RESUMO
OBJECTIVE: To determine patterns of adverse drug reactions (ADRs), including immediate drug hypersensitivity reactions (DHRs) and predictable ADRs, to thyroid replacement therapy (TRT). TRT is the treatment of choice for hypothyroidism. Levothyroxine (LT4) is among the most commonly prescribed medications in the United States, with over 70 million prescriptions annually. Documented immediate DHRs to TRT are rare, with only a few case reports. METHODS: An 11-year (2008-2018) retrospective medical chart review of identified patients with self-reported allergy to TRT. ADRs to TRT were divided into immediate DHRs and predictable ADRs. RESULTS: A total of 466 patients were included in our study. We found an overall incidence of ADRs to TRT of 0.3%. Median age was 61.2 years; 85.8% were women, and 94.4% were Caucasian. The principal indication for TRT was autoimmune hypothyroidism (73.6%), followed by postsurgical hypothyroidism (17.4%) and subclinical hypothyroidism (6.7%). Predictable ADR manifestations to TRT were reported more commonly than DHR manifestations (57.5% vs. 42.5%, respectively). The most frequently reported of the former were palpitations (16.4%), nausea/vomiting (9.3%), and tremor (6.3%), while rash (23.8%), hives (9.5%), and pruritus (7.1%) were the most common regarding the latter. Fifty-six percent of the patients with an ADR to TRT tolerated an alternative TRT presentation. CONCLUSION: In our cohort, the majority of self-reported allergies to TRT were due to predictable ADRs rather than an immediate DHR. ABBREVIATIONS: ADR = adverse drug reaction; DHR = drug hypersensitivity reaction; FDA = Food and Drug Administration; LT3 = liothyronine; LT4 = levothyroxine; SCAR = severe cutaneous adverse drug reaction; TRT = thyroid replacement therapy.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipersensibilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Autorrelato , Tiroxina/efeitos adversosRESUMO
OBJECTIVE: There is much reported variation in the impact of local anesthesia on thyroid fine-needle aspiration (FNA) related discomfort. We compare patients undergoing thyroid FNA with subcutaneous injection or topical anesthetic to no anesthetic. METHODS: We conducted a retrospective review of 585 sequential ultrasound guided thyroid FNA procedures in Mayo Clinic. Group 1 (n = 200), no anesthetic; Group 2 (n = 185), subcutaneous injection anesthetic; and Group 3 (n = 200), topical anesthetic. Patient demographics, number of FNA passes, needle gauge, and cytopathology were recorded plus a discomfort score (0 to 10) before and immediately post procedure in all 3 groups and peak discomfort during the FNA in Groups 1 and 2. RESULTS: There were no differences among the 3 groups in age, sex, FNA sufficiency rate, cytopathology, and FNA passes number. There was no significant difference between Groups 1 and 2 in peak discomfort score during the FNA: 0 (45%, 42.2%), 1 to 2 (19%, 24.9%), 3 to 5 (23.5%, 20.5%), 6 to 8 (9.5%, 10.8%), 9 to 10 (3%, 1.6%), respectively. Discomfort score post procedure: 0 (78.5%, 77.8%, 53.5%), 1 to 2 (13%, 13%, 36.5%), 3 to 5 (7%, 7%, 9%), 6 to 8 (1.5%, 2.2%, 1%), 9 to 10 (0%, 0%, 0%) for groups 1, 2, and 3, respectively. There were no significant differences among the 3 groups for a discomfort score ≥3. CONCLUSION: FNA associated patient discomfort was comparable during and after the procedure regardless of the use of anesthetic or the type utilized. Approximately 90% of patients experienced mild to moderate discomfort during the procedure. And 90% reported no more than a level 2 discomfort post procedure. ABBREVIATIONS: End = endocrinology; FNA = fine-needle aspiration; MCF = Mayo Clinic Florida; MCR = Mayo Clinic Rochester.
