Association between <Emphasis Type="Italic">IL-18</Emphasis>gene polymorphisms and biopsy-proven giant cell arteritis

Introduction  

The objective was to investigate the potential implication of the IL18 gene promoter polymorphisms in the susceptibility to giant-cell arteritis (GCA).     

Prognosis in giant-cell arteritis.

In a study to assess the natural history of giant-cell arteritis, 90 patients with proved disease were followed up from the time of diagnosis. Early mortality was low and most commonly due to vertebral arteritis, but cerebral infarction did not appear to be a late complication. High maintenance dose steroids and visual loss were associated significantly with a shortened life span (p=0.0003 and p=0.0024). One-third of the patients developed chronic relapsing disease, but serious late complications were not encountered. After the initial attack has been controlled steroid dosage should be reduced to the minimum needed to alleviate symptoms.     

Evidence Against Amplification of Four Genes in Giant Cells Induced by Meloidogyne incognita

Giant-cell DNA was isolated from pea (Pisum sativum) inoculated with Meloidogyne incognita and used in slot blots to test for selective sequence amplification. Four sequences representing low (ribulose 1,5-bisphosphate carboxylase and actin), mid-level (histone 3), and highly repetitive (large ribosomal repeat) sequence DNA were used as probes. Known amounts of root-tip DNA and giant-cell DNA were blotted onto hybridization membranes and probed. The signal strength on autoradiographs containing equal amounts of root-tip DNA and giant-cell DNA were compared with a scanning densitometer. No difference in signal strength between equal amounts of root-tip DNA and giant-cell DNA was found. Thus, for the probes tested, there is no difference in copy number and, hence, no selective DNA sequence amplification has occurred.     

Role of Ultrasonography in the Differential Diagnosis of Thyrotoxicosis: A Non Invasive,Cost-Effective,and Widely Available But Underutilized Diagnostic Tool

ObjectiveTo explore the use of ultrasonography as a diagnostic alternative to the traditional “gold standard” imaging study of nuclear scintigraphy in the evaluation of thyrotoxicosis.MethodsWe review the relevant literature and share our own experience to highlight the promising role of ultrasonography in thyrotoxicosis. In addition, we present a diagnostic algorithm suggesting liberal use of ultrasonography in the evaluation of thyrotoxicosis.ResultsUltrasonography has proved effective not only in the differentiation of Graves disease from other types and causes of thyrotoxicosis but also in the detection of subtle thyroid nodules. The latter role is emphasized in light of the recent observation of an increased risk of occurrence of papillary thyroid carcinoma in patients with Graves disease.ConclusionUltrasonography is a cost-effective, noninvasive, portable, and safe imaging modality in the evaluation of thyrotoxicosis, both for physiologic assessment and for detection of nonpalpable thyroid cancers that may elude identification on physical examination and nuclear imaging studies. Although thyroid scintigraphy remains a standard radiologic study, thyroid ultrasonography can be a practical alternative in many cases and the primary imaging modality in some situations such as during pregnancy and lactation and for evaluation and management of amiodarone-induced thyrotoxicosis. (Endocr Pract. 2012;18: 567-578)     

Fine needle aspiration biopsy diagnosis of giant-cell tumor of bone. An experience with nine cases

The cytologic findings in nine cases of giant-cell tumor (osteoclastoma) of bone diagnosed by fine needle aspiration (FNA) biopsy are described. The aspirates contained a dual population of cells, consisting of mononucleated tumor cells and multinucleated giant cells (osteoclasts). The tumor cells were usually evident in the FNA smears as cohesive perivascular clusters; some were present as sheets or single cells. The most striking feature, which may best suggest the diagnosis of giant-cell tumor in an FNA smear, was the attachment of the osteoclasts to the cohesive groups of tumor cells. Even when the cells were more dissociated, there was a rather regular distribution of the two types of cells. This series further demonstrates that FNA biopsy permits an accurate cytopathologic diagnosis of giant-cell tumor and that its use can clarify the clinical and radiologic impressions of these bony lesions preoperatively. The differential diagnosis between osteoclastoma and other giant-cell containing bone lesions is discussed in detail.     

Hyperthyroidism—a Disease of Old Age?

In a three-year project in which thyroid studies were undertaken for broad indications 49 cases of thyrotoxicosis were diagnosed; 28 of these patients were 60 years of age or older. Sixteen of these older patients had different forms of atypical thyrotoxicosis, and most were completely without the usual symptoms of the condition. It is concluded that thyrotoxicosis is more frequent in persons over 60 than in younger persons. Many older patients have various forms of masked thyrotoxicosis, and in many cases the correct diagnosis can be made only by undertaking thyroid studies on very wide indications.     

