Archives of Endocrinology Metabolism最新文献

Introduction: Providing widespread access to thyroidectomies while consolidating services in high-volume centers is a significant challenge in healthcare. In this context, from a national perspective, we aimed to analyze the impact of the COVID-19 pandemic on the institutional case volumes of thyroid surgery in Brazil.

Material and methods: We analyzed retrospective thyroidectomy data from the Department of Informatics of the Unified Health System (Datasus), stratifying institutions into low-volume, intermediate-volume, and high-volume centers (<10, 10-100, and >100 thyroidectomies/year, respectively). We assessed the differences in absolute numbers and percentages of thyroidectomies performed during the pandemic years (2020-2022) compared with the pre-pandemic year (2019). Differences in the proportion of institutions based on case volumes from 2019 to 2022 were assessed using Cochran's Q test.

Results and discussion: In 2019, 556 Brazilian institutions performed 15,331 thyroidectomies. Of these, 46.4% were categorized as low-volume, 48.4% as intermediate-volume, and 5.2% as high-volume institutions, accounting for 5.5%, 61.4%, and 33.1% of the thyroidectomies, respectively. Compared with 2019, the volume of thyroidectomies was lower by 41.2% in 2020, 37.0% in 2021, and 12.8% in 2022. When analyzing the proportions of institutions that maintained their pre-pandemic case volume in the first pandemic year, the intermediate and high-volume institutions experienced reductions of 34.9% (p < 0.001) and 58.6% (p < 0.001), respectively, while low-volume institutions presented a 4.3% reduction (p = 0.081).

Conclusion: The COVID-19 pandemic disrupted the landscape of thyroidectomies in Brazil, particularly affecting intermediate-volume and high-volume institutions, while low-volume institutions showed greater resilience.

The main diagnostic dilemma in normocalcemic hyperparathyroidism is differentiating this condition from secondary hyperparathyroidism and other causes of elevated parathyroid hormone (PTH) levels in eucalcemic patients, including potential assay interferences. Despite the analytical sensitivity of immunoassays, they may lack adequate accuracy due to several analytical interferences, such as the presence of heterophilic antibodies. Immunoassays for PTH measurement use the immunometric "sandwich" technique, and only a few cases of interference with this assay have been reported to date. We describe herein two patients in whom PTH immunoassay interference was demonstrated. Both patients presented high serum PTH levels, measured using a second-generation Roche electrochemiluminescence assay (ECLIA; Elecsys Roche, Germany), and normocalcemia. When immunoassay interference was suspected, PTH measurements were repeated using a different analytical platform, the 1-84 PTH third-generation Roche Elecsys ECLIA, resulting in normal levels. We subsequently performed serial dilutions using normal mouse serum with the second-generation ECLIA and found no linearity, indicating the presence of interference in both patients. Immunoassay interference may lead to misinterpretation of a patient's results by the laboratory and incorrect treatment planning by the attending physician. Despite its rarity, the presence of interferences in the PTH immunoassay resulting in falsely high PTH levels should be considered when the laboratory result does not match the patient's clinical presentation, thus preventing erroneous diagnoses and unnecessary therapeutic procedures.

Zoledronic acid is a widely used bisphosphonate for treating osteoporosis and hypercalcemia related to malignancy. It is also used to prevent bone loss induced by cancer treatment and bone metastases in various cancer types. Zoledronic acid is safe for most patients and is generally not associated with severe side effects. However, there have been reports of acute kidney impairment occurring after administration of intravenous zoledronic acid, mostly in patients with cancer (who received a high cumulative dose of this medication) or preexisting kidney impairment, and in patients with a history of nephrotoxic treatment. We report herein the cases of two patients without history of cancer, who developed dialysis-requiring acute kidney impairment after a single administration of intravenous zoledronic acid. None of the patients had previously used nephrotoxic medications, and one of them had a normal kidney function before zoledronic acid treatment. To the best of our knowledge, this report describes the first case of acute kidney impairment in a patient without risk factors. The findings of this report show that acute kidney impairment following intravenous zoledronic acid treatment can also occur in low-risk patients, highlighting the need for monitoring kidney function in all patients receiving this treatment.

Objective: This study analyzed systemic inflammatory changes reflected by hematologic and biochemical indices in patients with hyperparathyroidism (PHPT) after parathyroidectomy.

Materials and methods: Retrospective study of 70 patients who underwent curative parathyroidectomy for PHPT treatment. Data on clinical presentation, biochemical assays, imaging studies, and postoperative outcomes were collected. Systemic inflammation was quantified using different indices, including the triglyceride-glucose (TyG) index, Fibrosis-4 (FIB-4) score, systemic immune-inflammation index (SII), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), platelet-to-lymphocyte ratio (PLR), and platelet distribution width (PDW).

