with Cd showed a significant improvement when compared with the Cd-treated rats only. Serum thyroid stimulating hormone (TSH) level was significantly increased in Cd-treated rats compared with the control group, while the addition of PA in diet decreased the high levels of TSH. These results indicated a prophylactic effect of PA against Cd-induced toxicity in rats.

[Alteration of thyroid hormone secretion after long-term exposure to low doses of endocrine disruptor DDT].

Endocrine disruptors are exogenous substances that exhibit hormone-like action and consequently disrupt homeostatic action of endogenous hormones. DDT is the most common disruptor. The objective was to evaluate changes in thyroid hormone secretion after long-term exposure to low doses of DDT. The experiment was performed on male Wistar rats. The rats were given DDT at doses of 1.89±0.86 мg/kg/day and 7.77±0.17 мg/kg/day for 6 and 10 weeks. Dose dependent increase of serum total thyroxine, total triiodthyronine, and thyroid peroxidase was revealed after 6 weeks exposure. After 10 weeks free thyroxine secretion was reduced. Such alterations of the thyroid status are typical for iodine deficient goiter. The data obtained indicate that the main mechanism of DDT action includes disruption of thyroxine secretion by thyrocytes, but not inhibition of deiodinase activity and decrease of blood thyroid binding proteins.

Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.

This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman(®) qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS-induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the low efficacy of TCS as thyroid hormone disruptor or highlight the possibility that other MOAs may also contribute to the observed maternal and early neonatal hypothyroxinemia.

Drug interaction of levothyroxine with infant colic drops.

Infacol (Forest Laboratories UK, Kent, UK) is a widely available over-the-counter preparation used to relieve colic symptoms in neonates and infants. The active ingredient is simeticone. No drug interactions with simeticone are documented in the current summary of product characteristics. The authors report the case of an infant with confirmed congenital hypothyroidism on levothyroxine who experienced a possible drug interaction with simeticone. Despite adequate levothyroxine dosage, thyroid stimulating hormone (TSH) was high, suggesting undertreatment. Questioning revealed the child was taking Infacol drops before feeds while on levothyroxine. The colic drops were immediately discontinued and TSH promptly normalised with a reduction in thyroxine requirement to an age appropriate dosage. Drug interaction of thyroxine with simeticone has not been reported previously and is not listed in the British National Formulary for Children. Clinicians and parents need to be aware of this interaction to avoid unnecessary undertreatment and prevent potential long-term neurological sequelae.

A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice.

Serum total thyroxine (T4) level was markedly decreased, without significant increases in the levels of hepatic T4-UDP-glucuronosyltransferase (T4-UGT) and serum thyroid-stimulating hormone, 3 days after treatment with 2,2',4,4',5,5'-hexachlorobiphenyl (CB153) (100mg/kg, ip) in both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. Likewise, in either strain of mice, no CB153-mediated changes in the binding levels of [(125)I]T4 to serum proteins, such as transthyretin, albumin, and thyroxine binding globulin, were observed, while in CB153-pretreated C57BL/6 mice, but not in CB153-pretreated DBA/2 mice, the levels of biliary [(125)I]4T and [(125)I]T4-glucuronide at 90-120 min after injection of [(125)I]T4 slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [(125)I]T4, liver-selective increases in the [(125)I]T4 accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [(125)I]T4 in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [(125)I]T4 dosed, respectively. The present findings indicated that the CB153-mediated decreases in the level of serum total T4in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T4 in the liver.

A volumetric analysis of the brain and hippocampus of rats rendered perinatal hypothyroid.

The thyroid hormone is essential for the proper development of the central nervous system (CNS). Hormone deficiency during CNS development causes neurological abnormalities in the brain. The hippocampus is one of the brain regions vulnerable to hormone deficiency, and the volume of dentate gyrus (DG) and cornu ammonis (CA) are reduced by transient hypothyroidism during CNS development. However, it remains unclear whether transient hypothyroidism specifically reduces the whole hippocampal volume. In the present study, we used magnetic resonance imaging (MRI) to examine the effects of perinatal hypothyroidism on the ratio of hippocampal volume to brain volume as well as brain and hippocampal volumes overall. Perinatal hypothyroidism was induced by adding the anti-thyroid drug, methimazole, to the drinking water of pregnant dams from gestational day 15 to postnatal day 21. The MRI experiment was conducted when the rats were between 7 and 11 months old. The results showed reductions of the hippocampal and brain volume of the treated group. However, the ratio of hippocampal volume to brain volume was comparable between the control and treated groups. These results indicate that perinatal hypothyroidism minimizes the brain as a whole, but does not minimize the hippocampus in particular.

In vivo assessment and potential diagnosis of xenobiotics that perturb the thyroid pathway: Proteomic analysis of Xenopus laevis brain tissue following exposure to model T4 inhibitors.

