Journal of Endocrinological Investigation最新文献

In a large fresco, which narrates brutal episodes of torture against Cirtercian monks, in the right corner of the background an ugly aggressor with a huge goiter, symbol of evil and sin, attacks a monk with a sword.

Objectives: Graves' disease induced by Alemtuzumab (GD-IA) is one of the most frequently observed adverse events in patients with multiple sclerosis (MS) treated with this drug. The aim of this study is the sequencing and description of these events, along with the identification of the risk factors leading to their development.

Materials and methods: We conducted a retrospective observational study identifying patients with relapsing-remitting multiple sclerosis (RRMS) and GD-IA, studying their baseline clinical features and variables related to the natural history of the disease.

Results: A total of 121 participants treated with Alemtuzumab were included, of whom 41 developed GD-IA (33.9%). A higher percentage of first-degree relatives with autoimmune thyroid disease was documented in the subgroup who developed the abovementioned event (14.6% vs 1.5%; p < 0.01). A total of 70.7% of patients diagnosed with GD-IA (n = 29/41) had fluctuations in thyroid function during follow-up, and 24.4% (n = 10/41) required total thyroidectomy for resolution of the condition. In 54.8% of participants diagnosed with GD-IA, a pattern of significant TSH decline was identified in the month prior to diagnosis of the event, with high predictive ability and associated with a more favorable clinical course (fewer weeks to normalization of thyroid function, HR = 8.99; 95% CI [2.11-38.44]; p = 0.0003).

Conclusion: GD-IA has an atypical course compared to classical forms of the disease. The identification of risk factors for the development of the disease before starting treatment with Alemtuzumab and early monitoring of thyroid function once this treatment is initiated prove to be useful strategies in the diagnosis and clinical management of this condition.

Purpose: Hypoparathyroidism (HypoPT) is a rare endocrine disease and conventional therapy is based on calcium and vitamin D analogues. Conventional therapy does not restore calcium homeostasis and patients complain with neuropsychological symptoms, which have been evaluated with nonspecific self-administered questionnaires. This study aims to evaluate cognitive functions of patients with chronic post-surgical (PS)-HypoPT compared to a control population, using a standardized neuropsychological approach and evaluating the relationship with serum calcium (Alb-Ca).

Methods: Observational, monocentric study on 33 patients with PS-HypoPT and 24 controls, in whom biochemical testing and a standardized neuropsychological assessment by a trained psychologist were performed.

Results: In patients with PS-HypoPT, low Alb-Ca correlated with a worse performance on semantic memory abilities and executive function, as suggested by a significant inverse correlation between Alb-Ca and Trail Making Test A (TMT-A) scores (r = - 0.423; p = 0.014) and by a positive correlation with Semantic Fluency Test scores (SF)(r = 0.510; p = 0.002). PS-HypoPT patients with Alb-Ca ≤ 8.9 mg/dl had a significantly lower test performance compared with PS-HypoPT patients with Alb-Ca > 8.9 mg/dl, both at the TMT-A test (mean score: 34.53-18.55; p < 0.0001) and at SF test (mean score: 41.94-48.68; p = 0.01) and also a significantly lower test performance compared with control patients' group at TMT-A (mean score: 34.53-25.5; p = 0.0057).

Conclusions: Patients with chronic PS-HypoPT in conventional therapy do not show a severe cognitive impairment; however, cognitive functions namely visuo-spatial attention, executive function and semantic memory appear to be modulated by Alb-Ca and impaired by its low levels.

Purpose: The current clinical practice in reproductive medicine should pose the couple at the centre of the diagnostic-therapeutic management of infertility and requires intense collaboration between the andrologist, the gynaecologist and the embryologist. The andrologist, in particular, to adequately support the infertile couple, must undertake important biological, psychological, economical and ethical task. Thus, this paper aims to provide a comprehensive overview of the multifaceted role of the andrologist in the study of male factor infertility.

Methods: A comprehensive Medline, Embase and Cochrane search was performed including publications between 1969 and 2021.

Results: Available evidence indicates that a careful medical history and physical examination, followed by semen analysis, always represent the basic starting points of the diagnostic work up in male partner of an infertile couple. Regarding treatment, gonadotropins are an effective treatment in case of hypogonadotropic hypogonadism and FSH may be used in men with idiopathic infertility, while evidence supporting other hormonal and nonhormonal treatments is either limited or conflicting. In the future, pharmacogenomics of FSHR and FSHB as well as innovative compounds may be considered to develop new therapeutic strategies in the management of infertility.