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Anestésicos Locais , Nódulo da Glândula Tireoide , Anestesia Local , Biópsia por Agulha Fina , Humanos , Estudos RetrospectivosRESUMO
Thyroid disorders and diabetes mellitus often coexist and are closely related. Several studies have shown a higher prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. Thyroid hormone affects glucose homeostasis by impacting pancreatic ß-cell development and glucose metabolism through several organs such as the liver, gastrointestinal tract, pancreas, adipose tissue, skeletal muscles, and the central nervous system. The present review discusses the effect of thyroid hormone on glucose homeostasis. We also review the relationship between thyroid disease and diabetes mellitus: type 1, type 2, and gestational diabetes, as well as guidelines for screening thyroid function with each disorder. Finally, we provide an overview of the effects of antidiabetic drugs on thyroid hormone and thyroid disorders.
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Diabetes Mellitus Tipo 2 , Doenças da Glândula Tireoide , Diabetes Mellitus Tipo 2/complicações , Glucose/metabolismo , Homeostase , Humanos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Hormônios TireóideosRESUMO
Thyroid nodules (TN) are prevalent in the general population and represent a common complaint in clinical practice. Most are asymptomatic and are associated with a 7%-15% risk of malignancy (1). Methods: PubMed and Medline were searched for articles with a focus on the epidemiology, diagnosis, and management of TN over the past 5 y. Results: The increase in frequency of imaging has led to a rise in the incidence of incidentally diagnosed TN. The initial evaluation of a TN includes assessing thyroid function, clinical risk factors, and neck imaging. Ultrasound remains the gold standard for assessing TN morphology, and biopsy is the standard method for determining whether a TN is benign. Recently published risk stratification systems using morphologic characteristics on ultrasonography have been effective in reducing the number of unnecessary biopsies. Advances in molecular testing have reduced the number of surgical procedures performed for diagnostic purposes on asymptomatic TN with indeterminate cytology. Scintigraphy is the first-line study for assessing a hyperfunctioning nodule. Many TN can be followed clinically or with serial ultrasound after the initial diagnosis. Surgical intervention is warranted when local symptoms are present, in patients with clinical risk factors, as well as in most situations with malignant cytology. Active surveillance is an option in cases of micropapillary thyroid cancer. Emerging nonsurgical approaches for treating TN include ethanol ablation for TN; sclerotherapy for thyroid cysts; and thermal techniques, such as radiofrequency ablation, laser ablation, microwaves, and high-intensity focused ultrasound. Conclusion: Most TN are benign and can be safely monitored. The indications for biopsy and frequency of imaging should be tailored on the basis of risk stratification. Treatment options should be individualized for each patient's particular situation. Active surveillance should be considered in certain cases of papillary microcarcinoma.
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Nódulo da Glândula Tireoide , Adulto , Carcinoma Papilar , Humanos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide , UltrassonografiaRESUMO
Background: The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. Summary: In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. Conclusions: The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.
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Radioisótopos do Iodo , Medicina de Precisão , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Consenso , Humanos , Medição de RiscoRESUMO
Thyroid hormone (TH) plays an essential role in human physiology and maintenance of appropriate levels is important for good health. Unfortunately, there are instances in which TH is misused or abused. Such misuse may be intentional such as when individuals take thyroid hormone for unapproved indications like stimulation of weight loss or improved energy. There are instances where healthcare providers prescribe thyroid hormone for controversial or out of date uses and sometimes in supraphysiologic doses. Othertimes, unintentional exposure may occur through supplements or food that unknowingly contain TH. No matter the reason, exposure to exogenous forms of TH places the public at risk for potential adverse side effects.
