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Aims: Factors influencing prognosis and long-term outcome of thyroid cancer have been described by several groups. We wished to asses the previously described prognostic factors in a moderately iodine deficient region in Hungary., Methods: Four hundred and fifty-four out of 492 patients who had surgery for papillary thyroid cancer (PTC, 386 cases) and follicular thyroid cancer (FTC, 106 cases) between 1971 and 1998 were analyzed. Survival curves were compared using the Kaplan-Meier method and Cox regression analysis., Results: The 10 and 20-year survival rates were 87.9 and 84% for PTC, and 78.2 and 78.2% for FTC. In PTC, extrathyroidal invasion (p<0.0001), lymph node metastasis (p<0.0001), distant metastasis (p<0.0001), and age over 40 years (p=0.002) were significant adverse predictors. In FTC, extrathyroidal invasion (p=0.003) distant metastases (p<0.0001), and age over 40 years (p=0.011) were significant adverse predictors., Conclusion: Iodine intake did not appear to influence survival. The incidence of follicular cancer, which has less favourable prognosis, was higher in iodine deficient regions. This supports the importance of iodine supplementation in these areas.

Currently available methods for the estimation of disease activity in the orbits of patients with Graves' ophthalmopathy (GO) have the disadvantages of being either expensive or time consuming. The aim of this study was to develop a quick, reliable method using Tc labelled diethylenetriaminepentaacetic acid (DTPA) and four-headed single photon emission computed tomography (SPECT) for this purpose. The theoretical basis of the method is that the high capillarization and oedema in the orbit may be reflected on Tc-DTPA images in GO. SPECT data of 28 orbits of 14 patients with GO were compared with magnetic resonance imaging (MRI) T2 relaxation time scores. Based on the number of 'active' muscles with T2 relaxation times of more than 70 ms in a given orbit, an MRI score of 0 (no active muscle) to 4 (all rectus muscles active) was assigned to the orbit. With MRI, 18 orbits were inactive, and 10 were active. Thirty minutes after the intravenous administration of 7 MBq.kg Tc-DTPA, 128 projections were acquired by a four-headed SPECT. On the sum of six transaxial slices containing the entire bulbar region of the skull, a triangle-like region of interest (ROI) was drawn (OR ROI). This ROI was 'slipped' to the right temporal region of the brain as reference site (B ROI). The count ratios of OR/B were calculated and compared to MRI score values. In the group of 18 inactive orbits (an MRI score of zero on both sides), in the transaxial plane, the mean OR/B value was 6.4+/-1.17, and in the group of 10 active orbits (an MRI score of 1-3) 8.30+/-2.08, the difference being significant (P <0.05). Tc-DTPA orbital SPECT is a promising method for the estimation of disease activity in the orbits of patients with Graves' ophthalmopathy.

Objective: The objective of this study was to find the most appropriate, accurate, and convenient muscle parameter that can be used as a substitute for volume in monitoring the effectiveness of therapy of patients with Graves' ophthalmopathy., Subjects and Methods: The four rectus muscles in 110 orbits (35 patients and 20 control subjects) were evaluated with MR imaging. The diameter at the largest extent of the muscle belly, as well as the long and the short diameters and the cross-sectional areas in a preselected coronal scan, were measured for each muscle and were compared with the corresponding muscle volume measured on contiguous T1-weighted transverse slices., Results: The measured coronal area correlated well with the volume of the superior (r = 0.694, p < 0.0001) and inferior (r = 0.783, p < 0.0001) recti, and the largest transverse diameter showed strong correlation with the volume of the lateral (r = 0.868, p < 0.0001) and medial (r = 0.869, p < 0.0001) recti. For the latter muscle, the coronal area also exhibited a good correlation with the volume (r = 0.838, p < 0.0001). Coronal cross-sectional areas can be well estimated by measuring both the short and long coronal muscle diameters (r values were between 0.914 and 0.966; p < 0.0001)., Conclusion: In Graves' ophthalmopathy, the volume of three of the rectus muscles can be well estimated by simple measurements on a single coronal slice, and the largest transverse diameter of the lateral rectus is suitable for the same purpose.

Factors influencing prognosis and long term outcome of thyroid cancer have been described by several groups. It is, however, not clear how the moderate iodine deficiency in Hungary can influence the previously described prognostic factors by other means than shifting differentiated cancer incidence toward the follicular type. Data of 423 out of 472 patients who had been operated on for papillary (372) and follicular (100) thyroid cancer between 1971 and 1997 at our institution have been analyzed retrospectively. Histological specimens were re-evaluated and, if needed, revised. Survival curves were compared using the Kaplan-Meier method. The overall 5 and 10 year survival rates were 93% and 89% for papillary, and 92% and 80% for follicular carcinoma. As an independent factor extrathyroidal invasion (papillary p = 0.000, follicular p = 0.000), lymph node involvement (papillary p = 0.000, follicular 0.011), distant metastases (papillary p = 0.000, follicular p = 0.000), and age over 40 years (papillary p = 0.000, follicular p = 0.000) had negative influence on survival. Multifocality, gender, type of surgery (total or near-total thyroidectomy vs. less than near-total thyroidectomy), and lymphocytic infiltration did not influence survival. Iodine intake did not influence survival, however, the incidence of follicular cancer was higher in iodine deficient regions. When analyzing the papillary and follicular groups separately by Cox regression, extrathyroidal invasion (p = 0.008), lymph node metastasis (p = 0.004), distant metastasis (p = 0.000), and age over 40 years (p = 0.000) were significant predictors in the papillary group, while only tumor extrathyroidal invasion (p = 0.019), and distant metastases (p = 0.000) were significant negative factors in the follicular group.