As part of a multi-endpoint systems approach to develop comprehensive methods for assessing endocrine stressors in vertebrates, differential protein profiling was used to investigate expression patterns in the brain of the amphibian model (Xenopus laevis) following in vivo exposure to a suite of T4 synthesis inhibitors. We specifically address the application of Two Dimensional Polyacrylamide Gel Electrophoresis (2D PAGE), Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and LC-MS/MS to assess changes in relative protein expression levels. 2D PAGE and iTRAQ proved to be effective complementary techniques for distinguishing protein changes in the developing amphibian brain in response to T4 synthesis inhibition. This information served to evaluate the use of distinctive protein profiles as a potential mechanism to screen chemicals for endocrine activity in anurans. Regulatory pathways associated with proteins expressed as a result of chemical effect are reported. To our knowledge, this is also the first account of the anuran larvae brain proteome characterization using proteomic technologies. Correlation of protein changes to other cellular and organism-level responses will aid in the development of a more rapid and cost-effective, non-mammalian screening assay for thyroid axis-disrupting chemicals.

The nature of the compensatory response to low thyroid hormone in the developing brain.

Thyroid hormone is essential for normal brain development, although the degree to which the developing brain is sensitive to small perturbations in serum thyroxin is not clear. An important concept related to this is that the developing brain possesses potent mechanisms to compensate for low serum thyroid hormone, and this concept is routinely employed in discussions concerning clinical treatments or public health. However, experimental studies have not directly tested whether (or the degree to which) putative compensatory mechanisms can ameliorate the consequences of small reductions in serum thyroxin (T(4)). To formally test this concept, we employed a model of graded T(4) reductions using doses of propylthiouracil (PTU) that were 200- to 67-fold lower than the dose traditionally used to produce hypothyroidism in rats. PTU produced a stepwise decrease in serum total T(4), and a stepwise increase in serum thyroid-stimulating hormone (TSH), in type 2 deiodinase mRNA expression and enzyme activity in the brain, and in the expression of the mRNA encoding the tri-iodothyronine (T(3)) transporter MCT8 in the postnatal day (P) 15 cortex. However, the mRNA encoding RC3/neurogranin, a direct target of T(3) action, exhibited a strong negative linear correlation with serum total T(4) despite these adaptive responses. In addition, single-cell analysis of RC3 mRNA levels in cortical neurones demonstrated that the co-expression of MCT8 did not alter the relationship between RC3 mRNA and serum T(4). These findings do not support the currently envisioned concept of the developing brain being capable of compensating for low T(4).

Characterizing the in vitro hepatic biotransformation of the flame retardant BDE 99 by common carp.

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardant chemicals known to biomagnify in aquatic foodwebs. However, significant biotransformation of some congeners via reductive dehalogenation has been observed during in vivo and in vitro laboratory exposures, particularly in fish models. Little information is available on the enzyme systems responsible for catalyzing this metabolic pathway in fish. This study was undertaken to characterize the biotransformation of one primary BDE congener, 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), using in vitro techniques. Hepatic sub-cellular fractions were first prepared from individual adult common carp (Cyprinus carpio) to examine metabolism in both microsomal and cytosolic sub-cellular fractions. Debromination rates (i.e. BDE-99 biotransformation to BDE-47) were generally higher in the microsomal fraction than in the cytosolic fraction, and some intra-species variability was observed. Further experiments were conducted to determine the biotransformation kinetics and the influence of specific co-factors, inhibitors and competitive substrates on metabolism using pooled carp liver microsomes. The apparent K(m) and V(max) values were 19.4microM and 1120pmolesh(-1)mgprotein(-1), respectively. Iodoacetate (IaC) and the two thyroid hormones, reverse triodothyronine (rT3) and thyroxine (T4), significantly inhibited the debromination of BDE-99 in microsomal sub-cellular fractions with IC(50) values of 2.2microM, 0.83microM, and >1.0microM, respectively. These results support our hypothesis that deiodinase enzymes may be catalyzing the metabolism of PBDEs in fish liver tissues. Further studies are needed to evaluate metabolic activity in other species and tissues that contain these enzymes.

The interaction of oxidative stress response with cytokines in the thyrotoxic rat: is there a link?

