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Context: Apalutamide (APT) is a nonsteroidal antiandrogen medication used to treat metastatic castrate-sensitive and nonmetastatic castrate-resistant prostate cancer. Early clinical trials of APT identified thyroid dysfunction as a common adverse effect of therapy, but the clinical presentation and management of APT-induced hypothyroidism has not been studied. Objective: The objective of our study is to elucidate the clinical presentation and treatment approach of APT-associated thyroid dysfunction in prostate cancer patients. Methods: We report a case series of 16 patients with APT-associated thyroid dysfunction during prostate cancer treatment at 2 academic medical centers. Patient clinical parameters, thyroid function laboratory data, and thyroid hormone requirements over the course of APT treatment were analyzed. Results: Among the 16 patients in our case series with APT-associated hypothyroidism, 3 had no prior thyroid disease and 13 had preexisting hypothyroidism. The patterns of thyroid dysfunction included overt and subclinical hypothyroidism. The median time from APT initiation to thyroid function test abnormality was 19 weeks, but occurred in some cases as early as 2 to 4 weeks. Hypothyroidism was effectively managed with thyroid hormone replacement using levothyroxine (LT4), though some patients with preexisting hypothyroidism required a 2- to 3-fold dose increase while on APT to achieve a euthyroid state. In the subset of patients who completed or stopped APT therapy, thyrotropin levels fell at a median of 11 weeks post APT therapy and thyroid hormone requirements decreased to near pre-APT levels. Conclusion: APT-associated thyroid dysfunction presents as new or worsening hypothyroidism and should prompt initiation or increase in thyroid hormone replacement. Monitoring of thyroid function tests is recommended every 1 to 2 months for all patients on APT and 2 to 3 months after completion of APT.
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Objective: To understand the quality of informational Graves' disease (GD) videos on YouTube for treatment decision-making quality and inclusion of American Thyroid Association (ATA) treatment guidelines. Study Design: Cross-sectional cohort. Setting: Informational YouTube videos with subject matter "Graves' Disease treatment." Method: The top 50 videos based on our query were assessed using the DISCERN instrument. This validated algorithm discretely rates treatment-related information from excellent (≥4.5) to very poor (<1.9). Videos were also screened for ATA guideline inclusion. Descriptive statistics were used for cohort characterization. Univariate and multivariate linear regressions characterized factors associated with DISCERN scores. Significance was set at P < .05. Results: The videos featured 57,513.43 views (SD = 162,579.25), 1054.70 likes (SD = 2329.77), and 168.80 comments (SD = 292.97). Most were patient education (52%) or patient experience (24%). A minority (40%) were made by thyroid specialists (endocrinologists, endocrine surgeons, or otolaryngologists). Under half did not mention all 3 treatment modalities (44%), and 54% did not mention any ATA recommendations. Overall, videos displayed poor reliability (mean = 2.26, SD = 0.67), treatment information quality (mean = 2.29, SD = 0.75), and overall video quality (mean = 2.47, SD = 1.07). Physician videos were associated with lower likes, views, and comments (P < .001) but higher DISCERN reliability (P = .015) and overall score (P = .019). Longer videos (P = .015), patient accounts (P = .013), and patient experience (P = .002) were associated with lower scores. Conclusion: The most available GD treatment content on YouTube varies significantly in the quality of medical information. This may contribute to suboptimal disease understanding, especially for patients highly engaged with online health information sources.
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Introduction: In 2020, teprotumumab became the first FDA-approved treatment for thyroid eye disease (TED). In clinical trials, hyperglycemia had been described as mild and controlled with medication. We present a case that occurred in 2020 of a 67-year-old male with TED and pre-existing glucose intolerance, who was hospitalized with severe hyperglycemia (1,059 mg/dL) after three doses of teprotumumab. Case Presentation: This patient's HbA1c was in the pre-diabetic range (6.3%) 6 months prior to initiating teprotumumab. After three doses, the patient was hospitalized with hyperosmolar hyperglycemic nonketotic syndrome and an HbA1c of 11.7%. He was diagnosed with type 2 diabetes mellitus and treated with insulin aspart mixed 70/30. He remained on this regimen for 14 months with an A1c of 6.0%. He then self-discontinued the insulin, with an A1c 4 months later measuring 5.5%. The patient's latest HbA1c approximately two and a half years after hospitalization was 6.1% on no medications. Conclusion: It appears that teprotumumab was a trigger for this transient case of diabetes, and detecting those that have underlying glucose intolerance ahead of time is important. We recommend blood glucose levels for patients with pre-diabetes prior to and ideally in the first few days after each infusion, to help determine patients at a greater risk for adverse hyperglycemic outcomes. A glucometer may be valuable for patients to self-monitor while on teprotumumab. If fasting blood glucose is ≥126 mg/dL or non-fasting glucose is >200 mg/dL, patients should be referred for further diabetes assessment and possible treatment initiation.
