Expert Review of Endocrinology & Metabolism最新文献

Introduction: Frail older people with diabetes will need regular medications review and individualized care, especially at the final phase of life. Although guidelines are detailed on escalation of medications, there is little detail on how to de-escalate therapy when need arises. In addition, there is no description of patients' criteria in whom de-escalation should be considered.

Area covered: In the guidelines, frailty is referred to as one homogeneous group. However, frailty is a metabolically heterogeneous condition with a span of variability in insulin resistance depending on proportional ratios of visceral body fat mass, muscle mass, and total body weight. Therefore, cardiovascular risk and the need for tight targets are variable depending on frailty metabolic phenotype. Taking this into consideration, the phenotype of frailty should be taken into account when considering de-escalation of therapy. Furthermore, de-escalation of cardiovascular therapy will differ by frailty phenotype and underlying cardiovascular risk.

Expert opinion: This manuscript addresses the issue of metabolic variability of frailty and suggests three chronological stages, from de-escalation, palliation to end-of-life care in a patient-centered perspective. Future research is required to develop de-escalation pathways and strategies, which will impact on health care costs, patients' safety, and quality of life.

Introduction: The administration of Menopausal Hormone Therapy (MHT) needs to be evaluated in relation to the individual patient's indications for therapy and risk estimations, which include the Breast Cancer (BC) risk estimation.

Areas covered: We reviewed the lifetime BC risk and the associated mortality in relation to MHT use.

Expert opinion: For many patients with climacteric symptoms and/or osteoporosis, the balance is in favor of MHT use. The risk of breast cancer can be estimated using unmodifiable risk factors, such as the patient's personal and family history, the breast density assessed on her mammogram, and modifiable risk factors such as alcohol intake. In complex situations, prediction models can be used to guide decision-making. When the 5-year BC risk is low (below 3%), MHT can be prescribed; caution is needed in women with a risk between 3% and 6%, and MHT should generally be avoided when the risk is high, i.e. above 6%.

Background: Hypothyroidism, characterized by insufficient thyroid hormone production, is a common endocrine disorder with significant health implications. Recent studies suggest that micronutrient deficiencies, particularly in vitamin D, vitamin B12, and ferritin, may contribute to thyroid dysfunction. This study aims to explore the relationship between hypothyroidism and these micronutrient deficiencies in a clinical setting.

Research design and methods: A case-control study was conducted between September and December 2024 at Public Central Health Lab., Duhok Azadi teaching Hospital, Iraq. A total of 885 participants were included, with 170 hypothyroid patients and 715 healthy controls. Serum levels of TSH, T3, T4, vitamin D, vitamin B12, and ferritin were measured. Multivariable regression analysis was used to examine the associations between thyroid function and micronutrient status.

Results: Hypothyroid patients had significantly higher TSH (9.4 ± 11.5 vs. 1.8 ± 0.8 mIU/L, p < 0.0001) and lower T4 (116.1 ± 28.6 vs. 129.2 ± 27.4 nmol/L, p < 0.0001) compared to controls. Vitamin B12 and ferritin levels were also lower in the hypothyroid group (p < 0.0001), while vitamin D showed no significant difference (p = 0.0524).

Conclusion: Hypothyroidism is associated with vitamin B12 and ferritin deficiencies, highlighting the importance of micronutrient in thyroid dysfunction management. Future studies should explore autoantibodies.

Clinical trial registration: http://duhokhealth.org/en/identifier/is/25092024-8-11.

Introduction: Paget's Disease of Bone (PDB) is a chronic, late-onset skeletal disorder characterized by highly localized regions of increased bone resorption, accompanied by excessive and abnormal new bone formation. Consequently, PDB serves as a crucial model for elucidating the genetic and molecular mechanisms governing both abnormal osteoclast formation and osteoclast-induced osteoblast/osteocyte activities.

Areas covered: This narrative review based on the available indexed literature examines the genetics of PDB and its connections with the pathophysiology of the disease, focusing on interactions with bone cells, environmental factors, clinical presentation, and complications.

