ORCID Profile
0000-0003-4763-3385
Current Organisations
Monash University
,
The Alfred Hospital
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Publisher: Elsevier BV
Date: 2010
DOI: 10.4158/EP09177.CR
Publisher: Wiley
Date: 04-1985
DOI: 10.1111/J.1365-2265.1985.TB00150.X
Abstract: Iopanoic acid (1 g/d) was used together with propylthiouracil (1200 mg/d) in the treatment of a patient with very severe hyperthyroidism and associated cardiac failure. Although serum total T3 decreased by 75% within 48 h and reached normal after 72 h, free T3 levels did not fall to normal. Total and free T4 remained markedly elevated and features of hyperthyroidism persisted. Estimations of theoretical in vivo occupancy of nuclear thyroid hormone receptors, based on serum free T4 and free T3, suggest that the marked decrease in total T3 would not result in a corresponding decrease in thyroid hormone action. Hence, estimates of potential benefit from oral cholecystographic contrast agents, based only on measurements of total T3, may be unduly optimistic. When temporary agranulocytosis developed in this patient, the prior use of iopanoic acid, by markedly reducing thyroidal iodine uptake, restricted the therapeutic options. Caution should, therefore, be exercised in the use of iodine-containing contrast media as adjunctive antithyroid agents.
Publisher: Medknow
Date: 07-2013
Publisher: The Endocrine Society
Date: 1980
DOI: 10.1210/JCEM-50-1-52
Abstract: Despite the high-demand work environment for field epidemiologists in field epidemiology training programs, little is known about their occupational stress. To identify occupational stress and its related factors, the occupational stress among trainees in field epidemiology training programs in Southeast Asia and Western Pacific regions from 2016 to 2018 was examined using six subscales: Role Overload, Role Insufficiency, Role Ambiguity, Role Boundary, Responsibility, and Physical Environment. Furthermore, the data on the year of training and type of training program as well as the level of burnout, which affects stress-coping strategies, were collected. Fisher's exact tests and logistic regression models were used to examine associations between occupational stress, burnout, the number of years of training, and the type of training program. Sixty-two trainees participated, and there were no significant associations between burnout, the year of training, and type of training program. A burden of occupational stress in Role Overload and Physical Environment was reported by 56% and 53% of respondents, respectively. The trainees affiliated with a university program were less likely to have a burden of occupational stress in Responsibility and Physical Environment. It is concerning that more than half of trainees in the programs experienced occupational stress in Role Overload and Physical Environment. Additional efforts to design improved training programs to reduce occupational stress are warranted.
Publisher: Korean Endocrine Society
Date: 2016
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Chemical Society (ACS)
Date: 04-1993
DOI: 10.1021/JM00061A019
Abstract: The synthesis of a series of mono- and disubstituted N-phenylanthranilic acids is described. Substituents on the phenyl ring include Cl, CN, OH, CF3, Br, I, CH3, OCH3, and OCF2CF2H. These compounds have been tested for their inhibitory effect on triiodothyronine (T3) uptake by H4 hepatocytes. The nonsteroidal antiinflammatory drugs flufenamic acid, mefenamic acid, and meclofenamic acid and the structurally related compounds 2,3-dimethyldiphenylamine and diclofenac were also tested. The most potent compounds were found to be, in order of decreasing activity, meclofenamic acid (2,6-Cl2,3-CH3), flufenamic acid (3-CF3), mefenamic acid (2,3-(CH3)2), and the compounds with 3,5-Cl2 and 3-OCF2CF2H substituents. The least potent compounds had 3-CN and 3-OH substituents. An analysis of quantitative structure-activity relationships (QSAR) for the series of phenylanthranilic acids showed that the inhibition of T3 uptake is highly dependent on the hydrophobicity of the compound. The relationship between uptake inhibition and the calculated octanol-water partition coefficient (clogP) was found to be parabolic, with optimum inhibitory activity found when the clogP of the phenylanthranilic acid was 5.7. It was also found that the 1-carboxylic acid group of the phenylanthranilic acids was not a prerequisite for uptake inhibition to occur, but its removal or alteration resulted in reduced inhibition.
Publisher: Elsevier BV
Date: 11-1977
Publisher: Wiley
Date: 08-2019
DOI: 10.1111/IMJ.14210
Abstract: Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 μg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman's general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up. Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.
Publisher: Mary Ann Liebert Inc
Date: 08-2011
Abstract: Cardiac metastasis from epithelial thyroid cancer is a very rare and potentially serious complication. We have identified only 54 reported cases over a 130-year period. Here we review this literature. Cardiac metastases are frequently asymptomatic, but when symptoms develop these tend to be severe and often fatal. The prognosis of cardiac metastases from thyroid cancer is unclear as survival data are often missing or absent in reported cases. However, as many patients died suddenly from cardiac complications, the prognosis seems poor. Of those patients who survived, all underwent surgical intervention. Trans-thoracic echocardiography is the diagnostic modality of choice as it allows dynamic evaluation of intracardiac masses. Metastatic involvement of the heart from thyroid cancer is uncommon. Left untreated this complication seems likely to be fatal. Therefore, in patients with established thyroid malignancy who develop cardiac arrhythmias, new murmurs, or signs of cardiac decompensation, we suggest that cardiac metastases be considered. Echocardiography should be performed in patients with advanced thyroid cancer and cardiac symptoms or signs. If a cardiac metastasis is present, we recommend surgical intervention if possible.
Publisher: Wiley
Date: 05-1987
Publisher: Massachusetts Medical Society
Date: 11-01-1979
Publisher: Georg Thieme Verlag KG
Date: 15-03-1996
Abstract: In nonthyroidal illness, numerous drugs such as glucocorticoids, dopamine, fenclofenac, furosemide and diphenylhydantoin may modify the close inverse-feedback relationship between circulating thyroid hormones and TSH. Such effects could involve altered hypothalamic TRH secretion, a direct effect on TSH production by the thyrotroph, alterations in circulating free thyroid hormone concentrations, or changes in thyroid hormone uptake by the thyrotroph. We therefore examined the effect of nonsteroidal antiinflammatory drugs (NSAID), diuretics, the synthetic flavonoid EMD 21388, and diphenylhydantoin, on [125I]T3 cellular uptake in rat pituitary primary cell cultures. Uptake of [125I]T3 (cell-associated counts of washed cells) was measured at 15 min after the addition of 50 pmol/L [125I]T3 in protein-free medium (37 degrees C, pH 7.4). Uptake of [125I]T3 by pituitary cells was 6.0 +/- 1.7% of total counts (mean +/- SD, n = 18). Unlabeled T3 (10 mumols/L) displaced 92% of total uptake. The IC50 of unlabeled T3 for the displacement of [125I]T3 was 1.2 mumols/L. T4 and rT3 were approximately 10% as effective as T3 itself in inhibiting [125I]T3 uptake, while triac did not affect cellular [125I]T3 uptake. Inhibition of [125I]T3 uptake at drug concentrations of 100 mumols/L was seen with the diuretics, furosemide (9%), bumetanide (14%), piretanide (12%) and ethacrynic acid (76%), the NSAID, meclofenamic acid (35%) and fenclofenac (52%), EMD 21388 (49%), and the anticonvulsant, diphenylhydantoin (23%). Aspirin, up to 500 mumols/L, had no effect on [125I]T3 uptake. Our results indicate that ethacrynic acid, meclofenamic acid, fenclofenac, EMD 21388 and diphenylhydantoin affect plasma membrane T3 uptake in the pituitary. This potential influence on TSH release will be contrary to the previously-demonstrated direct inhibitory effect of these drugs on TSH release.
Publisher: Wiley
Date: 12-1990
Publisher: The Endocrine Society
Date: 08-1996
DOI: 10.1210/ENDO.137.8.8754738
Abstract: Previous studies have suggested that there is an interrelationship between responses mediated by retinoic acid (RA) and those to thyroid hormone (T3). These experiments have used transfected gene constructs, often in receptor-negative cells. To study the relationship between RA- and T3-mediated responses in intact human cells, we incubated HepG2 cells for 4 days in serum-free medium with T3 and/or RA or 9-cis-RA. Measured responses were stimulation of secreted sex hormone-binding globulin (SHBG) or inhibition of secreted T4-binding globulin (TBG). T3 induced a dose-responsive increase in SHBG secretion that was maximal at 10nM (206 +/- 24% of untreated value) and half-maximal at 0.36 +/- 0.16 nM T3. RA and 9-cis-RA, up to 100 nM, induced a slight fall in SHBG secretion to 79 +/- 9% and 88 +/- 9%, respectively. T3 induction of SHBG secretion was significantly attenuated in cells coincubated with T3(0-10nM) and RA. With T3 (10 nM) together with RA (3, 10, or 100 nM), the maximal SHBG responses were reduced to 193 +/- 24%, 151 +/- 5% and 132 +/- 30%, respectively. With T3 and 9-cis-RA (100 nM), maximal stimulation was 169 +/- 20%. Importantly, the effective half-maximal stimulatory concentration of T3 in the presence of either retinoid (3-100 nM) was unchanged at 0.3 nM T3. In addition, the inhibitory effect of 9-cis RA could not be overcome even with 300 nM T3. The threshold for the RA effect was between 0.3-1 nM, with half-maximal inhibition at 30 nM. 9-cis-RA was approximately 10-fold less potent than RA. Preliminary studies suggested that changes in SHBG messenger RNA levels were similar to those in secreted SHBG. No effect was observed with vitamin D or clofibrate, either alone or combined with T3. Conversely, T3 reduced TBG secretion, with maximal suppression to 74 +/- 5% of the control value at a T3 concentration of 10 nM. RA alone reduced TBG secretion to 76% of the control value. RA did not attenuate the effect of T3, and the two agents combined showed no synergism. Neither T3 nor RA, alone or in combination, influenced secreted total protein or albumin. RA did not alter the concentration of nuclear T3-binding sites. These data suggest that retinoids act via a gene-dependent mechanism to modulate maximal, but not half-maximal, responses to T3 in HepG2 cells with the specificity of RA greater than that of 9-cis-RA.
Publisher: Wiley
Date: 02-1988
Publisher: Springer New York
Date: 26-09-2014
Publisher: Wiley
Date: 27-04-2020
DOI: 10.1111/APT.15723
Publisher: Oxford University Press (OUP)
Date: 11-1986
DOI: 10.1111/J.2042-7158.1986.TB04497.X
Abstract: A spectrophotometric method to measure the free fraction of highly-bound drugs in serum has been established for a range of non-steroidal anti-inflammatory drugs (NSAIDs) and for frusemide. Spectrophotometry is used to measure fractional transit of drug from a large volume of dialysate to a small volume of serum during dialysis to equilibrium. The method, which depends on the principle that drug transit from dialysate to serum is proportional to serum binding, requires neither isotopic drug preparations nor specific drug assays, is independent of extraction efficiency from the dialysate and requires no measurements from the serum compartment. Estimates of percent unbound fraction (%UF) for aspirin (6.0 ± 0.9%), phenylbutazone (0.9 ± 0.2%), and frusemide (1.8 ± 0.2%) were comparable with those obtained with 14C drug preparations. Values for %UF were determined for eleven additional NSAIDs. The method was valid for a four-fold change in serum: dialysate ratio. Kinetics of frusemide binding to serum were comparable using [14C]frusemide and the test method. This technique may have general application in establishing the %UF for substances that are extensively bound to serum proteins and for identifying sera that show abnormal binding.