The identification of antigenic targets in the retroocular autoimmune response of Graves' ophthalmopathy is likely to increase our understanding of mechanisms underlying this disorder. While a number of putative autoantigens have been identified on the basis of molecular weight or cell of origin, a determination of the significance of these antigens is contingent upon an identification of the amino acid sequence. Our group has previously identified immunoreactive retroocular fibroblast (ROF) proteins recognized by thyrotropin receptor (hTSH-R) antisera (anti-p1), at molecular weights of 95, 71, 41, and 14-25 kDa. In the present study, proteins detected by anti-p1 and visualized by Ponceau staining were isolated and processed for microsequencing. Ponceau staining revealed dense bands at molecular weights of 14 and 23 kDa, and a weak band at 41 kDa. N-terminal sequencing was performed on the prominent band at approximately 23 kDa, showing it to be manganese superoxide dismutase (MnSOD), a mitochondrial enzyme responsible for protection against oxygen free radical-associated cellular damage. Sequence comparison of MnSOD to the hTSH-R peptide, p1, revealed a linear segment of amino acid homology. Preincubation of anti-p1 with p1 blocked immunodetection of the 23 kDa band corresponding to MnSOD, and immunoprecipitation of ROF protein using anti-pi yielded protein recognized by anti-MnSOD. Autoimmunity against human recombinant MnSOD was further assessed by ELISA. Patients with Graves' disease (n = 53) had significantly higher ELISA indices than normal control subjects (n = 29), while patients with Hashimoto's thyroiditis had intermediate values. These results document MnSOD autoantibodies in patients with Graves' disease and suggest that this may result from an immune cross-reactivity between MnSOD and the TSH-receptor.

The oxidative processes (oxygen consumption, superoxoid anion generation, arachidonic acid cascade) of human polymorphonuclear granulocytes (PMNs) obtained from patients suffering from thyroid disorders of autoimmune origin (Graves' disease and Hashimoto's thyroiditis), and non autoimmune origin (toxic adenoma) were investigated. All Graves' and toxic adenoma patients were hyperthyroid. Hashimoto's thyroiditis patients were euthyroid. Healthy age and sex matched volunteers served as controls. The results are as follows: 1) In PMNs from both hyperthyroid groups (Graves' disease and toxic adenoma), independently from the autoimmune origin of the disease, a significantly increased Antimycin A sensitive mitochondrial oxygen consumption and a slightly increased superoxide anion generation were detected. 2) In both autoimmune thyroid disease groups (Graves' disease and Hashimoto's thyroiditis)--depending on the functional state of the thyroid gland--a significantly altered intracellular killing activity was measured. 3) An increased arachidonic acid cascade--triggered by opsonized zymozan (OZ)--was detected in both autoimmune thyroid diseases. The increased arachidonic acid cascade was sensitive to phospholipase A2 inhibiting Mepacrin treatment. 4) The PMNs from both autoimmune thyroid diseases produced large amount of leukotriens (LTs)--LTC4 and LTB4--after stimulation through their Fc receptors but the synthesis of prostagalandins (PGs) has not changed. There are no data indicating local, specific effects of circulating leukotriens in the thyroid gland itself, but based on authors' data, their general, regulating role on both the endocrine-- as well as on the immune system--seems to be plausible.

The human TSH receptor represents the primary target of thyroid-stimulating immunoglobulins responsible for the hyperthyroidism of Graves' disease. In the present series of investigations, the distribution of T cell epitopes has been mapped using synthetic peptides spanning the entire extracellular region of the human TSH receptor. In vitro proliferative responses of the mononuclear cells were measured using flow cytometric analysis of bromodeoxyuridine incorporation into nuclei. In 8 of 11 samples from patients with Graves' disease, at least one (and up to 9) regions of the human TSH receptor induced proliferation, with the mean stimulation index being 39.8 +/- 47.3. No single universal stimulatory peptide was identified. In contrast, stimulation was not observed in three control subjects, while one control subject showed minimal stimulation (index of 5.7) to peptides encompassing a limited area (amino acids 31-65). The immunodominant epitope of patients with recent-onset Graves' disease was localized between amino acids 271 and 365, whereas the immunodominant epitope of patients with disease duration greater than 1 year localized between amino acids 91 and 215. We conclude that the bromodeoxyuridine incorporation method is a useful and important tool for detecting antigen-induced lymphocyte proliferation. The TSH receptor-specific T cells from different Graves' disease patients recognize variable distinct sites within the extracellular region of the TSH receptor, and the immunodominant epitope apparently shifts toward the N-terminus of the receptor protein during the course of treated Graves' disease.

RNA was isolated from fibroblasts from the retroocular area, from endomysial fibroblasts obtained from orbital lateral rectus muscle, and from abdominal skin fibroblasts. The RNA was reverse transcribed into cDNA which was then used as a template for PCR with primers encompassing a portion (nucleotides 989-1235) of the extra-cellular domain of the human TSH receptor (hTSH-R). A definite 247 BP product was detected from fibroblast RNA by ethidium bromide staining, and was confirmed by hybridization with labelled hTSH-R cDNA. The product had homology with the known TSH-R cDNA. These studies indicate that human fibroblasts can express hTSH-R, and they suggest that a cross reactive immunologic response between anti-hTSH-R and these fibroblast TSH receptors may play a role in the genesis of Graves' ophthalmopathy.

Autoimmunity against the TSH receptor (hTSH-R) is known to be the proximate cause of thyroidal activation in Graves' disease, but has not been definitively linked to extrathyroidal manifestations of this disorder, such as ophthalmopathy and pretibial myxedema. In an effort to increase our knowledge concerning mechanisms responsible for Graves' ophthalmopathy, we used antiserum directed against a highly immunogenic portion of the hTSH-R (amino acids 352-367; P1) to assess the presence of this receptor or immunologically related protein in cultured human retroocular fibroblasts obtained from patients with Graves' ophthalmopathy. Immunoenzymatic and immunofluorescent studies revealed specific staining of both cytoplasmic and cell membrane-associated protein in discrete vesicles. To further evaluate the immunoreactive species present in these cells, immunoblotting experiments were performed using hTSH-R-specific antisera (anti-P1) and sera obtained from patients with Graves' disease. Several protein bands were identified using both anti-P1 and Graves' disease patient sera, including species at mol wt of 95, 71, and 18 kilodaltons, the possible significance of which is discussed. The results support the hypothesis that immunity against the hTSH-R or related proteins contributes to the ophthalmopathy of Graves' disease.