Oxidative stress is regarded as a pathogenic factor in hyperthyroidism. Our purpose was to determine the relationship between the oxidative stress and the inflammatory cytokines and to investigate how melatonin affects oxidative damage and cytokine response in thyrotoxic rats. Twenty-one rats were divided into three groups. Group A served as negative controls. Group B had untreated thyrotoxicosis, and Group C received melatonin. Serum malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and nitric oxide derivates (NO*x), and plasma IL-6, IL-10, and TNF-alpha were measured. MDA, GSH, NO*x, IL-10, and TNF-alpha levels increased after L-thyroxine induction. An inhibition of triiodothyronine and thyroxine was detected, as a result of melatonin administration. MDA, GSH, and NO*x levels were also affected by melatonin. Lowest TNF-alpha levels were observed in Group C. This study demonstrates that oxidative stress is related to cytokine response in the thyrotoxic rat. Melatonin treatment suppresses the hyperthyroidism-induced oxidative damage as well as TNF-alpha response.

Safety and subjective sleep effects of ramelteon administration in adults and older adults with chronic primary insomnia: a 1-year, open-label study.

OBJECTIVE: To evaluate the long-term safety and subjective sleep effects of ramelteon in adults with chronic insomnia. METHOD: Subjects with primary insomnia (DSM-IV-TR criteria) for >or= 3 months received ramelteon nightly for 1 year; a 3-day placebo run out followed. Subjects aged >or=65 years received open-label ramelteon 8 mg (N = 248); those aged 18 to 64 years received ramelteon 16 mg (N = 965). Subjects completed sleep diaries and returned to the clinic at week 1 and at months 1, 2, 3, 4, 6, 8, 10, and 12 for safety assessments and investigator-performed Clinical Global Impressions. The study was conducted from February 2003 through September 2004. RESULTS: There were no noteworthy changes in vital signs, physical examinations, clinical chemistry, hematology, or urinalysis values and no electrocardiogram changes to suggest adverse cardiac effects. Endocrine values remained within normal range throughout treatment. Consistent statistically significant (p

Exogenous subclinical hyperthyroidism impairs endothelial function in nodular goiter patients.

BACKGROUND: Exogenous subclinical hyperthyroidism is associated with cardiovascular and metabolic changes. The aim of this study was to evaluate the effect of levothyroxine (LT4) suppression on endothelial function and insulin sensitivity in euthyroid nodular goiter patients. METHODS: Twenty-two euthyroid patients with multinodular goiter (MNG) and 22 matched healthy controls were studied. LT4 was administered in doses ranging from 50 to 150 microg/day to reach target serum thyroid-stimulating hormone (TSH) levels <0.5 mIU/L. Patients were studied before and after 8 weeks after the target TSH level <0.5 mIU/L. The control group was studied twice, 16 weeks apart. Flow mediated vasodilatation (FMD), insulin sensitivity index (ISI), lipid peroxidation, and high-sensitivity C-reactive protein (hsCRP) were the outcome measures. RESULTS: LT4 treatment significantly suppressed TSH levels to 0.2 +/- 0.1 mIU/L (minimum and maximum range was 0.05-0.3 mIU/L). FMD decreased from 10.7 +/- 2.7% to 5.4 +/- 1.7% (p < 0.001) and mean ISI decreased from 2.56 +/- 1.10 to 1.41 +/- 0.50 (p < 0.001) with LT4 treatment in the MNG group. Lipid peroxidation measured as thiobarbituric acid reactive substances (Tbars) (p < 0.05), and hsCRP (p < 0.001) levels significantly increased compared to the baseline in the MNG group. FMD measurement inversely correlated with free T4 (p = 0.008) and Tbars (p = 0.004), and positively correlated with ISI (p = 0.004). Serum Tbars and hsCRP were independent predictors of FMD (p = 0.004) in multivariate analysis. All results expressed as mean +/- SD. CONCLUSIONS: TSH suppression therapy with LT4 leading to subclinical hyperthyroidism may cause impaired endothelial function, increased oxidative stress, and decreased insulin sensitivity in euthyroid nodular goiter patients.

[Study on thyroid defunctionalization method for the preoperative preparation of hyperthyroid operation].

OBJECTIVE: To set up and publicize the thyroid defunctionalization method for the preoperative preparation of hyperthyroid operation. METHODS: 476 hyperthyroid patients admitted in our hospital from March 1990 to February 2005 were studied by groups. They were divided randomly into a test group (244 patients), in which "preoperative preparation method of sequential thyroid defunctionalization" was applied to hyperthyroid patients, and based on the different drug dosages and treating terms used, further 4 subgroups (A, B, C and D) were divided to observe the treatment efficiency; And a control group (232 patients), in which antithyroid drugs and iodine preparation were applied preoperatively to cases. Thyroid functions in every stage of treatment were tested by radioimmunoassays (RIA), and operative bleeding volumes and postoperative complications were observed. RESULTS: Compared to the control group, the thyroid congestion and surface varices were alleviated in the test groups, in which the thyroid tissue of subgroup A most closed to euthyroidism histologically. The mean operative bleeding volume of test group was less than that of the control group. The bleeding volumes were (324.76 +/- 163.26) mL for the control group, (195.74 +/- 57.07) mL for the subgroup A, (230.00 +/- 70.81) mL for the subgroup B, (240.47 +/- 80.29) mL for the subgroup C and (314.75 +/- 96.46) mL for the subgroup D. There was no significant difference between the control group and subgroup D, but compared with the subgroup A, B, and C, there was the significant difference between control and treated subgroup (P < 0.05). The postoperative complication rate of the test group was 8.61% (21/244), while that of the control group was 17.24 (40/232). There was statistic difference between two groups (P < 0.005). CONCLUSION: The key to "preoperative preparation method of sequential thyroid defunctionalization" is as follows: the synthesis of thyroxin should be fully inhibited to thyroid defunctionalized; sufficient exogenous thyroxin should be supplemented; the term of thyroid function compensation should be long enough. The "preoperative preparation method of sequential thyroid defunctionalization" can decrease perioperational complications effectively and operation risks.