Conclusion: To provide a high-level of care, the andrologist must face several critical diagnostical and therapeutical steps. Even though ART may be the final and decisive stage of this decisional network, neglecting to treat the male partner may ultimately increase the risks of negative outcome, as well as costs and psychological burden for the couple itself.

Purpose: Acromegaly is a rare chronic disease characterized by systemic comorbidity and reduced quality of life. Although achieving biochemical control has always been the primary goal of acromegaly therapy, recent evidence has shown that the traditional assessment does not adequately capture the complexity of symptoms and patients' perception. These findings result in the need to improve a fast decision-making process of the clinician, who should not only take into account biochemical-instrumental criteria, but also patients' symptoms. With the aim of supporting the clinician in the diagnostic and therapeutic decision-making process several disease-specific tools have been developed. The aim of this review is to provide a description of the acromegaly-specific tools, presenting their main features, their application in daily practice, and their efficacy and utility.

Methods: A systematic search of Medline/PubMed, ISI-Web of Knowledge, and Google Scholar databases was done.

Results: Specific instruments and questionnaires have recently been developed to assist clinicians in the assessment of acromegaly. These are either Patient-Reported Outcome tools, such as Acromegaly Quality of Life Questionnaire (AcroQoL) and Pain Assessment Acromegaly Symptom Questionnaire (PASQ), or Clinician-Reported Outcome tools, such as ACROSCORE, SAGIT^® and Acromegaly Disease Activity Tool (ACRODAT^®). Such tools are extremely flexible and, therefore, have been widely adopted by endocrinologists and other professionals, so much so that they have also been included as recommendations in the 2018 international guidelines.

Conclusion: Questionnaires and tools are useful in the management of acromegaly patients. They help clinicians evaluate patients' symptoms and could assist in the evaluation of disease activity.

Purpose: This study aims to compare the accuracy of mean GH profile (GHP) < 2.5 ng/ml and single fasting GH (SGH) < 1 ng/ml in the evaluation of disease control in acromegaly patients during somatostatin receptor ligands (SRLs) therapy.

Methods: We retrospectively enrolled 100 acromegaly patients, 68 responder, and 32 partial responder to SRLs. Controlled disease has been defined as IGF-I levels within age-related normal limits, while partial response as pathological IGF-I values despite a reduction ≥ 50%. In all patients, GHP, SGH, IGF-I, and IGFBP-3 were evaluated.

Results: Median GHP levels (1.2 ng/ml, IQR 0.5-2.3 ng/ml) were lower (p = 0.001) than SGH (1.9 ng/ml, IQR 1.0-3.6 ng/ml). Accuracy of GHP was 81%, whereas that of SGH was 55%, with a Kappa index of 0.520 and 0.237, respectively. In multivariable analysis GHP (p = 0.002) and IGFBP-3 (p = 0.004), but not SGH, were independently associated with normal IGF-I levels. At receiver-operator characteristic curve (ROC) analysis GHP cut-off sensitivity and specificity were 94.1% and 50.0%, respectively, while SGH sensitivity and specificity were 35.3% and 93.7%, respectively. Finally, in obese patients the GH cut-off level (both as SGH and GHP) associated to good disease control was significantly different with respect to not obese ones.

Conclusions: GHP associates with IGF-I (and therefore with appropriate control of disease) with higher accuracy than SGH. When GH evaluation is needed, the measurement of mean GHP should be preferred and use of BMI-related cut-offs is suggested.

Introduction: In Prader-Willi syndrome (PWS) adult patients, sleep-breathing disorders, especially obstructive sleep apnoea syndrome (OSAS), are very common, whose missed or delayed diagnosis can contribute to further increase cardiovascular morbidity and mortality.

Purpose: The aim of this cross-sectional study was to evaluate differences in sleep-breathing parameters obtained by overnight cardiorespiratory polygraphy in 13 adult PWS patients and 13 individuals with non-syndromic obesity as controls matched by age, sex, and BMI.

Methods: In all subjects' anthropometric parameters, body composition using bioimpedance analysis and overnight cardiorespiratory monitoring parameters were obtained.