Clarifying the role of the TSH receptor protein in the autoimmune process may be the key to understanding the development of Graves' disease. In the present study we used a 16 amino acid peptide of the human TSH receptor (hTSHR) to immunize rabbits. A comparable, but theoretically less immunogenic, peptide was injected into other rabbits. The antibody response against these and other peptides, as well as against solubilized human thyroid membrane (TM) and guinea pig fat cell membrane (GPF) proteins, was tested using ELISA and Western blots. The GPF and TM binding pattern of rabbits' sera was compared to that of Graves' patients' sera. We have identified an area of antigenic cross-reactivity between GPF and TM; a 63 kD protein was present in both GPF and TM, and this protein uniformly bound IgG-s of the rabbits' postimmunization sera and one of eight Graves' patient's serum. We have shown that i) a theoretically immunogenic 16 amino acid peptide was indeed highly immunogenic in rabbits, ii) antibodies binding to GPF and TM were detected after immunization, and iii) the peak of thyroid stimulating immunoglobulin activity of sera was followed by a transient elevation of serum triiodothyronine levels. Further studies investigating the immunogenic epitopes of the hTSHR as well as characterizing the 63 kD protein are indicated.

The clinical applicability of a newly described polymerase chain reaction directed protein expression system was assessed for the in vitro synthesis and partial epitope mapping of large radiolabeled human thyrotropin receptor (hTSH-R) protein segments. PCR amplification of targeted regions within the hTSH-R cDNA followed by in vitro transcription and translation permitted rapid synthesis of protein segments ranging in size from 18 to 62 kDa. Initial epitope mapping was directed at a 52 amino acid segment unique to the hTSH-R compared to otherwise homologous glycoprotein hormone receptors. Sera from Graves' disease patients known to have autoantibodies against the hTSH-R were used to immunoprecipitate two protein fragments differing only by the presence of the unique region in the larger fragment (E5) but not in the smaller fragment (E4). Dense precipitation bands were obtained using Graves' sera to immunoprecipitate E5 whereas little or no specific immunoprecipitation of E4 occurred. Normal sera gave only weak immunoprecipitation bands of E5. The technique provides significant advantages over conventional cloning methods and should have general applicability in the study of other protein targets of autoimmune disease.

Twenty-nine peptides covering the full extracellular domain of the human thyrotropin receptor have been synthesized and tested for reactivity with Graves' patients' and normal sera in ELISA. Two peptides, amino acids 331-350 and the second extracellular loop of the transmembrane segment, bound IgG-s from 5 and 4 of 10 Graves' disease patients' sera, respectively. Neither of these two peptides showed enhanced binding to normal IgG. There were no apparent differences between the Graves' disease and normal group with respect to the other 27 peptides. We conclude that peptide 331-350 and the second extracellular loop carry important linear epitopes which may contribute to the disease process in selected Graves' patients.

A comparison of the nucleotide sequence of the human thyrotropin receptor (hTSH-R) with that of HIV-1 revealed 61% homology between a 161 base pair region encoding a unique portion of the hTSH-R and an immunogenic HIV-1 regulatory protein, nef. Amino acid analysis of this region shows 27% homology, including a segment in which 7/10 consecutive amino acids are identical. Sera from rabbits successfully immunized with a 16 amino acid portion of the hTSH-R (352-367, p1) was assessed for reactivity against a partially homologous nef peptide (nef-1) by ELISA, with a finding five-fold higher post-immunization values compared to pre-immune sera. The specificity of this response was verified with Western blot, using recombinant nef protein. An ELISA using nef-1 gave 64% higher values with sera from Graves' disease patients than with normal controls. This homology and immunologic cross-reactivity suggests an avenue through which a shared immune response against an HIV-1 related retrovirus could play a role in the pathogenesis of Graves' disease.

The retroocular connective tissue changes in the ophthalmopathy of Graves' disease are known, however, the mechanism which leads to the increase in fibroblast number and activity is poorly understood. Using human embryonal fibroblast monolayers, fibroblast biosynthetic activity in the presence of sera, immunoglobulin deprived sera or immunoglobulins of Graves' patients with and without ophthalmopathy has been measured. Both sera and immunoglobulin deprived sera of the ophthalmic Graves' patients caused a marked increase of protein synthesis and a moderate increase of the sulphated glycosaminoglycan synthesis of fibroblasts. The same stimulatory effect was not found when immunoglobulin in fetal calf serum was used instead of sera, though anti-fibroblast IgG-s were present both in the sera and separated immunoglobulin fractions, as it has been demonstrated in an ELISA system. We conclude that the sera of ophthalmic Graves' patients contains a factor which stimulates human embryonal fibroblasts' biosynthetic activity in culture; this factor is not an immunoglobulin. The system described here seems to be suitable for studying the accompanying connective tissue changes in Graves' disease.

