IODIDES: POTASSIUM IODIDE SOLUTION
Used in the past to decrease size and vascularity of hyperplastic
thyroid gland in Graves Disease, but no longer done because it is dangerous. Instead, make the patient euthyroid (normalized hormones) before sending them off to surgery. Why dangerous? Patients tended to lower the dose or discontinue meds after surgery, then develop hypothyroidism.
One hundred and eighteen patients were treated for GD at the author’s clinic over an 11-year period starting October 2003 until March 2014 when the clinic closed. Exclusions were made for 17 patients lost to follow-up. Forty-six patients presented to the author within three months of awareness of clinical manifestations and the rest were referred by other physicians. A diagnosis of GD was based on clinical manifestations, serum thyroid hormones, TSH, and TRAb. Patients were treated with either thiamathole (Mercazole TM , Asuka
Treatment of thyroid storm requires strict monitoring and proper care. Precipitating factors should be identified and treated. Supportive treatment include cooling blankets and drugs like acetaminophen, chlorpromazine or meperidine for hyperthermia, oxygen inhalation, intravenous fluids. Antithyroid drug of choice is prophylthiouracil but carbimazole can also be used. Prophylthiouracil 600 mg is given as loading dose by mouth or nasogastric tube or per rectum followed by 200-300 mg every 6-8 hourly. One hour after the first dose of propylthiouracil, stable iodide is given in the form of SSKI (3 drops twice daily) or Lugol's iodine (10 drops twice daily). Propranolol should also be given in a dose of 40-80 mg orally every 6 hours or 2 mg intravenously every 4 hours. If β blockers are contraindicated, calcium channel blockers like diltiazem can be used to control tachycardia. Large dose of dexamethasone (8 mg) by oral or intravenous route should be given to block the release of hormone from gland and peripheral conversion of T4 to T3.
We immunized rabbits with thyroid-stimulating hormone (TSH) to investigate the hypothesis that such immunization could result in production of thyroid-stimulating autoantiidiotypic antibodies to anti-TSH. Thyroid-stimulating immunoglobulin (TSI) appeared in the serum of several rabbits after immunization. At 160 d, TSI equivalent to 6-18 microU TSH/1.5 mg IgG was present in two of six human (h)TSH-, two of six hTSH beta chain-, and two of the four surviving bovine (b)TSH-immunized animals. Control (human serum albumin-immunized rabbits) serum TSI was 4.3 +/- 0.4 (mean +/- SD) at this time. Antiidiotypic antibodies that could bind to monoclonal anti-hTSH were found in the sera of the bTSH-immunized rabbits. The peak TSI activity occurred 3 mo after a TSH booster immunization and declined
by atrial fibrillation, reduce the rate and seriousness of paroxysmal atrial fibrillation and improve the cardiac systolic and diastolic function [12–14]. For example, the combination of β-blocker and TSH suppression has effect for the atrial arrhythmia and diastolic dysfunc- tion caused by TSH suppression  and reduces the death rate caused by adverse cardiovascular reactions [16–18]. The combination of atenolol , digoxin, angiotensin converting enzyme inhibitor and other cardiovascular drugs can effectively reduce the adverse cardiovascular reactions during the suppression pro- cess . Some studies have showed that TSH levels were associated in a positive and linear manner with the TC, non-HDL-C and TG levels in euthyroid non- diabetics with newly diagnosed asymptomatic CHD. TSH in the upper limits of normal range might exert adverse effects on the lipid profile and might repre- sent a risk factor for hypercholesterolaemia and hyper- triglyceridaemia in the context of CHD. Maintaining TSH in a relative low normal range might be beneficial for lipid profile in euthyroid non-diabetics with newly diagnosed asymptomatic CHD . At present, this study only applies to specific groups of people, and has not yet included dietary factors in the study, so the con- clusion can not be extended to other groups; our next study is to expand the sample size of multi-center study.
