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For many statistical methods that are commonly used in medical research, it is assumed that observations are independent. However, when this assumption is violated, alternative methods may be needed. In this paper, we describe why an analysis that ignores the dependencies within the data may provide biased results and outline possible alternatives. This paper aims to create awareness among researchers, readers, and reviewers for this possible source of bias in medical research. [ABSTRACT FROM AUTHOR]

Objective: Thyroglobulin measurement is the cornerstone of modern management of differentiated thyroid cancer, with clinical decisions on treatment and follow-up based on the results of such measurements. However, numerous factors need to be considered regarding measurement with and interpretation of thyroglobulin assay results. Design: The present document provides an integrated update to the 2013 and 2014 separate clinical position papers of our group on these issues. Methods: Issues concerning analytical and clinical aspects of highly-sensitive thyroglobulin measurement will be reviewed and discussed based on an extensive analysis of the available literature. Results: Thyroglobulin measurement remains a highly complex process with many pitfalls and major sources of interference, especially antithyroglobulin antibodies, need to be assessed, considered and, when necessary, dealt with appropriately. Conclusions: Our expert consensus group formulated 53 practical, graded recommendations for guidance on highly-sensitive thyroglobulin and TgAb in laboratory and clinical practice, especially valuable where current guidelines do not offer sufficient guidance. [ABSTRACT FROM AUTHOR]

In this methodology editorial, the problem of censored survival (or time-to-event) data in clinical research is discussed. In case of censored observations, part of the observation time for some participants in a study is unobserved, which means that measures such as an average survival time cannot be calculated. Instead, censored survival time should explicitly be accounted for in the analysis of a study, for example using the Kaplan–Meier method. Implications of censoring and how to deal with it in the analysis of a study or when reading a research paper are discussed. [ABSTRACT FROM AUTHOR]

Importance: This proof-of-concept paper demonstrates that driver mutations can be detected in plasma in differentiated thyroid tumors, and we were able to detect mutations in up to 80% malignant thyroid nodules. Additionally, cancer subtypes could also be predicted using a 8-gene panel. In almost 90% follicular adenoma, rat sarcoma virus (RAS) mutations were detectable. There was a strong agreement between driver mutations found in plasma samples, FNAC materials, and histopathology samples. This has potential as a noninvasive, preoperative diagnostic tool (particularly of clinical importance in indeterminate nodules) and may help in detection of residual tumor after surgery. Future research is warranted to test the role of this tool to detect tumor recurrence. Objective: Ultrasonographic (USG) evaluation and fine-needle aspiration (FNA) are cornerstone for evaluation of thyroid neoplasm. Molecular technique including detection of driver mutation from FNA cytology (FNAC) material is an established modality. In this study, we explored the feasibility of using plasma cell--free nucleic acids to identify known driver mutations in differentiated thyroid neoplasm. Design: Patients presenting with thyroid nodules underwent USG with Thyroid Image Reporting and Data Systems scoring and FNAC (Bethesda classification). All patients in Bethesda 3, 4, 5, 6 underwent surgery and histopathological confirmation. Patients in Bethesda 2 (cosmetic concerns, compressive symptoms) underwent surgery, and rest were presumed benign on the basis of USG, FNAC features, and clinical followup.). Setting: Endocrinology clinic. Participants: Subjects with thyroid nodule. Intervention(s) or Exposure(s): None. Main Outcome(s) and Measure(s): Plasma sample, FNA, and histopathology material were evaluated for driver mutations (8-gene panel comprising BRAF-V600E, RET/PTC3, RET/PTC1, TERT promoter, HRAS, NRAS, KRAS, and PAX8-PPARG). Results: A total of 223 subjects were recruited; of these 154 were benign and 69 had differentiated thyroid cancer. We were able to detect driver mutation from plasma in 55 subjects (79.71%) of all malignant patients, and 11 patients in benign category had RAS mutation (follicular adenoma). Rest of the benign nodules did not have any detectable driver mutations. Conclusions and Relevance: Plasma might be a viable noninvasive alternative source for detection of driver mutations (8-gene panel) in subjects with differentiated thyroid tumors and may have significant clinical utility. [ABSTRACT FROM AUTHOR]

