Assessment of The Bethesda System for Reporting Thyroid Cytopathology.

OBJECTIVES: Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). METHODS: Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. RESULTS: Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). CONCLUSIONS: Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers.

Background: Limited guidance exists for selecting a laboratory method for diagnosing GH deficiency (GHD) when it occurs as a late effect of radiotherapy in childhood cancer survivors (CCSs). Methods: We searched Medline, Embase, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus for studies evaluating GHD that used IGF-1 or IGF-binding protein 3 (IGFBP-3) measurements compared with GH dynamic testing. Results: We included 15 studies [IGF-1 (8 studies) and IGFBP-3 (7 studies)] enrolling 477 patients. Comparator tests varied widely. Overall, both IGF-1 and IGFBP-3 had suboptimal diagnostic accuracy but were strongly correlated. The use of both tests simultaneously in the same cohort did not improve the diagnostic accuracy. Despite high variability in the testing protocols, dynamic tests remained the most accurate for appropriately identifying patients with GHD. The insulin tolerance test (ITT) appears to be the most accepted reference test when used alone or in combination with arginine; however, standardized testing strategies among practice groups are absent. GHRH and arginine stimulation performed almost similarly to the ITT; however, in one study GHRH with arginine stimulation had 66% sensitivity and 88% specificity compared with the ITT. Insufficient data were available to assess the accuracy of serial GH testing (nocturnal or over 24 hours). Conclusion: The diagnostic accuracy of various dynamic tests for GHD in CCSs appears to follow the same patterns as those in non-CCSs. Interpreting GHRH stimulation is a challenge given the primarily hypothalamic dysfunction in CCSs. IGF-1 and IGFBP-3 perform poorly in this population.

GH Therapy in Childhood Cancer Survivors: A Systematic Review and Meta-Analysis.

Background: GH deficiency (GHD) is common among childhood cancer survivors (CCSs) with history of tumors, surgery, and/or radiotherapy involving the hypothalamus-pituitary region. We aimed to evaluate the effects of GH therapy (GHT) in CCSs on adult height, risk of diabetes mellitus, abnormal lipids, metabolic syndrome, quality of life, secondary tumors, and disease recurrence. Methods: We searched multiple databases for randomized and observational studies. Pairs of reviewers independently selected studies and collected data. Random effects meta-analysis was used to pool outcomes across the studies. Results: We included 29 observational studies at moderate to high risk of bias. Sixteen studies compared CCSs on GHT with those not on GHT (512 patients, GH dose: 0.3 to 0.9 IU/kg/week). GHT was significantly associated with height gain [standard deviation score, 0.61; 95% CI, 0.08 to 1.13] and was not significantly associated with the occurrence of secondary tumors [odds ratio (OR), 1.10; 95% CI, 0.72 to 1.67] or tumor recurrence (OR, 0.57; 95% CI, 0.31 to 1.02). Thirteen studies compared CCSs on GHT with normal age- or sex-matched controls or controls with idiopathic GHD or short stature. GHT was associated with either improved or unchanged risk of diabetes, lipid profiles, and metabolic syndrome. GHT was associated with improvements in quality of life. Conclusion: CCSs treated with GHT gain height compared with the untreated controls. GHT may improve lipid profiles and quality of life and does not appear to increase the risk of diabetes or the development of secondary tumors, although close monitoring for such complications remains warranted due to uncertainty in the current evidence.