Publisher: Elsevier BV
Date: 06-1979
DOI: 10.1016/0002-9343(79)90445-5
Abstract: When cells of Alteromonas haloplanktis 214 (ATCC 19855) were preloaded with alpha-[(14)C]aminoisobutyric acid or the K(+) in the cells was labeled with (42)K by incubation in a buffered salt solution containing 0.05 M MgSO(4), 0.01 M KCl, and 0.3 M NaCl, the cells retained their radioactivity when resuspended in the same salt solution. When NaCl was omitted from the solution, 80 to 90% of the radioactivity was lost from the cells. Cells suspended at intermediate concentrations of NaCl also lost radioactivity. New steady-state levels of the intracellular solutes were established within 15 s of suspending the cells the percentage of radioactivity retained at each level decreased proportionately as the osmolality of the NaCl in the suspending solution decreased. With minor variations in effectiveness, MgCl(2), LiCl, and sucrose could substitute for NaCl on an equiosmolal basis for the retention of radioactivity by the cells. KCl, RbCl, and CsCl were appreciably less effective as replacements for NaCl, particularly when their osmolalities in the suspending solutions were low. The amount of alpha-[(14)C]aminoisobutyric acid taken up by the cells at the steady-state level increased to a maximum as the NaCl concentration in the suspending medium increased to 0.3 M. At suboptimal levels of NaCl, either LiCl or sucrose could substitute for NaCl in increasing the steady-state levels. The results obtained indicate that the porosity of the cytoplasmic membrane of this organism is determined by the difference between the osmotic pressure of the cytoplasm and the suspending medium. The lesser effectiveness of K(+), Rb(+), and Cs(+) than Na(+), Li, or Mg(2+) in permitting the retention of solutes by the cells is attributed to the greater penetrability of the hydrated ions of the former group through the dilated pores of a stretched cytoplasmic membrane.
Publisher: Mary Ann Liebert Inc
Date: 1992
Publisher: Wiley
Date: 05-1987
Publisher: BMJ
Date: 02-07-1994
Publisher: Mary Ann Liebert Inc
Date: 02-1998
Abstract: In most trials, at least 50% of patients with Graves' disease treated with antithyroid drugs (ATD) relapse after achieving euthyroidism. At present, there are no definitive prognostic parameters available early in treatment to indicate those likely to achieve long-term remission. Because thyrotropin receptor antibodies (TRAb) are specific for Graves' disease, the possibility that their rate of change early in treatment (0 to 6 months) might be such an indicator was explored. TRAb were measured both as thyrotropin binding inhibitory immunoglobulins (TBII) and as thyroid-stimulating antibodies (TSAb) in 85 patients with untreated Graves' disease at 6-month intervals throughout their ATD treatment. The patients in the study were treated for a minimum period of 12 months and were categorized retrospectively into two groups depending on whether or not they remained in remission after ATD treatment. Remission was deemed as reached in patients who remained euthyroid for a minimum period of 15 months after cessation of ATD. The mean initial TBII and TSAb values in the nonremission group were significantly higher than in the remission group (p < 0.001 for both parameters). The rates of fall in mean TBII levels were similar for each group in the first 6 months of treatment, but while they continued to fall in the remission group over the next 6 to 12 months, mean values for the nonremission group plateaued and failed to fall to control levels within that period. These results indicate that changes in TRAb levels, measured either as TBII or TSAb, occur more rapidly in the second 6 months of treatment in patients who ultimately achieve remission than those who do not. If TBII fall to control levels by 12 months, the patient has at least a 70% chance of ultimately achieving remission with ATD treatment alone.
Publisher: The Endocrine Society
Date: 08-1981
Abstract: Responses of the pituitary-thyroid axis and T4 binding to plasma proteins were studied in three kindreds with familial euthyroid T4 excess, an autosomal dominant condition in which affected subjects have high concentrations of plasma T4 with a high free T4 index, but normal free T4 by equilibrium dialysis. Treatment of affected subjects with exogenous T4 or T3 led to gradual suppression of TSH secretion when the free level of T4 or T3 increased above normal. When total T4 was reduced toward normal by potassium iodide treatment or previous subtotal thyroidectomy, the findings suggested mild hormone deficiency. In affected subjects from all three families, equilibrium dialysis showed increased [125I]T4 binding, with evidence of abnormal high capacity binding when an excess of unlabeled T4 was added. In contrast, T3 binding showed no major abnormality. Serum concentrations of T4-binding globulin, prealbumin, and albumin were normal, but gel electrophoresis and immunoprecipitation of binding proteins indicated that 25-30% of tracer [125I]T4 was albumin bound (normal, 10-12%). Abnormal binding, studied by an adsorption separation system in the presence of T4 excess, was inhibited by increments of barbitone. These findings suggest that T4 excess is an appropriate response to abnormal T4 binding so as to maintain normal free T4. The excess bound T4 is associated with a normal quantity of albumin. The basis for increased T4-albumin binding remains to be determined.
Publisher: The Endocrine Society
Date: 07-1995
DOI: 10.1210/JCEM.80.7.7608285
Abstract: A sensitive [125I]-T4 binding assay was used to measure serum T4-binding globulin (TBG) in 60 in iduals selected on the basis of their total circulating T3 concentrations, and a relationship between TBG and circulating thyroid hormone levels in humans was confirmed. There was a significant correlation between serum TBG and T3 or free T4 index. TBG secretion and TBG messenger ribonucleic acid (mRNA) production were studied with a continuous culture of the human hepatoblastoma cell line, HepG2. Cells were maintained in serum-free media for experimental manipulations. The addition of 100 nmol/L T3 to the cell medium resulted in a time-dependent down-regulation of TBG mRNA to 33 +/- 6% (+/- SD, n = 4) of untreated control levels by 24 h. Suppression of TBG mRNA was first detectable at 8 h (57% of untreated control levels). The effect of T3 was dose-responsive, with half-maximal suppression of TBG mRNA occurring at a bioavailable T3 concentration of approximately 30 pmol/L. The effect of T3 on TBG mRNA was not caused by a change in mRNA stability. Proteins secreted by HepG2 cells bound T4 with an affinity identical to that of normal circulating TBG. Cell secretion of TBG was parallel to total protein secretion and consistent with a TBG secretion rate of 50 ng/10(6) cells per day. Variations in the concentration of secreted binding protein in the presence of T3 corresponded to the changes observed in TBG mRNA. These data show that circulating TBG concentration is negatively correlated with total serum T3 in vivo. The corresponding down-regulation observed between TBG mRNA and secreted protein in HepG2 cells suggests that this effect is the result of the action of T3 on cellular TBG mRNA synthesis.
Publisher: Springer Science and Business Media LLC
Date: 22-08-2005
Abstract: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of %, but nearly all had a 5-year stroke risk of %. Despite this, half of the cohort were obese (BMI 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
Publisher: The Endocrine Society
Date: 04-1986
Abstract: In a prospective study of critically ill hypothyroxinemic we assessed the relationship between serum TSH and T4 during the return of serum T4 to normal during recovery. In this longitudinal study of 60 patients with a variety of critical illnesses, including burns, septicemia, and acute renal failure, serum T4 fell to less than 2.7 micrograms/dl (35 nmol/liter) in 24 patients, of whom 14 survived with return of T4 to normal. A rise in total T4 of more than 1.9 microgram/dl (25 nmol/liter) within 96 h occurred 13 times in 10 patients, while 4 patients had slower increases in T4. All 13 episodes of rapid T4 rise [1.7 +/- 0.8 (+/- SD) to 5.6 +/- 2.1 micrograms/dl] were associated with a marked increase in serum TSH (1.1 +/- 0.8 to 7.0 +/- 5.2 mU/liter), and TSH was transiently above normal during 8 episodes of T4 recovery. In the 6 episodes with s ling less than 6 h apart, the TSH rise consistently preceded the T4 rise. In the 4 patients who received dopamine, TSH and T4 remained low until cessation of therapy. During the TSH rise, only minor changes, which could not account for the increase in total T4, occurred in T4-binding globulin (12.9 +/- 3.3 to 14.8 +/- 3.3 mg/liter), prealbumin (208 +/- 73 to 234 +/- 82 mg/liter), and albumin (28.3 +/- 2.9 to 31.9 +/- 2.9 g/liter). Mean free T4 increased (0.60 +/- 0.34 to 1.45 +/- 0.56 ng/dl), as did total T3 (16 +/- 14 to 76 +/- 44 ng/dl), during the phase of TSH rise, suggesting that the increase in TSH was not simply a consequence of diminished negative feedback due to increased plasma binding. The very close and consistent temporal relationship between TSH and T4 during the recovery phase suggests that TSH may have an essential role in the return of T4 to normal during recovery from critical nonthyroidal illness.
Publisher: Mary Ann Liebert Inc
Date: 11-2016
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/AJO.12829
Publisher: Wiley
Date: 24-04-2015
DOI: 10.1002/CNCR.29395
Publisher: Elsevier BV
Date: 09-1983
DOI: 10.1016/S0006-291X(83)80017-5
Abstract: We have examined the effects of ovine growth hormone and recombinant DNA synthesized human growth hormone on hepatocytes maintained in serum free cultures. Both growth hormone preparations augmented or attenuated 3 specific mRNA sequences as revealed by two-dimensional gel electrophoresis of [35S] methionine labeled products synthesized in vitro in an mRNA dependent rabbit reticulocyte lysate system. The results clearly indicate that growth hormone, free of potential pituitary contaminants, acts directly on hepatocytes at a pretranslational level.
