Abstract Objective Prolactin has been associated with cardiovascular mortality. The primary objective was to assess the association between prolactin and systolic function in patients with type 2 diabetes. Secondly, to assess the association between prolactin and diastolic function, NYHA classification, glucose, and lipid levels. Methods A cross-sectional study of the Thousand&2 cohort, including 1,030 individuals with type 2 diabetes from secondary care. Echocardiography and biochemical assessment were performed at baseline. Systolic function was estimated primarily as left ventricular ejection fraction (LVEF), secondly as global longitudinal strain (GLS), and E/e’ as a marker of diastolic function. The association between echocardiography and prolactin was assessed using linear regression, presented with crude as well as adjusted estimates for potential confounders. Results Prolactin assessments were available for 937/1030 (91%), and 14/937 (1.5%) individuals had prolactin levels above the upper reference limit. Prolactin was not associated with LVEF or GLS, whereas prolactin was associated with E/e’ and NYHA classification in fully adjusted analysis in men but not in women. Prolactin was not associated with glucose or lipid levels in men or women. Conclusion Prolactin was not associated with impaired systolic function in men or women with type 2 diabetes; on the other hand, prolactin was associated with poorer diastolic function in men with type 2 diabetes. The current results point towards a gender specific effect of prolactin on the diastolic function of the heart.
Abstract Background Musculoskeletal symptoms frequently persist in acromegaly despite biochemical remission, yet the impact of structured physiotherapy on pain, stiffness, and function remains poorly defined. Objective To evaluate the effects of a standardized knee-focused physiotherapy program in controlled acromegaly and to identify clinical predictors of treatment responsiveness. Methods Thirteen patients with acromegaly in remission and 13 age-, gender-, and BMI-matched individuals with primary knee osteoarthritis completed a 15-session physiotherapy program. Outcomes were assessed pre- and post-intervention using the Brief Pain Inventory (BPI) and WOMAC. Minimal clinically significant difference (MCID) thresholds (≥2 for BPI, ≥10 for WOMAC) determined meaningful improvement. Correlation analyses examined associations between clinical variables and Δ scores. Results Acromegaly patients showed significant improvements in all BPI and WOMAC domains (p<0.001). MCID was achieved by 85% for BPI and 100% for WOMAC Total. Pain and function improved most, whereas stiffness showed limited responsiveness. Compared with osteoarthritis controls, acromegaly patients demonstrated smaller Δ changes; baseline-adjusted analyses (ANCOVA) indicated that this attenuated response was largely explained by greater baseline severity in the control group, whereas the persistently greater stiffness in acromegaly remained significant even after adjustment. BMI correlated positively with improvements in BPI Total (r = 0.63) and BPI Pain Severity (r = 0.69), while adenoma size correlated negatively with both measures (r = –0.57 and –0.60). BMI showed a negative association with WOMAC Total improvement (r = –0.59). Stiffness changes were strongly negatively correlated with pretreatment IGF-1 (r = –0.77). Conclusion Structured physiotherapy yields clinically meaningful improvements in pain and function in acromegaly, while stiffness appears less reversible and more structurally driven. Early musculoskeletal assessment and physiotherapy integration may enhance long-term management.
Abstract Graphical Abstract Abstract P450 oxidoreductase deficiency (PORD) is a rare congenital disorder of steroidogenesis caused by pathogenic variants in POR, the obligate electron donor to all microsomal cytochrome P450 (CYP) enzymes. While the early clinical presentation of PORD – characterized by adrenal insufficiency, differences of sex development, and Antley–Bixler-like skeletal malformations – is well established, its long-term consequences remain poorly defined. This scoping review synthesizes current evidence on multisystem outcomes in PORD and integrates insights from the broader biology of POR-dependent enzymes to inform potential long-term risks. Across 51 known POR-partner enzymes, numerous polymorphisms have been associated with cardiovascular, metabolic, reproductive, skeletal, neurological, inflammatory, and oncological phenotypes in the general population. Although many of these conditions have not yet been reported in PORD, their mechanistic plausibility highlights important gaps in surveillance. Emerging clinical observations, including hypertension, altered drug metabolism, impaired fertility, and reduced bone health, further underscore the need for systematic long-term follow-up. Experimental models additionally suggest vulnerabilities related to lipid accumulation, bile acid dysregulation, and hepatocellular injury. Despite these concerns, no evidence-based guidelines exist for the lifelong management of PORD, and psychosocial outcomes remain entirely unexplored. Collectively, the available data indicate that PORD is a multisystem disorder with potential age-dependent manifestations extending beyond childhood. Prospective longitudinal studies, mechanistic investigations, and coordinated international registry efforts are essential to define the true long-term phenotype and to develop standardized monitoring and management strategies for affected individuals. Lay summary P450 oxidoreductase deficiency (PORD) is a rare genetic condition that affects many body systems because the POR enzyme supports dozens of important metabolic pathways. Most research has focused on early symptoms, such as hormone problems, differences in sex development, and bone abnormalities. Much less is known about how PORD affects people later in life. This review brings together current evidence and highlights possible long-term risks, including high blood pressure, liver and metabolic problems, reduced fertility, and bone health issues. Longer-term studies are urgently needed to understand these risks and to guide better care for individuals with PORD.
