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.

The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunction.

PURPOSE: Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized. METHODS: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having the oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed. CONCLUSIONS: These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving couple sexual satisfaction and overall general health.

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.

Obesity in Prader-Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches.

Prader-Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The three main genetic subtypes are represented by paternal 15q11-q13 deletion, maternal uniparental disomy 15, and imprinting defect. Clinical picture of PWS changes across life stages. The main clinical characteristics are represented by short stature, developmental delay, cognitive disability and behavioral diseases. Hypotonia and poor suck resulting in failure to thrive are typical of infancy. As the subjects with PWS age, clinical manifestations such as hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency due to hypothalamic dysfunction occur. Obesity and its complications are the most common causes of morbidity and mortality in PWS. Several mechanisms for the aetiology of obesity in PWS have been hypothesized, which include aberration in hypothalamic pathways of satiety control resulting in hyperphagia, disruption in hormones regulating appetite and satiety and reduced energy expenditure. However, despite the advancement in the research field of the genetic basis of obesity in PWS, there are contradictory data on the management. Although it is mandatory to adopt obesity strategy prevention from infancy, there is promising evidence regarding the management of obesity in adulthood with current obesity drugs along with lifestyle interventions, although the data are limited. Therefore, the current manuscript provides a review of the current evidence on obesity and PWS, covering physiopathological aspects, obesity-related complications and conservative management.

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.

Clinical inertia, reverse clinical inertia, and medication non-adherence in type 2 diabetes.

PURPOSE: Clinical inertia and medication non-adherence are thought to contribute largely to the suboptimal glycemic control in many patients with type 2 diabetes. The present review explores the relations between A1C targets, clinical inertia and medication non-adherence in type 2 diabetes. METHODS: We searched PubMed for English-language studies published from 2001 through June 1, 2018. We also manually searched the references of selected articles, reviews, meta-analyses, and practice guidelines. Selected articles were mutually agreed upon by the authors. RESULTS: Clinical inertia is the failure of clinicians to initiate or intensify therapy when indicated, while medication non-adherence is the failure of patients to start or continue therapy that a clinician has recommended. Although clinical inertia may occur at all stages of diabetes treatment, the longest delays were reported for initiation or intensification of insulin. Medication non-adherence to antidiabetic drugs may range from 53 to 65% at 1 year and may be responsible for uncontrolled A1C in about 23% of cases. Reverse clinical inertia can be acknowledged as the failure to reduce or change therapy when no longer needed or indicated. Clinical inertia and medication non-adherence are difficult to address: clinician-and patient-targeted educational programs, more connected communications between clinicians and patients, the help of other health professional figures (nurse, pharmacist) have been explored with mixed results. CONCLUSIONS: Both clinical inertia and medication non-adherence remain significant barriers to optimal glycemic targets in type 2 diabetes. Moreover, part of clinical inertia may be a way through which clinicians face current uncertainty in medicine, including some dissonance among therapeutic guidelines. Scientific associations should find an agreement about how to measure and report clinical inertia in clinical practice and should exhort clinicians to consider reverse clinical inertia as a cause of persisting inappropriate therapy in vulnerable patients.

Cardiovascular outcome trials and major cardiovascular events: does glucose matter? A systematic review with meta-analysis.

PURPOSE: We did a meta-analysis with meta-regression to evaluate the relationship between hemoglobin A1c (A1C) reduction and the primary CV outcome of cardiovascular outcome trials (CVOTs). METHODS: We used a random effects meta-analysis of the 12 CVOTs to quantify the effect of A1C reduction on major cardiovascular events (MACE) risk by stratifying the difference in achieved A1C (drug vs placebo) in three strata: A1c < 0.3%, A1c ≥ 0.3% and < 0.5%, and A1c ≥ 0.5%. RESULTS: We found a relation between the reduction in achieved A1C and the hazard ratio reduction for MACE (P = 0.002), explaining almost all (94.1%) the between-study variances: lowering A1C by 0.5% conferred a significant HRR of 20% (95% CI 4-33%) for MACE. CONCLUSIONS: Blood glucose reduction may play a more important role than previously thought in reducing the risk of MACE during treatment with the newer glucose-lowering drugs, including peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors.

