Elisa Gatta

Objective: To systematically evaluate and quantitatively synthesize the association between Klinefelter syndrome (47,XXY karyotype) and autoimmune susceptibility. Methods: PubMed/MEDLINE, Scopus, and Web of Science were systematically searched from database inception to April 30, 2026, for studies evaluating autoimmune diseases or autoimmune serological markers in individuals with KS. The protocol was registered in PROSPERO (CRD420261399097). Random-effects models were prespecified, summary data were extracted from published reports, and pooled effect estimates were expressed as odds ratios (ORs) with 95% CIs. Subgroup analyses were performed according to outcome definition (isolated autoantibody positivity vs clinically manifest autoimmune disease). Risk of bias was assessed using the Newcastle–Ottawa Scale. Results: Eight studies were included in the qualitative synthesis and six studies (eight datasets) in the quantitative analysis, comprising 2,289 individuals with KS and 51,250,114 controls. KS was associated with markedly increased autoimmune susceptibility compared with control populations (OR 23·25, 95% CI 9·96–54·31), with moderate-to-substantial between-study heterogeneity (I2 = 66·4%). Associations were stronger for clinically manifest autoimmune diseases (OR 48·46, 95% CI 17·68–132·87) than for isolated autoantibody positivity (OR 9·99, 95% CI 1·18–84·77). The autoimmune spectrum predominantly involved female-predominant and interferon-associated disorders, including systemic lupus erythematosus, Sjögren syndrome, systemic sclerosis, autoimmune thyroid disease, and type 1 diabetes mellitus. Conclusion: KS is associated with increased autoimmune susceptibility, particularly for clinically overt autoimmune diseases. These findings support a potential contribution of sex chromosome complement to immune dysregulation and reinforce the importance of clinical awareness of autoimmune comorbidities in individuals with KS.

Background: Testosterone replacement therapy (TRT) with transdermal gel is widely used in men with hypogonadism. Guidelines recommend once-daily application with monitoring of serum testosterone at peak levels. However, real-world clinical experience suggests that peak–trough fluctuations in some patients, potentially affecting hormonal stability and treatment tolerability. The impact of dose fractionation remains unclear. Objectives: To compare hormonal profiles and biochemical safety parameters between once-daily and twice-daily (fractionated) testosterone gel administration in hypogonadal men receivingh the same total daily dose. Methods: We retrospectively identified hypogonadal men treated with 2% testosterone gel who transitioned from once-daily to twice-daily dosing, maintaining the same total daily dose. Eligible patients had serum total testosterone (TT) measurements available at both peak (3 h post-application) and nadir (pre-dose). Hormonal and laboratory parameters under the two regimens were compared. Results: Twelve patients met inclusion criteria. Fractionated dosing was associated with lower peak TT levels [9.0 (5.3–13.0) vs. 5.7 (3.6–7.1) ng/mL, paired difference − 3.6 ng/mL (95% CI: −4.9 to − 1.8)] and higher nadir TT levels [1.4 (1.1–1.8) vs. 3.2 (2.6–5.4) ng/mL, paired difference 2.6 ng/mL (95% CI: 1.2 to 5.1)], resulting in a reduced difference between peak-to-pre-dose difference within the observed sampling window. The proportion of patients achieving target TT levels at peak increased (33% vs. 83%). Calculated free testosterone showed a similar pattern. No clinically relevant differences were observed in luteinizing hormone, prostate-specific antigen, haematocrit, or haemoglobin. Conclusion: In this real-world cohort, fractionated testosterone gel administration was associated with a higher proportion of patients achieving biochemical targets and with a reduced peak-to-pre-dose difference within the observed sampling window, without short-term biochemical safety signals. These findings should be considered hypothesis-generating.

Differentiated thyroid carcinoma (DTC) is the most common malignant endocrine tumor, with a generally favorable prognosis. Imaging, including iodine radioactive isotope scintigraphy (IRIS), is crucial for diagnosis and follow-up. While ¹³¹I has long been used for both therapeutic and diagnostic purposes, ¹²³I is reserved for diagnostic imaging due to its shorter half-life and γ emissions. This review highlights the utility of ¹²³I scintigraphy, especially in pre-treatment assessment and dosimetry for DTC. It is particularly valuable before radioiodine (RAI) ablation, providing accurate imaging in patients with iodine-refractory (IR) or biochemically incomplete response (BIR) DTC. When compared to post-therapeutic ¹³¹I scans, ¹²³I scintigraphy appears to have a lower sensitivity for detecting metastatic lesions, particularly in lymph nodes and lungs. However, its diagnostic performance compared to low-dose diagnostic ¹³¹I is more variable, with some studies suggesting superiority due to the absence of stunning. Further research is needed to standardize its use and optimize its role in guiding DTC management.