Results: Ten (76.9%) PWS patients were diagnosed with OSAS, most notably nine (69.2%) and one PWS (7.7%) with mild and severe OSAS, respectively. Compared with the control group, PWS patients had evidence of higher apnoea-hypopnea index (AHI) (p = 0.04) and oxyhaemoglobin desaturation index (ODI) (p = 0.009). However, no differences were found between the two groups regarding OSAS categories or diagnosis of nocturnal respiratory failure. In the PWS group, there were no significant correlations among AHI, ODI and hypoxemia index (T90) and anthropometric measurements, fat mass (FM), and FM percentage (%). Conversely, in the control group, the sleep-related respiratory indices evaluated correlated positively with BMI, waist circumference, FM and FM%.

Conclusions: This study confirmed that AHI and ODI indices were worse in PWS than in age, sex and BMI-matched controls. The lack of their significant association with the anthropometric parameters and FM supported the existence of PWS-related mechanisms in OSAS pathophysiology that are independent of visceral obesity and FM.

Purpose: To compare the effects of different thyroid screening scenarios, using the universal and targeted high-risk case-finding approaches with different diagnostic tests on the prevalence of subclinical hypothyroidism (SCH), thyroid autoimmunity, and pregnancy outcomes after adjustments for the intervention.

Methods: During a secondary analysis of data collected in Tehran Thyroid and Pregnancy Study, a total of 2277 women from the total population, including 1303 high-risk individuals for thyroid dysfunction. The Cochran-Mantel-Haenszel method, adjusted for the intervention, was also used to evaluate the relationships between different screening scenarios [i.e., universal approach using thyroid-stimulating hormone (TSH) and/or thyroid peroxidase antibody (TPOAb) tests and targeted high-risk case-finding approach using TSH and/or TPOAb tests] and pregnancy outcomes (i.e., preterm delivery and NICU admission). The universal approach using both TSH and TPOAb measurements was considered as the reference scenario. We analyzed outcomes of different screening methods in individuals treated with LT4, compared to those individuals who were not treated.

Results: Compared to the universal screening approach with both TSH and TPOAb measurements, the targeted high-risk case-finding approach overlooked approximately 42%, 62%, and 74% of women with elevated TSH (> 4 µlU/mL) when using both TSH and TPOAb tests, TSH alone, and TPO alone, respectively. After adjusting for the missed cases, 2.86% of women with preterm delivery and 2.76% of women with NICU admission were missed when they were screened using the targeted high-risk case-finding approach by measuring both TSH and TPOAb. The percentage of missed cases increased when applying the targeted approach with the TSH test alone, without measuring TPOAb. Overall, 4.16% and 4.02% of women with preterm delivery and NICU admission were overlooked in this scenario, respectively. After adjustments for the intervention, the probability of NICU admission in neonates of mothers, who were screened using the targeted high-risk case-finding approach with TPOAb measurement, was 2.31 folds higher than those screened by the reference scenario.

Conclusion: This study suggests that although the targeted high-risk case-finding approach including both TSH and TPOAb tests, may overlook some women with SCH, it is a reasonable option since it is not associated with a higher risk of adverse pregnancy outcomes.

Purpose: Impaired activity of the peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) isomerase might contribute to link disturbed glucose metabolism and risk of glucose related neurotoxicity, neurodegeneration and cognitive decline. The isomerase modulates also pathways of peripheral insulin sensitivity and secretion. We aimed at investigating the levels of circulating PIN1 in adolescents with obesity and any association with their glucose metabolism.

Methods: We enrolled 145 adolescents (age 12-17.8 years); 67 lean controls (46.2%) and 78 (53.8%) with overweight or obesity (males n = 62, 46%). We estimated glucose and insulin in fasting condition and after a standard oral glucose tolerance test; fasting serum levels of PIN1, amyloid β-protein 42 (Aβ42), presenilin 1 (PSEN1), glucagon-like peptide 1 (GLP1) and Non Esterified Fatty Acids (NEFA). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), the β cell function (HOMA-β) and the Adipo-IR.

Results: There was no difference in PIN1 serum levels between normal weight individuals and patients with obesity. However, there was an inverse correlation between serum fasting PIN1 and glucose (r - 0.183 and p = 0.027). We confirmed levels of Aβ42 and PSEN1 were higher in teens with obesity than in lean controls and their correlation with the body mass index (Aβ42: r = 0.302, p = 0.0001, PSEN1 r = 0.231, p = 0.005) and the HOMA-IR (Aβ42: r = 0.219, p = 0.009, r = 0.170, p < 0.042).

Conclusions: There was no significant rise of circulating PIN1 levels in young individuals with obesity. Increased levels reported in the literature in adult patients are likely to occur late in the natural history of the disease with the onset of an overt impairment of glucose homeostasis.