Endocrine rhythms and sport: it is time to take time into account.

BACKGROUND: Studies of time-related biological phenomena have contributed to establishing a new scientific discipline, the chronobiology, which considers biological phenomena in relation to time. Sports activity profoundly affects the temporal organization of the organism and endocrine rhythms play a key role in the chronoorganization of individuals and are particularly important for correct physical activity. Correctly reading rhythmic hormonal variations of the human organism opens new horizons to sports medicine. OBJECTIVE: This review is aimed at clarifying the relationship between endocrine rhythms and sports activities on the basis of the latest data in the literature. METHOD: Data acquisition was obtained from three databases (PubMed, Scopus and SPORTDiscus), paying particular attention to reviews, meta-analysis, original and observational studies on this issue. RESULTS: After the description of the general characteristics and parameters of biological rhythms, the main endocrine rhythms will be described, highlighting in particular the interrelationships with sports activity and focusing on the factors which can affect negatively their characteristics and consequently the psychophysical performances of the athletes. CONCLUSION: Knowledge of this issue may allow establishing the best form of competitive or amateur activity, through the collaboration of an informed athlete and a sports physician attentive to biological rhythms. By taking into account that alteration of physiological rhythmic temporal organization can favour the onset of important diseases, including cancer, this will lead to the expected performances without impairing the correct chronoorganization of the athlete.

From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome.

Metabolic diseases are associated with chronic low-grade inflammation, which has been indicated as a potential mediator of endothelial dysfunction and cardiovascular disease. Visceral adiposity is thought to be the starting condition of the inflammatory state through the release of inflammatory cytokines, including TNF-alpha, CRP, and IL-6, which in turn promote endothelial dysfunction, endothelial expression of chemokines (IL-1) and adhesion molecules (ICAM-1, VCAM-1, and P-selectin), and the inhibition of anti-atherogenic factors (adiponectin). Obesity, metabolic diseases, and diabetes, all conditions characterized by abdominal fat, are well-recognized risk factors for sexual dysfunction in both sexes. Evidence from randomized-controlled trials supports the association between inflammatory milieau and erectile dysfunction in men suffering from metabolic diseases, whereas, in women, this has to be confirmed in further studies. A healthy lifestyle based on dietary pattern with high content of whole grain, fruit, nuts and seeds, and vegetables and low in sodium and saturated fatty acids plus regular physical activity may help to modulate the pro-inflammatory state associated with metabolic diseases and the related burden of sexual dysfunctions.

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.

Sexual function in young women with type 1 diabetes: the METRO study.

PURPOSE: The aim of this study was to evaluate the prevalence and risk factors associated with female sexual dysfunction (FSD) in young women with type 1 diabetes treated with different intensive insulin regimens. METHODS: Type 1 diabetic women aged 18-35 years were included in this study if they had stable couple relationship and no oral contraceptive use. All women were asked to complete the Female Sexual Function Index (FSFI) and other validated multiple-choice questionnaires assessing sexual-related distress (Female Sexual Distress Scale, FSDS), quality of life (SF-36 Health Survey), physical activity (International Physical Activity Questionnaire), depressive symptoms (Zung Self-Rating Depression Scale, SRDS) and diabetes-related problems (Diabetes Integration Scale ATT-19). FSD was diagnosed according to a FSFI score higher than 26.55 and a FSDS score lower than 15. RESULTS: The overall prevalence of FSD in diabetic and control women was 20 and 15 %, respectively (P = 0.446). Compared with the continuous subcutaneous insulin infusion group and control women, diabetic women on multiple daily injections (MDI) had lower global FSFI score (P = 0.007), FSDS score (P = 0.045) and domains such as arousal (P = 0.006), lubrication and satisfaction scores (P < 0.001 for both). In the multiple regression analysis, only the mental component summary (P = 0.047) and the SRDS score (P = 0.042) were independent predictors of FSFI score in the overall diabetic women. CONCLUSION: Young women with type 1 diabetes wearing an insulin pump show a prevalence of sexual dysfunction similar to that of healthy age-matched women, but sexual function was significantly impaired in diabetic women on MDI therapy. Depression and the mental health status were independent predictors for FSD in diabetic women.

Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes?

PURPOSE: To evaluate the Vitamin D status of patients with a single autoimmune disease and of patients with several autoimmune diseases. METHODS: We enrolled 35 patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among patients with APS, 10 were classified as type 2 (Addison's disease + T1DM), whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a chemiluminescent immunoassay in all patients and controls on samples drawn in the morning of the same months. RESULTS: Both groups of APS and T1DM patients showed 25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs controls), without any significant difference between the two groups (p = 0.80). The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in APS type 3 subgroup (8 out of 50 patients, 16%). CONCLUSIONS: Patients with APS present reduced vitamin D circulating levels, but the vitamin D status is not different between patients with single or multiple autoimmune diseases. The kind of autoimmune disease, rather than the association of several autoimmune diseases, may influence negatively the levels of vitamin D. Further prospective studies are needed to clarify if impaired vitamin D level is a causal factor in the pathogenesis of autoimmune diseases or a consequence of them.

Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis.

BACKGROUND: Literature data examining the role of metabolic syndrome and its components in prostate cancer risk are limited and contradictory. AIM: We did a meta-analysis of studies that evaluated the association between metabolic syndrome, its components, and risk of prostate cancer. SUBJECTS AND METHODS: We conducted an electronic search for articles published through September 2012 without restrictions. Every included study was to report risk estimates with 95% confidence intervals for the association between metabolic syndrome and prostate cancer. RESULTS: The final number of papers included in the meta-analysis was 14, all published in English, with 4728 prostate cancer cases. Metabolic syndrome was associated with a 12% increase in prostate cancer risk (p=0.231), that was lower in cohort studies (7 studies, RR=1.04, p=0.791) than other studies (RR=1.23, p=0.125). The association was significant in the 8 European studies (RR=1.30, p=0.034), but not in the 4 U.S. or 2 Asiatic studies. The risk estimates of prostate cancer for higher values of body mass index, dysglycemia or dyslipidemia (high triglycerides, low HDL-cholesterol) were not significant; on the contrary, hypertension and waist circumference >102 cm were associated with a significant 15% (p=0.035) and 56% (p=0.007) greater risk of prostate cancer, respectively. CONCLUSIONS: Metabolic syndrome is weakly and non significantly associated with prostate cancer risk, but associations vary with geography. Among single components of the syndrome, hypertension and higher waist circumference are significantly associated with increased risk of prostate cancer.

Female sexual dysfunction in women with thyroid disorders.

BACKGROUND: Few data exist on the prevalence of female sexual dysfunction (FSD) in thyroid disorders. AIM: We evaluated FSD in women with thyroid diseases and in control age-matched healthy women to investigate the relationship between sexual function and thyroid hormones. METHODS: One hundred and four women with thyroid diseases and 53 controls participated in the study. Eighteen with hyperthyroidism (Group 1), 22 hypothyroidism (Group 2), 45 Hashimoto's thyroiditis (Group 3), 19 nodular goiter (Group 4) underwent thyroid function evaluation and sonography. The Female Sexual Function Index (FSFI) assessed sexual function. RESULTS: The prevalence of FSD was 46.1% in thyroid diseases and 20.7% in controls. Only in Group 4, the prevalence (68.4%) was significantly higher than in controls (p<0.005). The mean total FSFI score was 20.1 ± 7.1 in women with thyroid diseases and 25.6 ± 4.7 in the controls (p<0.001). Compared with controls, there was a significant decrease of desire in Group 2; desire, arousal and lubrication in Group 3; desire, arousal, lubrication, orgasm and satisfaction in Group 4. In thyroid diseases the prevalence of FSD was 53% and 42%, while in the controls was 55% and 20%, in menopausal and pre-menopausal groups, respectively. We found a significant inverse correlation between TSH and FSFI (r=-0.7, p=0.01) in Group 4, which showed the lowest FSFI score (17.8 ± 5.7) and the highest body mass index (28.4 ± 7.1 kg/m(2)). CONCLUSIONS: Women with thyroid diseases present a higher prevalence of FSD than controls. Although our findings suggest a higher impairment of sexual function in Group 4 and a role for TSH in FSD, further researches are needed.