Abstract Purpose Benign thyroid diseases are common conditions that often require long-term treatment. In some patients, symptoms persist despite normalization of biochemical parameters, significantly affecting quality of life (QoL). This study evaluated treatment-associated changes in QoL using the Thyroid Patient Reported Outcome (ThyPRO) questionnaire and summarized differences in QoL profiles reported across thyroid conditions. Methods A systematic review and meta-analysis were performed according to PRISMA guidelines. PubMed, Scopus, and Embase were searched up to April 2024. Data were extracted and synthesized using standardized mean differences. Results Twenty-five studies were included. Significant pre-post-treatment improvements in overall QoL and selected symptom domains were observed. In Graves’ disease, improvements were observed in hyperthyroid symptoms, anxiety, impaired daily life, and overall QoL. In non-toxic goiter, improvements were observed in goiter symptoms, cosmetic complaints, anxiety, tiredness, and overall QoL. In toxic nodular goiter, significant improvements were observed in hyperthyroid and goiter symptoms and overall QoL, whereas several other domains did not change significantly. In hypothyroidism, significant improvements were observed in selected domains, including tiredness, impaired daily life, mood-related symptoms, and overall QoL. Analyses comparing ThyPRO scores between patient groups showed differences in selected domains; these comparisons were interpreted descriptively. Conclusions Treatment was associated with improvements in QoL across the analyzed benign thyroid conditions, varying by disease group. Given the heterogeneity of the included studies and the absence of head-to-head comparisons of treatment efficacy across conditions, these findings should be interpreted descriptively. Disease-specific QoL assessment may help clinicians identify persistent symptom domains requiring attention during follow-up.
Abstract Bone metastases in neuroendocrine neoplasms are uncommon but cause significant morbidity. A recent Italian survey of 320 patients with neuroendocrine neoplasms and bone metastases reported skeletal-related events in 23% and bone-targeted agent use in 31%, highlighting limited evidence for bone-modifying agents. We identified adults with confirmed or clinically suspected neuroendocrine bone involvement who received a bone-modifying agent at a UK tertiary centre (January 2019–September 2024), using institutional prescribing records. Demographic, tumour, treatment, and toxicity data were extracted from records. Twenty-two patients received treatment (denosumab 17 (77%); zoledronic acid 5 (23%)). Most (91%) had grade 1–2 tumours; 64% had gastroenteropancreatic primaries. Bone metastases were synchronous in 45% and widespread (more than three lesions) in 73%. At diagnosis, 23% were symptomatic; during follow-up, 77% developed pain, high blood calcium, or a skeletal-related event. Skeletal-related events, a composite of pathological fracture, spinal cord compression, radiotherapy to bone, or orthopaedic surgery, occurred in 41% (radiotherapy alone in 36%); pain-relieving medication was used universally. Treatment was mainly given every 12 weeks (median six doses). Low blood calcium occurred in 9% and osteonecrosis of the jaw in 5%; dental assessment before therapy was recorded in only 9%. Treatment use was heterogeneous, reflecting a lack of disease-specific guidelines, and recorded toxicity was infrequent and generally manageable, although exposure varied s. Our findings highlight the need for prospective studies and structured registries to clarify treatment use, dosing, and impact on quality of life and prognosis.