In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7-2 mg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is treated with daily levothyroxine (LT4). In recent years, soft gel caps of LT4 (LT4-C) have been commercialized, and their performance has been optimized. Since guidelines recommend dose LT4 according to the tablet preparation efficacy, the present study was undertaken to obtain data about the daily requirement, normalized per body weight, of LT4-C. Methods: Patients undergoing LT4-C after total thyroidectomy and radioiodine treatment for differentiated thyroid carcinoma were selected. There was no specific indication of suppression of TSH (i.e., <0.5 or <0.1 mIU/L). Patients were required to maintain a stable LT4 dose during the study period. Patients with interfering factors were excluded from this study. Results: Thirty patients were enrolled (18 females and 12 males; median age, 50 years; median body weight, 71 kg; median LT4-C dose, 1.71 μg/kg/day). The analysis of patient age did not reveal any differences. The LT4-C dose correlated with free-T4 p = 0.03), but not with TSH (p = 0.42) and free-T3 (p = 0.13). TSH was <1.0 mIU/L in 90% of the cases. The LT4-C dose-TSH response effect was analysed by probit regression model: the probability to achieve TSH <1.0 mIU/l was 99% with a dose of 1.84 (95%CI 1.57-2.12) μg/kg/day, 75% with a dose of 1.38 μg/kg/day (95%CI 1.17-1.59), and 50% with a dose of 1.20 (95%CI 0.96-1.43). At ROC curve analysis, the most accurate cut-off of LT4-C dose to achieve TSH <1.0 mIU/l was 1.53 ug/kg/day with 70% sensitivity and 100% specificity. Conclusions: Athyreotic patients can be initially treated with an LT4-C dose lower than previously stated. Therefore, further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the rates of necessary diagnostic and therapeutic procedures in a cohort of patients undergoing their first endocrine consultation for thyroid nodular disease. Methods: This was an observational study conducted between January 1 and June 30, 2023, on patients undergoing their first endocrine consultation for thyroid nodular disease. Data were collected, including age, thyroid-stimulating hormone (TSH) concentration, reasons for performing thyroid ultrasound (US), and thyroid US reports. The US was performed at the time of the endocrine consultation according to the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR-TIRADS) risk stratification system. Patients underwent further investigations/treatment or simple US follow-up as necessary. Results: A total of 373 patients with thyroid nodules were evaluated. Reasons for undergoing thyroid US were unrelated to suspected thyroid disease in 126 (33.8%), incidentalomas in 91 (24.4%), dysfunction or positivity for thyroid antibodies in 67 (18%), symptoms or visible nodules in 61 (16.3%), and family history of thyroid disease in 28 (7.5%). A total of 193 diagnostic or therapeutic procedures were performed in 133 (35.7%) patients [fine-needle aspiration (FNA): 121 (62.7%), surgery: 28 (14.5%), percutaneous ethanol injection: 20 (10.4%), scintigraphy: 10 (5.2%); thermal ablation: 7 (3.6%), and radioactive treatment: 7 (3.6%)]. Conclusions: In the present study only one-third of the patients undergoing endocrine consultation with first detected thyroid nodules required any diagnostic or therapeutic procedures. [ABSTRACT FROM AUTHOR]

Mushrooms are important organisms because of their human nutritional and medicinal value. With the expansion of the cultivation of edible mushrooms, fungal diseases have become a major problem in limiting their production. Numerous fungi can cause mushroom deformation or rots. In this publication we report on fungal diseases found during Morchella cultivation in China, with emphasis on morphology and phylogeny to characterise species. The key findings include 1) establishment of a new family Albomorchellophilaceae in Hypocreales, and a novel monotypic genus Albomorchellophila with the type species A. morchellae. Divergence time estimates indicate that Albomorchellophilaceae diverged from its sister family Calcarisporiaceae at ca. 105 (92–120) MYA; 2) the phylogeny and morphology of the family Pseudodiploosporeaceae (Hypocreales) is revised. The family contains a single genus Pseudodiploospora. Intraspecific genetic analyses of Pseudodiploospora longispora reveals significant base differences within strains, especially in the regions of protein-coding genes RPB 2 and TEF; 3) four fungicolous taxa, i.e., Cylindrodendrum alicantinum, Hypomyces aurantius, Hypomyces rosellus, and Trichothecium roseum, are reported as putative pathogens on cultivated morels for the first time. In addition, the previously reported pathogens of morels, Clonostachys rosea, Clonostachys solani, Hypomyces odoratus, and Pseudodiploospora longispora are also detailed in their symptoms and morphology; 4) the phylogeny and morphology of "Zelopaecilomyces" previously placed within Pseudodiploosporeaceae are re-assessed. "Zelopaecilomyces" is proved to be introduced through a chimerism of gene fragments sourced from two distinct organisms. Consequently, it is recommended that "Zelopaecilomyces" should not be recognised due to the mixed up molecular data in phylogeny and a lack of support from morphological evidence. Furthermore, this study discusses the voucher specimen Paecilomyces penicillatus (CBS 448.69), which may contain two mixed taxa, i.e., Pseudodiploospora longispora and a member of Penicillium. Publications on pathogenic fungi of cultivated mushrooms is sporadically, which leads to a lack of understanding of causal agents. As a follow up to the diseases of morel cultivation, we also review the fungal diseases of cultivated mushrooms reported over the last four decades. More than 130 pathogens affect the growth and development of the main cultivated mushrooms. The taxonomic diversity of these pathogens is high, distributed in 58 genera, 40 families, 20 orders, 12 classes and six phyla. The host infected are from Ascomycota to Basidiomycota, mainly being reported from Agaricus bisporus, Cordyceps militaris, Morchella spp., and Pleurotus spp. This study not only enriches our current knowledge on the diversity of pathogens of cultivated mushrooms, especially morels, but also recognizes the importance of some taxa as potential pathogens. Taxonomic investigation and accurate identification are initial and key steps to understanding pathogen-mushroom interactions, and will result in better disease management strategies in the mushroom industry. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional printing (3D printing) technology and computer navigation technology have been gradually applied in surgeries for orbital blowout fractures. This study compared the efficacy of traditional techniques (group I) and 3D printing combined with computer navigation technology-assisted techniques (group II) in the management of orbital blowout fractures., Methods: All patients treated for orbital blowout fractures in the Affiliated Hospital of Yangzhou University from March 2018 to February 2021 were reviewed. The primary predictive variable was surgical techniques used for orbital fractures (traditional techniques or 3D printing combined with computer navigation technology-assisted techniques). Outcome variables included diplopia, limitation of extraocular muscle movement, and enophthalmos orbital volume., Results: All the surgeries were successfully performed without serious complications. Six months after the operation, the degree of diplopia and limitation of extraocular muscle movement in the traditional techniques group and 3D printing combined with computer navigation technology-assisted techniques group were significantly improved (the former Z= -2.670, P=0.008, the latter Z=-3.584, P<0.001 and the former Z=-4.852, P<0.001, the latter Z=-5.427, P<0.001, respectively). There were no significant differences in the degree of diplopia and limitation of extraocular muscle movement between the 2 groups before the operation (the former Z=-0.842, P=0.400; the latter Z=-0.567, P=0.571), and there were significant differences after the operation (the former Z=-2.773, P=0.006; the latter Z=-2.892, P=0.004), and the 3D printing combined with computer navigation technology-assisted techniques group showed an advantage over the traditional techniques group. The difference in bilateral enophthalmos and orbital volume in traditional techniques groups and 3D printing combined with computer navigation technology-assisted techniques groups was dramatically decreased (the former t=12.558, P<0.001, the latter t=12.659, P<0.001, and the former t=19.194, P<0.001, the latter t=17.770, P<0.001, respectively). There were no significant differences in bilateral enophthalmos and orbital volume between the 2 groups before the operation (the former t=-0.410, P=0.683; the latter t=0.311, P=0.756), and there were significant differences after the operation (the former t=4.081, P<0.001; the latter t=4.078, P<0.001). There were statistically significant differences in surgical time and cost between the traditional technology group and the 3D printing combined with computer navigation technology-assisted technology group (the former t=8.445, P<0.001, and the latter t=3.534, P<0.001); 3D printing combined with computer navigation technology-assisted techniques group spent more surgical time and money than the traditional techniques group., Conclusions: The application of 3D printing combined with computer navigation techniques in the management of orbital blowout fractures can significantly improve the accuracy and safety of the operation. 3D printing combined with computer navigation technology-assisted techniques group spent more surgical time and money., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

