Sunitinib malate is an oral tyrosine kinase inhibitor recently approved for the treatment of gastrointestinal stromal tumors and renal cell carcinoma. Because the ret proto-oncogene is also inhibited ...by this agent, clinical evaluation of thyroid function was performed.
To describe the prevalence and clinical presentation of thyroid dysfunction related to sunitinib therapy.
Prospective, observational cohort study.
Tertiary care hospital.
42 patients treated for a median of 37 weeks (range, 10 to 167 weeks).
Following analysis of serial thyroid-stimulating hormone (TSH) measurements collected prospectively during a clinical trial of sunitinib, the authors determined the proportion of patients with thyroid dysfunction.
Abnormal serum TSH concentrations were documented in 26 of 42 patients (62%): 15 (36%) developed persistent, primary hypothyroidism; 4 (10%) developed isolated TSH suppression; and 7 (17%) experienced transient, mild TSH elevations. The risk for hypothyroidism increased with the duration of sunitinib therapy. Six of 15 (40%) hypothyroid patients had suppressed TSH concentrations before developing hypothyroidism, suggesting thyroiditis. Two hypothyroid patients evaluated with thyroid ultrasonography had no visualized thyroid tissue despite normal baseline thyroid function.
The exploratory nature of this study precluded more frequent biochemical and sonographic analysis that may better define the mechanism of sunitinib-associated thyroid dysfunction.
Hypothyroidism is a frequent complication of sunitinib therapy. Regular surveillance of thyroid function is warranted in patients receiving the drug. Although the mechanism by which this complication occurs is unknown, the observations of preceding TSH suppression and subsequent absence of visualized thyroid tissue in some patients suggest that sunitinib may induce a destructive thyroiditis through follicular cell apoptosis. This provides a rationale for further investigation of sunitinib treatment in patients with advanced thyroid cancer.
The Society of Radiologists in Ultrasound convened a panel of specialists from a variety of medical disciplines to come to a consensus on the management of thyroid nodules identified with thyroid ...ultrasonography (US), with particular focus on which nodules should be subjected to US-guided fine needle aspiration and which thyroid nodules need not be subjected to fine-needle aspiration. The panel met in Washington, DC, October 26-27, 2004, and created this consensus statement. The recommendations in this consensus statement, which are based on analysis of the current literature and common practice strategies, are thought to represent a reasonable approach to thyroid nodular disease.
Context:
The Afirma gene expression classifier (GEC) is a molecular diagnostic test that has a high negative predictive value for ruling out malignancy in thyroid nodules with indeterminate cytology. ...Many patients with a cytologically indeterminate and GEC benign (Cyto-I/GEC-B) nodule undergo monitoring instead of diagnostic surgery, but few data describe their follow-up.
Objective:
The objective of the study was to determine the sonographic changes and clinical outcomes for patients with Cyto-I/GEC-B nodules compared with patients with cytologically benign (Cyto-B) nodules.
Design:
This was a retrospective analysis of consecutive Cyto-I/GEC-B nodules evaluated at Brigham and Women's Hospital compared with Cyto-B nodules.
Main Outcomes:
Nodule growth of 20% or greater in two dimensions or of 50% or greater in volume, change in sonographic features, and rates of repeat fine-needle aspiration, thyroidectomy, and malignancy.
Results:
Ninety-five Cyto-I/GEC-B nodules in 90 patients were identified. Five patients underwent primary surgical resection. Of the remaining 90 nodules, 58 (64.4%) had sonographic follow-up available at a median of 13 months (range 4–40 mo). Cyto-I/GEC-B nodules showed similar growth compared with 1224 Cyto-B nodules using either of the following criteria: 20% or greater in two dimensions (8.6% vs 8.3%, P = .80) or 50% or greater in volume (17.2% vs 13.8%, P = .44). Thyroidectomies were more frequent in the Cyto-I/GEC-B group (13.8% vs 0.9%, P < .0001), but cancer was found in only one patient, with no evidence of persistent disease after initial treatment.
Conclusions:
Cyto-I/GEC-B nodules demonstrate similar growth to Cyto-B nodules during follow-up. Although Cyto-I/GEC-B nodules were more frequently resected, only one malignancy was found. These data suggest that reassessment of Cyto-I/GEC-B nodules may be performed similarly to those with benign cytology.