Publisher: Springer Science and Business Media LLC
Date: 05-1988
DOI: 10.1007/BF03349054
Publisher: Elsevier BV
Date: 12-2006
Publisher: Wiley
Date: 09-2003
DOI: 10.1046/J.1445-5994.2003.00463.X
Abstract: Abstract Background: Amiodarone‐induced thyrotoxicosis (AIT) presents a therapeutic challenge because of its resistance to standard antithyroid therapy. In iodine‐deplete environments, colour‐flow Doppler sonography (CFDS) has allowed distinction between two types of AIT: (i) Type I AIT, associated with increased vascularity (CFDS I−III) and response to thionamide antithyroid drug and (ii) type II AIT, with no/little thyroid vascularity (CFDS 0) and prednisolone responsiveness. Aim: To clarify if CFDS patterns correlated with treatment outcomes in a retrospective study of 24 patients with AIT in an iodine‐replete environment. Methods: Medical records of patients who presented to a teaching hospital between January 1998 to December 2000 were reviewed. Results of CFDS, ultrasound measurement of thyroid size and technetium scanning of the thyroid were correlated with treatment responses, especially prednisolone responsiveness. Results: Thirteen of 24 patients showed CFDS 0. Twelve of these 13 were evaluable for prednisolone responsiveness, of whom seven (58%) were prednisolone‐responsive. Of 11 patients with CFDS I−III, four (36%) responded to antithyroid medication alone and only one of seven (14%) was prednisolone‐responsive. Euthyroidism was achieved twice as rapidly in patients with CFDS 0 than those with CFDS I‐III. Because of medical treatment failure, seven patients, from both CFDS groups, required urgent near‐total thyroidectomy which was successful and uncomplicated in all cases. Conclusions: CFDS is useful in the management of AIT because CFDS 0 correlates better with prednisolone response (58%) than CFDS I−III (14%). However, unlike experience in iodine‐deficient regions, the results of the present study revealed that treatment responses to thionamide or prednisolone were heterogeneous within uniform CFDS patterns. Thus, prednisolone‐responsiveness was not consistently predicted by CFDS 0, but the presence of flow appeared to correlate with non‐response to prednisolone. (Intern Med J 2003 33: 420−426)
Publisher: The Endocrine Society
Date: 11-1981
Abstract: The allo-suppressor effect of normal T lymphocytes on the production of migration inhibition factor by sensitized T lymphocytes of Graves' disease in response to human thyroid antigen has been studied further by a modified migration inhibition factor test employing purified T lymphocyte preparations. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with the Graves' disease lymphocytes in various ratios (1:9, 2:8, and 5:5). However, pretreatment of the normal T lymphocytes with cimetidine (an H-2 histamine receptor antagonist) led to a demonstrable loss in their allo-suppressor properties, whereas pretreatment with chlorpheniramine (an H-1 histamine receptor antagonist) had no such effect. These studies indicate that a subset of normal T lymphocytes bearing H-2 histamine receptors suppresses the production or release of migration inhibition factor by sensitized T lymphocytes, and further suggest the possibility that there may be an abnormality in the H-2 receptors on Graves' disease suppressor T lymphocytes. It is conceivable that this defect is fundamental in the pathogenesis of Graves' disease.
Publisher: The Endocrine Society
Date: 10-1988
Abstract: We directly compared the competitor potency for serum T4 binding of 11 nonsteroidal antiinflammatory drugs the diuretics furosemide, ethacrynic acid, and bumetanide diphenylhydantoin the cholecystographic contrast agents iopanoate and ipodate and six long-chain nonesterified fatty acids (NEFA) using equilibrium dialysis. To avoid artefacts that occur in competitor studies with diluted serum or isolated binding proteins, we used undiluted normal serum, with drugs added at concentrations that achieved high therapeutic total and free serum levels at equilibrium. Drug addition was based on the measured free fraction of each drug in serum. The free T4 fraction in normal serum (Tris buffer, pH 7.4 37 C) was between 1.40 X 10(-4) and 1.53 X 10(-4). Drug-induced increases in T4 free fraction were: fenclofenac, 90% aspirin, 62% meclofenamic acid, 39% diflunisal, 37% mefenamic acid, 31% and furosemide, 31%. Significant increases of 7-15% occurred with diclofenac, flufenamic acid, phenylbutazone, and diphenylhydantoin. Indomethacin, ketoprofen, tolmetin, ethacrynic acid, bumetanide, iopanoate, and ipodate were inactive at the concentrations studied. Addition of 2.0 mmol/L oleic acid had a negligible effect, but 3.5 mmol/L oleic acid inhibited T3 and T4 binding significantly. Other long chain NEFA (addition of 1.5 mmol/L) gave increases in free T4 fraction as follows: arachidonic acid, 26% linolenic acid, 23% and linoleic acid, 11%. Stearic and palmitic acids were inactive. The effect of 5 mmol/L oleic acid in serum could be reproduced by addition of 0.5 mmol/L to serum diluted 1:10, indicating that protein binding of NEFA is the major determinant that limits their competitor potency. These findings provide a basis for anticipating which potential inhibitors may cause important changes in serum thyroid hormone binding. The time course of such effects will be influenced by the pharmacokinetics of the inhibitor itself as well as the equilibrium findings described here.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.COLEGN.2013.06.001
Abstract: Coronary heart disease is common in Type 2 diabetes and often requires cardiac surgery. However poorer outcomes have been reported including increased rates of post-operative infection and prolonged hospital stay. The aim of the study was to determine the feasibility and acceptability of a specialist consultation model (pre-operative medical and educational intervention) for type 2 diabetes in the cardiac surgery setting. Twenty four patients were assigned usual care or to the intervention group. The intervention group were assessed by a diabetes clinical nurse consultant, dietitian, and endocrinologist during a pre-operative visit. Specific diabetes questionnaires were administered, education was delivered, and protocol-driven changes to the medical regimen were instituted. Length of stay, incidence of post-operative complications, and number of post-operative inpatient review endocrinology visits required were recorded. Twenty four patients with a pre-operative HbA(1c) greater than 6.5% (48 mmol/mol) were studied (17 males and 7 females). In the usual care group (n = 15), HbA(1c) pre-operatively was 7.2% (55.2 mmol/mol) compared to 10.1% (86.9 mmol/mol) in the intervention group (n = 9). Six weeks post-operatively HbA(1c) fell significantly in the intervention group by 1.9% (to 8.2% [66.1 mmol/mol]) compared to a reduction of 1.2% (to 7.0% [53 mmol/mol]) in the usual care group (p < 0.05). No significant differences were observed in length of stay in intensive care or in total hospital stay between the groups: length of ICU stay 54 h for intervention versus 47 h for usual care, total hospital stay (mean 8 days for both) or in rates of post-operative infection. Differences were seen between in the diabetes questionnaires: in the Problem Areas in Diabetes questionnaire and in the Diabetes Treatment Satisfaction Questionnaire (p = 0.048). This small pilot feasibility study suggests there is potential benefit in the acute optimisation of diabetes treatment before elective cardiac surgery.
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1445-5994.2008.01735.X
Abstract: Recombinant human thyroid-stimulating hormone (Thyrogen Genzyme Corporation, Cambridge, MA, USA) (rhTSH)-stimulated serum thyroglobulin (Tg) (stim-Tg) and (131)I whole-body scanning (WBS) have been reported to allow follow up of patients with thyroid cancer without the symptoms of thyroxine withdrawal and with equivalent diagnostic information to that obtained after thyroxine withdrawal. The aim of the study was to report results of rhTSH use at the Alfred Hospital, Melbourne, from 1999 to 2006 and in particular to examine the significance of detectable serum Tg after rhTSH in relation to thyroid cancer staging and to compare the sensitivity of rhTSH-stimulated serum Tg to whole-body (131)I scanning (WBS) in the detection of residual and recurrent thyroid cancer. The study was a retrospective chart review. In 90 patients, rhTSH was used for 96 diagnostic episodes and 18 doses of rhTSH were used to facilitate treatment with (131)I. In stages I and II cancer (n = 42), of three patients with stim-Tg 1-2 microg/L, none had identifiable disease, and the three patients who had stim-Tg >2 microg/L did not experience recurrent disease during follow up. In contrast, in stages III and IV cancer (n = 43) 2 of 5 with stim-Tg 1-2 microg/L had identifiable disease and 7 of 10 with stim-Tg >2 microg/L had identifiable disease. In Tg-positive, WBS-negative disease, further imaging identified persistent/recurrent disease. rhTSH was effective and safe in the management of thyroid cancer follow up for diagnosis of persistent/recurrent cancer and to enable (131)I treatment. In no case did rhTSH-stimulated WBS identify the presence of disease not also identified by raised basal Tg or stim-Tg. Therefore, in low risk cancer WBS may be omitted.
Publisher: The Endocrine Society
Date: 10-1983
Abstract: Migration inhibition of purified peripheral T lymphocytes in response to pancreatic islet cell antigen or thyroid antigen was used to study cell-mediated immune mechanisms in patients with diabetes mellitus (IDDM) and Graves' disease (GD). In response to islet cell antigen, T lymphocytes of subjects with IDDM for less than 3 yr exhibited migration inhibition, whereas those of normal subjects, noninsulin dependent diabetics, and subjects with IDDM for longer than 3 yr did not. Admixture of T lymphocytes from normal subjects with T lymphocytes from patients with IDDM for less than 3 yr substantially ameliorated the migration inhibition of the IDDM subjects to islet cell antigen. Migration of T lymphocytes from GD subjects was markedly inhibited by thyroid antigen and marginally inhibited by islet cell antigen. Admixture of GD T lymphocytes significantly ameliorated the migration inhibition of IDDM T lymphocytes to islet cell antigen, despite sensitization to thyroid antigen of the GD T lymphocytes. We conclude: 1) sensitization to islet cell antigen in IDDM of recent onset is confirmed 2) the ability of normal and GD T lymphocytes to ameliorate the migration inhibition of IDDM T lymphocytes strongly suggests correction of deficient suppressor T lymphocyte function 3) the ability of GD T lymphocytes to ameliorate migration inhibition of IDDM T lymphocytes to islet cell antigen is evidence for an antigen-specific rather than a generalized suppressor T lymphocyte defect in GD and 4) similarly, the normalization of migration index of GD T lymphocytes in response to thyroid antigen by those IDDM T lymphocytes not sensitized to thyroid antigen is again evidence for an antigen-specific and not a generalized suppressor T lymphocyte defect in IDDM.
Publisher: AMPCo
Date: 08-2016
DOI: 10.5694/MJA16.00435
Publisher: SAGE Publications
Date: 06-2011
DOI: 10.3109/00048674.2011.572852
Abstract: Objective: To develop an evidence-based monitoring protocol for clozapine-induced myocarditis. Methods: Potential cases of clozapine-related myocarditis occurring between January 1994 and January 2009 and a comparative group of patients taking clozapine for at least 45 days without cardiac disease were documented from the patients’ medical records. Results: A total of 75 cases and 94 controls were included. Nine cases died. The time to onset was 10–33 days with 83% of cases developing between days 14 and 21 inclusive. At least twice the upper limit of normal troponin was found in 90% of cases, but 5 cases had C-reactive protein more than 100 mg/L and left ventricular impairment by echocardiography without a clinically significant rise in troponin. The proposed monitoring protocol recommends obtaining baseline troponin I/T, C-reactive protein and echocardiography, and monitoring troponin and C-reactive protein on days 7, 14, 21 and 28. Mild elevation in troponin or C-reactive protein, persistent abnormally high heart rate or signs or symptoms consistent with infective illness should be followed by daily troponin and C-reactive protein investigation until features resolve. Cessation of clozapine is advised if troponin is more than twice the upper limit of normal or C-reactive protein is over 100 mg/L. Combining these two parameters has an estimated sensitivity for symptomatic clozapine-induced myocarditis of 100%. The sensitivity for asymptomatic disease is unknown. Conclusion: This protocol recommends active monitoring for 4 weeks, relying predominantly on troponin and C-reactive protein results. It encourages continuation of clozapine in the presence of mild illness, but defines a threshold for cessation.