Autoimmune thyroid diseases are the more prevalent organ-specific autoimmune disorders in humans. They encompass a wide spectrum of clinical presentations, with hyperthyroid Graves’ disease at one end and atrophic myxedema at the other. Whether Graves’ disease and lymphocytic thyroiditis represent different aspects of the same disease or different diseases remains unclear. Autoimmune thyroid diseases share common immunologic markers-mono nuclear cell infiltration of the thyroid-and circulating antithyroid antibodies, the specificities of which might, in part, account for the diversity of these diseases. Autoantibodies against the thyroid-stimulating hormone receptor (TSH receptor antibodies, (TSHR-Ab) represent only one family of thyroid autoantibodies. Others include antithyroperoxidase (TPO- Ab), the former antithyroid microsomal antibodies, antithyroglobulin, and the recently identified anti-sodium/iodide symporter antibodies. Historically, TSHR-Ab have been associated with hyperthyroid Graves’ disease. 7 Indeed, contrary to the other antithyroid antibodies, TSHR-Ab are pathogenic, capable of activating or blocking TSH receptor functions, as demonstrated by the occurrence of transplacentally transmitted hyperthyroidism or hypothyroidism in the fetus of mothers with high enough levels of circulating stimulating or blocking TSHR-Ab.
at the time of diagnosis. If diagnosed while the tumor is confined to the thyroid, MTC has a favorable prognosis (10 year survival rate 70-80%) . Common sites of meta- static disease include cervical and mediastinal lymph nodes, as well as lungs, liver, and bone; in the case of metastatic disease the 10 year survival rate drops to ap- proximately 40% [4-7]. Metastatic or locally advanced MTC is unresponsive to cytotoxic chemotherapy or radi- ation [4,8]. Targeted therapy with Tyrosine Kinase inhibi- tors (TKIs) are now approved to treat progressive and advanced MTC. TKIs compete with the ATP-binding do- mains of the TK catalytic unit inhibiting the activation of oncogenic intracellular signaling pathways . Vandetanib (Caprelsa, Astra Zeneca Pharmaceuticals) is an orally bio- available multi-RTK (receptor Tyrosine kinase) inhibitor that blocks the mutant RET gene product and has anti- tumor activity in adults with hereditary MTC [10,11]. At the National Cancer Institute, a phase I/II trial of vandeta- nib for children and adolescents with MTC was conducted to define a recommended dose and assess antitumor activ- ity, as described by Fox et al. . A common non-dose limiting toxicity was TSH elevation necessitating an in- crease in levothyroxine (LT) dosage – however, this was only noted in athyreotic patients who were previously on a stable dose. TKIs have been associated with elevated TSH as a drug class effect ; two prior studies of vandetanib in adults with MTC described an increase in LT require- ment [14,15]. Little is known about the effect of vandeta- nib on thyroidhormone levels in children. Our objective was to describe the TSH and free T4 levels and LT dosing in children and adolescents enrolled in the phase I/II trial of vandetanib for Multiple Endocrine Neoplasia Type 2B (MEN 2B) and MTC, NCT00514046.