Management of Thyrotoxicosis: Preconception,Pregnancy, and the Postpartum Period

Objective: To review the diagnosis and management of thyrotoxicosis in women who are preconception, pregnant, and in the postpartum period.Methods: Literature review of English-language papers published between 1980 and 2018.Results: Overt thyrotoxicosis occurs in 0.2% of pregnancies and subclinical thyrotoxicosis in 2.5%. Hyperthyroidism in women of childbearing age most frequently is caused by Graves disease (GD). Gestational thyrotoxicosis, transient human chorionic gonadotropin (hCG)-mediated hyperthyroidism, may develop in the first trimester. In the first year following delivery, postpartum thyroiditis, which frequently includes a thyrotoxic phase, occurs in 5% of women. Hyperthyroidism from nodular autonomy is uncommon in women of childbearing age. It is essential to understand the underlying etiology for thyrotoxicosis in order to recommend appropriate treatment. Gestational thyrotoxicosis requires supportive care, without antithyroid drug therapy. GD may be treated with antithyroid drugs, radioactive iodine, or thyroidectomy. Pregnancy, plans for pregnancy, and lactation have important implications for the choice of GD treatment. When thyrotoxicosis presents following delivery, postpartum thyroiditis must be differentiated from GD.Conclusion: The diagnosis and management of thyrotoxicosis in the peripregnancy period present specific challenges. In making management decisions, it is essential to weigh the risks and benefits of treatments not just for the mother but also for the fetus and for breastfed infants. A team approach to management is critical, with close collaboration among endocrinologists, maternal-fetal medicine specialists, and neonatologists.Abbreviations: GD = Graves disease; hCG = human chorionic gonadotropin; MMI = methimazole; PPT = postpartum thyroiditis; PTU = propylthiouracil; T3 = triiodothyronine; T4 = thyroxine; TBG = thyroxine-binding globulin; TRAb = TSH receptor antibody; TSH = thyroid-stimulating hormone     

Sleepwalking Associated with Hyperthyroidism

ObjectiveTo report several cases of hyperthyroidism in patients presenting with the unusual symptom of sleepwalking and to discuss the possible pathophysiologic basis for this novel association.MethodsAfter encountering and reporting the first case of new-onset somnambulism in a patient presenting with thyrotoxicosis at our institution, we routinely inquired about the sleep history of patients with thyrotox-icosis, questioning both the patients and family members when applicable. Those patients who actually had sleepwalking episodes coinciding with the onset of thyrotoxi-cosis underwent close follow-up, and the relationship between the sleepwalking and the results of thyroid function tests was analyzed. In addition, we reviewed the literature on psychiatric disorders and sleep problems, and the pathophysiologic rationale for a cause-and-effect relationship is discussed.ResultsWe collected 8 cases of patients with new-onset sleepwalking episodes that coincided with the start of thyrotoxicosis. The disappearance of the sleepwalking with successful achievement of euthyroidism supports a cause-and-effect relationship. This hypothesis is further supported by the absence of a family history, the adult onset, and the relapse of sleepwalking in 2 of the patients when their thyrotoxicosis became poorly controlled as a result of noncompliance with medications and its subsequent disappearance with reachievement of euthyroidism. Of note, such a presentation was seen only in patients with thyrotoxicosis caused by diffuse toxic goiter or Graves’ disease and never in patients with other causes of thyro-toxicosis.ConclusionNew-onset sleepwalking could be caused by thyrotoxicosis or, more specifically, by thyrotoxicosis resulting from diffuse toxic goiter. The mechanism is hypothesized to be related to the combination of prolongation of non-rapid eye movement sleep and the associated fatigue. Specific inquiry about this unusual presentation of thyrotoxicosis is encouraged, and more studies are needed to confirm and evaluate its extent. (Endocr Pract. 2005;11:5-10)     

Acute Liver Failure with Thyrotoxicosis Treated with Liver Transplantation

ObjectiveWe describe a young woman with previously undiagnosed thyrotoxicosis who presented with acute liver failure (ALF).MethodsWe present a case report and review the relevant literature.ResultsAn extensive evaluation excluded possible causes of ALF other than thyrotoxicosis. The management of thyrotoxicosis posed several unique challenges in the setting of ALF, particularly because we did not want to use potentially hepatotoxic thionamides. The patient was treated with prednisone and propranolol and was started on potassium iodide when she was listed for liver transplantation. She underwent an uncomplicated liver transplant and subsequent thyroidectomy and is doing well.ConclusionThis well-characterized case describes thyrotoxicosis as a possible cause of ALF after thoroughly excluding other possible causes and illustrates the challenges of simultaneously managing both disorders. To our knowledge, this is the first report of ALF possibly resulting from untreated thyrotoxicosis that was successfully treated with liver transplantation. (Endocr Pract. 2013;19:e57-e60)     

