Thymic hyperplasia is accurate to detect new-onset Graves' hyperthyroidism and resolves after restoring euthyroidism.

PURPOSE: Abnormal liver blood tests (ALBTs), neutropenia (NEU) and thymic hyperplasia (TH) are new features of Graves' disease (GD). Our objectives were: (a) to calculate the accuracy of TH in discriminating between Graves' and non-Graves' thyrotoxicosis, compared to ALBTs, NEU and Graves' orbitopathy (GO); (b) to explore the outcome of GD-associated TH and non-GD-associated TH. METHODS: We prospectively analyzed consecutive adult patients with newly diagnosed thyrotoxicosis from January 2018 to June 2023. TH was detected via neck ultrasound (nUS) then confirmed and followed by magnetic resonance imaging (MRI). For GD vs non-GD clinical sensitivity (SE) and specificity (SPEC), accuracy, positive predictive value (PPV) and negative predictive value (NPV) of GO, TH, ALBTs and NEU were calculated. RESULTS: 264 thyrotoxic patients were included. TH was found in 16.4% (20/122) of GD vs 1.4% (2/142) in non-GD (p < 0.001). SE, SPEC, accuracy, PPV and NPV of the four extrathyroidal manifestations of GD were as follows, respectively: GO 26%, 100%, 66%, 100%, 61%; ALBTs 41%, 89%, 69%, 76%, 66%; NEU 5%, 100%, 56%, 100%, 55%; TH 16%, 98%, 61%, 91%, 98%. In 18 of them, TH regressed within 12 months after achieving euthyroidism under anti-thyroid drug therapy, while in the remaining 2, TH regressed 6 months after thyroid surgery. In the two non-GD patients with TH, thymus disappeared along with euthyroidism. CONCLUSIONS: TH in the hyperthyroidism scenario provides a high PPV for GD. A conservative approach for the diagnostic work-up and initial management of thyrotoxicosis-associated TH should be adopted.

Semen quality and metabolic profile in people with type 1 diabetes with and without erectile dysfunction: a cross-sectional study.

PURPOSE: The aim of the present study is to evaluate the association of metabolic and glycemic variables with semen parameters in patients with type 1 diabetes (T1D) with and without erectile dysfunction (ED). METHODS: The study population included 88 adults with T1D using a continuous glucose monitoring, of whom 28 with ED (ED group) and 60 without it (NO ED group). All men completed the International Index of Erectile Function (IIEF-5) and underwent body composition analysis (BIA) and semen analysis. RESULTS: ED group showed worse HbA1c levels [median (IQR), 8.4 (7.7, 9.9) vs 7.4 (7, 8.2) %, P < 0.001)], higher insulin dose [60 (51, 65) vs 45 (38, 56) UI/die, P = 0.004)] and a higher total body water and intracellular water as compared with ED group. Men in the ED group presented higher semen volume [2.8 (2.6, 4.2) vs 2.5 (2.2, 2.7) mL, P < 0.001] and sperm concentration [24 (19, 29) vs 20 (12, 23) mil/mL, P = 0.010], but reduced sperm progressive motility [28 (25, 35) vs 35 (25, 36) %, P = 0.011], higher rate of non-progressive motility [15 (10, 15) vs 10 (5, 10) %, P < 0.001] and higher rate of typical morphology [7(5, 8) vs 5 (4, 5) %, P = 0.001]. Based on multivariate logistic regression analysis performed to assess the association between clinical variables and ED, intracellular water (OR 3.829, 95% CI 1.205, 12.163, P = 0.023) resulted as the only independent predictor of ED. CONCLUSION: Men with T1D and ED showed worse metabolic profile which is associated with poor semen quality, as compared with those without ED.

Case Report: Post-gastrectomy reactive hyperinsulinemic hypoglicaemia: glucose trends before and after canagliflozin treatment.

