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To develop an index for the differential diagnosis of corticotropin-dependent Cushing syndrome (CS). The development cohort included 112 consecutive patients with clinicopathologically confirmed corticotropin-dependent CS at the Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, from December 2004 to May 2020, and data of 126 patients from studies published from 2016 to August 2020, identified through search in PubMed, Embase and the Cochrane Library, was extracted for external validation. The index was calculated as the product of plasma adrenocorticotropic hormone (ACTH, pmol/L) and urinary free cortisol (UFC, nmol/24 h) divided by 10,000. The discriminative ability was tested using receiver operating characteristics (ROC) curve analysis. In development cohort, area under curve of ROC analysis of the ACTH-UFC index in identifying Cushing disease (CD) was 0.977. The diagnostic accuracy of ACTH-UFC index ≤ 11 was comparable to that of 48 h 8 mg/d high-dose dexamethasone test (HDDST) in identifying CD, with sensitivity, specificity, positive and negative likelihood ratios of 96.6%, 87.5%, 7.73, and 0.04, respectively. The sensitivity of ACTH-UFC index ≤ 11 in parallel combination with pituitary magnetic resonance imaging (MRI) was 100% for identifying CD. The performance of the ACTH-UFC index in parallel or serial combination with pituitary MRI was similar in the validation cohort. ACTH-UFC index provides a rapid, convenient and non-invasive adjunctive approach for the differential diagnosis of corticotropin-dependent CS, with no risk of aggravating metabolic disturbances. Investigations for ectopic causes of corticotropin-dependent CS should be performed with ACTH-UFC index > 11 and negative contrasted pituitary MRI.

Both thyroid-stimulating immunoglobulins immunoassay (TSI IA) and thyrotrophin receptor antibody immunoassay (TRAb IA) are commonly used for the diagnosis of Graves’ disease (GD). The aim of the present study was to compare the clinical diagnostic performance of these two methods. Sera were obtained from 1103 subjects presenting a variety of clinical conditions from three centers: 100 subjects with untreated GD, 200 with treated GD, 62 with autoimmune thyroid disease(AIT), 216 with other thyroid diseases (OTHER-T), 214 with non-thyroid autoimmune diseases (NTAD), 191 with other diseases (OD), and 120 healthy subjects (HS). Both TSI and TRAb IAs were performed for all 1013 serum samples. Bioassay was performed for 86 samples whose TSI results were inconsistent the TRAb assay results. Comparing untreated GD patients with the control groups (AIT, NTAD, OTHER-T, OD, and HS) resulted in an area under the curve (AUC) of 0.992 for the TSI IA and 0.989 for the TRAb IA with no statistically significant difference observed between these AUC values (P = 0.2733). The best TSI CDP (clinical decision point) value was 0.42 IU/L. The differences in sensitivity (100% vs. 95%, P = 0.7991) and specificity (97.1% vs. 97.6%, P = 0.9426) between the TSI and TRAb IA were not statistically significant. TSI IA had a higher agreement with the TSI bioassay than TRAb IA. The clinical diagnostic performance of the TSI IA for diagnosing Graves’ disease was very similar to that of the TRAb IA. TSI IA can be used to diagnose GD in the Chinese.

Introduction: Thyroid hormone autoantibody (THAAb) is one of the important factors affecting the measurement of thyroid function. By studying the results of a patient suffered with Hashimoto's thyroiditis, we fully communicated with the clinician, looked for reasons, and achieved the purpose of restoring the truth and sorting out solutions. Material and Methods: During routine examination by ADVIA-Centaur XP system, we found the test of a case was inconsistent with her clinical manifestations, with abnormal elevation of free thyroxine (FT4) that did not conform to the rule of the hypothalamic-pituitary-thyroid axis. Then, different platforms and demonstration of THAAbs with polyethylene glycol (PEG) precipitation were performed to eliminate the influence of THAAbs. Results: The results showed that the thyroid function of the patient was consistent with the clinical manifestations and conformed to the law of the hypothalamic-pituitary-thyroid axis at Architect-i2000sr platform and Roche-Cobas-601 system. The content of FT4 was significantly reduced and lower than the normal reference range, after the patients' serum was treated with PEG, which was in line with the clinical practice. The serum THAAb titer of the patients was nearly 100 times higher than that of the control group. Conclusions: Once the thyroid function of the patients do not conform to their own laws and clinical manifestations, laboratory staff should consider the interference of THAAbs. It is necessary to change the detection platform and retest the serum after PEG treatment while communicating with the clinicians, which is of great significance to provide a true and accurate result to clinicians and patients.

ContextEvidence indicates that there is substantial impairment/loss of β-cell function/mass even before prediabetes. Elevated plasma proinsulin is a sign of β-cell dysfunction in patients with diabetes/prediabetes. However, the dynamic changes of glucose stimulated proinsulin secretion (GSPS) among nondiabetic individuals remain obscure.ObjectiveTo examine GSPS and glucose-stimulated insulin secretion (GSIS) among individuals with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) and to evaluate whether impaired GSPS is an early biomarker of β-cell impairment in individuals with NGT who have subthreshold postprandial plasma glucose (PPG).Design and ParticipantsWe evaluated GSPS and GSIS in 116 Chinese adults without diabetes (mean age ± SD, 33.31 ± 9.10 years; mean BMI, 25.24 ± 4.20 kg/m2) with fasting plasma glucose (FPG) < 5.6 mmol/L. Based on 2hPPG, the participants were divided into three groups: NGT1 (2hPPG < 6.67 mmol/L), NGT2 (6.67 ≤ 2hPPG < 7.78 mmol/L), and IGT (7.78 ≤ 2hPPGResultsAlthough not diagnosed with prediabetes, the individuals with NGT2 have clinical characteristics and high diabetes risk factors similar to those of the IGT group. However, unlike individuals with IGT, NGT2 participants did not exhibit a delayed GSIS. Instead, GSPS was impaired in NGT2 groups but not in NGT1 group.ConclusionsThis study suggests that impaired GSPS, but not impaired GSIS, may serve as an early biomarker to identify a subpopulation of NGT with a high risk of diabetes.