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Uso Indevido de Medicamentos sob Prescrição , Hormônios Tireóideos , HumanosRESUMO
BACKGROUND: Publication of the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer was met with disagreement by the extended nuclear medicine community with regard to some of the recommendations related to the diagnostic and therapeutic use of radioiodine (131I). Because of these concerns, the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging declined to endorse the ATA guidelines. As a result of these differences in opinion, patients and clinicians risk receiving conflicting advice with regard to several key thyroid cancer management issues. SUMMARY: To address some of the differences in opinion and controversies associated with the therapeutic uses of 131I in differentiated thyroid cancer constructively, the ATA, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association each sent senior leadership and subject-matter experts to a two-day interactive meeting. The goals of this first meeting were to (i) formalize the dialogue and activities between the four societies; (ii) discuss indications for 131I adjuvant treatment; (iii) define the optimal prescribed activity of 131I for adjuvant treatment; and (iv) clarify the definition and classification of 131I-refractory thyroid cancer. CONCLUSION: By fostering an open, productive, and evidence-based discussion, the Martinique meeting restored trust, confidence, and a sense of collegiality between individuals and organizations that are committed to optimal thyroid disease management. The result of this first meeting is a set of nine principles (The Martinique Principles) that (i) describe a commitment to proactive, purposeful, and inclusive interdisciplinary cooperation; (ii) define the goals of 131I therapy as remnant ablation, adjuvant treatment, or treatment of known disease; (iii) describe the importance of evaluating postoperative disease status and multiple other factors beyond clinicopathologic staging in 131I therapy decision making; (iv) recognize that the optimal administered activity of 131I adjuvant treatment cannot be definitely determined from the published literature; and (v) acknowledge that current definitions of 131I-refractory disease are suboptimal and do not represent definitive criteria to mandate whether 131I therapy should be recommended.
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Diferenciação Celular , Radioisótopos do Iodo/uso terapêutico , Radioterapia (Especialidade)/normas , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Consenso , Medicina Baseada em Evidências/normas , Humanos , Radioisótopos do Iodo/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Neoplasias da Glândula Tireoide/patologiaRESUMO
OBJECTIVE: To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. METHODS: Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. RESULTS: Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. CONCLUSION: All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements.
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Corticosteroides/análise , Suplementos Nutricionais/análise , Medicamentos sem Prescrição/análise , Hormônios Tireóideos/análise , Animais , Humanos , Estados UnidosRESUMO
BACKGROUND: Hypoparathyroidism (hypoPT) is the most common complication following bilateral thyroid operations. Thyroid surgeons must employ strategies for minimizing and preventing post-thyroidectomy hypoPT. The objective of this American Thyroid Association Surgical Affairs Committee Statement is to provide an overview of its diagnosis, prevention, and treatment. SUMMARY: HypoPT occurs when a low intact parathyroid hormone (PTH) level is accompanied by hypocalcemia. Risk factors for post-thyroidectomy hypoPT include bilateral thyroid operations, autoimmune thyroid disease, central neck dissection, substernal goiter, surgeon inexperience, and malabsorptive conditions. Medical and surgical strategies to minimize perioperative hypoPT include optimizing vitamin D levels, preserving parathyroid blood supply, and autotransplanting ischemic parathyroid glands. Measurement of intraoperative or early postoperative intact PTH levels following thyroidectomy can help guide patient management. In general, a postoperative PTH level <15 pg/mL indicates increased risk for acute hypoPT. Effective management of mild to moderate potential or actual postoperative hypoPT can be achieved by administering either empiric/prophylactic oral calcium and vitamin D, selective oral calcium, and vitamin D based on rapid postoperative PTH level(s), or serial serum calcium levels as a guide. Monitoring for rebound hypercalcemia is necessary to avoid metabolic and renal complications. For more severe hypocalcemia, inpatient management may be necessary. Permanent hypoPT has long-term consequences for both objective and subjective well-being, and should be prevented whenever possible.
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Hipoparatireoidismo/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Tireoidectomia/efeitos adversos , Humanos , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/prevenção & controle , Hipoparatireoidismo/terapia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapiaRESUMO
The newly introduced pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) will result in less bilateral thyroid surgery as well as deescalation in T4 suppressive and radioactive iodine treatment. Although, NIFTP is a nonmalignant lesion that has nuclear features of some papillary malignancies, the challenge for the surgeon is to identify a lesion as possibly NIFTP before the pathologic diagnosis. NIFTP, due to its reduction of overall rates of malignancy, will result in the initial surgical pendulum swinging toward lobectomy instead of initial total thyroidectomy. This American Head and Neck Society endocrine section consensus statement is intended to inform preoperative evaluation to attempt to identify those patients whose final pathology report may ultimately harbor NIFTP and can be offered a conservative surgical plan to assist in cost-effective, optimal management of patients with NIFTP.