Context: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a complex disorder caused by germline-inactivating mutations of the PTEN tumor suppressor gene. Carriers develop ...benign and malignant tumors of multiple tissues, including the breast, thyroid, intestine, and skin. Surveillance to facilitate the early detection and treatment of malignancies is recommended but, because thyroid cancers have been reported almost exclusively in adults, childhood risk is considered to be low, and consensus guidelines recommend that surveillance imaging begin at 18 yr of age.
Objective/Patients: Seven children with PHTS referred to two thyroidologists form the basis of this report. Medical records, operative histology, and PTEN mutational analysis were reviewed to evaluate the pediatric presentation of PHTS-associated thyroid neoplasia.
Results: Five of the seven children presented with thyroid nodules or thyroid cancer between the ages of 6 and 12 yr, often as the initially identified component of their PHTS. Two others were diagnosed with PHTS on the basis of extrathyroidal features but had markedly abnormal screening ultrasounds with solid thyroid nodule(s) of at least 2 cm, despite the documentation of normal physical examinations. Five of the seven children in this cohort developed thyroid cancer.
Conclusions: Patients with PHTS can develop thyroid nodules and thyroid cancer in early childhood. This argues both for a high index of suspicion for PHTS in children diagnosed with multiple thyroid nodules and for careful thyroid surveillance in children diagnosed with PHTS. Because early detection improves the outcome of thyroid cancer, we recommend ultrasound surveillance for all patients upon the confirmation of a germline PTEN mutation, regardless of their age.
Patients with PTEN hamartoma tumor syndrome can develop thyroid nodules and thyroid cancer in early childhood; this argues for vigilance and the initiation of surveillance imaging in childhood.
Objectives
To assess the etiology and clinical implications of ultrasound (US)‐diagnosed urothelial thickening (UT) in renal transplants.
Methods
Patients with renal transplants who had UT diagnosed ...by US from January 2000 to December 2018 were retrospectively identified and compared to patients with transplants without UT scanned during the study period. Medical records were reviewed for demographics, US findings, pathologic results, laboratory values, and clinical outcomes and compared between groups by Fisher exact and t tests.
Results
A total of 143 patients with UT and 128 controls comprised our cohorts. The patient age in the UT group versus controls (mean ± SD, 50.2 ± 16.5 versus 51.2 ± 15.3 years) and the time since transplant (2.9 ± 4.2 versus 2.4 ± 5.8 years) were similar. Patients with UT were more likely to be female than controls (76 of 143 53.1% versus 53 of 128 41.4%; P = .07), but the difference was not statistically significant, and patients with UT were more likely to have indwelling stents (31 of 143 21.7% versus 9 of 128 7.0%; P = .001) and hydronephrosis (25 of 143 17.4% versus 11 of 128 8.6%; P = .03). At biopsy, rejection and vascular sclerosis were more likely in patients with UT compared to controls (24 of 25 49.0% versus 11 of 43 25.6%; P = .031; 42 of 49 85.7% versus 22 of 43 51.2%; P = .0005, respectively), whereas acute tubular necrosis was similar. The sensitivity (50.0%) and specificity (74.4%) of UT for rejection were low.
Conclusions
Urothelial thickening correlates with US findings of urinary obstruction and indwelling stents, suggesting a possible mechanical component to UT's etiology. Although transplant rejection and vascular sclerosis were more frequent at biopsy in the UT group than controls, UT had low sensitivity and specificity for rejection.
Abstract
Context
Thyroid nodule growth was once considered concerning for malignancy, but data showing that benign nodules grow questioned the use of this paradigm. To date, however, no studies have ...adequately evaluated whether growth rates differ in malignant vs. benign nodules.
Objective
To sonographically evaluate growth rates in benign and malignant thyroid nodules ≥1 cm.
Design
Prospective, cohort study of patients with tissue diagnosis of benign or malignant disease, with repeated ultrasound evaluation six or more months apart.
Main Outcomes
Growth rate in largest dimension of malignant compared with benign thyroid nodules. Regression models were used to evaluate predictors of growth.
Results
Malignant nodules (126) met inclusion criteria (≥6-month nonoperative followup) and were compared with 1363 benign nodules. Malignant nodules were not found to be uniquely selected or prospectively observed solely for low-risk phenotype. Median ultrasound intervals were similar (21.8 months for benign nodules; 20.9 months for malignant nodules). Malignant nodules were more likely to grow >2 mm/y compared with benign nodules relative risk (RR) = 2.5, 95% confidence interval (CI), 1.6 to 3.1; P < 0.001, which remained true after adjustment for clinical factors. The RR of a nodule being malignant increased with faster growth rates. Malignant nodules growing >2 mm/y had greater odds of being more aggressive cancers intermediate risk: odds ratio (OR) = 2.99; 95% CI, 1.20 to 7.47; P = 0.03; higher risk: OR = 8.69; 95% CI, 1.78 to 42.34; P = 0.02.