Radioiodine therapy in non-toxic multinodular goitre. The possibility of effect-amplification with recombinant human TSH (rhTSH).

There is no consensus regarding the optimum treatment of benign non-toxic goitre. L-thyroxine suppressive therapy is widely used, but there is poor evidence of its efficacy, and it may have serious adverse effects on health. Surgery is first choice in large goitres or if malignancy is suspected. 131I therapy results in a one-year goitre reduction of around 40% in multinodular goitres, usually with a high degree of patient satisfaction and improvement of the inspiratory capacity. The effect is attenuated with increasing goitre size. The risk of hypothyroidism is 22-58% within 5-8 years. A sufficient thyroid 131I uptake is mandatory for 131I therapy to be feasible and pre-stimulation with recombinant human TSH (rhTSH) increases this considerably. This leads to an increased absorbed thyroid dose by approx.75%, mainly in those patients with the lowest thyroid 131I uptake, and a more homogeneous intrathyroidal isotope distribution. Pre-stimulation with even a small dose of rhTSH seems to allow a reduction of the 131I activity while still achieving a mean goitre reduction of approximately 40% within a year. A significantly lower extrathyroidal radiation is achieved by this approach. With an unchanged 131I activity, rhTSH pre-stimulation improves the goitre reduction by 30-50%. However, this is at the expense of a higher rate of hypothyroidism, cervical pain and transient thyrotoxicosis. Of particular concern is the observation made in healthy persons, that rhTSH results in a transient average thyroid volume increase of 35%. A similar goitre swelling may cause problems in susceptible patients during rhTSH-augmented 131I therapy. Thus, this concept still needs a closer evaluation before routine use.

The effect of thyroxine-suppressive therapy in patients with solitary non-toxic thyroid nodules -- a randomised, double-blind, placebo-controlled study.

The efficacy of thyroxine (T(4)) for solitary non-toxic thyroid nodule remains uncertain. In this study, 60 patients with solitary non-toxic thyroid nodule were divided randomly into two groups. Group I (n = 30) received thyroxine 100 microg/day for 6 months and group II (n = 30) received placebo. The volume of the thyroid nodules in 11 patients decreased more than 50% after thyroxine therapy (36.7%, responders). In these 11 patients, the mean serum thyroglobulin level decreased significantly (340 +/- 115 to 162 +/- 86 microg/l, p < 0.01). Compared with the non-responders (n = 19, 63.3%), the serum thyroglobulin level before treatment was significantly higher (340 +/- 115 vs. 220 +/- 102 microg/l, p < 0.05). Thyroxine-suppressive therapy is proved as a useful tool in reducing nodule size in some patients with solitary thyroid nodules. The patients with a higher serum thyroglobulin level generally respond better to thyroxine-suppressive therapy.

Comparative analysis of thyroxine distribution in ascidian larvae.

The ascidian endostyle is a mucus-secreting pharyngeal organ, it has iodine-concentrating activity and the biosynthesis of thyroid hormones has been well documented. According to our recent findings, ascidians possess thyroid hormones, which are localized in mesenchymal cells. We have studied the presence and localization of L: -thyroxine (T(4)) in Ascidia malaca (Traustedt), Ascidiella aspersa (Müller), Phallusia mamillata (Cuvier) and Ciona intestinalis (Linnaeus) larvae and its involvement in metamorphosis. In vivo treatment of swimming larvae with exogenous T(4) and thiourea (a thyroid hormone synthesis inhibitor), demonstrate the presence of T4 during larval development. These results were confirmed by in vitro experiments utilizing dot blotting, radioimmunoassay and immunoperoxidase staining. The hormone was localized in mesenchymal cells of all four ascidians, spread out in the body cavity, under the adhesive papillae and around the intestine. The presence of TH in mesenchymal cells could be related to blood cells, musculature and heart tissue differentiation. The results suggest that this hormone could be involved in the control of metamorphosis.