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Importance: Standard treatment for patients with medullary thyroid cancer (MTC) consists of total thyroidectomy with central neck dissection, but the rationale for bilateral surgery in patients with unilateral disease on ultrasonography remains unclear. Objective: To determine the presence of occult contralateral disease (lesions not seen on preoperative ultrasonography) in patients with MTC as a rationale for total thyroidectomy. Design, Setting, and Participants: This multi-institutional, retrospective cohort study was conducted from September 1998 to April 2022 in academic medical centers and included patients with MTC who underwent thyroidectomy with preoperative imaging. Main Outcomes and Measures: The primary end point was the prevalence of sonographically occult foci of MTC in the contralateral lobe among patients with sporadic MTC. Results: The cohort comprised 176 patients with a median age at diagnosis of 55 years (range, 2-87 years), 69 (57.6%) of whom were female. Genetic testing was performed in 109 patients (61.9%), 48 (27.5%) of whom carried germline RET variants. Initial surgical management consisted of total thyroidectomy (161 [91.0%]), lobectomy followed by completion thyroidectomy (7 [4.0%]), and lobectomy alone (8 [4.5%]). Central and lateral neck dissections were performed as part of initial therapy for 146 patients (83.1%). In the entire cohort of 176 patients, 46 (26.0%) had contralateral foci disease and 9 (5.1%) had occult contralateral foci that were not identified on preoperative ultrasonography. Among 109 patients who underwent genetic testing, 38 (34.9%) had contralateral disease, 8 (7.3%) of whom had occult contralateral disease not seen on preoperative ultrasonography. Patients with sporadic MTC experienced a 95.7% reduction in the odds of having a focus of MTC in the contralateral lobe compared with patients with a germline RET variant (odds ratio, 0.043; 95% CI, 0.013-0.123). When adjusting for age, sex, tumor size, and lymph node involvement, the odds ratio of having contralateral MTC in patients with sporadic disease was 0.034 (95% CI, 0.007-0.116). Among patients who underwent lobectomy alone with postoperative calcitonin levels, 5 of 12 (41.7%) achieved undetectable calcitonin levels (<2.0 pg/mL; to convert to pmol/L, multiply by 0.292). Conclusions and Relevance: The results of this cohort study suggest that a staged approach involving initial thyroid lobectomy could be considered in patients with sporadic MTC and no contralateral ultrasonography findings, with no further surgery if calcitonin levels became undetectable. Further work using prospective randomized clinical trials to evaluate lobectomy as a biochemical cure in patients presenting with unilateral disease is warranted.