Animals and drugs. All studies performed were approved by the Animal Research Committee, Veterans Affairs Greater Los Angeles Healthcare System. All drugs and reagents, unless otherwise specified, were purchased from Sigma Chemical Co. (St. Louis, Missouri, USA). Male C57 mice were obtained from Harlan Sprague Dawley (Indianapolis, Indiana, USA). Mice were kept in cages with no more than five animals per cage; chow and tap water were available ad libitum; and the mice were kept at 23 ± 1°C and light cycles of 12 hours. All mice were 70–80 days old at the beginning of the exper- iments and weighed 22–28 g. Hypothyroidism was induced by feeding a low-iodine diet supplemented with 0.15% propylthiouracil (PTU) purchased from Harlan Teklad Co. (Indianapolis, Indiana, USA), for 8–10 days. Four groups of mice were then treated daily for 10 days with intraperitoneal injections of 0 (vehicle only) or of 7, 14, or 28 ng/g/day T3. These amounts correspond to approximately two, four, and eight times the physio- logical replacement dose. Another four groups of mice were treated with 0, 3.6, 7.2, and 14.4 ng/g/day GC-1. The GC-1 doses are equimolar to T3 doses. After treat- ment, the interscapular brown adipose tissue (IBAT) thermogenic response to NE infusion was measured. IBAT thermal response to NE infusion. In these studies, we have adapted a protocol described for rats, with minor modifications (5). All animals were anesthetized with a mixture of urethane (560 mg/kg intraperitoneally) and chloralose (38 mg/kg intraperitoneally) the morning of the experiment. Mice were kept on a warm (30°C) pad through the course of the experiment. A polyethylene (P-50) cannula was inserted into the left jugular vein and later used for NE infusion. IBAT temperatures were measured using a precalibrated thermistor probe YSI 427 (Yellow Springs Instrument Co., Yellow Springs, Ohio, USA) secured under the brown fat pad. Core tem- perature was measured with a colonic probe YSI 423 (Yellow Springs Instrument Co.). The probes were con- nected to a high-precision thermometer (YSI Precision 4000A Thermometer; Yellow Springs Instrument Co.). Core temperature and IBAT temperature were moni- tored during a period of 10 minutes to obtain a stable baseline, and then NE infusion was started. NE infusion (1,075 pmol/min) was performed with an infusion pump (Harvard Model 2274; Harvard Apparatus, Hol- liston, Massachusetts, USA) at a rate of 0.459 µ l/min for 30 minutes. Raw data were plotted over time and expressed in term of maximum ∆IBAT temperature (°C). Heart rate was also monitored electrocardio- graphically during NE infusion.
An important indication for the use of rhTSH is disease monitoring. The first assessment concerning the effectiveness of ablation therapy is carried out 6-12 months after radioiodine treatment. The assessment includes rhTSH-stimulated Tg levels, anti-Tg antibodies levels, thyroid ultrasound and whole-body scintigraphy. In more than 80% of patients, serum Tg levels reach the highest values at day 5 after administration of rhTSH. Evaluation of serum Tg levels after TSH stimulation is the most effective method of disease monitoring. The sensitivity of Tg measurement during the treatment with L-T4 is definitely lower: in 20% of patients with metastases to the lymph nodes and in 5% with distant metastases it may be false negative .
Against this background, it is not surprising that thyroidhormone is anti-apoptotic in tumor cells and in certain non-tumor cells. Anti-apoptosis may be desirable in nondividing neurons or endothelial cells, but is an obvious disadvantage in the setting of cancer management. Indeed, the anti-apoptotic activity of host thyroidhormone could contribute to chemotherapeutic resistance . In this brief analysis, we examine the evidence that thyroidhormone is anti-apoptotic in cancer cells and the mechanisms that are involved. For example, thyroidhormone and hormone analogues affect the function of pro-apoptotic p53 ; that is, T 4 blocks p53-dependent apoptosis and the T 4 antagonist, and tetraiodothyroacetic acid (tetrac) and its formulations, facilitate apoptosis. Thyroidhormone and certain of its analogues also affect transcription of a variety of genes relevant to apoptosis [31–33]. This effect includes downregulation of expression of certain caspase genes . Activated caspases are proteases essential to apoptosis by assuring structural disorganization of the nucleus and activation of DNAses, as well as contributing to degradation of cytoplasmic proteins. Tetrac is pro- apoptotic and acts at integrin αvβ3 to upregulate caspase gene transcription [31, 34]. The hypoxia-inducible factor- 1α (HIF1α) gene in cancer cells is also upregulated by T 4 ; the gene product has a number of defensive actions in tumor cells, including support of anti-apoptosis [35, 36]. Other examples of the actions of hormone analogues on apoptosis-modulating genes are discussed below.