Purpose: To elucidate the long-term efficacy and safety of growth hormone replacement therapy (GHRT) in Japanese patients with adult growth hormone deficiency (AGHD)., Methods: We conducted a retrospective study. A total of 110 patients with AGHD receiving GHRT were enrolled. Clinical and laboratory data were collected annually from the beginning of the study. Statistical analysis was performed using a linear mixed-effects model., Results: Of all patients, 46.4% were males, 70.9% had adult-onset GHD, and follow-up was up to 196 months, with a median of 68 months. The insulin-like growth factor-1 standard deviation score increased after the start of GHRT and remained constant for more than 11 years. Seventeen patients were followed up for more than 11 years. The body mass index increased. Waist circumference decreased in the short term but increased in the long term. The diastolic blood pressure decreased 1-5 years after the start of GHRT, and the systolic blood pressure increased 11 years after GHRT. Moreover, a long-term decrease in low-density lipoprotein cholesterol, an increase in high-density lipoprotein cholesterol, and a decrease in aspartate aminotransferase and alanine aminotransferase levels were observed. The glycosylated hemoglobin level increased after 3 years. The bone mineral density in the lumbar spine and total hip increased significantly 3 years after the start of GHRT. Finally, the number of adverse events was eight., Conclusion: We demonstrated the metabolic effectiveness and safety of GHRT in Japanese patients with AGHD over a long follow-up period of 16 years., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This review focuses on post-operative thyroid hormone replacement and thyrotropin suppression therapy in patients with differentiated thyroid cancer. Methods: A clinical review. Results: Differentiated thyroid cancers (DTC), including papillary and follicular thyroid cancers, have an excellent prognosis and their management leverages a unique set of clinical tools arising from homology to the normal thyroid follicular cell. Surgery is the cornerstone of initial management, and post-operative care often requires thyroid hormone replacement therapy, which may be approached with the intent of physiologic normalization or used pharmacologically to suppress TSH as part of a DTC treatment. Conclusion: Management of DTC and approaches to TSH suppression are tailored to an individual's risk of DTC recurrence and are adjusted to a patient's clinical status and comorbidities over time with the goal of mitigating risk and maximizing benefit. [ABSTRACT FROM AUTHOR]

Primary cilia (PC) are non-motile and microtube-based organelles protruding from the surface of almost all thyroid follicle cells. They maintain homeostasis in thyrocytes and loss of PC can result in diverse thyroid diseases. The dysfunction of structure and function of PC are found in many patients with common thyroid diseases. The alterations are associated with the cause, development, and recovery of the diseases and are regulated by PCmediated signals. Restoring normal PC structure and function in thyrocytes is a promising therapeutic strategy to treat thyroid diseases. This review explores the function of PC in normal thyroid glands. It summarizes the pathology caused by PC alterations in thyroid cancer (TC), autoimmune thyroid diseases (AITD), hypothyroidism, and thyroid nodules (TN) to provide comprehensive references for further study. [ABSTRACT FROM AUTHOR]

Selenium, a trace element present in specific selenoproteins, is essential for thyroid hormone metabolism. Selenium is also an antioxidant with immunosuppressive properties and may help in managing thyroid autoimmune diseases, including Graves' (GD) hyperthyroidism and Graves' ophthalmopathy (GO). There were 320 clinical studies related to selenium and thyroid published in English and French between January 1, 2000, and June 1, 2023. Our focus was to identify studies reporting levels of serum selenium in patients with GD and studies that assessed the effect of selenium supplementation on outcomes of GD hyperthyroidism and GO. We also reviewed 20 systematic reviews and meta-analyses of randomized controlled trials that reported selenium levels in GD and the effects of supplementation on GD and GO outcomes. Our review showed that patients with GD had serum selenium levels lower than those of various control patients. In the short-term, a selenium supplement to antithyroid drugs showed benefit for GD hyperthyroidism in most studies, but long-term benefits and positive effects on remission rate were unclear. Some studies did not show benefit. The benefits may depend on baseline selenium deficiency. Two randomized controlled trials showed positive effects of supplementation for mild GO; however, studies about moderate and severe GO are still needed. There is evidence for benefit with short-term selenium supplementation for GD hyperthyroidism, but controlled studies are needed to assess long-term benefits, and benefits in selenium-sufficient areas. [ABSTRACT FROM AUTHOR]