The pathogenesis of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia is not yet fully clarified. Recent studies suggest an up-regulation of the intestinal glucose transporter SGLT-1 aimed to prevent carbohydrate malabsorption. The overexpression of SGLT-1 could therefore represents one of the mechanisms underlying the wide glycemic excursions found in patients after gastrectomy, but studies investigating the use of SGLT-1/SGLT-2 inhibitors in patients with post-gastrectomy reactive hyperinsulinemic hypoglycaemia are very scant in the literature. We report the case of a 37-year-old non diabetic man who frequently presented symptoms of hypoglycaemia in the postprandial period. In 2012, he underwent Roux en-Y gastric bypass (RYGB) and after two years, he started to experience typical symptoms of reactive hyperinsulinaemic hypoglycaemia. We suggested healthy modifications of dietary habits and periodic follow-up visits with a dietitian. After three months, the patient still presented symptoms of reactive hypoglycaemia; we provided him with Flash Glucose Monitoring (FGM) to assess trend of glucose levels in interstitial fluid during the day and we decided to introduce canagliflozin 300 mg/day before the main meal. Hypoglycaemic events previously referred by the patient and clearly recorded by FGM completely disappeared taking canagliflozin. We found a reduction of time spent in hypoglycaemia, an improvement of glycemic variability and an increase of time in target range. It was also noted a reduction of time spent in hyperglicemia with consequent improvement of average glucose values and of glucose main indicator. This is the first report with FGM supporting a role of canagliflozin in the management of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia. Our preliminary results are very limited but in line with those of the literature and showed for the first time a reduction of hypoglycaemic events and an improvement of glycemic variability through a flash glucose monitoring system. Further studies are mandatory to confirm this therapeutic opportunity.

Glucose control in home-isolated adults with type 1 diabetes affected by COVID-19 using continuous glucose monitoring.

PURPOSE: This study is aimed at evaluating changes in metrics of glucose control in home-isolated patients with type 1 diabetes and COVID-19 using a continuous glucose monitoring (CGM) system. METHODS: We included adults aged 18-45 years with type 1 diabetes, using CGM, followed by telemedicine at a Southern Italian University Hospital. Thirty-two home-quarantined subjects with SARS-CoV-2 positive swab constituted the COVID-19 group. Thirty age-matched diabetic individuals without COVID-19 formed the control group. The effects of COVID-19 on glycemic control in patients infected were assessed at different time points [2 weeks before-COVID-19 (Time 1), 2 weeks during-COVID-19 (Time 2) and 2 weeks after COVID-19 (Time 3)] and compared with those without infection. RESULTS: A significant reduction of TIR (Time 1 vs Time 2, %, 60.1 ± 16.6 vs 55.4 ± 19.2, P = 0.03), associated with a significant increase of TAR level 2 (10.1 ± 7.3 vs 16.7 ± 12.9, P < 0.001), GMI (7.1 ± 0.6 vs 7.5 ± 0.8, P < 0.001), CV (37.3 ± 7.1 vs 39.6 ± 7.0, P = 0.04), mean glucose values (mg/dL, 160.2 ± 26.5 vs 175.5 ± 32.6, P = 0.001) and standard deviation (59.2 ± 13.1 vs 68.6 ± 17.7, P = 0.001) was observed in patients with COVID-19. No significant change of glycemic metrics was found in the NO COVID-19 group across the time. CONCLUSION: Young home-isolated patients with type 1 diabetes and COVID-19 showed a worsening of glucose control during COVID-19, as compared with age-matched diabetic subjects without the infection.

Thyroid surgery during the COVID-19 pandemic: results from a systematic review.