MDA-MB-468 cells were a generous gift from Ana Aranda (Universidad Auto´noma de Madrid, Madrid, Spain). Establishment of MDA-MB-468 cells stably expressing human TRβ1, the C-terminal mutants (PV, Mkar, Mdbs, and AM), or the control gene (Neo) was described previously . The plasmids for expression cDNA for Mkar, Mdbs, and AM were generous gifts from Roy Weiss of the University of Chicago. Briefly, MDA-MB-468 cells were transfected with the expres- sion plasmid containing cDNA encoding 3Flag-TRβ1 (pcDNA3.1-3Flag-TRβ1), 3Flag-PV (pcDNA3.1-3Flag- PV), 3Flag-Mkar (pcDNA3.1-3Flag-Mkar), 3Flag-Mdbs (pcDNA3.1-3Flag-Mdbs), 3Flag-AM (pcDNA3.1-3Flag- AM), or the empty vec tor containing only the cDNA for the selector marker, the Neo gene. After transfection, cells were selected with 200 μg/ml G418 (Invitrogen, Carlsbad, CA) for 2 weeks. G418-resistant colo nies expressing TRβ1 and C-terminal mutants were expanded for sub sequent experiments. The expression of TRβ1 and C-terminal mutant protein was verified by Western blot analysis using monoclonal anti-TRβ (J53)  or anti- Flag antibody (Sigma Aldrich. Cat. F3165).
insert, Genzyme Corporation). According to the Genzyme package insert, post-marketing experience has shown that administration of rhTSH can cause transient ﬂ u-like symptoms for up to 48 hours. Hypersensitivity has also been reported in patients with advanced disease, as mani- fested by urticaria, rash, pruritis, ﬂ ushing, and respiratory symptoms. Similar to THW, there are case reports of tumor enlargement, edema, and hemorrhage resulting in pares- thesias, hemiplegia, pathologic vertebral fractures, neck edema as well as exacerbation of bone pain seen within 12 to 48 hours of rhTSH administration (Vargas et al 1999; Robbins et al 2000; Braga et al 2001; Lippi et al 2001; Berg et al 2002; Goffman et al 2003; Jarzab et al 2003). For this reason, it is recommended that pretreatment with glucocorticoids be considered in patients with tumors located where transient expansion may compromise vital anatomic structures (eg, CNS and spinal metastases, bulky neck metastases). It is also recommended that patients who have extensive functional thyroid tissue or cardiac condi- tions (for whom rhTSH-induced stimulation of thyroidhormone production causing hyperthyroidism could have serious consequences) be hospitalized for administration and observation.
The influence of serum triiodothyronine (T 3 ) and thyroxine (T 4 ) concentrations on the release of prolactin in man was studied by determining the prolactin response to synthetic thyrotropin-releasing hormone (TRH) in hypothyroid and hyperthyroid patients before and after correction of their serum thyroidhormone abnormalities. The maximum increment in serum prolactin above the basal level (maximum Δ prolactin) was used as the index of response to TRH.
decreased responsiveness of the adenylate cyclase-cylic AMP system. Such refractoriness is hormone specific since initial exposure to prostaglandin E1 decreases the subsequent response to this substance but not to TSH. Refractoriness to TSH develops only when the first incubation is at least 30 min. It is not reversed by 5 h of incubation without hormone. Incubation of thyroid slices with puromycin does not eliminate refractoriness. The decreased response to TSH cannot be explained by release of thyroxine, triiodothyronine, or iodide from the slices. Phosphodiesterase activity is not increased during the refractory period. The decreased cyclic AMP […]
Received 8 January 2002; accepted 2 April 2002. Endocrine Disruptors
Thyroidhormone is essential for normal brain development. Therefore, it is a genuine concern that thyroid function can be altered by a very large number of chemicals routinely found in the environment and in samples of human and wildlife tissues. These chemicals range from natural to manufactured compounds. They can produce thyroid dysfunction when they are absent from the diet, as in the case of iodine, or when they are present in the diet, as in the case of thionamides. Recent clinical evidence strongly suggests that brain development is much more sensitive to thy- roid hormone excess or deficit than previously believed. In addition, recent experimental research provides new insight into the developmental processes affected by thyroidhormone. Based on the authors’ research focusing on the ability of polychlorinated biphenyls to alter the expression of thyroidhormone-responsive genes in the developing brain, this review provides background information supporting a new way of approaching risk analysis of thyroid disruptors. Key words: brain development, cerebral cortex, endocrine disruption, HES-1, Notch, NSP-A, thyroidhormone. Environ Health Perspect 110(suppl 3):355–361 (2002).