Publisher: American Medical Association (AMA)
Date: 23-10-1981
Publisher: Oxford University Press (OUP)
Date: 04-1994
Abstract: Barlow JW, Curtis AJ, Raggatt LE, Loidl NM, Topliss DJ. Stockigt JR. Drug competition for intracellular triiodothyronine-binding sites. Eur J Endocrinol 1944 :417–21. ISSN 0804–4643 A variety of substances, including frusemide, non-esterified fatty acids (NEFAs) and non-steroidal antiinflammatory drugs (NSAIDs), can compete for triiodothyronine (T 3 )-binding sites in serum and at the cell surface. We examined the competitive potency of these agents at intracellular T 3 -binding sites in order to assess their potential to act as T 3 antagonists. Competition for [ 125 I]T 3 binding was determined using hydroxyapatite separation in cytosols and nuclear extracts prepared from livers of Macaca fascicularis . The T 3 affinities were 15.8 ± 1.2 nmol/l in cytosol and 0.23 ± 0.02 nmol/l in nuclear extract. Does–response curves were analysed by a four-parameter sigmoid curve-fitting program to determine competitor potency. The nineteen agents tested included various NSAIDs, NEFAs, non-bile acid cholephils (NBACs), frusemide, amiodarone and the flavonoid EMD 21388. In nuclear extract the most active competitors were linoleic acid (8.5 μmol/l) and linolenic acid (7.8 μmol/l), Potencies of NSAIDs varied between 66 μmol/l (meclofenamic acid) and 525 μmol/l (diclofenac). In cytosol, NEFAs were less potent but NSAIDs were stronger competitors than in nuclear extract. Half-inhibitory potencies in cytosol were between 13.2 μmol/l (meclofenamic acid) and 63.1 μmol/l (flufenamic acid). The NBAC bromosulphthalein was one of the most potent inhibitors in both cytosol and nuclear extract. When expressed relative to T 3 , diclofenac was a more effective competitor in cytosol than it was in nuclear extract. Amiodarone and EMD 21388 were without effect both in cytosol and nuclear extract. Frusemide (759 μmol/l) was weakly active in cytosol only. The action of T 3 was assessed by measuring secretion of sex hormone-binding globulin (SHBG) in Hep-G2 cells. After 3 days with total T 3 (0.1 μmol/l), SHBG was 155 ± 15% of the control. Amiodarone (100 μmol/l) and meclofenamic acid (100 μmol/l) were cytotoxic. Bromosulphthalein (10 μmol/l), one of the most potent competitors at both the cytoplasmic and the nuclear level, did not influence the T 3 -induced rise in SHBG secretion. None of the drugs tested affected the magnitude of maximal induction of SHBG by T 3 . Substances that compete for serum and cell surface T 3 -binding sites are also weak competitors for intracellular T 3 -binding proteins, although the heirarchy of potency differs. Frusemide and diclofenac, with a greater relative potency for cytosolic binding than nuclear binding, may have potential use in investigating the function of cytosolic T 3 -binding. Amiodarone shows no binding activity and is not a hormone antagonist in primate hepatic tissue. John W Barlow, Ewen Downie Metabolic Unit, Alfred Hospital, Commercial Road, Melbourne, Victoria 3181, Australia
Publisher: Oxford University Press (OUP)
Date: 10-1997
Abstract: We have shown previously that tri-iodothyronine (T3)-induced sex hormone-binding globulin (SHBG) secretion by the human hepatoblastoma cell line, HepG2, can be modulated by retinoids. We have now used this model to study a range of other compounds that are known to influence T3 responsiveness in various cell systems. HepG2 cells were incubated for 4 days in serum-free medium containing T3, together with insulin, dexamethasone, phorbol myristate (PMA), sodium butyrate or estradiol. T3 (10 nmol/l) alone induced a concentration of SHBG secreted by HepG2 cells that was 187 +/- 20% (mean +/- S.D., n = 9) of control. Insulin (100 nmol/l) reduced basal SHBG secretion from 24.7 +/- 5.2 nmol/l to 16.1 +/- 1.7 nmol/l (P 0.01). This effect was dose responsive, half-maximal at 3.4 +/- 3.0 nmol/l (approximately 600 mU/l) and maximal with 100 nmol/l insulin. Co-incubating 0-10 nmol/l T3 with 100 nmol/l insulin resulted in a downward shift in the dose-response curve without a change in the half-maximal response to T3. Conversely, 0-100 nmol/l insulin reduced SHBG production induced by 10 nmol/l T3. In contrast while dexamethasone alone was without effect on SHBG secretion, 100 nmol/l dexamethasone induced a shift to the left in half-maximal T3 stimulation from 0.37 nmol/l to 0.10 nmol/l. The effect of PMA on SHBG secretion was reminiscent of the previously observed retinoid effect. PMA 100 nmol/l abolished maximal T3 stimulation. This effect was dose responsive, with a threshold at 1 nmol/l PMA. Sodium butyrate, up to 1 mmol/l was without effect with greater concentrations, SHBG secretion was reduced. T3 responsiveness was virtually abolished by 3 mmol/l sodium butyrate higher concentrations were cytotoxic and secretion was reduced to less than 20% of basal. Lack of an effect of estradiol on SHBG secretion by HepG2 cells was confirmed. These studies suggest that T3-induced SHBG secretion by HepG2 cells is independently influenced by insulin, potentiated by dexamethasone, and modulated by PMA. Detailed molecular analysis of this model will increase our understanding of the mechanism of action of T3, specifically in human liver cells.
Publisher: SAGE Publications
Date: 2003
DOI: 10.1345/APH.1C293
Publisher: American Diabetes Association
Date: 18-12-2014
DOI: 10.2337/DC14-0180
Abstract: People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and utation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial. A total of 50% of the patients had low vitamin D concentrations, as indicated by median blood 25OH-D concentration of 49 nmol/L. These patients with a blood 25OH-D concentration & nmol/L had a higher cumulative incidence of macrovascular and microvascular events than those with levels ≥50 nmol/L. Multivariate analysis, stratified by treatment and adjusted for relevant confounders, identified blood 25OH-D concentration as an independent predictor of macrovascular events. A 50 nmol/L difference in blood 25OH-D concentration was associated with a 23% (P = 0.007) change in risk of macrovascular complications during the study, and further adjustments for seasonality, hs-CRP, and physical activity level had little impact. The unadjusted risk of microvascular complications was 18% (P = 0.006) higher during the study, though the excess risk declined to 11–14% and lost significance with adjustment for HbA1c, seasonality, or physical activity. Low blood 25OH-D concentrations are associated with an increased risk of macrovascular and microvascular disease events in type 2 diabetes. However, a causal link remains to be demonstrated.
Publisher: Wiley
Date: 10-1981
DOI: 10.1111/J.1365-2265.1981.TB00673.X
Abstract: The ability of normal T lymphocytes to abolish the production of migration inhibition factor by antigen-sensitized T lymphocytes of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in response to thyroid antigen has been studied by a modified migration inhibition factor test using isolated T lymphocytes alone. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with GD or HT T lymphocytes in various ratios (1:9, 2:8, 5:5) as reported previously (Okita et al. 1980b). However, prior in-vitro irradiation (1000 rad) of the normal T lymphocytes resulted in loss of their ability to abolish migration inhibition factor production by the antigen-sensitized T lymphocytes of GD and HT. The effect is consistent with the radiosensitivity of suppressor T lymphocytes and indicates that the effect of normal T lymphocytes on GD and HT T lymphocytes is one of allosuppression. The results support the view that there is a defect in suppressor T cell function in GD and HT.
Publisher: Wiley
Date: 12-11-2008
DOI: 10.1111/J.1365-2265.2008.03276.X
Abstract: To evaluate the relationships between thyroid remnant (131)I uptake, radiation thyroiditis and remnant ablation success rate between lower (1110 MBq) and higher (3700 MBq) initial ablative (131)I dose for post-surgical ablation therapy for differentiated thyroid cancer. Patients having post-surgical administration of 1110 MBq (68 patients) or 3700 MBq (115 patients) (131)I were retrospectively reviewed. Thyroid remnant (131)I uptake on a 48 h post-administration scan was correlated with neck symptoms experienced. Patients were classified as having insignificant, mild or severe thyroiditis based on symptoms. Absent thyroid bed (131)I uptake on a follow-up 74 MBq (131)I study was considered successful ablation. 183 patients were included. Median (131)I remnant uptake was 37 MBq. 21% (39/183) of patients developed thyroiditis. Incidence and severity of thyroiditis increased with increasing remnant (131)I activity (P 73 MBq. For patients treated with 1110 MBq and 3700 MBq, incidence of thyroiditis was 12% and 27% (P = 0.02) and remnant ablation success rate was 76% and 84% (P = NS), respectively. Occurrence of thyroiditis did not correlate with successful ablation. Incidence and severity of radiation thyroiditis following (131)I remnant ablation therapy is directly related to thyroid remnant (131)I uptake. As 1110 MBq (131)I is associated with a significantly lower frequency of thyroiditis but similar remnant ablation rate to 3700 MBq, it warrants consideration for thyroid remnant ablation particularly in patients with low risk disease.
Publisher: Massachusetts Medical Society
Date: 24-05-1979
Publisher: Wiley
Date: 09-02-2007
DOI: 10.1111/J.1365-2265.2007.02771.X
Abstract: The aim of this study was to evaluate whether subclinical thyroid disease is associated with impaired health-related quality of life and a more adverse cardiovascular disease risk profile. A community-based cross-sectional study. A total of 1423 non-healthcare-seeking women, aged 18-75 years were randomly recruited from the community via the electoral roll from April 2002 to August 2003. These were the scores for the Short-Form 36 (SF-36), the Psychological General Well-being Index (PGWI), thyroid hormone levels, serum lipids and high sensitivity C-reactive protein (hsCRP). Subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (SCHyper) were defined as serum TSH > 4.0 mIU/l and < 0.5 mIU/l, respectively, with a normal free thyroxine (free T4) level. Evaluable data were available for all participants. 10.7% of all women had an abnormal TSH value. The prevalence of a low TSH level by age group ranged from 1.2% to 6.4%, whereas the prevalence of an elevated TSH level ranged from 2.8% to 9.2% and increased with age (P = 0.002). There were no significant differences between women with SCH or SCHyper and age-matched controls for the total PGWI score or the Mental and Physical Component Scores of the SF-36. Women with SCH were no different from controls for serum lipids or hsCRP. Using linear regression, SCH vs. euthyroidism did not make an independent contribution to variation in either total cholesterol or triglycerides, with or without adjustment for age +/- age(2) +/- BMI. Our data indicate that subclinical thyroid disease in women in the community is not associated with lower well-being or impaired health-related quality of life and SCH is not associated with increased serum markers of CVD risk.