Objective: Upper gastrointestinal complaints are common in patients with euthyroid goiter and subclinical hypothyroidism for whom follow-ups are performed without treatment. This study evaluated gastroparesis using radionuclide imaging in patients with dyspepsia. Methods: A total of 56 adult patients were included in this retrospective study. The average age of the patients was calculated as 70.88±2.33 years. Euthyroid goiter was observed in 29 patients and subclinical hypothyroidism in 27 patients. A liquid gastric emptying scintigraphy test was performed on all patients, and thyroid function tests, thyroid ultrasonography, and body mass index evaluations were performed. Regions of interest, including the antrum and fundus, were drawn from anterior images. A time activity curve was obtained. Results: The gastric emptying half-time was calculated using liquid gastric emptying scintigraphy. This value was found to be significantly higher in patients with subclinical hypothyroidism than in those with euthyroid goiter (p=0.033). Gastric emptying was prolonged in 17 subclinical hypothyroidism patients (63%) and 10 (34.5%) patients diagnosed with euthyroid goiter. Conclusion: Liquid gastric emptying scintigraphy may be preferred in elderly patients with suspected gastroparesis because of its easy application and short duration. Detecting the prolongation of gastric emptying time due to the presence of gastroparesis in subclinical hypothyroidism and euthyroid goiter cases followed up without treatment may guide the prescription of treatment. [ABSTRACT FROM AUTHOR]

Background Although thyroid eye disease (TED) can impact social and psychological well-being, the epidemiological evidence of TED is lacking in Japan. Methods Nationwide claims databases provided by JMDC Inc. and Medical Data Vision Co. Ltd. and national population statistics are used. Three TED definitions ranging from a strict definition only including a TED diagnosis to a broad definition including a TED diagnosis and considering ocular symptoms are considered. The proportion of patients by severity and disease activity are estimated based on definitions that would allow identification of those patients within the claims data. Results The incidence rate per 100 000 person-years ranged from 7.3 to 11.1 for the strict and broad TED definitions, respectively. For fiscal year 2020 (April 2020 to March 2021) the prevalence rate ranged between 24.65 (strict TED) and 37.58 (broad TED) per 100 000 persons. These correspond to 25 383 and 38 697 patients for the strict and broad TED definitions, respectively. Regardless of the definition used, a predominance of female patients was observed, and the highest burden of the disease was seen in the age group of 35 to 59. Mild and inactive forms of TED were predominant (about 85% and 74%, respectively). Conclusion The incidence and prevalence of TED in Japan were 7.3 to 11.1 per 100 000 person-years and 24.65 to 37.58 per 100 000 persons, respectively. The robust results of this database study add valuable real-world evidence on the incidence and prevalence of TED in Japan. [ABSTRACT FROM AUTHOR]

Context GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. Objective We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. Methods We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Results Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P <.001) and significantly correlated with the peak GH (r = −0.50, P <.001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (β = −0.345; 95% CI, −0.533 to −0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [β] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (β = −0.391; 95% CI, −0.675 to −0.108), independent of alterations in other anterior hormones and metabolic parameters. Conclusion The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP. [ABSTRACT FROM AUTHOR]

Approximately 10%–15% of subjects with hypothyroidism on L-thyroxine (LT4) alone have persistent symptoms affecting their quality of life (QoL). Although the cause is unclear, there is evidence that “tissue T3 lack” may be responsible. If so, combining liothyronine (LT3) with LT4 would be helpful. However, randomized controlled trials (RCT), have not established greater efficacy for the LT3 + LT4 combination in these subjects than for LT4 alone. While the trial design may have been responsible, the use of unphysiological, short-acting LT3 preparations and non-thyroid-specific patient-reported outcome measures (PROMs) may have contributed. We recommend attention to the following aspects of trial design for future RCTs of LT3 + LT4 compared to LT4 alone: (a) Subject selection—(i) measurable symptoms (disadvantages should be recognized); (ii) using a validated thyroid specific PROM such as ThyPRO39 or the Composite scale derived from it; (iii) those taking over 1.2 mg/day or 100 mg/day (for pragmatic reasons) of LT4 defining a population likely without intrinsic thyroid activity who depend on exogenous LT4; (iv) recruiting a preponderance of subjects with autoimmune thyroiditis increasing generalisability; and (v) those with a high symptom load with a greater response to combination therapy e.g. those with the deiodinase 2 polymorphism. (b) The use of physiological LT3 preparations producing pharmacokinetic similarities to T3 profiles in unaffected subjects: two long-acting LT3 preparations are currently available and must be tested in phase 2b/3 RCTs. (c) The superiority of a crossover design in limiting numbers and costs while maintaining statistical power and ensuring that all subjects experienced the investigative medication. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of thyroid eye disease (TED) on patients in various stages of the disease. Background: TED is a debilitating and potentially sight-threatening inflammatory autoimmune disease that is frequently misdiagnosed. Challenging quality-of-life (QoL) issues can persist long after the active phase of disease has subsided. Methods: A 62-question survey was designed as a hypothesis-generating instrument to identify key issues confronting patients ≥18 years old with physician-diagnosed TED. Questions focused primarily on physical and emotional status, and QoL experiences in the 2 months prior to the survey. Data for individual questions are presented as summary statistics. Correlations between questions were determined using X² analyses. Results: The 443 respondents were 18 to >80 years old; >90% female, and >80% from the United States. Time since TED diagnosis ranged from <1 year to >10 years. Participants provided >500 free-form responses describing experiences of living with TED. Physical signs/symptoms were experienced by 307/443 (69%) patients. Of those responding to the QoL questions (N = 394), 53 (13%) reported symptoms improving, 73 (19%) reported symptoms worsening, and 255 (65%) reported no change in the 2 months prior to the survey. The most bothersome signs/symptoms were dry/gritty eyes, light sensitivity, bulging eyes, and pressure or pain behind the eyes. Respondents <60 years were significantly (p < 0.0001) more likely to report symptomatic TED than older patients. Of 394 respondents, 179 (45%) reported feeling depressed and/or anxious, 174 (44%) reported concern about their appearance, and 73 (19%) avoided public situations; 192 (49%) reported declines in confidence or feelings of general well-being, and 78 (20%) reported an inability to achieve goals. Activities limited by TED included reading, driving, and socializing. The proportion of respondents experiencing these negative QoL measures was higher when patients reported experiencing >5 symptoms, had been diagnosed within the last 5 years, or were <60 years of age. [ABSTRACT FROM AUTHOR]