Conclusions
Malignant nodules, especially higher-risk phenotypes, grow faster than benign nodules. As growth >2 mm/y predicts malignant compared with benign disease, this clinical parameter can contribute to the assessment of thyroid cancer risk.
Thyroid nodule growth by sonographic reassessment shows that malignant nodules grow substantially faster than benign nodules and that more rapid growth is associated with higher-risk thyroid cancers.
In older patients, thyroid nodules are frequently detected and referred for evaluation, though usually prove to be benign disease or low-risk cancer. Therefore, management should be guided not solely ...by malignancy risk, but also by the relative risks of any intervention. Unfortunately, few such data are available for patients ≥70 years old.
All consecutive patients ≥70 years old assessed by ultrasound (US) and fine-needle aspiration (FNA) between 1995 and 2015 were analyzed. Clinical, US, and histologic data, including patient comorbidities and outcomes, were obtained. Imaging and cytology results from initial evaluation were reviewed to detect significant-risk thyroid cancer (SRTC), which was defined as anaplastic, medullary, or poorly differentiated carcinoma, or the presence of distant metastases. Overall survival analyses were then performed to assist with risk-to-benefit assessment.
A total of 1129 patients ≥70 years old with 2527 nodules ≥1 cm were evaluated. FNA was safe in all, and cytology proved benign in 67.3% of patients. However, FNA led to surgery in 208 patients, of whom 93 (44.7%) had benign histopathology. Among all patients who underwent FNA, only 17 (1.5%) SRTC were identified, all of which were preoperatively identifiable by imaging and/or cytology. These SRTC were responsible for all (n = 10; 0.9%) thyroid cancer deaths. Among all other patients (n = 1112), 160 deaths (14.4%) were confirmed during a median follow-up of four years. None of these were thyroid cancer related. Survival analysis for these 1112 patients demonstrated that a separate non-thyroidal malignancy or coronary artery disease at the time of nodule evaluation was associated with increased mortality compared to those without these diagnoses (hazard ratio = 2.32 confidence interval 1.66-3.26; p < 0.01), confirming these are important variables to identify prior to thyroid nodule evaluation.
For patients ≥70 years old, US and FNA are safe and prove helpful in identifying SRTC and benign cytology. However, the surgical management of patients ≥70 years old presenting without high-risk findings should be tempered, especially when comorbid illness is identified.
Ectopic intrathyroidal thymic tissue is a benign lesion of nonthyroid origin occasionally found in the pediatric thyroid gland. Accurate diagnosis of such lesions is critical to avoid unnecessary ...biopsy or surgery. Twelve children referred to our center for the concern of thyroid nodules were found to have intrathyroidal thymic tissue. Most of the lesions had a classic sonographic appearance of a hypoechoic mass with sharp margins and multiple focal internal nonshadowing echogenicities identical to thymic tissue. Sonography and, in select cases, fine‐needle aspiration can be used to diagnose benign thymic tissue within the thyroid and avoid unnecessary surgery.
Objective. To determine whether color Doppler interrogation of a thyroid nodule can aid in the prediction of malignancy. Methods. We obtained color Doppler images of thyroid nodules undergoing ...sonographically guided fine‐needle aspiration. The color Doppler appearance of each nodule was graded from 0 for no visible flow through 4 for extensive internal flow. The size, sonographic appearance, results of fine‐needle aspiration, and surgical pathologic findings, if available, were recorded for each nodule. Results. There were 254 nodules sampled, of which 32 were malignant (all confirmed at surgery) and 177 were benign. Fourteen (43.8%) of the 32 malignant nodules were color type 4, compared with only 26 (14.7%) of the 177 benign nodules (P = .0004, Fisher exact test). Thirteen (40.1%) of the 32 malignant nodules were solid, as were 18 (10.2%) of the 177 benign nodules (P = .006, Fisher exact test). Among solid nodules, the prevalence of malignancy was greater when the nodule was hypervascular (13 41.9% of 31) than when the color type was less than 4 (11 14.7% of 77; P = .004, Fisher exact test). Conclusions. Solid hypervascular thyroid nodules have a high likelihood of malignancy (nearly 42% in our series). The color characteristics of a thyroid nodule, however, cannot be used to exclude malignancy, because 14% of solid nonhypervascular nodules were malignant
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