Publisher: Springer Science and Business Media LLC
Date: 07-1991
DOI: 10.1007/BF03346877
Publisher: BMJ
Date: 2019
DOI: 10.1136/BMJOPEN-2018-023723
Abstract: The occurrence of thyroid cancer is increasing throughout the developed world and since the 1990s has become the fastest increasing malignancy. In 2014, a total of 2693 Australians and 302 New Zealanders were diagnosed with thyroid cancer, with this number projected to rise to 3650 in 2018. The purpose of this protocol is to establish a binational population-based clinical quality registry with the aim of monitoring and improving the quality of care provided to patients diagnosed with thyroid cancer in Australia and New Zealand. The Australian and New Zealand Thyroid Cancer Registry (ANZTCR) aims to capture clinical data for all patients over the age of 16 years with thyroid cancer, confirmed by histopathology report, who have been diagnosed, assessed or treated at a contributing hospital. A multidisciplinary steering committee was formed which, with operational support from Monash University, established the ANZTCR in early 2017. The pilot phase of the registry is currently operating in Victoria, New South Wales, Queensland, Western Australia and South Australia, with over 20 sites expected to come on board across Australia in 2018. A modified Delphi process was undertaken to determine the clinical quality indicators to be reported by the registry, and a minimum data set was developed comprising information regarding thyroid cancer diagnosis, pathology, surgery and 90-day follow-up. The establishment of the ANZTCR provides the opportunity for Australia and New Zealand to further understand current practice in the treatment of thyroid cancer and identify variation in outcomes. The engagement of endocrine surgeons in supporting this initiative is crucial. While the pilot registry has a focus on early clinical outcomes, it is anticipated that future collection of longer term outcome data particularly for patients with poor prognostic disease will add significant further value to the registry.
Publisher: Wiley
Date: 2022
DOI: 10.1111/IMJ.15067
Abstract: Thyroid eye disease is an autoimmune inflammatory disease strongly associated with thyroid disease, principally Graves disease. It can range from mild disease requiring observation or symptomatic treatments only, through to sight‐threatening disease requiring major drug therapy and orbital surgery. Severity is graded by the NOSPECS system and activity by the clinical activity score (CAS) to assist in treatment selection. Non‐surgical management can extend from observation alone to minor therapy such as oral selenium, then glucocorticoid therapy, cyclosporin, mycophenolate, rituximab, immunoglobulin, teprotumumab, and orbital radiotherapy. High‐dose intravenous methylprednisolone therapy is used in active vision‐threatening disease with early use of tarsorrhaphy and orbital decompression. Inactive but moderate to severe disease may be treated by orbital decompression, strabismus and eyelid surgery. Systematic assessment and management by both an endocrinologist and ophthalmologist to achieve and maintain euthyroidism and select and sequence treatments according to activity and severity of thyroid eye disease gives the best results for quality of life and vision.
Publisher: Wiley
Date: 2018
DOI: 10.1111/IMJ.13682
Abstract: Hyponatraemia (serum sodium concentration below 135 mmol/L) is the most common electrolyte disturbance and occurs commonly in older people. The causes can be complex to diagnose and treat and many published guidelines do not focus on the issues in an older patient group. Here, we are principally concerned with diagnosis and management of euvolaemic and hypervolaemic hyponatraemia in hospitalised patients over 70 years old. We also aim to increase awareness of hyponatraemia in residential aged care facilities and the community. Hyponatraemia can have many causes in older people, chronic hyponatraemia can often be the result of medications used to treat chronic disease, particularly thiazide or thiazide-like drugs (such as indapamide) or drugs acting on the central nervous system. Where a reversible trigger (such as drug-induced hyponatraemia) can be identified, hyponatraemia may be treated relatively simply. Chronic hyponatraemia due to an irreversible cause will require ongoing treatment. Fluid restriction can be an effective therapy in dilutional hyponatraemia, although poor compliance and the burdensome nature of the restrictions are important considerations. Tolvaptan is an oral vasopressin receptor antagonist that can increase serum sodium concentrations by increasing electrolyte-free water excretion. Tolvaptan use is supported by clinical trial evidence in patients with hypervolaemic or euvolaemic hyponatraemia below 125 mmol/L. Clinical trial evidence also supports its use after a trial of fluid restriction in patients with symptomatic hyponatraemia above 125 mmol/L. The use of tolvaptan is affected by regulatory restriction of chronic therapy due to safety concern and the non-subsidised cost of treatment.
Publisher: The Endocrine Society
Date: 1998
DOI: 10.1210/JC.83.1.107
Publisher: Wiley
Date: 06-2004
Publisher: Springer Science and Business Media LLC
Date: 03-1989
DOI: 10.2165/00003495-198937030-00006
Abstract: The choice of treatment for hyperthyroidism should be preceded by considering: (a) whether the diagnosis is correct (b) the severity of the disorder (c) the cause of the thyroid hormone excess (d) factors such as patient age, size of goitre, associated diseases, previous treatment, and (e) patient preference. If hyperthyroidism appears to be severe, a judgement based on clinical rather than biochemical features, there is generally no safe alternative to the initial use of a drug from the thioamide thioureylene group (carbimazole, methimazole or propylthiouracil) to make the patient euthyroid as rapidly as possible. There are numerous different schedules for the use of these drugs, alone or in conjunction with surgery, radioactive iodine, or drugs such as beta-blocking agents, iodide or thyroxine. Patients can be made euthyroid with reasonable certainty, but an underlying abnormality often remains. The patient's understanding of the natural history of his or her condition is crucial in achieving adequate follow-up.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.SCHRES.2012.08.018
Abstract: Despite the implementation of cardiac monitoring guidelines, clozapine-induced myocarditis continues to cause deaths in Australia, and the risk is a barrier to prescription of this effective drug for the treatment of schizophrenia. This study was designed to identify clinical and phenotypic risk factors for clozapine-induced myocarditis. Possible cases of clozapine related myocarditis occurring between June 1993 and November 2009 and a comparative group of controls taking clozapine for at least 45days without cardiac disease were documented from the patients' medical records. 105 cases, with time to onset of 10-33days, and 296 controls were included in the study. In multivariate analysis, the risk of myocarditis increased by 26% for each additional 250mg of clozapine administered in the first nine days of clozapine titration (odds ratio 1.26 95% confidence interval 1.02-1.55 p=0.03) and concomitant sodium valproate more than doubled the risk (2.59 1.51-4.42 0.001). Further, each successive decade in age was associated with a 31% increase in risk (1.31 1.07-1.60 0.009). Nevertheless, 33 cases received less than 920mg of clozapine during the first nine days of dose titration, did not take sodium valproate and were aged less than 40years and nine control patients received sodium valproate and more than 920mg of clozapine in the first nine days without developing myocarditis. Clozapine should be initiated by slow dose titration and sodium valproate is best avoided, if clinically feasible, during this period. All patients commencing clozapine should be monitored for myocarditis up to Day 28.
Publisher: The Endocrine Society
Date: 05-1985
Abstract: The diuretic furosemide inhibits serum protein binding of T4 in equilibrium dialysis, dextran-charcoal, and competitive ligand binding separation systems and displaces [125I]T4 from isolated preparations of T4-binding globulin (TBG), prealbumin, and albumin. Equilibrium dialysis studies of undiluted normal serum showed that about 10 micrograms/ml furosemide increased the free T4 and free T3 fractions. Displacement occurred at lower drug concentrations in sera with subnormal albumin and TBG levels. Binding of [14C]furosemide to TBG was inhibited by unlabeled T4, suggesting that furosemide and T4 share a common binding site. A single oral dose of 500 mg furosemide given to five patients maintained on peritoneal dialysis increased the percentage of charcoal uptake of [125I]T4 (using serum diluted 1:10) from 4.1 +/- 1.0 (+/- SE) to 10.8 +/- 4.3 (P less than 0.01) after 2 h, while decreasing total T3 from 75 +/- 5 to 56 +/- 13 ng/dl (P less than 0.01) and total T4 from 6.7 +/- 0.9 to 4.8 +/- 0.8 micrograms/dl (P less than 0.01) after 5 h. Various ligands inhibited [125I]T4 binding to serum proteins in the following relative molar relationship: T4, 1 furosemide, 1.5 X 10(3) fenclofenac, 2 X 10(4) mefenamic acid. 2.5 X 10(4) diphenylhydantoin, 4 X 10[4) ethacrynic acid, 10(5) heparin 5 X 10(5) 2-hydroxybenzoylglycine, 10(6) and sodium salicylate, 1.5 X 10(6). These studies demonstrate that furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower total T4 and T3 levels. The drug is much more potent on a molar basis than other drug inhibitors of T4 binding, but at normal therapeutic concentrations, furosemide is unlikely to decrease serum T4 or T3. However, high doses, diminished renal clearance, hypoalbuminemia, and low TBG accentuate its T4- and T3-lowering effect. Hence, furosemide should be considered a possible cause of low thyroid hormone levels in patients with critical illness. The significance of this drug in reports of impaired hormone and drug binding in renal failure requires further assessment.
Publisher: Elsevier BV
Date: 08-1995
DOI: 10.1016/0026-0495(95)90097-7
Abstract: The close inverse-feedback relationship between serum free thyroxine (T4) and thyrotropin (TSH) is altered in some patients receiving therapeutic doses of drugs such as furosemide, fenclofenac, and diphenylhydantoin. We therefore examined the effect of nonsteroidal antiinflammatory drugs (NSAID), diuretics, and diphenylhydantoin on TSH release in rat anterior pituitary cells in primary culture. TSH content of the culture medium was measured at 22 hours at 37 degrees C either with or without thyrotropin-releasing hormone ([TRH] 10 nmol/L) in medium containing 0.5% bovine serum albumin. The mean basal TSH release by pituitary cells was 6.2 +/- 1.2 ng/mL (n = 10) and was not influenced by unlabeled triiodothyronine ([T3] 100 nmol/L) or any of the drugs tested at < or = 400 mumol/L, except ethyacrynic acid. TRH 10 nmol/L increased mean TSH release by 346% +/- 95% (n = 10). T3 1 and 100 nmol/L inhibited TRH-stimulated TSH release by 24% and 31%, respectively (P < .001), whereas TRH-stimulated TSH release was inhibited by 100 mumol/L meclofenamic acid (29%), fenclofenac (28%), furosemide (24%), and diphenylhydantoin (48%) (P < .001 v TRH alone). Meclofenamic acid and furosemide (100 mumol/L) did not significantly alter the inhibitory effect of T3 1 nmol/L on TRH-stimulated TSH release. These in vitro studies suggest that meclofenamic acid, fenclofenac, furosemide, and diphenylhydantoin could influence TSH release by attenuating the TSH response to TRH. This effect may influence T4-TSH relationships when these agents are used in vivo.