Context: Klinefelter syndrome and Kallmann syndrome are 2 rare genetic disorders characterized by reduced testosterone (T) levels but differing in their gonadotrophin profiles. To date, no studies have directly compared body composition in these 2 syndromes. Objective: This work aimed to assess the prevalence of altered body composition parameters in patients with Klinefelter and Kallmann syndromes and to compare body composition between the 2 groups. Secondary objectives included evaluating associations between body composition, bone mineral density (BMD), and serum follicle-stimulating hormone (FSH) levels. Methods: This single-center, retrospective observational study included 50 patients, 29 with Klinefelter and 21 with Kallmann syndrome receiving T replacement therapy. Body composition was evaluated using whole-body dual-energy x-ray absorptiometry (DXA), which provided measurements of appendicular lean mass (ALM), total body fat (TBF), visceral adipose tissue (VAT), the ALM-to-height² ratio (appendicular lean mass index, ALMI), and the ALM-to-weight ratio. Results: Radiologic sarcopenic obesity was identified in 7 patients (14%; 6/29 Klinefelter, 1/21 Kallmann), while osteosarcopenic obesity was found in 2 patients (4%), both with Klinefelter syndrome. Patients with Kallmann syndrome had significantly higher ALMI values than those with Klinefelter syndrome (8.37 ± 1.15 vs 7.28 ± 1.20 kg/m²; P < .001). Univariable analysis revealed an inverse association between FSH levels and ALMI (B = −0.026; P = .002), which remained statistically significant after adjustment for confounders (B = −0.030; P = .0022). Conclusion: This study demonstrated a significant difference in lean mass between Klinefelter and Kallmann syndromes, supporting a potential role for FSH in modulating muscle mass independently of T levels.

Background: Thyroid dysfunction and psychiatric disorders often coexist, raising interest in their potential interplay. In particular, the relationship between thyroid-stimulating hormone (TSH) levels and schizophrenia has been investigated, though findings remain inconsistent. We performed a systematic review and meta-analysis to clarify whether TSH levels differ in patients with schizophrenia compared with healthy controls. Methods: A systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted up to May 2025. Eligible studies were selected based on predefined criteria according to the PICO framework: What are the TSH levels in first-episode, drug-naïve patients diagnosed with schizophrenia compared with healthy subjects, and do TSH levels influence different psychiatric phenotypes? PRISMA guidelines were followed. Study quality and risk of bias were assessed using QUADAS-2. Results: Of 2068 records screened, 35 studies met the inclusion criteria. Quality assessment revealed a generally unclear risk of bias, with few studies showing a high risk. The meta-analysis included 3669 patients and 1391 controls from ten Asian, eight European, and three North American studies. TSH levels were similar between patients and controls (SMD = –0.059 mIU/L; 95% CI: –0.260 to 0.141), with substantial heterogeneity (I² = 84%, p < 0.001). Conclusions: This meta-analysis found no significant association between TSH levels and schizophrenia, despite decades of research and methodological diversity.

Radioactive iodine therapy has been a well-established treatment for various thyroid conditions since the 1940s, targeting both benign diseases and malignancies. Treatment for benign conditions typically involves low doses of 131I, often requiring no more than two treatments, with the dose either fixed or personalized based on thyroid tissue mass and iodine uptake. In contrast, differentiated thyroid cancer treatment often requires higher doses and multiple administrations, especially for metastatic cases. Recent guidelines and studies have proposed more conservative management strategies, including careful follow-up, due to concerns over the high risk–benefit ratio in selected cases with a low risk of disease recrudescence. Despite its possible efficacy, radioiodine therapy is associated with dose-dependent side effects, the most common of which is salivary gland dysfunction or inflammation, affecting approximately 30% of adult patients. These effects pose significant challenges in nuclear medicine practice. This review aims to summarize the latest evidence on the incidence, impact on quality of life, prevention strategies and the role of these side effects in the decision-making process regarding RAI therapy.