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Carcinoma Medular , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Tireoidectomia/métodos , Calcitonina , Estudos de Coortes , Estudos Retrospectivos , Estudos Prospectivos , Prevalência , Carcinoma Medular/genética , Carcinoma Medular/patologia , Carcinoma Medular/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/genéticaRESUMO
Background: Hypothyroidism is a common endocrine condition and chronic thyroid hormone deficiency is associated with adverse effects across multiple organ systems. In compensated hypothyroidism, however, patients remain clinically stable due to gradual physiological adaptation. In contrast, the clinical syndrome of decompensated hypothyroidism referred to as myxedema coma (MC) is an endocrine emergency with high risk of mortality. Because of its rarity, there are currently limited data regarding MC. This study analyzes the clinical features and hospital outcomes of MC compared with hypothyroid patients without MC (nonMChypo) in national United States hospital data. Methods: A retrospective analysis of the National Inpatient Sample, a public database of inpatient admissions to nonfederal hospitals in the United States, 2016-2018, including adult patients with primary diagnosis of MC (International Classification of Diseases 10th Revision [ICD-10]: E03.5) or nonMChypo (E03.0-E03.9, E89.0). Patient demographics, relevant clinical features, mortality, length of stay (LOS), and hospital costs were compared. Results: Of 18,635 patients hospitalized for hypothyroidism, 2495 (13.4%) had a diagnosis of MC. Sex distribution and race/ethnicity were similar between patients with MC and nonMChypo, whereas MC was associated with older patient age (p = 0.02), public insurance (p = 0.01), and unhoused status (p = 0.04). More admissions with MC occurred in winter compared with other seasons (p = 0.01). The overall mortality rate for MC was 6.8% versus 0.7% for nonMChypo (p < 0.001), and MC was independently associated with in-hospital mortality after adjusted regression analysis (adjusted odds ratio = 9.92 [CI 5.69-17.28], p < 0.001). Mean LOS ± standard error was 9.64 ± 0.73 days for MC versus 4.62 ± 0.12 days for nonMChypo (p < 0.001), and total hospital cost for MC was $21,768 ± $1759 versus $8941 ± $276 for nonMChypo (p = 0.07). In linear regression analyses, MC was an independent predictor of both increased LOS and total hospital cost. Conclusions: In summary, MC remains a clinically significant diagnosis in the modern era, independently associated with high mortality and health care costs. This continued burden demonstrates a need for further efforts to prevent, identify, and optimize treatment for patients with MC.
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Hipotireoidismo , Mixedema , Adulto , Humanos , Estados Unidos/epidemiologia , Pacientes Internados , Mixedema/complicações , Mixedema/terapia , Estudos Retrospectivos , Coma/complicações , Coma/diagnóstico , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Tempo de InternaçãoRESUMO
Introduction: Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM. Methods: This retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class. Results: Of 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2-3.56), p = 0.81, and OR 1.69 (0.31-9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy. Discussion: These data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.
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Antineoplásicos Imunológicos , Doenças Autoimunes , Diabetes Mellitus Tipo 1 , Neoplasias , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inibidores de Checkpoint Imunológico/efeitos adversos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/induzido quimicamente , Estudos Retrospectivos , Estudos Prospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Doenças Autoimunes/complicaçõesRESUMO
Background/Objective: Immune checkpoint inhibitors (CPIs) activate antitumoral immune responses and are used to treat multiple types of primary and metastatic malignancies. Thyroid dysfunction is a known immune-related adverse event of CPI therapy. There are few data on the effect of CPI and CPI-induced thyroiditis on primary papillary thyroid carcinoma (PTC). We present a patient who developed CPI-induced thyroiditis during treatment for a nonthyroid malignancy and subsequent regression of a coexisting untreated primary PTC. Case Report: A 49-year-old man with metastatic colon adenocarcinoma was found to have a large right thyroid nodule with biopsy confirmation of PTC. He did not have compressive symptoms or evidence of metastatic PTC. Resection was not performed because of colon cancer therapy. Treatment with CPI (ezabenlimab, an anti-programmed cell death protein 1 antibody) was initiated for the treatment of colon cancer. Four months after the initiation of CPI therapy, testing showed thyroid-stimulating hormone and free thyroxine levels of 174.9 (0.3-4.0 mIU/L) and 0.67 (0.93-1.70 ng/dL), respectively, consistent with CPI-induced hypothyroidism. Levothyroxine therapy was initiated. Repeat imaging 3 months later demonstrated a decrease in the tumor size to 4.1 × 4.9 × 4.2 cm (calculated volume change, -8.3% from baseline). At the last imaging, 1 year after the onset of CPI-induced thyroiditis, the PTC continued to decrease in size and measured 2.9 × 3.9 × 3.2 cm (volume change, -60.7% from baseline). Discussion: CPI-induced thyroiditis suggests the development of an immune response against thyroid tissue and may reflect a similar increased immune response against PTC cells leading to tumor regression in this case. Conclusion: Further research to assess the immunologic mechanism underlying this association is warranted to potentially develop improved immunotherapy for PTC.