Publisher: SAGE Publications
Date: 10-2012
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.4158/EP10213.CR
Publisher: Wiley
Date: 11-2017
DOI: 10.1111/IMJ.13607
Abstract: This study evaluates the clinical efficacy and safety of NovoRapid (insulin aspart) compared to Actrapid™ (human neutral insulin) for diabetic ketoacidosis (DKA). In this retrospective study involving 40 patients, no statistically significant differences were observed between biochemical variables, infusion duration or complications in patients treated with insulin aspart or human neutral insulin. These results support the use of insulin aspart as an effective and safe alternative to human neutral insulin in DKA.
Publisher: Wiley
Date: 13-05-2009
DOI: 10.1111/J.1365-2265.2008.03434.X
Abstract: Reduced bone mineral density (BMD) and increased rates of atraumatic fracture are observed in cystic fibrosis (CF) patients, causing increasing morbidity as this population ages. The study aimed to assess the safety, tolerability and effect on BMD of intravenous zoledronate in adults with CF and osteopaenia. Randomized, double-blind, placebo-controlled clinical trial. Adult CF outpatient clinics at two hospitals. Twenty-two non-transplanted CF patients aged > or = 18 years with a bone densitometry T-score of < -1.5 at one of three sites (lumbar spine, femoral neck, distal forearm) were studied. Participants were randomized to receive either 2 mg zoledronate i.v. (n = 10) or normal saline (placebo, n = 12) every 3 months for 2 years (8 infusions). All participants received calcium and vitamin D supplements twice daily. Percentage change in areal BMD from baseline. Lumbar spine BMD increased from baseline more with zoledronate than placebo at 6 months (5.35 +/- 0.76 vs. 1.19 +/- 1.20%, P = 0.012), 12 months (6.6 +/- 1.5 vs. 0.35 +/- 1.55%, P = 0.011) and 24 months (6.14 +/- 1.86 vs. 0.44 +/- 0.10, P = 0.021). Femoral neck BMD increased more after zoledronate than placebo at 6 months (3.2 +/- 1.6 vs.-1.43 +/- 0.43%, P = 0.019), 12 months (4.12 +/- 1.8 vs.-1.59 +/- 1.4%, P = 0.024) and 24 months (4.23 +/- 1.3 vs.-2.5 +/- 1.41%, P = 0.0028). Forearm BMD did not change. Zoledronate was associated with flu-like and musculoskeletal side effects, particularly after the first infusion. There were no fractures in either group. Intravenous zoledronate was significantly more effective than placebo for increasing BMD in adults with CF and osteopaenia, but side effects limited its tolerability.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.4158/EP13143.OR
Publisher: Wiley
Date: 31-10-2007
Publisher: The Endocrine Society
Date: 07-1984
DOI: 10.1210/JCEM-59-1-62
Abstract: Serum s les taken from four patients who had low serum T4 concentrations (less than 2 micrograms/dl) during severe non-thyroidal illness were found to contain a heat-stable, dialyzable inhibitor of 125I T4 binding to plasma proteins. Inhibitory activity coincided with high dose furosemide treatment for oliguric renal failure. Inhibition was proportional to the serum furosemide concentration and the effect was reproduced in vitro by addition of furosemide to normal serum. The inhibitory effect diminished with serum dilution while maintaining the same relative concentration of furosemide. A time-course study in one patient demonstrated a close temporal relationship between high serum concentrations of furosemide and subnormal T4, associated with T3 resin uptake values compatible with increased occupancy of T4-binding globulin by a competitor. These findings demonstrate that furosemide in high concentrations can inhibit T4 binding in plasma and may be a factor contributing to the development of the low T4 state in critical illness.
Publisher: Springer Science and Business Media LLC
Date: 1993
DOI: 10.1007/BF03345833
Publisher: Wiley
Date: 03-2019
DOI: 10.1111/IMJ.14085
Abstract: Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multi-drug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. To identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia. Retrospective multicentre study of MDR-TB patients from five academic centres covering tuberculosis (TB) services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if the thyroid-stimulating hormone was elevated and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions. Our main outcome measured was the cumulative proportion of hypothyroidism (at 5 years from treatment initiation). Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% confidence interval (CI): 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (P = 0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication. Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement, if initiated, may not need to be continued after MDR-TB treatment is completed.
Publisher: Oxford University Press (OUP)
Date: 1987
DOI: 10.1093/RHEUMATOLOGY/26.1.17
Abstract: To elucidate further the clinical significance of the anticentromere antibody (ACA), 32 Australian-born Caucasian patients with scleroderma (SD) or CREST (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia) were reclassified as ACA-positive (19 patients) or ACA-negative (13 patients). The clinical features of the two groups were compared. Mean disease duration was 11.7 years for the ACA-positive group and 1.1 years for the ACA-negative group. No ACA-positive patient had generalized skin SD, whereas all ACA-negative patients with disease duration greater than 6 months had moderate or severe proximal scleroderma. Only one ACA-positive patient had serious extra-oesophageal internal organ involvement, excluding primary biliary cirrhosis (three patients) which is itself associated with ACA. Three ACA-negative patients had serious extra-oesophageal internal organ involvement. No ACA-positive patient had been treated with penicillamine or captopril compared with 11 ACA-negative patients. Thus ACA appears to be a favourable prognostic indicator. Analysis of in idual CREST manifestations in ACA-positive patients revealed that most had 'incomplete CREST', lacking one or two of the five features. The classification of SD patients as ACA-positive or ACA-negative is suggested.
Publisher: The Endocrine Society
Date: 02-1989
Publisher: Wiley
Date: 04-1987
Publisher: The Endocrine Society
Date: 05-1983
Abstract: Both thyroid hormone and carbohydrate feeding are known to influence hepatic gene expression in vivo. In order to determine whether these compounds act directly on the liver, we have utilized an isolated adult rat hepatocyte culture to examine the in vitro influence of either T3 or glucose on a wide range of mRNA activities. RNA was extracted from hepatocyte cultures, translated in the rabbit reticulocyte system, and the translated products separated by two-dimensional gel electrophoresis. We have found a strong similarity between the hepatic mRNA response to T3 administered either to the animal or added to the culture medium and between the response to high carbohydrate feeding and an increase in the medium glucose concentration. Our studies suggest that the isolated hepatocyte culture is a useful model for the study of the influence of hormones and metabolites on the expression of specific mRNA's.
Publisher: Portland Press Ltd.
Date: 05-1989
DOI: 10.1042/CS0760495
Abstract: 1. We studied a brominated thyroid hormone analogue, SKF L-94901, which has the potential to lower serum cholesterol without adverse cardiovascular effects. This compound is about 50% as active as tri-iodothyronine (T3) in liver nuclear receptor binding in vivo but only 1% as active in vitro and has nearly 200 times more enzyme-inducing activity in liver than in heart. Our aim was to examine the interaction of SKF L-94901 with [125I]T3 binding to the intact nuclei in whole cells, isolated nuclei and nuclear extracts of human HeLa cells and to investigate the binding of this compound to human serum. 2. Relative to thyroxine (T4), the affinity of this compound for T4-binding globulin was 0.0035%, for transthyretin 1.66% and for albumin 1.26%. Low affinity for serum proteins, with a relatively high circulating free fraction, could explain why SKF L-94901 is more potent in vivo than in vitro. 3. Human HeLa cell nuclei, isolated after whole-cell incubations, bound [125I]T3 with high affinity (Kd = 78 ± 8 pmol/l, mean ± sem), which was displaceable by T3 analogues in the order Triac {[4-(4-hydroxy-3-iodophenoxy)-3,5-di-iodophenyl]acetic acid} & T3 & T4 ≫ reverse T3. Similar high-affinity (Kd = 58 ± 6 pmol/l, mean ± sem) and identical specificity was observed in high-salt (0.4 mol/l KCl) nuclear extracts. In nuclei of whole cells incubated with [125I]T3 and SKF L-94901, the analogue was 0.8% as potent as T3, whereas in experiments with nuclear extract, the analogue was 7.7% as potent as T3. Results from incubation of T3 with isolated nuclei were virtually identical to those obtained with nuclear extracts. 4. These results suggest an extranuclear component may be involved in restricting access of SKF L-94901 to the nucleus. Whether such mechanisms account for observed differences in its effects on different tissues with reduced influence of SKF L-94901 on cardiac tissue remains to be established. 5. We conclude that SKF L-94901 is weakly bound in serum and shows less potent competition for T3 nuclear binding after incubation of whole cells than after incubation with nuclear extracts or isolated nuclei. This compound may allow further analysis of intracellular mechanisms of thyroid hormone transport and action.
Publisher: Elsevier BV
Date: 10-1977
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.SCHRES.2011.01.017
Abstract: Fatal clozapine-induced myocarditis has not been investigated systematically. We describe the clinical course of 10 fatal cases of myocarditis with clozapine and identify factors associated with fatality. Cases of myocarditis were documented from the patient's medical records and fatal cases also from autopsy reports. The fatal cases of myocarditis occurred 1996-2009 and were diagnosed at autopsy. Before death, three had no symptoms of illness and only three had cardiac-specific diagnostic results. None was investigated by cardiac imaging techniques, and in none was myocarditis suspected before death. Duration of clozapine for the fatal cases was 14-33 days with an outlier at 4.5 months. Only 3 cases had significant coronary artery disease at autopsy. Comparison of these ten cases with 66 non-fatal cases indicated no significant difference in gender, age, smoking status, dose at onset or concomitant sodium valproate. However, obesity (BMI > 30 kg/m2) was significantly more frequent among fatal than non-fatal cases (60% vs. 26% p < 0.03) and duration of clozapine was significantly longer for fatal cases (20.8 vs. 17.0 days p 1000 U/L was also associated with death (p = 0.0004). Routine monitoring for myocarditis for the first 4 weeks of clozapine, and discontinuation of clozapine in the presence of evidence consistent with myocarditis may assist to prevent fatalities occurring from early-onset myocarditis. Investigation by cardiac imaging will give a measure of severity and need for intervention. Obesity may increase the risk of mortality and CK > 1000 U/L may indicate life-threatening illness.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-03-2015
Publisher: BMJ
Date: 12-04-2011
DOI: 10.1136/BMJQS.2010.049668
Abstract: Insulin is a high-risk medicine which may cause significant patient harm or death when given incorrectly. A 10-fold error in administered insulin dose commonly occurs when the abbreviation 'u' is used for 'units' and subsequently misinterpreted as a 'zero.' A multidisciplinary working party was convened and mapped insulin prescribing, dispensing and administration. All inpatient orders above 25 units for short-acting insulin and 50 units for other insulin require validation by an additional source. Educational strategies to support adherence to the guideline and product-labelling alerts were developed. Implementation occurred in August 2008 across the three hospital sites. In 90 weeks after implementation, there were 150 patients identified in which 200 high doses of insulin were prescribed (>25 units for short-acting insulin and 50 units for other insulin). There were eight instances where high doses of insulin were prescribed in error but were detected and rectified through the new validation process. There were 12 dosing errors that occurred, including two 10-fold dosing errors. In contrast, seven major errors resulting in excessive insulin administration were identified over a 2-year period prior to the introduction of the insulin high-dose validation system. A structured validation process was successful in reducing incorrect prescription and administration of high-dose insulin and has reduced the risk of associated fatalities or significant patient harm. Consideration should be given to adopting this process in any setting where insulin is prescribed and administered.