PURPOSE: During the COVID-19 pandemic, elective thyroid surgery is experiencing delays. The problem is that the COVID-19 pandemic is ongoing. The research purposes were to systematically collect the literature data on the characteristics of those thyroid operations performed and to assess the safety/risks associated with thyroid surgery during the COVID-19 pandemic. METHODS: We used all the procedures consistent with the PRISMA guidelines. A comprehensive literature in MEDLINE (PubMed) and Scopus was made using ''Thyroid'' and "coronavirus" as search terms. RESULTS: Of a total of 293 articles identified, 9 studies met the inclusion criteria. The total number of patients undergoing thyroid surgery was 2217. The indication for surgery was malignancy in 1347 cases (60.8%). Screening protocols varied depending on hospital protocol and maximum levels of personal protection equipment were adopted. The hospital length of stay was 2-3 days. Total thyroidectomy was chosen for 1557 patients (1557/1868, 83.4%), of which 596 procedures (596/1558, 38.3%) were combined with lymph node dissections. Cross-infections were registered in 14 cases (14/721, 1.9%), of which three (3/721, 0.4%) with severe pulmonary complications of COVID-19. 377 patients (377/1868, 20.2%) had complications after surgery, of which 285 (285/377, 75.6%) hypoparathyroidism and 71 (71/377, 18.8%) recurrent laryngeal nerve injury. CONCLUSION: The risk of SARS-CoV-2 transmission after thyroid surgery is relatively low. Our study could promote the restart of planned thyroid surgery due to COVID-19. Future studies are warranted to obtain more solid data about the risk of complications after thyroid surgery during the COVID-19 era.

New insights into vitamin D regulation: is there a role for alkaline phosphatase?

PURPOSE: The diagnosis of vitamin D deficiency is based on the determination of total plasma 25-hydroxyvitamin D (25-OHD) concentrations, but the regulation of vitamin D 25-hydroxylation is not a major consideration and very little information is available on this activity. To check what factors could interfere with the activity of vitamin D-25-hydroxylase and thus alter the 25-OHD concentrations, we looked for potential correlations between 25-OHD and results of liver function tests in healthy adults. METHODS: This single-centre study was retrospective and consisted of evaluating the correlations between 25-OHD and the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and bone alkaline phosphatase (BALP) in 349 healthy subjects aged from 18 to 65 years. In particular, in Group 1 (n = 119), we looked for correlations between 25OHD and all liver function tests and in Group 2 (n = 230) the correlation between 25OHD and BALP. RESULTS: In Group 1, we found no correlation between 25OHD and AST (r = - 0.03; p = 0.8), ALT (r = - 0.02; p = 0.91), GGT (r = - 0.08; p = 0.68), direct bilirubin (r = - 0.02; p = 0.89), indirect bilirubin (r = - 0.24; p = 0.21), and total bilirubin (r = - 0.24; p = 0.21) but one between 25OHD and ALP (r = - 0.2; p = 0.007); in Group 2, we found a significant negative correlation between 25-OHD and BALP (r = - 0.2; p = 0.0008). CONCLUSIONS: The correlations that we found suggest that ALP and BALP might be involved in the regulation of vitamin D-25-hydroxylase activity, but further studies are mandatory to confirm our assumptions.

Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis.

PURPOSE: Autoimmune thyroid events (ATEs) are common side effects after alemtuzumab (ALZ) therapy in patients with multiple sclerosis (MS). Our purpose was to reach more robust evidence on prevalence and outcome of the spectrum of alemtuzumab-induced autoimmune thyroid events in patients with multiple sclerosis. METHODS: PubMed and Scopus were systematically searched through July 2019. Studies dealing with patients without personal history of thyroid dysfunctions and affected by MS treated with ALZ and reporting ATEs were selected. Data on prevalence and outcome of ATEs were extracted. A proportion of meta-analysis with random-effects model was performed. RESULTS: Considering the overall pooled number of 1362 MS patients treated with ALZ (seven included studies), a 33% prevalence of newly diagnosed ATEs was recorded. Among all ATEs, Graves' disease (GD) was the most represented [63% of cases, 95% confidence interval (CI) 52-74%], followed by Hashimoto thyroiditis (15%, 95% CI 10-22%). Interestingly, GD showed a fluctuating course in 15% of cases (95% CI 8-25%). Of all GD, 12% (95% CI 2-42%) likely had spontaneous remission, 56% (95% CI 34-76%) required only antithyroid drugs, 22% (95% CI 13-32%) needed additional RAI, and 11% (95% CI 0.9-29%) underwent definitive surgery. CONCLUSION: Among different categories of ATEs, Graves' hyperthyroidism was the most common thyroid dysfunction, occurring in more than half of cases. Antithyroid drugs should represent the first-line treatment for ALZ-induced GD patients. However, alemtuzumab-induced GD could not be considered as having a more favourable outcome than conventional GD, given the substantial chance to encounter a fluctuating and unpredictable course.