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Autoimmune toxicity occurs in up to 60% of patients treated with immune checkpoint inhibitor (ICI) therapy for cancer and represents an increasing clinical challenge for expanding the use of these treatments. To date, human immunopathogenic studies of immune-related adverse events (IRAEs) have relied on sampling of circulating peripheral blood cells rather than affected tissues. Here, we directly obtained thyroid specimens from individuals with ICI-thyroiditis, one of the most common IRAEs, and compared immune infiltrates with those from individuals with spontaneous autoimmune Hashimoto's thyroiditis (HT) or no thyroid disease. Single-cell RNA sequencing revealed a dominant, clonally expanded population of thyroid-infiltrating cytotoxic CXCR6+ CD8+ T cells (effector CD8+ T cells) present in ICI-thyroiditis but not HT or healthy controls. Furthermore, we identified a crucial role for interleukin-21 (IL-21), a cytokine secreted by intrathyroidal T follicular (TFH) and T peripheral helper (TPH) cells, as a driver of these thyrotoxic effector CD8+ T cells. In the presence of IL-21, human CD8+ T cells acquired the activated effector phenotype with up-regulation of the cytotoxic molecules interferon-γ (IFN-γ) and granzyme B, increased expression of the chemokine receptor CXCR6, and thyrotoxic capacity. We validated these findings in vivo using a mouse model of IRAEs and further demonstrated that genetic deletion of IL-21 signaling protected ICI-treated mice from thyroid immune infiltration. Together, these studies reveal mechanisms and candidate therapeutic targets for individuals who develop IRAEs.
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Tireoidite , Humanos , Linfócitos T CD8-Positivos/metabolismo , Doença de Hashimoto , Interleucinas , Tireoidite Autoimune/genética , Tireoidite Autoimune/patologia , Tireoidite/induzido quimicamente , Tireoidite/imunologiaRESUMO
Background: Sonographic evaluation is fundamental to thyroid nodule assessment. The American Thyroid Association (ATA) ultrasound risk stratification system (USRSS) is widely used, but the appearance of some nodules has been considered nonclassifiable (NC-ATA). The risk of malignancy (RoM) of NC-ATA nodules varies widely between studies, leading to uncertainty in clinical management. The aim of this study was to comprehensively evaluate the prevalence and malignancy risk of NC-ATA nodules. Methods: A systematic review was performed searching PubMed/MEDLINE and EMBASE to identify original studies of thyroid nodules classified using the ATA USRSS from 2016 to 2022 and reporting the outcome of NC-ATA nodules. Meta-analysis was conducted to obtain pooled RoM estimates and meta-regression sensitivity analyses were used to explore sources of between-study heterogeneity. Results: Of 6377 screened studies, 135 underwent full-text review, and 16 studies reporting 21,271 nodules were included. Within these, the pooled prevalence of NC-ATA nodules was 7.8% (1872 nodules; [confidence interval; CI 5.1-11.1]). The pooled RoM estimate for NC-ATA nodules was 20.3% [CI 13.0-28.7] and there was significant heterogeneity between studies (I2 = 92.8%, p < 0.001). NC-ATA nodule RoM estimates were significantly different by study type: single-center versus multicenter studies (24.8% vs. 12.3%, respectively, p = 0.031) and study design: retrospective versus prospective studies (25.1% vs. 8.5%, respectively, p = 0.003). No significant difference was observed in RoM based on inclusion of <1 cm nodules or geographic region. Meta-regression analysis showed study design and use of surgical histology for diagnostic criteria contributed significantly to differences in the reported RoM estimates. Conclusion: In this first meta-analysis comprehensively assessing the RoM of NC-ATA nodules, the malignancy risk was found to be comparable with the current ATA USRSS intermediate suspicion category. Significant heterogeneity was observed between studies and limits the interpretation of these results. In future iterations of the ATA USRSS that seek into incorporate categorization of NC-ATA nodules, these meta-analysis data may help to inform proper malignancy risk stratification. The study protocol was registered on PROSPERO, the international prospective register of systematic reviews (CRD42020182498), on July 14, 2020.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Estados Unidos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Estudos Prospectivos , Medição de Risco , Ultrassonografia/métodosRESUMO