Publisher: Informa UK Limited
Date: 23-04-2012
DOI: 10.3109/00365521.2012.677955
Abstract: Type 2 diabetes mellitus (T2DM) is a major risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and subsequently hepatic fibrosis. Transient elastography (TE) is a rapid, reproducible non-invasive test that may be appropriate as a screening tool for the presence of hepatic fibrosis. Assess the utility of TE as a screening tool for the presence of hepatic fibrosis in a T2DM population with no known liver disease. T2DM patients without known liver disease were included. Patients were assessed with TE in addition to biochemical parameters. A successful TE evaluation could be obtained in 74 of 81 (91%) included subjects. Of these, 26 (35%) had a liver stiffness measurement (LSM) ≥ 7.65 kPa. Sixteen of these subjects had confirmatory liver biopsies with significant (≥ F2 fibrosis) present in 12 (75%) and cirrhosis diagnosed in 2 subjects. 15/16 (94%) had histological steatohepatitis. Compared with those with a lower LSM, subjects with an LSM ≥ 7.65 kPa had higher ALT levels (38.0 ± 21.7 vs 26.1 ± 11.1 U/L, p = 0.021) and increased prevalence of hepatic steatosis by ultrasound (85% vs 63%, p = 0.005). Significant hepatic fibrosis in the T2DM population is frequently under-recognized. TE may be a feasible tool for the screening of T2DM patients for the presence of hepatic fibrosis.
Publisher: The Endocrine Society
Date: 06-1989
Publisher: European Respiratory Society (ERS)
Date: 2005
DOI: 10.1183/09031936.04.00050204
Abstract: The aim of this cross-sectional study was to determine the prevalence and identify determinants of reduced bone mineral density (BMD) in adults with cystic fibrosis (CF). Adults (88) with CF (mean+/-SD age 29.9+/-7.7 yrs forced expiratory volume in one second (FEV1) 58.2+/-21.5% of the predicted value) were studied. BMD at the lumbar spine (LS) and femoral neck (FN) and body composition were measured using dual-energy X-ray absorptiometry. Blood and urine were analysed for hormones, bone turnover markers, and the cytokines tumour necrosis factor-alpha, and interleukin-6 and -1beta. FEV1 (% pred) CF genotype malnutrition history of growth, development or weight gain delays and corticosteroid use were analysed. BMD Z-scores were -0.58+/-1.30 (mean+/-SD) at the LS and -0.24+/-1.19 at the FN. Z-scores of <-2.0 were found in 17% of subjects. Subjects who were homozygous or heterozygous for the DeltaF508 mutation exhibited significantly lower Z-scores than those with no DeltaF508 allele. Multiple linear regression showed that the DeltaF508 genotype and male sex were independently associated with lower BMD at both sites. Other factors also independently associated with lower BMD included malnutrition, lower 25-hydroxyvitamin D level, lower fat-free mass and lower FEV1 (% pred). In conclusion, reduced bone mineral density in cystic fibrosis is associated with a number of factors, including DeltaF508 genotype, male sex, greater lung disease severity and malnutrition.
Publisher: Wiley
Date: 08-03-2022
DOI: 10.1111/CEN.14705
Abstract: The management of Graves' disease (GD) in women of childbearing potential has multiple specific complexities. Many factors are involved, which differ at the various stages from preconception, conception, first trimester, later pregnancy, postpartum and lactation, with both maternal and foetal considerations. The incidence and significance of the risks incurred from antithyroid drugs (ATDs) in pregnancy have been re-evaluated recently and must be balanced against the risks of uncontrolled hyperthyroidism during childbearing years. Contraception is advised until hyperthyroidism is controlled. ATD cessation should be considered in those who are well controlled on low dose therapy before conception and in early pregnancy. Advice on iodine supplementation does not generally differ in those with GD. Radioiodine (RAI) is contraindicated from 6 months preconception until completion of breastfeeding. In all women who have a history of GD, monitoring of TSH receptor antibodies (TRAb) is strongly recommended during pregnancy, and if elevated, foetal monitoring and assessment of thyroid function in the neonate are required. Of note, RAI increases TRAb for up to a year, making this treatment option even less attractive in this patient group. A small amount of ATD is transferred into breast milk but low doses are safe during lactation. Routine periodic thyroid function testing is recommended in remission to detect postpartum GD recurrence. We present our approach to the Clinical Question 'How to manage GD in women of childbearing potential?'
Publisher: The Endocrine Society
Date: 09-2013
DOI: 10.1210/JC.2012-4050
Abstract: A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of i.v. rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2021
DOI: 10.1007/S00381-021-05313-6
Abstract: To investigate the incidence of persistent, open metopic sutures in contemporary Australians aged 24 months and older. Metopic suture evaluation was conducted on retrospective cranial/cervical computed tomography scans of patients aged 24 to 252 months who presented to the Women's and Children's Hospital in Adelaide, Australia, between 2010 and 2020. Suture ossification was graded according to Lottering scoring system based on 4 stages, on three-dimensional volume-rendered reconstructions (stage 1: fibrous tissue interface, stage 2: commenced fusion, stage 3: complete fusion and stage 4: obliterated suture). The complete persistent sutures were classified as stage 1. Partially closed sutures were classified into stages 2 and 3, while completely closed sutures were defined as stage 4. One thousand thirty-four patients (61.2% male and 38.8% female) were included, with a mean age at scan of 66 months. More than half of patients were subject to scanning due to closed-head injuries. The incidence of persistent (completely open) metopic suture was 4.8% (2.3% in males and 2.5% in females). In comparison, a partially closed metopic suture was found in 6.3% of the study cohort, with the remaining sutures located along the metopic suture line, at the glabella, mid-part of the suture, bregma and glabella-bregma areas. The prevalence of persistent metopic sutures in our study of the Australian population is 4.8%, and it is equally distributed between the genders. The pattern of suture closure can commence from any location along the suture line, which is in contrast to the existing literature.
Publisher: Wiley
Date: 17-12-2004
Publisher: SAGE Publications
Date: 19-12-2022
DOI: 10.1177/10556656221146598
Abstract: Fibrodysplasia ossificans progressiva (FOP) is a rare condition characterized by progressive heterotopic ossifications and congenital hallux valgus deformities. The common underlying genetic cause is an ACVR1 mutation, resulting in altered bone morphogenetic protein (BMP) regulation. Trauma and/or minor procedures aggravate the abnormal bony formation in soft tissues. This report presents a 3-year-old child with this condition who presented pseudo-ankylosis of the temporomandibular joint (TMJ) after minor craniofacial trauma. Abnormal ossification in the medial pterygoid muscle was identified as the causative abnormality for the presentation with trismus.
Publisher: Elsevier BV
Date: 11-1993
DOI: 10.1016/0026-0495(93)90200-8
Abstract: We studied the thyroxine (T4)-displacing effects of a naturally occurring, highly albumin-bound furanoid acid that accumulates in serum in renal failure to concentrations in excess of 0.2 mmol/L. This substance, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), has been shown to displace acidic drugs from albumin binding. The effects of CMPF on ligand binding were assessed in the following systems: (1) T4 binding to T4-binding globulin (TBG) and transthyretin (TTR), (2) T4 binding in undiluted serum, (3) T4-displacing potency of fenclofenac, furosemide, diflunisal, and aspirin in undiluted serum, (4) serum binding of [14C]-drug preparations, and (5) serum binding of [14C]-oleic acid. CMPF had a minor direct effect on T4 binding to TBG comparable in relative affinity to that of aspirin, ie, almost 7 orders of magnitude less than T4 itself. CMPF alone at a concentration of 0.3 mmol/L, which produced only a 10% to 14% increase in free T4 augmented the T4-displacing effects of high therapeutic concentrations of the various drugs in undiluted serum as follows: furosemide by 180%, fenclofenac by 160%, diflunisal by 130%, and aspirin by 40%. In the presence of fenclofenac, increments of CMPF from 0.075 to 0.3 mmol/L progressively augmented the T4-displacing effect of this drug, associated with a progressive increase in its calculated free concentration. CMPF also inhibited the binding of [14C]-oleic acid, suggesting that in some situations CMPF could also indirectly influence thyroid hormone binding by increasing the unbound concentration of nonesterified fatty acids (NEFA), as previously described.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Mary Ann Liebert Inc
Date: 02-1996
Abstract: Previous studies from our laboratory have suggested that the nonsteroidal antiinflammatory drug, diclofenac (DCF), is a more potent competitor for T3 binding sites in cytoplasm than for those in the nucleus. In the present study we have examined the competitive potency for DCF and its effect on nuclear binding of T3 in cultured cells. DCF was a weak competitor for T3 binding sites in cytosol and nuclear extracts prepared from HepG2 cells with a potency of 21 and 295 microM, respectively. When expressed relative to T3, DCF was 135-fold more potent in cytosol than in nuclear extract. In intact cells, T3 was bound by nuclei with an affinity, Kd of 0.22 +/- 0.07 nM whereas in nuclear extract the affinity was 0.60 +/- 0.21 nM. DCF was a competitive inhibitor in both preparations but reduced the apparent affinity 4-fold in intact cells but only 2-fold in nuclear extract. In whole-cell experiments, DCF increased the rate of dissociation of T3 from cells prelabeled with hormone for 30 min. When these prelabeled cells were incubated with DCF, 0.1 mM, cell-associated T3 was significantly lower at 30 and 60 min than in cells reincubated without the drug. These data show that cellular transport mechanisms precede nuclear binding by T3 and suggest that there is a critical role for nonnuclear binding proteins in thyroid hormone action.