Transient Thyrotoxicosis Following Minimally Invasive Radio-Guided Parathyroidectomy

ObjectiveWe report a case of thyrotoxicosis following minimally invasive parathyroidectomy.MethodsCase report with literature review.ResultsA 70-year-old woman with primary hyperparathyroidism developed thyrotoxicosis 2 weeks following minimally invasive radio-guided parathyroidectomy. A diagnosis of postparathyroidectomy transient thyrotoxicosis (PTT) was made after excluding other causes of thyrotoxicosis. The patient reverted back to a euthyroid state in 4 weeks with conservative management.ConclusionPTT should be considered in the differential diagnosis in patients developing features of thyrotoxicosis following parathyroidectomy. (Endocr Pract. 2014;20:e1-e3)     

Review of Oral Cholecystographic Agents for the Management of Hyperthyroidism

ObjectiveAlthough the use of oral cholecystographic agents (OCAs) had declined due to limited availability, there is literature to suggest it is an effective medication for thyrotoxicosis in appropriate clinical situations.MethodsThe authors performed a PubMed search and systematically reviewed all the English written case reports, original studies and reviews from 1953 to 2012. Additional information was supplemented from available online pharmacologic databases.ResultsThe off-label use of OCAs was reviewed for the management of neonatal and adult Graves’ disease, subacute thyroiditis, amiodarone-induced thyroiditis (AIT), exogenous hyperthyroidism, toxic multinodular goiter (TMNG), thyrotropinoma, thyrotoxicosis during pregnancy, rapid pre-operative control of hyperthyroidism, and thyroid storm. Adverse effects were also reviewed.ConclusionOCAs generally are effective agents in treating thyrotoxicosis in the etiologies reviewed. OCAs are clinically relevant in patients who require rapid control, such as in the pre-operative state or patient who cannot tolerate a thyrotoxicosis state. OCA may also be beneficial in situations where other anti-thyroidal medication would be hazardous or ineffective, such as thionamide allergy or exogenous thyrotoxicosis. Given concern for long-term relapse, OCAs should be considered a short-term bridge to definitive therapy. OCAs are limited in TMNG and should be second line after glucocorticoids in AIT II. OCAs do not preclude the use of radioactive iodine, which can be performed one week after OCA therapy. (Endocr Pract. 2014;20:1084-1092)     

Role of Thyroid Doppler in Differential Diagnosis of Thyrotoxicosis

ObjectiveTo evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis.MethodsConsecutive patients with thyrotoxicosis presenting to our center between June 2007 and March 2008 were included in the study. Clinical data were collected, and thyroid function tests including measurements of thyrotropin, total thyroxine, and total triiodothyronine were performed. Thyroid glands of all patients were evaluated with color-flow Doppler ultrasonography for size, vascularity, and peak systolic velocity of the inferior thyroid artery. Technetium Tc 99m pertechnetate scan was done when the diagnosis was not clear on the basis of clinical findings. Patients were divided into 2 groups for analysis: patients with destructive thyrotoxicosis and patients with Graves disease. Paired t tests and Fisher exact tests were used for statistical analysis.ResultsA total of 65 patients participated in the study; 31 had destructive thyrotoxicosis and 34 had Graves disease. Thyroid blood flow, as assessed by peak systolic velocity of the inferior thyroid artery, was significantly higher in patients with Graves disease than in patients with destructive thyroiditis (57.6 ± 13.1 cm/s vs 22.4 ± 5.4 cm/s; P < .05). All patients with destructive thyroiditis had low peak systolic velocity of the inferior thyroid artery, and 32 of 34 patients with Graves disease had high peak systolic velocity. Color-flow Doppler ultrasonography parameters correlated significantly with pertechnetate scan results, demonstrating a comparable sensitivity of 96% and specificity of 95%.ConclusionsDifferentiating Graves thyrotoxicosis from destructive thyrotoxicosis is essential for proper selection of therapy. Assessment of thyroid blood flow by color-flow Doppler ultrasonography is useful in this differentiation. (Endocr Pract. 2009;15:6-9)     