Context: Graves disease (GD) can occur as an isolated condition or as part of an autoimmune polyglandular syndrome; there are no data regarding the differences in phenotype between these 2 forms. Objective: To assess differences in clinical presentation, complications, and outcomes in patients with isolated GD compared to those in whom GD is part of an autoimmune polyglandular syndrome. Methods: The GRAPHE study is a retrospective observational study. The medical records of all patients with GD diagnosed and regularly followed at outpatient clinics for Endocrinology, Nuclear Medicine and Clinical Surgery, from January 1, 2010, to June 30, 2024, were retrieved. All the patients were followed by the same endocrinologists and treated in accordance with existing guidelines. Results: The enrolled patients (n = 567; 77% women) were divided into 3 different groups based on GD phenotypes: subjects affected by isolated GD (isolated GD); patients who developed autoimmune polyglandular syndrome (GD1-APS); and patients with autoimmune polyglandular syndrome who developed GD during follow-up (GD2-APS). The 3 groups were superimposable for gender (P = .086), fT4 (P = .899), fT3 (P = .434), TRAb titers (P = .882), and thyroid volume (P = .840) at disease onset. Isolated GD patients exhibited Graves orbitopathy more frequently (P < .001), a higher rate of definitive therapy (P < .001) and shorter time between disease onset and definitive therapy (P < .001) compared to the GD1-APS and GD2-APS patients. Conclusion: The results of the present study show that, despite similar clinical and biochemical phenotype at presentation, a more severe clinical course characterizes isolated GD patients compared to those whose disease is a feature of autoimmune polyglandular syndrome.

Background: Struma ovarii (SO) is an ovarian teratoma with the presence of ectopic thyroid tissue. Differentiated thyroid cancer (DTC) in SO is a rare finding. Management of DTC in SO is currently not clearly established. We performed a systematic review of the literature to assess the role of 131I radiometabolic therapy in the treatment of DTC in SO. Methods: a wide literature search in the Scopus, PubMed/MEDLINE, and Web of Science databases was made to find published articles regarding the treatment of patients with DTC and SO. The quality assessment of studies was performed by QUADAS-2 evaluation. Results: eleven studies were included in the systematic review. All of them were retrospective studies and/or case series, and two of them also included a review of the literature. Most of the studies describe cases of DTC in SO treated by total thyroidectomy (TT) and subsequent radioiodine (RAI) therapy, especially in patients with distant metastases and/or concomitant thyroid cancer. However, the majority of patients apparently did not require radiometabolic therapy. Conclusions: TT and subsequent RAI therapy is usually performed in metastatic disease, not recommended in patients with intraovarian disease without risk factors, and it appeared possible but not mandatory in patients with risk factors.

SUMMARY Treating hypothyroidism can be challenging in patients with malabsorption, as they require a higher daily dose of oral levothyroxine (L-T4). Oral L-T4 absorption occurs mainly in the jejunum and the ileum and is affected by gastric acidity. As a result, absorption can be impaired by bariatric surgery. This paper presents a case of myxedema in a young man who had previously undergone biliopancreatic diversion. He was referred to the Emergency Department with deteriorated mental state, hypotension, bradycardia and hypothermia. [...] SUMMARY Treating hypothyroidism can be challenging in patients with malabsorption, as they require a higher daily dose of oral levothyroxine (L-T4). Oral L-T4 absorption occurs mainly in the jejunum and the ileum and is affected by gastric acidity. As a result, absorption can be impaired by bariatric surgery. This paper presents a case of myxedema in a young man who had previously undergone biliopancreatic diversion. He was referred to the Emergency Department with deteriorated mental state, hypotension, bradycardia and hypothermia.

To evaluate the effect of thyroid function on male fertility, focusing on hypo- and hyperthyroidism. A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Original studies in English published online up to 31 May 2023 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. The available data in animals (31 studies) and human (26 studies) showed conflicting results. However, thyroid dysfunction altered erection and ejaculation both in animal models than in men. Both hypothyroidism and hyperthyroidism seem to cause ejaculation and erectile dysfunction. Hence, Guidelines recommend against the systematic screening for thyroid disorders in the men in sub-fertile couples, but only in men with ejaculation and erectile dysfunction and/or altered semen parameters.