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Background: Subclinical hyperthyroidism (SCH) is found to be associated with renal dysfunction. Hyperthyroidism is a well-known cause of secondary systolic hypertension. However, the effect of SCH on the kidney and its vasculature is still unknown. Aim: To assess the presence of renal function changes and renal vasodysfunction in SCH patients and their relation to hypertension. Methods: The study included 321 patients with SCH and 80 healthy matched controls. Laboratory investigations included thyroid function tests, anti-TSH receptor antibody (TRAb), creatinine, estimated glomerular filtration rate (eGFR), serum osmolarity (S. Osmol), urine osmolarity (U. Osmol), Fractional Excretion of Sodium (FeNa), Fractional Excretion of Potassium (FeK), copeptin (CPP), and aldosterone/renin ratio (ARR). Ultrasound for the thyroid gland, echocardiography, total peripheral resistance (TPR), flow-mediated dilatation (FMD), and Renal Arterial distensibility (RAD) was also done. Results: Serum creatinine was significantly lower while eGFR was significantly higher in SCH patients compared to euthyroid subjects (mean 0.59 ± 0.11 mg/dl Vs mean 0.8 ± 0.1 mg/dl, p = 0.001 and mean 128.28 ± 14.69 ml/min/1.73m2 Vs mean 100.49 ± 14.9 ml/min/1.73m2, p = 0.013, respectively). The TPR and FMD showed a significant decrease in SCH group compared to controls (mean 975.85 ± 159.33 mmHg.min/L Vs mean 1120.24 ± 135.15 mmHg.min/L, p = 0.045 and mean 7.03 ± 4.02% Vs mean 13.48 ± 4.57%, p = 0.003, respectively). RAD was significantly higher in hypertensive SCH patients compared to normotensive SCH patients (mean 17.82 ± 2.46 mmHg Vs mean 11.98 ± 3.21 mmHg, p = 0.001). Conclusion: SCH patients showed vascular resistance reduction. Alterations in thyroid hormones and blood pressure could be the driving mechanisms for the change in renal functions in patients with SCH. [ABSTRACT FROM AUTHOR]

Purpose: Orbital [99mTc]TcDTPA orbital single-photon emission computed tomography (SPECT)/CT is an important method for assessing inflammatory activity in patients with Graves' orbitopathy (GO). However, interpreting the results requires substantial physician workload. We aim to propose an automated method called GO-Net to detect inflammatory activity in patients with GO. Materials and methods: GO-Net had two stages: (1) a semantic V-Net segmentation network (SV-Net) that extracts extraocular muscles (EOMs) in orbital CT images and (2) a convolutional neural network (CNN) that uses SPECT/CT images and the segmentation results to classify inflammatory activity. A total of 956 eyes from 478 patients with GO (active: 475; inactive: 481) at Xiangya Hospital of Central South University were investigated. For the segmentation task, five-fold cross-validation with 194 eyes was used for training and internal validation. For the classification task, 80% of the eye data were used for training and internal fivefold cross-validation, and the remaining 20% of the eye data were used for testing. The EOM regions of interest (ROIs) were manually drawn by two readers and reviewed by an experienced physician as ground truth for segmentation GO activity was diagnosed according to clinical activity scores (CASs) and the SPECT/CT images. Furthermore, results are interpreted and visualized using gradient-weighted class activation mapping (Grad-CAM). Results: The GO-Net model combining CT, SPECT, and EOM masks achieved a sensitivity of 84.63%, a specificity of 83.87%, and an area under the receiver operating curve (AUC) of 0.89 (p < 0.01) on the test set for distinguishing active and inactive GO. Compared with the CT-only model, the GO-Net model showed superior diagnostic performance. Moreover, Grad-CAM demonstrated that the GO-Net model placed focus on the GO-active regions. For EOM segmentation, our segmentation model achieved a mean intersection over union (IOU) of 0.82. Conclusion: The proposed Go-Net model accurately detected GO activity and has great potential in the diagnosis of GO. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the association between health-related quality of life (HRQL) and the severity of hypothyroidism at diagnosis in patients referred to a secondary hospital clinic. Methods: Sixty-seven adult patients referred from primary care were enrolled. All patients had newly diagnosed hypothyroidism due to autoimmune thyroiditis and were treated with levothyroxine (LT4). The dose was adjusted according to thyroid function tests aiming at a normal plasma thyrotropin. Patients were stratified according to the severity of hypothyroidism in two different ways: the conventional approach (subclinical or overt hypothyroidism) and a novel approach according to the change (decrease or increase) in plasma level of free triiodothyronine index (FT3I) following LT4 treatment. The ThyPRO-39 questionnaire was used for measurement of HRQL at referral to the Endocrine Outpatient Clinic (higher score corresponds to worse HRQL). Results: Free thyroxine index (FT4I) at diagnosis correlated positively with the scores on the Hypothyroid Symptoms and Tiredness scales (p = 0.018 for both). In accordance, patients with subclinical hypothyroidism (n = 36) scored higher on Hypothyroid Symptoms (p = 0.029) than patients with overt hypothyroidism (n = 31). The difference in HRQL was more pronounced if patients were stratified according to the dynamics in FT3I following LT4 treatment. Thus, patients who showed a decrease in FT3I following treatment (n = 24) scored significantly worse for Anxiety (p = 0.032) and Emotional Susceptibility (p = 0.035) than patients with an increase in FT3I (n = 43). Conclusion: Patients referred to an endocrine clinic with mild hypothyroidism had an impaired HRQL, compared to patients with more severe hypothyroidism. The most likely explanation of this finding is a lower threshold for seeking medical consultation and secondary care referral if HRQL is deteriorated. The dynamics in plasma FT3I following treatment may be more sensitive for such a discrimination in HRQL than a stratification according to the thyroid function tests at diagnosis. [ABSTRACT FROM AUTHOR]

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The most frequent extrathyroidal Graves' disease manifestation is Graves' orbitopathy (GO). The treatment of GO is determined by its severity and activity. There is currently no reliable, impartial method for assessing it clinically or distinguishing fibrosis from active inflammatory disorders. Today, imaging methods including orbital ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are frequently employed to show pathological abnormalities in the ocular adnexa of GO patients. In addition, a not widely accepted technique -- 99mTc-DTPA SPECT -- has some potential to evaluate retrobulbar inflammation in GO patients. However, FDG-PET/CT is possibly superior to other imaging modalities in detecting inflammation in GO and it may be useful in assessing disease activity in case of clinical or serological uncertainty. It might also act as an early indicator of GO development and its aggravation before irreversible tissue alterations take place and may be used in the differential diagnosis of inflammatory disorders of the orbit. However, before FDG-PET/CT could be applied in daily clinical practice, the methodology of GO activity assessment with defined cut-off values for radionuclide concentration -- standardized units of value (SUV) have to be established and validated. In addition, the limitations of this technique have to be recognized. [ABSTRACT FROM AUTHOR]