Functional thyroid nodules (eg toxic adenoma) have a very low risk of malignancy and do not require sonographic assessment for further risk stratification. Therefore, a low TSH level should prompt scintigraphy as the first investigation of thyroid nodules (Figure 3). A palpable nodule that is not clearly hyper-functioning on scintigraphy requires sonographic assessment, as it may be caused by a solid, discrete nodule (higher risk of malignancy) or simple cyst (benign).
Human skin fibroblasts synthesize and accumulate glycosaminoglycans (GAG). Recently, we reported that fibroblasts incubated in thyroidhormone-deficient media accumulate more GAG than do cultures incubated in the same media enriched with 0.1 µM triiodothyronine (T 3 ) (1981. Endocrinology. 108: 2397). The current study characterizes that enhanced accumulation. Confluent cultures were maintained in thyroidhormone-deficient media without or with added T 3 , labeled with [ 3 H]acetate and analyzed for total [ 3 H]GAG and [ 3 H]hyaluronic acid content.
An 8-year old boy with a small goiter, normal basal metabolic rate (BMR), and elevated serum thyroidhormone levels (thyroxine [T 4 ] 19.5 µg per 100 ml, free T 4 4 ng per 100 ml, triiodothyronine [T 3 ] 505 ng per 100 ml) was studied. He had measurable serum thyroid- stimulating hormone (TSH) levels (average 5.5 µU per ml), and the thyroxine-binding proteins, hearing, and epiphyseal structures were normal. There was no parental consanguinity nor were there thyroid abnormalities either in the parents or six siblings. Methimazole, 50 mg daily, depressed thyroxine synthesis (T 4 10.5, free T 4 2.5) and caused a rise in TSH to 11 µU per ml. After discontinuation of treatment, TSH declined to 4.2 µU per ml and chemical hyperthyroidism returned (T 4 21.0 µg per 100 ml, free T 4 4.2, and total T 3 475 ng per 100 ml, radioactive iodine [RAI] uptake 68%), but studies of BMR and insensible water loss showed the patient to be clinically euthyroid. Thyrotropin-releasing hormone (TRH), 200 µg i.v., caused a brisk rise in TSH to 28 µU per ml, with T 4 rising to 28 µg per 100 ml, free T 4 to 5.6, and T 3 to 730 ng per 100 ml, thus indicating that the pituitary-thyroid system was intact and that the patient's TSH was biologically active. The unusual sensitivity of the pituitary cells to TRH […]
Generalized resistance to thyroidhormone (GRTH) is a syndrome of hyposensitivity to triiodothyronine (T3) that displays autosomal dominant inheritance. The genetic defect commonly lies in the ligand-binding domain of one of the TR beta alleles. Since there are two major thyroidhormone receptor (TR) isoforms, TR alpha and TR beta, it is not known how the mutant receptor mediates a dominant negative effect. Previously, we showed that T3 caused dissociation of TR homodimers and TR alpha/TR beta dimers from several thyroidhormone response elements (TREs). Hence, we used the electrophoretic mobility shift assay to compare the effect of T3 on the DNA binding of mutant TR beta-1 (Mf-1) from a kindred with GRTH with normal TR beta. Mf-1 bound better as a homodimer than TR beta, but dissociated from DNA only at high T3 concentrations. Both receptors heterodimerized with nuclear auxiliary proteins. They also dimerized with TR alpha and with each other. Surprisingly, T3 disrupted the DNA binding of the Mf-1/TR isoform dimers. Thus,