CONTEXT: The Afirma® GSC aids in risk stratifying indeterminate thyroid nodule cytology (ITN). The 2018 GSC validation study (VS) reported a sensitivity (SN) of 91%, specificity (SP) of 68%, positive predictive value (PPV) of 47%, and negative predictive value (NPV) of 96%. Since then, 13 independent real-world (RW) postvalidation studies have been published. OBJECTIVE: This study's objective is to compare the RW GSC performance to the VS metrics. METHODS: Rules and assumptions applying to this analysis include: (1) At least 1 patient with molecular benign results must have surgery for that study to be included in SN, SP, and NPV analyses. (2) Molecular benign results without surgical histology are considered true negatives (TN) (as are molecular benign results with benign surgical histology). (3) Unoperated patients with suspicious results are either excluded from analysis (observed PPV [oPPV] and observed SP [oSP]) or assumed histology negatives (false positives; conservative PPV [cPPV] and conservative SP [cSP]) 4. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features is considered malignant. RESULTS: In RW studies, the GSC demonstrates a SN, oSP, oPPV, and NPV of 97%, 88%, 65%, 99% respectively, and conservative RW performance showed cSP of 80% and cPPV of 49%, all significantly higher than the VS except for SN and cPPV. There was also a higher benign call rate (BCR) of 67% in RW studies compared to 54% in the VS (P < 0.05). CONCLUSION: RW data for the Afirma GSC demonstrates significantly better oSP and oPPV performance than the VS, indicating an increased yield of cancers for resected GSC suspicious nodules. The higher BCR likely increases the overall rate of clinical observation in lieu of surgery.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Estudos Retrospectivos , Biópsia por Agulha Fina , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Genômica , Perfilação da Expressão GênicaRESUMO
Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9-100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1-100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina , Carcinoma Neuroendócrino , Perfilação da Expressão Gênica/métodos , Humanos , RNA , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgiaRESUMO
Immune checkpoint inhibitor (ICI) immunotherapy leverages the body's own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune-related adverse events (IrAEs) may lead to treatment interruption, permanent organ dysfunction, hospitalization, and premature death. Thyroiditis is one of the most common IrAEs, but the cause of thyroid IrAEs remains unknown. In this study, we use a new, physiologically relevant mouse model of ICI-associated autoimmunity to identify a key role for type 3 immune cells in the development of thyroid IrAEs. Multiple lineages of IL-17A-producing T cells expand in thyroid tissue with ICI treatment. Intrathyroidal IL-17A-producing innate-like γδT17 cells were increased in tumor-free mice, whereas adaptive Th17 cells were also prominent in tumor-bearing mice, following ICI treatment. Furthermore, Ab-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice with and without tumor challenge. Finally, combination of IL-17A neutralization with ICI treatment in multiple tumor models did not reduce ICI antitumor efficacy. These studies suggest that targeting Th17 and γδT17 cell function via the IL-17A axis may reduce IrAEs without impairing ICI antitumor efficacy and may be a generalizable strategy to address type 3 immune-mediated IrAEs.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Animais , Imunoterapia , Interleucina-17 , Camundongos , Neoplasias/patologia , Glândula Tireoide/patologiaRESUMO
Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many advanced cancers but are recognized to cause treatment-limiting immune-related adverse events (IrAE). ICI-associated thyroiditis is the most common endocrine IrAE and usually resolves to permanent hypothyroidism. Optimal thyroid hormone replacement in these patients remains unclear. We report the levothyroxine (LT4) dose needed to achieve stable euthyroid state in patients with hypothyroidism from ICI-associated thyroiditis, with comparison to patients with Hashimoto's thyroiditis (HT) and athyreotic state. Methods: We conducted a retrospective study of adults with ICI-associated hypothyroidism treated with LT4 at an academic medical center. Patient data were collected from the electronic medical record. Cases had ICI exposure followed first by hyperthyroidism and then subsequent hypothyroidism. Controls were HT (positive thyroid autoantibodies, requiring LT4) and athyreotic (total thyroidectomy or radioiodine ablation, requiring LT4) patients. Patients with central hypothyroidism, thyroid cancer, pregnancy, gastrointestinal stromal tumors, and use of L-triiodothyronine were excluded. Our primary outcome compared LT4 dose needed to achieve euthyroid state (thyrotropin 0.3-4.7 mIU/L over >6 consecutive weeks) for ICI-associated hypothyroidism, HT, and athyreotic patients, considering the impact of age and possible interfering medications by linear regression modeling. Secondary analysis considered the impact of endocrine specialty care on the time to euthyroid state. Results: One hundred three patients with ICI-associated thyroiditis were identified. Sixty-six of the 103 