TSH oscillations in young patients with type 1 diabetes may be due to glycemic variability.

PURPOSE: A relationship between thyroid dysfunction and diabetes mellitus has been described by several authors but the role of glycemic variability is still unclear. We planned the present study to evaluate the influence of glycemic variability on thyroid hormones and TSH concentrations in patients with type 1 diabetes mellitus (T1DM). METHODS: Seventy-seven young patients with T1DM were enrolled and evaluated for basal glucose concentrations, HbA1c, thyroid hormones and TSH concentrations. Glucose variability was investigated by considering the standard deviation of blood glucose readings and by calculating the mean amplitude of glycemic excursions and continuous overlapping net glycemic action (CONGA). The low (LBGI) and high (HBGI) blood glucose indices were also calculated. The correlations between TSH, thyroid hormones, glycemia and HbA1c were studied in patients and in controls, whereas those between TSH, thyroid hormones and indices of glucose variability only in patients. RESULTS: No correlations were observed in T1DM patients between free thyroid hormones and glycemic values, HbA1c and indices of glucose variability, while an inverse correlation was observed between TSH levels and glycemic values (r = -0.27; p = 0.01), CONGA index (r = -0.35; p = 0.001) and HBGI (r = -0.28; p = 0.01) but not with HbA1c (r = -0.1; p = 0.47). CONCLUSIONS: Our results suggest a direct action of glycemic excursions on TSH secretion, regardless of variations of thyroid hormone concentrations. Thus, the evaluation of thyroid function through the assay of TSH concentrations in these patients should be made, if possible, by multiple samples on patients in euglycemic state to avoid underestimation or overestimation of thyroid dysfunction due to a wrong diagnosis of euthyroidism or dysthyroidism with consequent inappropriate choice of therapeutic options.

Erectile dysfunction in young men with type 1 diabetes.

Erectile dysfunction (ED) is a common comorbidity of diabetes mellitus, but few studies investigated its prevalence in type 1 diabetes. The objective of this study was to evaluate the prevalence and correlates of ED in young men with type 1 diabetes treated with different intensive insulin regimens. The study population included 151 type 1 diabetic men, aged 18-35 years, and 60 healthy age-matched controls. Ninety-four men were treated with multiple daily injections of insulin (MDI), and the remaining 71 with continuous subcutaneous insulin infusion (CSII). All participants in the study completed the International Index of Erectile function (IIEF-5), and other validated multiple-choice questionnaires assessing quality of life, physical activity, depressive symptoms and diabetes-related problems. The overall prevalence of ED was higher in diabetic men (37%), as compared with controls (6%, P<0.001). ED prevalence rates were similar in both MDI (36%) and CSII (39%) groups (P=0.326); both were higher compared with controls (P<0.001 for both). More than half of diabetic men (58%) had mild ED. Compared with men without ED, diabetic men with ED showed lower weight, body mass index, fasting glucose, insulin dose and high-density lipoprotein cholesterol levels, and higher self-rating depression score (SRDS). In the multiple regression analysis only the SRDS (P=0.032) were independent predictors of IIEF-5 score in the overall diabetic men. Young men with type 1 diabetes treated with MDI or CSII show a higher prevalence of ED, as compared with healthy age-matched men. Depression was associated with ED in diabetic population.