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Carcinoma Papilar, Variante Folicular/diagnóstico , Carcinoma Papilar, Variante Folicular/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Carcinoma Papilar, Variante Folicular/etiologia , Humanos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Neoplasias da Glândula Tireoide/etiologiaRESUMO
PURPOSE: Previous studies suggest the association of recipient hepatitis C seropositivity (HCV+) and use of tacrolimus (TAC) with post-transplant diabetes mellitus (PTDM) may differ by manifestations of type I or type II diabetes, but this has not been assessed in the era of current immunosuppression. METHODS: We performed a retrospective cohort study of 10,342 Medicare primary renal transplantation recipients without evidence of diabetes at the time of listing in the United States Renal Data System between January 1, 1998 and July 31, 2000, followed until December 31, 2000. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS). Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for time to DKA or HHS, stratified by diabetes status at the time of transplant. RESULTS: In Cox regression analysis, use of TAC at discharge was independently associated with shorter time to DKA (AHR, 1.88; 95% CI, 1.05-3.37, p=0.034) but not HHS. In contrast, recipient HCV+ was independently associated with shorter time to HHS (AHR, 3.90; 1.59-9.60, p=.003), but not DKA. There was no interaction between TAC and HCV+ for either outcome. CONCLUSION: These results confirm earlier findings that TAC and HCV+ may mediate the risk of PTDM through different mechanisms, even in the modern era.
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Diabetes Mellitus/etiologia , Hepatite C/epidemiologia , Hospitalização/estatística & dados numéricos , Imunossupressores/efeitos adversos , Transplante de Rim , Tacrolimo/efeitos adversos , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Estados UnidosRESUMO
A 28-year-old trumpet player underwent multiple treatments with radioactive iodine for Graves disease associated with an unusually large goiter. Following his second treatment, the patient developed acute neck pain and swelling. Radiographic studies and a laryngoscopy demonstrated bilateral symptomatic external laryngoceles, a very rare entity, not previously known to be associated with radioiodine treatment or Graves disease. The patient's profession placed him at risk for the development of a laryngocele, but the temporal relationship to goiter regression following radioiodine therapy suggests that this occurred as a result of this treatment. The patient's disease was managed nonsurgically, and he has subsequently done well. This represents the first known association of symptomatic laryngocele with radioiodine treatment for Graves disease.
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Doença de Graves/complicações , Doença de Graves/radioterapia , Radioisótopos do Iodo/uso terapêutico , Laringe/anormalidades , Adulto , Bócio Subesternal/complicações , Bócio Subesternal/radioterapia , Humanos , Masculino , Falha de TratamentoRESUMO
CONTEXT: Hürthle cell cancer (HCC) of the thyroid remains the subject of controversy with respect to natural course, treatment, and follow-up. OBJECTIVE: The objective of the study was to evaluate the clinical and molecular features associated with outcome in HCC. DESIGN: The study was a review of 173 HCC cases treated at Mayo Clinic over 11 years with a median 5.8-year follow-up. RESULTS: None of the patients with minimally invasive histology had persistent disease, clinical recurrence, or disease-related death. Male gender and TNM stage were independently associated with increased risk of clinical recurrence or death in widely invasive patients. The 5-year cumulative probability of clinical recurrence or death was higher in patients with TNM stage III-IV (females, 74%; males, 91%) compared with patients with TNM stage I-II (females, 0%; males, 17%). Pulmonary metastases were best identified by computed tomography, whereas radioactive iodine scans were positive in only two of 27 cases. Thyroglobulin was detectable in patients with clinical disease, with the notable exception of five patients with distant metastases. The common TERT C228T promoter mutation was detected in both widely invasive and minimally invasive tumors. TERT mRNA was below the limit of detection in all samples. CONCLUSION: Widely invasive HCC with TNM stage III-IV is aggressive, with low probability of recurrence-free survival. Males have worse outcomes than females. Minimally invasive HCC appears to be considerably less aggressive. Radioactive iodine scan performs poorly in detecting distant disease. Although the TERT gene is mutated in HCC, the role of this mutation remains to be demonstrated.