patients achieved euthyroid state; 2 with intrinsic thyroid gland function recovery and 64 on LT4. The mean LT4 dose achieving stable euthyroid state was 1.45 ± standard deviation (SD) 0.47 mcg/[kg·day] in ICI-associated hypothyroidism, 1.25 ± SD 0.49 mcg/[kg·day] in HT, and 1.54 ± SD 0.38 mcg/[kg·day] in athyreotic patients, using actual body weight. The difference in dose between ICI-associated hypothyroidism and HT was statistically significant (p = 0.0093). Dosing differences were not explained by age or use of interfering medications. Conclusions: ICI-associated thyroiditis represents an increasingly recognized cause of hypothyroidism. Our study demonstrates that patients with ICI-associated hypothyroidism have different thyroid hormone dosing requirements than patients with HT. Based on our findings and prior reports, we recommend that in patients with ICI-associated thyroiditis LT4 therapy be started at an initial weight-based dose of 1.45 mcg/[kg·day] once serum free thyroxine levels fall below the reference range.
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Doença de Hashimoto , Hipotireoidismo , Tireoidite , Adulto , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Radioisótopos do Iodo/efeitos adversos , Gravidez , Estudos Retrospectivos , Hormônios Tireóideos/uso terapêutico , Tireoidite/complicações , Tireotropina , TiroxinaRESUMO
Background: Large scale epidemiology studies have suggested obesity may increase the risk of thyroid cancer, though no prospective analyses using real-world measurement of BMI at a time proximate to initial thyroid nodule evaluation have been performed. Methods: We performed a prospective, cohort analysis over 3 years of consecutive patients presenting for thyroid nodule evaluation. We measured BMI proximate to the time of initial evaluation and correlated this with the final diagnosis of benign or malignant disease. We further correlated patient BMI with aggressivity of thyroid cancer, if detected. Results: Among 1,259 consecutive patients with clinically relevant nodules, 199(15%) were malignant. BMI averaged 28.6 kg/m2 (SD: 6.35, range:16.46-59.26). There was no correlation between the measurement of BMI and risk of thyroid cancer (p=0.58) as mean BMI was 28.9 kg/m2 and 28.6 kg/m2 in cancerous and benign cohorts, respectively. Similarly, BMI did not predict aggressive thyroid cancer (p=0.15). While overall nodule size was associated with increased BMI (p<0.01), these data require further validation as obesity may hinder nodule detection until large. Conclusion: In contrast to findings published from large scale association studies drawn from national databases, these prospective data of consecutive patients presenting for nodule evaluation detect no association of obesity (as measured by BMI) with thyroid cancer. Real time measurement of BMI at the time of thyroid nodule evaluation does not contribute to cancer risk assessment.
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Nódulo da Glândula Tireoide , Biópsia por Agulha Fina , Índice de Massa Corporal , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/patologiaRESUMO
BACKGROUND: The SARS-CoV-2 virus has infected and killed millions of people worldwide. Breast cancer is the most prevalent cancer in women and few studies have investigated the outcomes of patients with a history of breast cancer and COVID-19. We report the clinical outcomes of patients with invasive breast cancer who tested positive for SARS-CoV-2, including hospitalization and death, and evaluate demographic and cancer-related factors associated with these outcomes. PATIENTS: Patients with a history of invasive breast cancer and positive SARS-CoV-2 test from January 1 to December 31, 2020 at two large, academic Los Angeles health systems were included. METHODS: Retrospective chart review of the electronic medical record was performed. Data for demographic and cancer-related factors were manually abstracted. Relationships between outcomes and clinical variables were evaluated using Fisher's exact test and linear regression analysis. RESULTS: Among a total of 132 patients, 40 (30.3%) were hospitalized, while 11 (8.3%) required intensive care support, and 8 patients (6.1%) died. Older age and presence of one or more additional comorbidities were associated with hospitalization and death (P = .010, P = .003, P = .034, P < .001). Hispanic/Latinx ethnicity was associated with hospitalization (P = .047). Cancer treatment was not associated with hospitalization or death. CONCLUSION: In our diverse, multi-center, breast cancer cohort, Hispanic/Latinx ethnicity, older age and presence of other comorbidities were associated with worse outcomes from COVID-19. Breast cancer treatment, including surgery, radiation, systemic therapy, and endocrine therapy, was not associated with hospitalization in our cohort. Further studies are needed to explore the relationship between breast cancer and COVID-19 outcomes.