MEN1 is an autosomal dominant hereditary syndrome characterized by several endocrine tumors, in most cases affecting the parathyroid glands, pancreas, and anterior pituita ry. It is the result of inactivating mutations in the tumor suppressor gene MEN1. More than 1300 different mutations have been identified in this gene. Mosaic MEN1 mutations have been previously described in only a few patients in the li terature. In this paper, we provide a review of six cases of MEN1 mosaicism reported in the literature supplemented with six add itional cases described by the French TENgen network of laboratories. This review highlights that (i) MEN1 mosaicism is not associated with a mild phenotype and results in the same natural history as heterozygous MEN1 mutation and (ii) that more systematic detection of MEN1 mosaic mutation enables improvements in both patient monitoring and genetic counseling. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients. [ABSTRACT FROM AUTHOR]

Obesity, the growing pandemic of the 21st century, is associated with multiple organ dysfunction, either by a direct increase in fatty organ content or by indirect modifications related to general metabolic changes driven by a specific increase in biologic products. The pituitary gland is not protected against such a situation. Different hypothalamic–pituitary axes experience functional modifications initially oriented to an adaptive situation that, with years of obesity, turn to maladaptive dynamics that contribute to perpetuating obesity and specific symptoms of their hormonal nature. This paper reviews the recent knowledge on obesity-related pituitary dysfunction and its pathogenic mechanisms and discusses potential therapeutic actions aimed at contributing to ameliorating the complex treatment of severe cases of obesity. [ABSTRACT FROM AUTHOR]

Objective: Thyroid surgery may lead to postoperative complications. The a im of this paper was to determine whether the rate of postoperative hypoparathyroidism (HPT) is influenced by whether surgery is staged. Design: Single-institution retrospective observational study. Methods: The clinical records of 786 patients treated at the Otolaryngo logy Unit of the Azienda USL-IRCCS di Reggio Emilia between January 1990 and December 2015 were reviewed. Pa tients were divided into two groups according to the surgical treatment received: group TT (637 patients, 81.04%) underwent single-stage total thyroidectomy; Group cT (149 patients, 18.96%) underwent loboisthmusectomy and delay ed completion total thyroidectomy. Transient and permanent HPT, assessed after 6 months of follow-up, were the p rimary endpoints. Risk factors of postoperative HPT were also analysed as secondary outcomes. Results: Rates of transient HPT in group TT were higher than those obse rved in group cT, (P = 0.0057). Analysis of risk factors identified sex as an independent risk factor for transie nt HPT only for group TT (P = 0.0012) and the number of parathyroid glands remaining in situ (PGRIS) as an independent risk factor for transient and perman ent HPT for group TT (P < 0.0001 and P = 0.0002, respectively). Conclusions: This study suggests that the risk of transient postoperative H PT is lower in patients that undergo completion thyroidectomy. Further independent risk factors for postoperative HPT are female sex and PGRIS score. In light of the growing use of conservative surgery for thyroid ne oplasms, these findings could help to adequately plan surgery in order to reduce endocrine complications. [ABSTRACT FROM AUTHOR]

In a recent paper, Subramanian and collaborators reported a 52% increased risk of COVID-19 infection in women with polycystic ovary syndrome (PCOS) and an incidence nearly twice that of women without PCOS. The authors focused, as important factors of the increased prevalence of infection, both the inflammatory characteristic of PCOS and the increase in androgens that facilitate the entry of the virus into the cells of the target organs. We asked 200 consecutive, unvaccinated women with PCOS who had been followed with spirono lactone for more than 4 months, about COVID-19 infection and found only four patients who were infected. No ne of the infected patients were hospitalized and only one had fever and other manifestations of the syndrome, but the se symptoms resolved in a few days. The other three reported only mild or minimal symptoms. This observation needs confirmation with specific studies, considering the possibility that many other patients may have been infected by being asymptomatic and not swabbing for COVID-19. Spironolactone can increase the circulating angiotensin-converting enzyme 2 and antagonize the androgen receptor, preventing activation of transmembrane protease serine 2 in cel ls of the respiratory tract and other tissues. Drug also has potent anti-inflammatory and antithrombotic actions by antag onizing the mineralocorticoid receptor in target tissues and inflammatory cells. From Subramanian's study and rep orted observations, a proper evaluation of the use of spironolactone in COVID-19 in both PCOS and the general popu lation is urged. [ABSTRACT FROM AUTHOR]