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Adenocarcinoma Folicular/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Regiões Promotoras Genéticas , Estudos Retrospectivos , Fatores Sexuais , Telomerase/genética , Telomerase/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Adulto JovemRESUMO
Galectin-3, a lectin-family protein that appears to be involved in malignant transformation, has been reported to be an accurate immunohistochemical marker for thyroid cancer. However, immunohistochemistry is a subjective method that can be difficult to apply to cytologic specimens. Therefore, we sought to develop an objective and quantitative assay to measure galectin-3 mRNA in thyroid tissue to enhance potential clinical use of galectin-3 in the molecular analysis of thyroid nodules. In this study, total RNA from 37 snap-frozen thyroid tissue specimens was isolated from eight papillary and nine follicular thyroid cancers, six follicular adenomas, seven adenomatoid nodules, and seven normal thyroid lobes from patients undergoing thyroidectomy. Normalized levels of galectin-3 mRNA, expressed as picograms per nanogram GAPDH mRNA, were higher in papillary carcinomas (3327 pg/ng) and follicular adenomas (1314 pg/ng) than in thyroid normal tissue (426 pg/ng; P = 0.0012 and 0.032, respectively). Galectin-3 mRNA levels were also higher in papillary cancers than in adenomatoid nodules (P = 0.0012). However, galectin-3 mRNA levels were not statistically greater in follicular carcinomas than either normal tissue or follicular adenomas (P = 0.068 and 0.12, respectively). In summary, in comparison to galectin-3 immunohistochemistry, quantitative measurement of galectin-3 mRNA appears useful in the identification of papillary thyroid cancers (PTCs) but does not appear to be useful in distinguishing follicular carcinomas from follicular adenomas.
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Antígenos de Diferenciação/genética , Carcinoma Papilar/diagnóstico , Expressão Gênica , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/diagnóstico , Adenocarcinoma Folicular/química , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/patologia , Adenoma/química , Adenoma/diagnóstico , Adenoma/patologia , Antígenos de Diferenciação/análise , Biópsia por Agulha , Carcinoma Papilar/química , Carcinoma Papilar/patologia , Diagnóstico Diferencial , Galectina 3 , Gliceraldeído-3-Fosfato Desidrogenases/genética , Humanos , Imuno-Histoquímica , Glândula Tireoide/química , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/patologiaRESUMO
The development of distant metastasis is the most important predictor of death from thyroid cancer. KiSS-1 is a recently cloned human metastasis suppressor gene whose product, metastin, was recently identified as the endogenous agonist for a novel Gq/11 coupled receptor (metastin receptor). The expression and functional consequences of metastin and the metastin receptor have not been evaluated in thyroid cancer. We measured metastin and metastin receptor mRNA levels in 10 FCs and 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas (FAs), and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Paired normal and tumor samples were available for 4 PC and 3 PFC samples. Metastin mRNA was detected in 6/11 normal samples, and 0/2 FA, 2/10 FC, and 9/13 PC samples (p < 0.05 for PC vs. FC). Metastin receptor was not expressed in any normal thyroid or benign FA samples, and was expressed in only a minority (2/10) of FC samples. However, the receptor was expressed in the majority (10/13) of PCs (p = 0.002 for PC vs. normal tissue). Increased levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. Taken together, these data suggest a potential role for metastin and/or metastin receptors in modulating the biological behavior of thyroid cancers.
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Carcinoma Papilar/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Receptores de Superfície Celular/fisiologia , Receptores de Neuropeptídeos , Neoplasias da Glândula Tireoide/metabolismo , Ativação Enzimática/fisiologia , Humanos , Receptores Acoplados a Proteínas G , Receptores de Kisspeptina-1 , Valores de Referência , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Células Tumorais CultivadasRESUMO
The paired box-8 protein (Pax-8) has been observed in the nucleus of normal adult thyroids, follicular adenomas, follicular thyroid cancers, and papillary thyroid cancers (PTC) but not undifferentiated thyroid cancers. To our knowledge, Pax-8 has not been studied in pediatric thyroid cancer. Because of the more favorable prognosis for PTC in children compared to young patients, we hypothesized that Pax-8 expression might be different in pediatric thyroid cancers. To test this, we stained 47 thyroid lesions from children and young patients for Pax-8. Pax-8 was located in the cytoplasm (cPAX) or nucleus (nPAX) in the majority of samples. There was no significant difference in nPAX between benign and malignant lesions. However, cPAX was more commonly seen in PTC than autoimmune diseases (p = 0.01) and the intensity of cPAX staining correlated with tumor size (p = 0.041), metastasis, age, completeness of resection, local invasion, and tumor size (MACIS) scores (p = 0.045), and the presence of invasion, metastasis, recurrence, or persistence (p = 0.012). Disease-free survival was significantly reduced for cancers with intense cPAX staining (p = 0.0003). These data show that cPAX is common in PTC, and although limited by small sample size, suggest an association with higher MACIS scores, an aggressive clinical course, and an increased risk of clinically evident recurrence for children and young patients.