Results: Significant pre-surgical to post-surgical decreases were observed in serum levels of mean normalized calcium (11 ± 0.65 mg/dL and 9.1 ± 0.42 mg/dL, respectively, p = 0.001) and parathyroid hormone (PTH) (235.5 ± 132.9 and 78.1 ± 60.5 ng/L, respectively, p = 0.001). The inflammatory indices changed substantially, with decreases in SII (from 564.8 ± 257.5 to 516.6 ± 201.1, p = 0.001) and PLR (from 143.0 ± 46.2 to 133.6 ± 38.6, p = 0.001). Additionally, PDW decreased from 52.8 ± 8.2% to 47.5 ± 9.3% (p = 0.001) and MHR increased from 7.19 ± 3.06 to 7.81 ± 3.13 (p = 0.001). No significant changes occurred in other inflammatory markers, including the TyG index (p = 0.431) and FIB-4 score (p = 0.401). Logistic regression analysis identified PDW (odds ratio [OR] 0.920, 95% confidence interval [CI] 0.879-0.963, p = 0.001) and PLR (OR 0.991, 95% CI 0.983-1, p = 0.042) as significant predictors of inflammation.

Conclusions: Successful parathyroidectomy in patients with PHPT reduces systemic inflammation, as evidenced by decreased PDW and PLR. Our results indicate the importance of integrating PDW and PLR in the postoperative assessment of PHPT for monitoring inflammatory activity.

Objective: To investigate the association between the long noncoding RNAs (lncRNAs) maternally expressed gene 3 (MEG3) rs7158663 polymorphism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

Subjects and methods: The study included 628 patients with T2DM and DR ("case group," including 283 with proliferative DR [PDR] and 345 with nonproliferative DR [NPDR]), and 381 patients with T2DM but no DR ("control group"). The diagnosis of DR was established using indirect ophthalmoscopy. The rs7158663 A/G polymorphism was genotyped using real-time polymerase chain reaction (PCR) with TaqMan probes.

Results: Patients with DR, compared with those without DR, had lower frequencies of both the G/G genotype (17.5% and 23.6%, respectively, p = 0.044) and the G allele (p = 0.017). When only patients with PDR were compared with controls, the G/G genotype was associated with increased protection against PDR after adjustment (odds ratio 0.551, 95% confidence interval 0.314-0.966, p = 0.038). This association also remained in the dominant (p = 0.036) and additive (p = 0.031) genetic models.

Conclusion: This study reveals, for the first time, that the G/G genotype of the lncRNA MEG3 rs7158663 single-nucleotide polymorphism is associated with a protective effect against advanced-stage DR in patients with T2DM. Additional studies are warranted to validate this finding.

Denosumab is a potent antiresorptive medication, commonly used in the treatment of osteoporosis, as well as in a variety of other diseases. Potential adverse rebound effects after its cessation include a loss in bone mineral density and an increased risk of osteoporotic fractures. Hypercalcemia is a less frequently reported rebound phenomenon after denosumab discontinuation, that may pose a diagnostic challenge to physicians as a rare non-parathyroid hormone (PTH) dependent cause of hypercalcemia. In our case, a 47-year-old male presented with rebound hypercalcemia after denosumab cessation during follow-up after surgical treatment for parathyroid carcinoma. This non-PTH-dependent hypercalcemia resolved after re-initiation of denosumab. We performed a systematic literature review on rebound hypercalcemia after denosumab cessation and identified 52 individual patient cases. Children appear to be more prone to developing rebound hypercalcemia, which could be attributed to their higher baseline bone turnover, underlying conditions, or denosumab dosage regimens. In most cases, patients initially presented with acute and often severe symptoms of hypercalcemia that occur from 1.75 to 9 months after denosumab cessation (4 to 9 months in adults). Most effective treatment approaches to sufficiently decrease serum calcium levels were bisphosphonates or re-administration of denosumab. A watch and wait strategy may be sufficient in asymptomatic cases, which are less common and probably underdiagnosed. Subsequent antiresorptive treatment after denosumab cessation, which is a common practice in osteoporosis treatment, may reduce the risk of rebound hypercalcemia. As denosumab is a frequently used drug in patients with advanced malignant diseases and rebound hypercalcemia with low PTH levels may raise the suspicion for skeletal metastases, awareness of this rebound effect may be for particular relevance in such settings.

Objective: This pilot study investigated whether single nucleotide polymorphisms (SNP) in the NOX5 gene (NADPH oxidase 5) are associated with the type 2 diabetes (T2D) risk.

Subjects and methods: A total of 1579 patients with T2D and 1627 age- and sex-matched healthy subjects were recruited for this study. Genotyping of common SNPs, namely rs35672233, rs3743093, rs2036343, rs311886, and rs438866, was performed using the MassArray-4 system.

Results: SNP rs35672233 was associated with an increased risk of T2D (OR = 1.67, 95% CI 1.29-2.17, FDR = 0.003). The H3 haplotype (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C) increased T2D risk (OR = 1.65, 95% CI 1.27-2.13, FDR = 0.001). The rs35672233 polymorphism and H3 haplotype were found to have an association with T2D risk only in subjects with a body mass index greater than 25 kg/m² (FDR < 0.01). Environmental risk factors, such as chronic psycho-emotional stress, sedentary lifestyle, high-calorie diet and SNP rs35672233 were jointly associated with T2D susceptibility. A haplotype comprising the allele rs35672233-C and conferring protection against T2D, was associated with elevated levels of antioxidants such as total glutathione and uric acid, as well as reduced levels of two-hour postprandial glucose in the plasma of patients. The NOX5 polymorphisms showed no associations with diabetic complications.