Hürthle cell carcinoma of the thyroid presenting as thyrotoxicosis

ObjectiveTo report a case of hyperthyroidism associated with Hülllnnvl-ürthle cellcarcinoma and to review the literature regarding this relationship.MethodsWe describe the clinical, biochemical, radiologic, and pathologic data of a patient with Hürthle cellcarcinoma associated with thyrotoxicosis and reversible heart failure. We discuss the mechanistic aspects and review previously reported cases of functionalHürthle cellcarcinomas.ResultsA 43-year-old womanpresented with thyrotoxicosis and nonischemic cardiomyopathy. She had a “hot” nodule inthe left lobe of the thyroid onsodium pertechnetate scan. She underwent a left hemithyroidec-tomy and isthmusectomy. Pathologic findings revealed a minimally invasive Hürthle cellcarcinoma. Onfollow-up, the dilated cardiomyopathy had resolved. The associationof thyroid carcinoma with thyrotoxicosis is rare.ConclusionsSome Hürthle cellcarcinomas canbe functionaland lead to thyrotoxicosis. To our knowledge, we present the first case of reversible dilated cardiomyopathy due to thyrotoxicosis originating from Hülll-ürthle cellcarcinoma. (Endocr Pract. 2012;18:e5-e9)     

Fine needle aspiration of pleomorphic giant-cell carcinoma of the pancreas. Case report with ultrastructural observations

The fine needle aspirate in a case of pleomorphic giant-cell carcinoma of the pancreas, an unusual but highly malignant variant of ductal carcinoma of the pancreas, was characterized by bizarre tumor giant cells, "osteoclastlike" giant cells and abundant mitoses. The differential diagnostic possibilities include sarcoma (rhabdomyosarcoma, malignant fibrous histiocytoma and liposarcoma), melanoma, choriocarcinoma, metastatic giant-cell carcinoma of the lung and giant-cell tumor of the pancreas. A combination of clinical history, imaging findings and fine needle aspiration biopsy with transmission electron microscopy could lead to the appropriate diagnosis and help differentiate this entity from the other possible considerations.     

Hipertiroidismo y captaciones de yodo bajas en una paciente con enfermedad de Graves

Thyrotoxicosis factitia is defined as thyrotoxicosis resulting from exogenous ingestion of thyroid hormone, usually in patients with a psychiatric disorder. Diagnosis can be difficult and this entity should be suspected in patients with high free tiroxine (T4) concentrations, low or suppressed thyroglobulin concentrations, normal urinary iodide excretion and low or suppressed ¹³¹I uptake. To establish the differential diagnosis, thyrotoxicosis factitia must be distinguished from several diseases with low ¹³¹I uptake, such as Graves’ disease, subacute thyroiditis, hyperthyroidism due to excessive iodine intake, struma ovarii and metastasis from thyroid cancer. Treatment is based on b-blockers to reduce symptoms and avoid iatrogeny. We present a case of thyrotoxicosis factitia treated in our outpatient clinic.     

Histology of the Interactions of Paecilomyces lilacinus with Meloidogyne incognita on Tomato

Excised tomato roots were examined histologically for interactions of the fungus Paecilomyces lilacinus and Meloidogyne incognita race 1. Root galling and giant-cell formation were absent in tomato roots inoculated with nematode eggs infected with P. lilacinus. Few to no galls and no giant-cell formation were found in roots dipped in a spore suspension of P. lilacinus and inoculated with M. incognita. Numerous large galls and giant cells were present in roots inoculated only with M. incognita. P. lilacinus colonized the surface of epidermal cells as well as the internal cells of epidermis and cortex. The possibility of biological protection of plant surfaces with P. lilacinus against root-knot nematodes is discussed.     

Trophoblast giant-cell differentiation involves changes in cytoskeleton and cell motility

Trophoblast giant-cell differentiation is well-characterized at the molecular level, yet very little is known about how molecular changes affect the cellular functions of trophoblast in embryo implantation. We have found, using both explanted E7.5 mouse embryo ectoplacental cone and the rat choriocarcinoma (Rcho-1) cell line, that trophoblast differentiation is distinguished by dramatic changes in cytoarchitecture and cell behavior. Undifferentiated trophoblast cells contain little organized actin and few small, peripheral focal complexes and exhibit high membrane protrusive activity, while differentiated trophoblast giant cells contain prominent stress fibers, large internal as well as peripheral focal adhesions, and become immotile. The dramatic changes in cell behavior and cytoskeletal organization of giant cells correlate with changes in the activities of the Rho family of small GTPases and a decrease in tyrosine phosphorylation of focal adhesion kinase. Together, these data provide detailed insight into the cellular properties of trophoblast giant cells and suggest that giant-cell differentiation is characterized by a transition from a motile to a specialized epithelial phenotype. Furthermore, our data support a phagocytic erosion, rather than a migratory infiltration, mechanism for trophoblast giant-cell invasion of the uterine stroma.     