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Citoplasma/patologia , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Neoplasias da Glândula Tireoide/patologia , Transativadores/genética , Adolescente , Adulto , Biomarcadores Tumorais , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Criança , Citoplasma/metabolismo , Citoplasma/ultraestrutura , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Recidiva Local de Neoplasia/epidemiologia , Fator de Transcrição PAX8 , Fatores de Transcrição Box Pareados , Risco , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/ultraestruturaRESUMO
BACKGROUND: The incidence and risk factors for diabetic ketoacidosis (diabetic ketoacidosis) and hyperglycemic hyperosmolar syndrome (hyperglycemic hyperosmolar syndrome, previously called non-ketotic hyperosmolar coma) have not been reported in a national population of renal transplant (renal transplantation) recipients. METHODS: We performed a historical cohort study of 39,628 renal transplantation recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998, followed until 31 Dec 1999. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (ICD-9 code 250.1x) and hyperglycemic hyperosmolar syndrome (code 250.2x). Cox Regression analysis was used to calculate adjusted hazard ratios for time to hospitalization for diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. RESULTS: The incidence of diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were 33.2/1000 person years (PY) and 2.7/1000 PY respectively for recipients with a prior diagnosis of diabetes mellitus (DM), and 2.0/1000 PY and 1.1/1000 PY in patients without DM. In Cox Regression analysis, African Americans (AHR, 2.71, 95 %CI, 1.96-3.75), females, recipients of cadaver kidneys, patients age 33-44 (vs. >55), more recent year of transplant, and patients with maintenance TAC (tacrolimus, vs. cyclosporine) had significantly higher risk of diabetic ketoacidosis. However, the rate of diabetic ketoacidosis decreased more over time in TAC users than overall. Risk factors for hyperglycemic hyperosmolar syndrome were similar except for the significance of positive recipient hepatitis C serology and non-significance of female gender. Both diabetic ketoacidosis (AHR, 2.44, 95% CI, 2.10-2.85, p < 0.0001) and hyperglycemic hyperosmolar syndrome (AHR 1.87, 95% CI, 1.22-2.88, p = 0.004) were independently associated with increased mortality. CONCLUSIONS: We conclude that diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were associated with increased risk of mortality and were not uncommon after renal transplantation. High-risk groups were identified.
RESUMO
OBJECTIVE: To present a case of papillary thyroid carcinoma and the need for follow-up surveillance in a patient with type 2 diabetes mellitus who was being treated with metformin. METHODS: The clinical and laboratory findings are summarized, and results of whole-body scanning are described. A discussion addresses the importance of monitoring renal function during thyroid hormone withdrawal for scintigraphic imaging with use of radioactive iodine. RESULTS: A 60-year-old man with type 2 diabetes was diagnosed with metastatic papillary thyroid carcinoma, and renal insufficiency developed during withdrawal from thyroid hormone for surveillance 131 I whole-body scanning. An increase in thyroglobulin attributable to recombinant human thyrotropin stimulation led to detection of persistent cancer, and thyroid hormone withdrawal was begun in preparation for further 131 I treatment. Pretherapy laboratory results revealed a thyrotropin level of 46.1 mIU/mL, a thyroglobulin level of 13.7 ng/mL, and an increased serum creatinine (Cr) concentration from a baseline of 0.9 mg/dL to 1.9 mg/dL while the creatinine clearance (CrCl) was 67 mL/min. Therapy with metformin was immediately discontinued. On the basis of results from 131 I whole-body dosimetry, the patient was treated with 250 mCi of 131 I. Levothyroxine therapy was resumed approximately 72 hours after 131 I therapy, and blood tests 2 weeks thereafter revealed a Cr of 1.1 mg/dL and a CrCl of 105 mL/min. The metformin treatment was then reinitiated without any complications. CONCLUSION: Patients with hypothyroidism can have up to a 20 to 30% decrease in glomerular filtration rate, which tends to resolve when euthyroidism is achieved. In patients with diabetes taking metformin who have hypothyroidism for any reason including thyroid hormone withdrawal, serum Cr levels should be monitored until thyroid hormone levels normalize. Metformin therapy should be discontinued in patients with significant renal impairment, defined as either a serum Cr level of 1.5 mg/dL or more in men and 1.4 mg/dL or more in women or a CrCl of less than 60 mL/min.