Purpose: Iodine deficiency disorder (IDD) is an ongoing worldwide recognized problem with over two billion individuals having insufficient iodine intake. School-aged children and pregnant women are often target groups for epidemiological studies, but there is a lack of knowledge on the general adult population. The aim of this study was to assess the iodine status among a Portuguese public university staff as a proxy for the adult working population. Methods: The population study covered 103 adults within the iMC Salt randomized clinical trial, aged 24–69 years. Urinary iodine concentration was measured spectrophotometrically using the Sandell–Kolthoff reaction. Iodine food intake was assessed using a 24-h dietary recall. The contribution of discretionary salt to the iodine daily intake was assessed through 24-h urinary sodium excretion (UIE) and potentiometric iodine determination of household salt. Results: The mean urine volume in 24 h was 1.5 L. The median daily iodine intake estimated from 24-h UIE was 113 µg/day, being lower among women (p < 0.05). Only 22% of participants showed iodine intake above the WHO-recommended cutoff (150 µg/day). The median daily iodine intake estimated from the 24-h dietary recall was 58 µg/day (51 and 68 µg/day in women and men, respectively). Dairy, including yoghurt and milk products, were the primary dietary iodine source (55%). Iodine intake estimated from 24-h UIE and 24-h dietary recall was moderately correlated (Spearman rank correlation coefficient r = 0.34, p < 0.05). The average iodine concentration in household salt was 14 mg I/kg, with 45% of the samples below the minimum threshold preconized by WHO (15 mg I/kg). The contribution of discretionary salt to the daily iodine intake was around 38%. Conclusion: This study contributes new knowledge about iodine status in Portuguese working adults. The results revealed moderate iodine deficiency, particularly in women. Public health strategies and monitoring programs are needed to ensure iodine adequacy in all population groups. [ABSTRACT FROM AUTHOR]

Persistent symptoms in patients treated for hypothyroidism are common. Despite more than 20 years of debate, the use of liothyronine for this indication remains controversial, as numerous randomised trials have failed to show a benefit of treatment regimens that combine liothyronine (T3) with levothyroxine over levothyroxine monotherapy. This consensus statement attempts to provide practical guidance to clinicians faced with patients who have persistent symptoms during thyroid hormone replacement therapy. It applies to non‐pregnant adults and is focussed on care delivered within the UK National Health Service, although it may be relevant in other healthcare environments. The statement emphasises several key clinical practice points for patients dissatisfied with treatment for hypothyroidism. Firstly, it is important to establish a diagnosis of overt hypothyroidism; patients with persistent symptoms during thyroid hormone replacement but with no clear biochemical evidence of overt hypothyroidism should first have a trial without thyroid hormone replacement. In those with established overt hypothyroidism, levothyroxine doses should be optimised aiming for a TSH in the 0.3–2.0 mU/L range for 3 to 6 months before a therapeutic response can be assessed. In some patients, it may be acceptable to have serum TSH below reference range (e.g. 0.1–0.3 mU/L), but not fully suppressed in the long term. We suggest that for some patients with confirmed overt hypothyroidism and persistent symptoms who have had adequate treatment with levothyroxine and in whom other comorbidities have been excluded, a trial of liothyronine/levothyroxine combined therapy may be warranted. The decision to start treatment with liothyronine should be a shared decision between patient and clinician. However, individual clinicians should not feel obliged to start liothyronine or to continue liothyronine medication provided by other health care practitioners or accessed without medical advice, if they judge this not to be in the patient's best interest. [ABSTRACT FROM AUTHOR]

Background: Subclinical hypothyroidism (SCH) is a common endocrine problem with prevalence estimates between 4% and 20%. Symptoms are often non-specific but can substantially affect well-being leading to repeated medical consultations. The effect of thyroid hormone replacement therapy (THRT) in patients with SCH remains uncertain. Current guidelines, limited by the lack of high-quality evidence, have been controversial with limited adherence in clinical practice. Methods: Three-round modified Delphi method to establish consensus regarding diagnosis and treatment of individuals with SCH with and without affective disorder or anxiety, conducted with clinicians from three specialties, general practice, endocrinology and psychiatry, and two countries, Sweden and the United Kingdom. Results: Sixty clinicians, 20 per specialty, were recruited. Fifty-three (88%) participants completed all three rounds. The participants reached consensus on five of the 26 practice statements that (a) repeated testing was required for the diagnosis of subclinical hypothyroidism, (b) antibody screening should usually occur, and (c and d) antibody screening would strengthen the indication for thyroid hormone replacement therapy in both individuals with or without affective disorder or anxiety. The participants disagreed with (e) a requirement of a TSH threshold = 20 mIU/L for thyroid hormone replacement therapy start. Psychiatrists and GPs but not endocrinologists, agreed that there was a frequent discrepancy between laboratory results and clinical symptoms, and disagreed that testing for thyroid dysfunction was overused in patients presenting with depression or anxiety, or fatigue. Conclusions: In many aspects, attitudes toward diagnosing and treating SCH remain diverse. The inability of our Delphi panel to achieve consensus on most items and the disagreement with a TSH = 20 mIU/L threshold for treatment suggest that the concept of SCH may need rethinking with a better understanding of the hypothalamic-pituitary-thyroid physiology. Given that the scientific evidence is currently not conclusive, guidelines in this area should not be taken as definitive. [ABSTRACT FROM AUTHOR]

Purpose: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. Methods: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. Results: We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD (P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (DLDL) was the only factor correlated negatively with the change of FMD (DFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Conclusion: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy. [ABSTRACT FROM AUTHOR]