MRI 在脊柱骨巨细胞瘤诊疗中的临床意义

目的:探讨MRI在脊柱骨巨细胞瘤诊疗中的临床应用价值。方法:回顾性分析2005年4月-2010年11月我院5例经病理证实为脊柱骨巨细胞瘤患者的MRI检查表现。结果:椎体内病灶呈不同程度膨胀性破坏,T1WI呈等、低信号改变,T2WI呈混杂信号,增强扫描呈不同程度均匀强化。结论:MRI能有效显示骨巨细胞瘤的病变部位及范围,。     

Performance of Thyroid-Stimulating Immunoglobulin Bioassay and Thyrotropin-Binding Inhibitory Immunoglobulin Assay for the Diagnosis of Graves' Disease in Patients With Active Thyrotoxicosis

ObjectiveGraves' disease (GD) is caused by the stimulation of thyrotropin receptors by autoantibodies. We compared the diagnostic accuracy of the thyroid-stimulating immunoglobulin (TSI) bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) assay in differentiating GD from other causes of thyrotoxicosis.MethodsWe retrospectively evaluated 493 patients with thyrotoxicosis who were tested with the third-generation TSI and TBII assays simultaneously. Patients were classified according to the clinical, histopathologic, and imaging criteria into the following groups: positive reference group (PRG) (patients with GD), negative reference group (NRG) (patients without GD), and inconclusive group (patients without a definitive diagnosis).ResultsTSI and TBII assays were concordant in 88% of the cases and showed a strong positive correlation (r_s = 0.844, P < .01). When analyzed collectively, TSI and TBII assays confirmed the diagnosis of GD in 79% of the PRG cases and excluded GD in 92.5% of patients in NRG. Combined TSI and TBII assays or TBII assay alone showed similar accuracy to the diagnosis of GD (81.4% and 77.5%, respectively). Tests in 40 of 191 patients in PRG were negative for both TSI and TBII assays, whereas 3 of 40 cases in NRG had at least 1 positive thyrotropin receptor antibody test. False-negative cases were associated with subclinical hyperthyroidism, normal radionuclide uptake, longer duration of thyrotoxicosis, and absence of goiter or Graves' ophthalmopathy.ConclusionTSI and TBII assays showed similar performance in differentiating GD from other causes of thyrotoxicosis in a real-world sample of patients with active thyrotoxicosis. In combination, both tests showed little benefit compared with the TBII assay alone. Thyrotropin receptor antibody assay results should be carefully interpreted in patients with mild GD or longstanding disease.     

Peak Systolic Velocity of Superior Thyroid Artery for the Differential Diagnosis of Thyrotoxicosis

Aim

The differentiation of destruction-induced thyrotoxicosis and Graves’ disease (GD) is of great importance for selection of proper therapy. Radioactive iodine uptake (RAIU) is the gold standard for differentiating these two conditions but its application has remained somewhat limited. Thyroid color Doppler flow sonography (CDFS) is a potential alternative of RAIU but more supporting evidence is warranted. In the present study, a standard operative procedure was developed to measure the mean peak systolic velocity of superior thyroid artery (STA-PSV) and evaluate its role in the differential diagnosis of thyrotoxicosis.

Methods

A total of 135 patients with untreated thyrotoxicosis were enrolled into one retrospective study (GD, n = 103; thyroiditis, n = 32) and another prospective study recruited 169 patients (GD, n = 118; thyroiditis, n = 51). Thirty normal controls were also enrolled. Thyroid function, anti-TSH-receptor antibody (TRAb), RAIU, CFDS of thyroid and STA-PSV were performed for each patient. Receiver operator curve (ROC) was used to evaluate the diagnostic value of STA-PSV in a retrospective study so as to seek the optimal cutoff point. Then the cutoff point value was used to validate its diagnostic value in a prospective study and in another thyrotoxicosis population.

Results

STA-PSV of GD was significantly higher than that of thyroiditis in both retrospective and prospective studies. The area under the ROC curve of mean STA-PSV was 0.8799 and 0.9447 in the retrospective and prospective studies respectively. If a mean STA-PSV cutoff point of 50.5 cm/s was set from the retrospective analysis for the prospective study, the sensitivity and specificity in distinguishing GD from thyroiditis were 81.04% and 96.08% respectively. Mean STA-PSV and TRAb had similar area under ROC. The coefficients of variation in STA-PSV measurement were lower than 10% for the euthyroid, thyroiditis and GD groups.

Conclusions

STA-PSV is a feasible supplement alternative of RAIU for differentiating the causes of thyrotoxicosis.