Publisher: Physicians Postgraduate Press, Inc
Date: 09-03-2010
Publisher: Wiley
Date: 05-04-2012
DOI: 10.1111/J.1365-2265.2011.04278.X
Abstract: To evaluate the incidence and clinical implications of a positive whole-body I-131 scan but negative stimulated serum Tg/TgAb level following an ablative or diagnostic I-131 dose in patients with well-differentiated thyroid cancer and whether there is a difference in incidence if prepared with thyroid hormone withdrawal compared with rhTSH stimulation. I-131 scan findings, serum Tg/TgAb levels, TNM stage and method of thyroid tissue stimulation in 193 consecutive patients (138F, 55M) with well-differentiated thyroid cancer undergoing postoperative ablative I-131 therapy and 121 consecutive (94F, 27M) patients undergoing diagnostic I-131 surveillance scans were retrospectively reviewed. Comparisons of proportions were performed using Chi-square tests. Clinical, biochemical and I-131 scan follow-up data were obtained for each patient cohort. 39/193 (20·2%) postablative I-131 and 10/121 (8·3%) diagnostic I-131 patients had negative stimulated serum Tg/TgAb levels but positive I-131 scans for residual thyroid tissue. Nine (4·7%) of the postablative patients had I-131 uptake in the lateral neck suspicious for loco-regional metastatic disease. In the postablative I-131 group, 38/169 (22·5%) prepared with rhTSH compared to 1/24 (4·2%) prepared with thyroid hormone withdrawal were Tg/TgAb negative but I-131 scan positive (P = 0·04). Follow-up of 21/39 postablative I-131 patients with negative Tg/TgAb but positive I-131 scans confirmed a significant proportion of patients (4/21) (19·1%), remained Tg/TgAb negative/I-131 scan positive, some of whom had higher-risk disease at original diagnosis (2/4) (50%). Our study confirms that in the setting of I-131 ablation therapy or diagnostic I-131 scanning, a significant proportion of patients (20·2% and 8·3%, respectively) have residual benign or malignant thyroid tissue on whole-body scanning despite a negative stimulated serum Tg level. Whether such patients who would otherwise be missed as having residual thyroid tissue on serum Tg testing alone have a worse clinical outcome remains uncertain. Our findings do however suggest performing both stimulated serum Tg/TgAb levels and I-131 scans for the follow-up of patients with higher-risk thyroid cancer may be important. There may also be a slightly higher incidence of this phenomenon in patients prepared with rhTSH rather than by thyroxine withdrawal.
Publisher: Oxford University Press (OUP)
Date: 02-1994
Abstract: Barlow JW, Crowe TC, Cowen NL, Raggatt LE, Topliss DJ, Stockigt JR. Stimulation of sex hormone-binding globulin mRNA and attenuation of corticosteroid-binding globulin mRNA by triiodothyronine in human hepatoma cells. Eur J Endocrinol 1994 :166–70. ISSN 0804–4643 We examined the time course and dose response of the triiodothyronine (T 3 ) effect on mRNAs for sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in cells of the human hepatoma line HepG2. After 7 h of exposure to a saturating dose of T 3 , SHBG mRNA was unchanged but increased to 1.5±0.1 times the unstimulated control at 22 h. Maximal stimulation (2.3±0.6) was observed at 2–3 days. Corticosteroid-binding globulin mRNA was unchanged for 22 h after exposure to T 3 but diminished thereafter to 64% by day 3. At 3–4 days of exposure, the changes in both SHBG mRNA and CBG mRNA were dose-responsive to the T 3 concentration. For both mRNAs, half-maximal response occurred between 10 and 20 pmol/l bioavailable T 3 . Cortisol-binding proteins secreted by HepG2 cells after 3 days in culture also were T 3 dose-responsive. No re-uptake of secreted CBG by the cells was observed, suggesting that the T 3 effect on CBG secretion occurs during production of the mature protein. These data suggest that T 3 stimulates the expression of the SHBG gene and attenuates the expression of the CBG gene. The effects of T 3 on these genes are consistent with the increase in circulating SHBG and decrease in circulating CBG observed in hyperthyroidism. The HepG2 cells may be a useful human cell line in which to study the ersity of the molecular mechanisms of T 3 action. JW Barlow, Ewen Downie Metabolic Unit, Alfred Hospital, Commercial Rd. Melbourne, Victoria 3181, Australia
Publisher: The Endocrine Society
Date: 02-1994
DOI: 10.1210/JC.78.2.459
Publisher: Elsevier BV
Date: 03-1993
Publisher: The Endocrine Society
Date: 11-1991
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.4158/EP.14.5.592
Publisher: Wiley
Date: 25-02-2014
DOI: 10.1111/CEN.12419
Abstract: To determine the prevalence of thyroglossal tract thyroid tissue on SPECT/CT and to assess the contribution of this tissue to total neck radioactive iodine (RAI) activity in patients given (131) I ablation therapy after total thyroidectomy for thyroid cancer. Eighty-three consecutive patients with thyroid cancer treated with total thyroidectomy underwent whole-body planar and SPECT/CT imaging of the neck following initial RAI ablation. On SPECT/CT, thyroglossal tract thyroid tissue was defined as RAI in the anterior neck, superior to the thyroid bed in close proximity to the midline without evidence of localization to lymph nodes. Quantification was performed using region of interest analysis on planar imaging following localization on SPECT/CT. SPECT/CT, and planar images were classified by two reviewers as positive, negative or equivocal with interobserver agreement quantified using a Kappa score. Disagreement was resolved using a third reviewer. Thyroglossal tract thyroid tissue was present in 39/83 (47% 95%CI: 36-58%) patients on SPECT/CT. In these 39 patients, this tissue contributed to a significant amount of total neck activity (median = 50% IQR 19-74%). Interobserver agreement for the presence of thyroglossal tract thyroid tissue was substantial on SPECT/CT (Kappa = 0.73) and fair on planar imaging (Kappa = 0.31). Thyroglossal tract thyroid tissue was present in one half of our study population and contributed to a significant amount of total neck RAI activity. Given the high prevalence of this tissue, our results suggest that total neck RAI activity on planar imaging may not be suitable to assess the completeness of thyroid bed surgery.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Wiley
Date: 24-11-2017
DOI: 10.1111/CEN.13508
Abstract: Prognosis from differentiated thyroid cancer is worse when the disease becomes refractory to radioiodine. Until recently, treatment options have been limited to local therapies such as surgery and radiotherapy, but the recent availability of systemic therapies now provides some potential for disease control. Multitargeted kinase inhibitors (TKIs) including lenvatinib and sorafenib have been shown to improve progression-free survival in phase III clinical trials, but are also associated with a spectrum of adverse effects. Other TKIs have been utilized as "redifferentiation" agents, increasing sodium iodide symporter expression in metastases and thus restoring radioiodine avidity. Some patients whose disease progresses on initial TKI therapy will still respond to a different TKI and clinical trials currently in progress will clarify the best options for such patients. As these drugs are not inexpensive, care needs to be taken to minimize not only biological but also financial toxicity. In this review, we examine the basic biology of radioiodine refractory disease and discuss optimal treatment approaches, with specific focus on choice and timing of TKI treatment. This clinical field remains fluid, and directions for future research include exploring biomarkers and considering adjuvant TKI use in certain patient groups.
Publisher: Mary Ann Liebert Inc
Date: 08-1995
Abstract: The hydrolysis of lecithin by phospholipase produces equimolar amounts of nonesterified fatty acids (NEFAs) and lysolecithin. In this study, we have evaluated the effect of lysolecithins and NEFAs on thyroid hormone binding by examining their interactions with thyroxine-binding globulin (TBG)(serum 1:10,000 dilution) and purified transthyretin (TTR). Unsaturated NEFAs (palmitoleic, oleic, linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acid) inhibited [125I]T4 binding to TBG. Their affinities, relative to unlabeled T4, ranged from 0.005 to 0.0016%, except for oleic acid with relative affinity of < 0.0005%. Saturated NEFAs, lauric, myristic, palmitic, and stearic acid were inactive. After purification by high-performance liquid chromatography, 1-oleoyl and 2-oleoyl lysolecithin displaced [125I]T4 from TBG with an affinity of 0.0006 and 0.0005%, respectively. On a molar basis, this affinity was approximately 10-fold lower than arachidonic acid, the most potent NEFA in inhibiting T4 binding to TBG in this assay system. Of all the NEFAs tested, only arachidonic acid inhibited [125I]T4 binding to TTR, with an affinity relative to unlabeled T4 of 0.49%. 1-Oleoyl, 1-palmitoyl, and 1-stearoyl lysolecithin were without effect on TTR binding. The T4-displacing effects of NEFAs are markedly attenuated by their extensive binding to albumin. Using purified [14C]NEFA preparations and heptane partitioning, the mean unbound percentages of linoleic, eicosapentaenoic, and docosahexaenoic acid in undiluted normal human serum were 0.00099, 0.0050, and 0.0042%, respectively (n = 3). In view of the very high degree of albumin binding of NEFAs, studies in diluted serum will grossly overestimate their competitor potency. The affinities of lysolecithins for the T4 binding sites of TBG and TTR are lower than those of NEFAs and depend on the fatty acid component. Lysolecithins are unlikely to influence plasma protein binding of T4 during critical illness.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2008
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: The Endocrine Society
Date: 03-1981
Abstract: T-Lymphocyte sensitization in Graves' disease (GD) and Hashimoto's thyroiditis (HT) was studied by an indirect migration inhibition factor test using normal T-lymphocytes as second stage indicator cells. In the first stage, mononuclear cells or T-lymphocytes, fractionated by the standard Ficoll-Hypaque procedure from the blood of patients with untreated GD and HT, were cultured in Eagle's medium containing thyroid antigen, and their cell-free supernatants were saved. Normal T-lymphocytes as second stage indicator cells were packed in capillary tubes and placed in planchettes with the above supernatants to complete the indirect migration inhibition factor test. Inhibition of the migration of indicator T-lymphocytes was demonstrated when either GD or HT culture supernatants were employed. Moreover, there was a good correlation between the indirect using the culture supernatants and the direct migration inhibition factor test using mononuclear cells or T-lymphocytes. On the other hand, in both direct and indirect migration inhibition factor tests using mononuclear cells and mononuclear cell culture supernatants, respectively, in the presence of human liver antigen as a nonspecific antigen, there was no significant difference between controls and patients. From these results, we can conclude that GD and HT T-lymphocytes are sensitized to thyroid antigen and produce the lymphokine, migration inhibition factor, into the supernatant when exposed to this antigen.
No related grants have been discovered for Duncan Topliss.