Conclusion: The present study is the first to establish associations between polymorphisms in NOX5 and the risk of type 2 diabetes mellitus, and provides a new line of evidence for the crucial role of oxidative stress-related genes in disease susceptibility.

Objective: Fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) index are relatively simple and reliable noninvasive markers of insulin resistance (IR). Given the relevance of correctly diagnosing IR, we emphasize the importance of establishing reliable reference intervals (RIs) for these markers. This study aimed to determine the RIs of fasting insulin and HOMA-IR index in adults living in Rio de Janeiro and, secondarily, to verify potential RI differences between sexes.

Subjects and methods: Serum insulin levels of 146,497 individuals (ages 20-60 years) who underwent blood sampling in the state of Rio de Janeiro were obtained retrospectively through access to an extensive laboratory database. Insulin was measured using the electrochemiluminescence immunoassay method. After applying exclusion criteria, 21,684 individuals (18,576 [86%] women) were included. The RIs were estimated using a computational mining approach that integrates a selection of R packages.

Results: The 95% RIs in women and men and in the overall population were, respectively, 2.54-13.30 μU/mL (15.3-80.12 pmol/L), 2.43-11.89 μU/mL (14.6-71.7 pmol/L), and 2.52-13.14 μU/mL (15.2-79.2 pmol/L) for fasting insulin levels and 0.39-2.86, 0.38-2.81, and 0.39-2.86 for HOMA-IR values. Despite significant differences in insulin levels and HOMA-IR index between men and women, the use of sex-specific RIs was not justified.

Conclusion: The RIs of fasting insulin levels and HOMA-IR values found in the overall population can be applied to both sexes. Thus, for our population, we suggest the RIs of 2.52-13.14 μU/mL (15.1-78.8 pmol/L) for fasting insulin and 0.39-2.86 for the HOMA-IR index.

Objective: This study aimed to evaluate the association of detectable C-peptide levels with various continuous glucose monitoring (CGM) metrics and diabetes complications in patients with type 1 diabetes mellitus (T1DM).

Subjects and methods: Retrospective, descriptive study of 112 patients with T1DM undergoing intensive insulin therapy, categorized according to fasting C-peptide level into undetectable (<0.05 ng/mL) and detectable (≥0.05 ng/mL) groups.

Results: The patients' median age at diagnosis was 22 (12-34) years and the median T1DM duration was 18.5 (12-29) years. Patients with detectable versus undetectable C-peptide levels were older (27.5 [16.5-38.5] versus 17.5 [9.8-28.8] years, respectively, p = 0.002) and had shorter disease duration (14 [9-24] versus 20 [14-32] years, respectively, p = 0.004). After adjustment for covariates (sex, disease duration, body mass index, and use of continuous subcutaneous insulin infusion), detectable C-peptide level was associated with lower time above range (TAR; aβ -11.03, p = 0.002), glucose management indicator (GMI, aβ -0.55, p = 0.024), and average glucose (aβ -14.48, p = 0.045) and HbA1c (aβ -0.41, p = 0.035) levels. Patients with detectable versus those with undetectable C-peptide level had significantly higher time in range (TIR) before (β = 7.13, p = 0.044) and after (aβ = 11.42, p = 0.001) adjustments. Detectable C-peptide level was not associated with lower time below range (TBR), coefficient of variation (CV), or prevalence of chronic microvascular and macrovascular complications.

Conclusions: Persistent C-peptide secretion in patients with T1DM was associated with significantly better metabolic control reflected by different glucose metrics, namely, TIR, TAR, GMI, and HbA1c.

Objective: Patients with pediatric differentiated thyroid carcinoma (DTC) treated with radioiodine (RAI) therapy may experience long-term side effects, such as gonadal dysfunction. Therefore, it is crucial to understand the impact of this therapy on ovarian reserve and future pregnancy rates.

Subjects and methods: Retrospective analysis of 64 female DTC survivors of childbearing age to assess the risk of infertility due to RAI performed before the age of 19 years.

Results: Thirty-two out of the 64 DTC survivors had a history of at least one pregnancy during follow-up. No significant differences were observed between the cumulative RAI activity, treatment regimens (multiple versus single RAI treatment), age at first treatment, or presence of lymph node or distant metastases. Notably, the group without a history of pregnancy had a younger age at the time of diagnosis and larger tumors. Age at first pregnancy was slightly higher than that in the general population, but no increase in negative maternal or fetal outcomes was observed.

Conclusions: The results of this study show little observational evidence suggesting important adverse effects of RAI on fertility or pregnancy outcomes among female survivors of childhood DTC. Still, studies including larger populations are warranted.