Assuntos
Adenocarcinoma Papilar/diagnóstico por imagem , Insuficiência Renal/etiologia , Hormônios Tireóideos/efeitos adversos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Suspensão de Tratamento , Adenocarcinoma Papilar/complicações , Adenocarcinoma Papilar/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Técnicas de Diagnóstico por Radioisótopos , Humanos , Hipoglicemiantes/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Esvaziamento Cervical , Cintilografia , Compostos Radiofarmacêuticos/uso terapêutico , Testes de Função Tireóidea/métodos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/terapia , TireoidectomiaRESUMO
BACKGROUND: Goiter, or benign enlargement of the thyroid gland, can be asymptomatic or can cause compression of surrounding structures such as the esophagus and/or trachea. The options for medical treatment of euthyroid goiter are short-lived and are limited to thyroxine hormone suppression and radioactive iodine ablation. The objective of this statement article is to discuss optimal surgical management of goiter. METHODS: A task force was convened by the Surgical Affairs Committee of the American Thyroid Association and was tasked with writing of this article. RESULTS/CONCLUSIONS: Surgical management is recommended for goiters with compressive symptoms. Symptoms of dyspnea, orthopnea, and dysphagia are more commonly associated with thyromegaly, in particular, substernal goiters. Several studies have demonstrated improved breathing and swallowing outcomes after thyroidectomy. With careful preoperative testing and thoughtful consideration of the type of anesthesia, including the type of intubation, preparation for surgery can be optimized. In addition, planning the extent of surgery and postoperative care are necessary to achieve optimal results. Close collaboration of an experienced surgical and anesthesia team is essential for induction and reversal of anesthesia. In addition, this team must be cognizant of complications from massive goiter surgery such as bleeding, airway distress, recurrent laryngeal nerve injury, and transient hypoparathyroidism. With careful preparation and teamwork, successful thyroid surgery can be achieved.
Assuntos
Bócio Nodular/cirurgia , Glândula Tireoide/cirurgia , Bócio Nodular/diagnóstico por imagem , Bócio Subesternal/diagnóstico por imagem , Bócio Subesternal/cirurgia , Humanos , Glândula Tireoide/diagnóstico por imagem , Tireoidectomia/métodos , UltrassonografiaRESUMO
BACKGROUND: As defined by the Dietary Supplement Health and Education Act 1997, such substances as herbs and dietary supplements fall under general Food and Drug Administration supervision but have not been closely regulated to date. We examined the thyroid hormone content in readily available dietary health supplements marketed for "thyroid support." METHODS: Ten commercially available thyroid dietary supplements were purchased. Thyroid supplements were dissolved in 10 mL of acetonitrile and water with 0.1% trifloroacetic acid and analyzed using high-performance liquid chromatography for the presence of both thyroxine (T4) and triiodothyronine (T3) using levothyroxine and liothyronine as a positive controls and standards. RESULTS: The amount of T4 and T3 was measured separately for each supplement sample. Nine out of 10 supplements revealed a detectable amount of T3 (1.3-25.4 µg/tablet) and 5 of 10 contained T4 (5.77-22.9 µg/tablet). Taken at the recommended dose, 5 supplements delivered T3 quantities of greater than 10 µg/day, and 4 delivered T4 quantities ranging from 8.57 to 91.6 µg/day. CONCLUSIONS: The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of alterations in thyroid levels even to the point of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products, which hold potential danger to public health.