Change in Circulating Levels of Endothelial Progenitor Cells and Sexual Function in Women With Type 1 Diabetes.

CONTEXT: Endothelial progenitor cells (EPCs), which are involved in the mechanisms of vascular repair and sexual function, are decreased in diabetic women compared with general population. OBJECTIVE: This work aimed to investigate the circulating levels of EPCs and the change in sexual function during the menstrual cycle in women with type 1 diabetes (T1DM) compared with healthy women. METHODS: This case-control observational study was conducted at the Unit of Endocrinology and Metabolic Diseases at University Hospital "Luigi Vanvitelli'' of Naples. Participants included 36 women with T1DM and 64 age-matched healthy controls. EPCs were quantified by flow cytometry and sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale. All assessments were made at the follicular, ovulatory, and luteal phases of the same menstrual cycle. Main outcome measures included differences in EPCs levels and sexual function between patients and controls. RESULTS: Compared with controls, women with T1DM showed significantly lower levels of both CD34 + (P < .001) and CD34 + CD133 + cells (P < .001) in the ovulatory phase, and CD34 + KDR + cells both in the ovulatory phase and in the luteal phase (P < .001 for both). Diabetic women showed significantly lower total FSFI scores and higher FSDS score than control women in all phases of the menstrual cycle. FSFI total score was predicted by both CD34 + CD133 + and CD34 + KDR + cells in the follicular phase, CD34 + and CD34 + KDR + CD133 + cells in the ovulatory phase, and CD34 + KDR + and CD34 + KDR + CD133 + cells in the luteal phase. CONCLUSION: Women with T1DM show lower levels of EPCs during the menstrual cycle compared with controls. EPCs count predicts sexual function in this selected population.

Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome.

CONTEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. OBJECTIVE: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. METHODS: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukuda, Canadian, and Institute of Medicine criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands. APA and AHA titers both were assessed and the prevalence of pituitary hormone deficiencies was also investigated. RESULTS: Patients in group 1 showed a high prevalence of AHA (33%) and APA (56%) and significantly lower levels of adrenocorticotropin (ACTH)/cortisol, and growth hormone (GH) peak/insulin-like growth factor-1 (IGF-1) vs controls (all AHA/APA negative). Patients in group 1A (13 patients positive at high titers, ≥ 1:32) showed ACTH/cortisol and GH peak/IGF-1 levels significantly lower and more severe forms of ME/CFS with respect to patients in group 1B (7 positive at middle/low titers, 1:16-1:8) and 1C (10 antibody-negative patients). CONCLUSION: Both AHA and/or APA at high titers were associated with hypothalamic/pituitary dysfunction, suggesting that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Abnormal Liver Blood Tests in Patients with Hyperthyroidism: Systematic Review and Meta-Analysis.

Background: Abnormal liver blood tests (LBTs) in hyperthyroid patients are not uncommonly encountered. One major adverse event of antithyroid drug (ATD) therapy is drug-induced hepatotoxicity. Abnormal LBT in the hyperthyroidism scenario is a main diagnostic and therapeutic dilemma. We aimed to assess the prevalence and the response to ATD therapy of LBT abnormalities in newly diagnosed and uncomplicated hyperthyroidism through a systematic review and meta-analysis. Methods: A literature search was performed reporting LBTs at presentation and after ATD therapy in hyperthyroid patients. A proportion meta-analysis was performed with random-effects model. Pooled data were presented with 95% confidence intervals (CI). I2 statistic index was used to quantify the heterogeneity. Sensitivity analyses for prevalence of hyperthyroid patients with at least one abnormal LBT were performed. p-Value of <0.05 was regarded as significant. Results: The literature search yielded 2286 studies, of which 25 were included for systematic review and meta-analysis. The prevalence of untreated hyperthyroid and Graves' disease patients with at least one abnormal LBT was 55% ([CI 46-63%], I2 96%) and 60% ([CI 53-67%], I2 92%), respectively. The prevalence of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (BIL), and γ-glutamyltransferase (GGT) abnormalities in hyperthyroid patients were 33% ([CI 24-44%], I2 95%), 23% ([CI 17-29%], I2 89%), 44% ([CI 35-52%], I2 93%), 12% ([CI 7-20%], I2 92%), and 24% ([CI 16-36%], I2 95%), respectively. ATD therapy, along with euthyroidism restoration, was accompanied by normalization of LBT abnormalities in the following percentage of cases: ALT 83% ([CI 72-90%], I2 46%), AST 87% ([CI 74-94%], I2 2%), ALP 53% ([CI 32-73%], I2 76%), BIL 50% (CI cannot be calculated), and GGT 70% ([CI 47-87%], I2 74%). The sensitivity analyses showed similar results as those of the main analyses. The publication bias was not statistically significant for all outcomes, except for the prevalence of resolved BIL abnormalities that was not calculable. Conclusions: LBT abnormalities are common in newly diagnosed and untreated hyperthyroidism setting. A high chance of safely normalizing elevated transaminases, up to fivefold above the upper limit of normal, accompanies the use of ATDs in the treatment of hyperthyroidism.