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Neoplasias da Mama , COVID-19 , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Hospitalização , Humanos , Los Angeles/epidemiologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
OBJECTIVE: Graves' 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. METHODS: We 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). RESULTS: TSI and TBII assays were concordant in 88% of the cases and showed a strong positive correlation (rs = 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. CONCLUSION: TSI 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.
Assuntos
Doença de Graves , Oftalmopatia de Graves , Tireotoxicose , Autoanticorpos , Bioensaio , Doença de Graves/complicações , Doença de Graves/diagnóstico , Oftalmopatia de Graves/diagnóstico , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide , Receptores da Tireotropina , Estudos Retrospectivos , Tireotoxicose/diagnóstico , TireotropinaRESUMO
Hypoglycemic episodes are associated with worse hospital outcomes. All adult patients admitted to our burn center from 2015 to 2019 were retrospectively reviewed. Patient demographics and burn characteristics were recorded. The primary outcome was mortality, and secondary outcomes were total length-of-stay and intensive care unit length-of-stay. All patients experiencing at least one hypoglycemic episode were compared to patients who did not experience hypoglycemia. There were 914 patients with acute burns admitted during the study period, 33 of which (4%) experienced hypoglycemic episodes. Of these, 17 patients (52%) experienced a single hypoglycemic episode, while the remainder experienced multiple hypoglycemic episodes. Patients with one or more hypoglycemic events were matched to non-hypoglycemic controls using propensity matching. Patients that experienced hypoglycemia had significantly less TBSA involvement (5% vs. 13%,median, p < 0.0002), higher prevalence of diabetes (48% vs. 18%, p < 0.0001), higher mortality (18% vs. 7%, p = 0.01), longer total length-of-stay (22 vs. 8 days, median, p < 0.0001), and longer ICU length-of-stay (12 vs. 0 days, median, p < 0.0001). A single hypoglycemic episode was associated with prolonged total (IRR = 1.91, p < 0.0001) and ICU length-of-stay (IRR = 3.86, p < 0.0001). Hypoglycemia was not associated with higher mortality in the survival analysis (p = 0.46).
Assuntos
Hipoglicemia , Adulto , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Unidades de Terapia Intensiva , Tempo de Internação , Estudos RetrospectivosRESUMO
OBJECTIVE: Cancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history. METHODS: This is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes. RESULTS: Of 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19-attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers. CONCLUSION: These data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.
Assuntos
COVID-19 , Neoplasias da Glândula Tireoide , Idoso , Estudos de Coortes , Comorbidade , Hospitalização , Humanos , Los Angeles/epidemiologia , RNA Viral , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Neoplasias da Glândula Tireoide/epidemiologiaRESUMO
Hürthle cell-predominant thyroid fine needle aspirations (FNA) are encountered frequently in routine practice, yet they are often challenging to diagnose accurately and are associated with significant interobserver variability. This is largely due to the ubiquity of Hürthle cells in thyroid pathology, ranging from nonneoplastic conditions to aggressive malignancies. Although limitations in cytomorphologic diagnoses likely will remain for the foreseeable future, our knowledge of the molecular pathogenesis of Hürthle cell neoplasia and application of molecular testing to cytologic material have increased dramatically within the past decade. This review provides context behind the challenges in diagnosis of Hürthle cell lesions and summarizes the more recent advances in diagnostic tools.