Female Sexual Function in Young Women With Type 1 Diabetes and Additional Autoimmune Diseases.

BACKGROUND: Female sexual dysfunctions (FSDs) are frequent concerns in women with type 1 diabetes (T1D), which is frequently associated with other autoimmune diseases (ADs). AIM: To assess sexual function in young type 1 diabetic women with or without additional ADs. METHODS: Women with T1D aged 18-35 years with a stable couple relationship and no oral contraceptive use were enrolled. Diabetic women with concomitant ADs were also identified. All women completed the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale. OUTCOMES: The main outcome was the prevalence of FSD. The FSFI-single domain scores were also evaluated in diabetic women with or without additional ADs. RESULTS: The global population included 154 diabetic women, of whom 66 (42%) had at least one additional AD. The prevalence of FSD was similar among diabetic women with and those without (30% vs 32%, P = .980) additional ADs. The FSFI-desire score was significantly lower among diabetic women with concomitant ADs than those without ADs [median (interquartile range), 4.1 (3.6, 4.8) vs 4.6 (4.0, 5.0), P = .042]. CLINICAL IMPLICATIONS: An early evaluation of sexual function in women with T1D and concomitant ADs should be encouraged. STRENGTHS & LIMITATIONS: Major strengths are the use of 2 validated tools to diagnose FSD and the relatively large number of subjects investigated. The limitations include the cross-sectional nature of the study, which does not allow to make inference regarding the cause and effect. CONCLUSION: Diabetic women with additional ADs show an impairment in sexual desire as compared with those suffering only from diabetes. Longo M, Cirillo P, Scappaticcio L, et al. Female Sexual Function in Young Women With Type 1 Diabetes and Additional Autoimmune Diseases. J Sex Med 2021;18:219-223.

Remission of Pituitary Autoimmunity Induced by Gluten-Free Diet in Patients With Celiac Disease.

CONTEXT: An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD). OBJECTIVE: The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH). DESIGN: Five-year longitudinal observational study. SETTING: Tertiary referral center for immunoendocrinology at the University of Campania "Luigi Vanvitelli". PATIENTS: Ninety-three newly diagnosed LYH patients (high titer of antipituitary antibodies [APA] and normal or subclinically impaired pituitary function) were enrolled from 2000 to 2013 and grouped as follows: group 1, consisting of 43 patients with LYH + CD, and group 2, consisting of 50 patients with isolated LYH only. INTERVENTION: A GFD was started in patients in group 1 after the diagnosis of CD. MAIN OUTCOME MEASURES: APA titers and pituitary function were evaluated at the beginning of the study and then yearly for 5 years in both groups. Patients progressing to a clinically overt LYH were excluded from the follow-up. RESULTS: Complete remission of LYH (disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism) occurred in 15 patients in group 1 after a GFD (34%) and spontaneously in only 1 patient in group 2 (2%) (P < .001). Two patients in group 1 and 25 in group 2 progressed to a clinically overt hypopituitarism and dropped out from the study to receive an appropriate replacement therapy. The presence of CD was the only independent predictor of pituitary function recovery (hazard ratio [HR] 0.059, 95% confidence interval [CI] 0.01-0.54, P = .012). CONCLUSION: In patients with LYH and CD, a GFD may be able to induce remission of subclinical LYH, or prevent the progression to clinical stage of this disease.

Alterations in the Levels of Circulating and Endothelial Progenitor Cells Levels in Young Adults with Type 1 Diabetes: A 2-Year Follow-Up from the Observational METRO Study.

PURPOSE: Type 1 diabetes is associated with high risk of cardiovascular disease (CVD). Reduced levels of circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) have been indicated as a risk factor for adverse cardiovascular outcomes and death in people at high cardiovascular risk. The aim of the present study was to evaluate the change in CPCs and EPCs levels in a population of young type 1 diabetic patients treated with intensive insulin regimen over a period of 2 years. PATIENTS AND METHODS: A total of 204 type 1 diabetic patients, of whom 84 treated with insulin pump (CSII) and 120 with multiple daily insulin injections (MDI), completed a 2-year follow-up. Clinical measurements, including the indices of glycemic control and glucose variability, were collected at baseline and after 2 years. Both CPC and EPC cell count were assessed by flow cytometry. RESULTS: Mean age of participants was 24.5 years and mean diabetes duration was 13.6 years. After 2 years, we found a significant reduction of HbA1c (-0.3% versus baseline, P <0.001), associated with decrease in mean amplitude of glucose excursion (MAGE) (-0.5 mmol/L versus baseline, P<0.001), continuous overall net glycemic action (CONGA) (-0.2 mmol/L versus baseline, P=0.006), and blood glucose standard deviation (BGSD) (-0.2 mmol/L versus baseline, P<0.001). The number of all EPCs phenotypes, but not CPC cell count, significantly raised up in the entire population, with higher increase in CSII group. MAGE resulted as an independent predictor for increased levels of both CD34+ (P = 0.020) and CD34+KDR+ (P = 0.004) cell count in the whole population. CONCLUSION: Over a 2-year follow-up, young type 1 diabetic patients showed an increase in circulating EPCs levels, which was higher in patients with CSII. Glucose variability resulted as an independent predictor of the raised levels of EPCs in this selected population.

The role of autoimmunity in pituitary dysfunction due to traumatic brain injury.

PURPOSE: Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic-pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. METHODS: Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence. RESULTS: The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP. CONCLUSIONS: HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.

Circulating regulatory T cells (Treg), leptin and induction of proinflammatory activity in obese Labrador Retriever dogs.

Over-nutrition and obesity have been associated with impaired immunity and low-grade inflammation in humans and mouse models. In this context, a causal role for unbalanced T regulatory cell (Treg)-dependent mechanisms has been largely suggested. Obesity is the most common nutritional disorder in dogs. However, it is not defined whether canine obesity may influence circulating Treg as well as if their number variation might be associated with the occurrence of systemic inflammation. The present study investigated the immune profile of healthy adult obese dogs belonging to the Labrador Retriever breed, in comparison with the normal weight counterpart. Indeed, obesity has been described as particularly evident in this dogs. With this purpose, 26 healthy dogs were enrolled and divided into two groups based on body condition score (BCS): controls (CTR: BCS 4-5) and obeses (OB: BCS ≥ 7). Our data indicate that adult obese Labrador Retrievers are characterised by the inverse correlation between leptin serum concentration and circulating Treg (CD4+CD25highFoxp3+) levels. In addition, an increased number of cytotoxic T cell effectors (CD3+CD8+) and a higher IFN-γ production by cytotoxic T lymphocytes were observed in OB group. These results may provide new insights into the immunological dysregulation frequently associated to obesity in humans and still undefined in dogs.