Expert opinion: PDB research highlights the importance of genetic studies, and the need for further research especially in families not linked to SQSTM1 pathogenic variants. Enhancing education for health care professionals is critical, given PDB's rarity and its exclusion from medical curricula, which leads to diagnostic delays and mismanagement. Further exploration of gene-environmental interactions and the role of bone cells in lesion formation remains a priority. Advances in precision medicine may soon allow genetic testing to predict the risk of PDB using polygenic risk scores, leading to targeted prevention strategies. Future treatments may involve SQSTM1 gene inhibitors, such as siRNA, offering a personalized approach to early prevention and management of PDB.

Introduction: Metformin is a metabolic drug widely used in women with polycystic ovary syndrome (PCOS). It is effective for improving metabolic pattern and fertility, alone or combined with other treatments. Sparse data suggest that its administration before and during pregnancy may be also effective for reducing the PCOS-related pregnancy complications.

Areas covered: Maternal, neonatal and offspring efficacy and safety of metformin administration in pregnant patients with PCOS.

Expert opinion: A comprehensive literature search was conducted in March 2025 in PubMed, The Cochrane Library, and Web of Science databases using specific keywords related to metformin and PCOS. The search covered all articles published up to March 2025. Clinical evidence supports the efficacy of metformin in reducing the risk of preterm birth and pregnancy-induced hypertension in PCOS, but benefits for miscarriage or gestational diabetes mellitus (GDM) prevention are unclear. Notably, there is a lack of high-quality data on metformin as treatment for GDM or type 2 DM in PCOS pregnancies. Methodological differences and heterogeneous patient profiles limit clinical adoption. The use of metformin as strategy for preventing pregnancy complications in women with PCOS remains inconsistent due to limited consensus and concerns about long-term offspring safety.

Background: Diabetes mellitus (DM) is an important cause of morbidity and mortality worldwide. DM patients develop both macrovascular and microvascular complications, erectile dysfunction (ED) being one of them. The risk of developing ED in DM patients as compared to those without DM is 3-4 times. Our study has reported the burden of ED in DM patients.

Methods: Literature search was done by using PubMed and EMBASE databases for studies published from 1 January 2013 to 31 December 2013 by using terms such as diabetes, erectile dysfunction, and their synonyms. Pooled prevalence was calculated by using random effect model and Der Simonian-Laird method. Joanna Briggs Institute (JBI) Critical Appraisal scale for cross-sectional studies was used for assessing the study quality.

Results: Five hundred and sixty-seven studies were identified, out of which 10 studies were selected. The prevalence of ED in Type 2 DM patients in India was estimated 60.57% (95% CI: 48.84-72.30%).

Conclusion: Prevalence of ED in DM patients is high in India. Stigma, stress, and phobia related to ED needs to be addressed. Screening, awareness, early diagnosis, and management for ED and DM will help in improving morbidity and mortality of the nation.

Introduction: Endogenous Cushing's syndrome (CS) is associated with substantial morbidity and mortality. Patients in remission may experience many comorbidities, including growth hormone deficiency (GHD).

Areas covered: Electronic searches (PubMed) were conducted through July 2025. The published data largely pertain to patients with Cushing's disease (CS caused by a pituitary tumor). This article reviews the epidemiology of GHD in patients with CS in remission, underlying mechanisms, and clinical manifestations. The diagnosis of GHD is discussed along with data on the effectiveness and safety of growth hormone replacement.

Expert opinion: GHD is common in patients with active CS and may persist among patients in remission. In children, decreased linear growth is prevalent. In adults in remission, GHD has been associated with a higher prevalence of cardiometabolic burden (hypertension, diabetes mellitus, cardiovascular and cerebrovascular disease), decreased muscle strength, lower bone mineral density and increased prevalence of fractures. The diagnosis of GHD generally requires stimulation testing and should only be undertaken in patients in remission. In children with CS in remission, growth hormone replacement improves adult height. In adults, growth hormone replacement may improve quality of life, bone mineral density, muscle strength and dyslipidemia but requires careful monitoring for the possible development of hyperglycemia.

Introduction: Prader-Willi syndrome (PWS) is a rare disorder caused by the lack of expression of paternal genes on chromosome 15q11.2-q13. The clinical picture of PWS is characterized by neonatal hypotonia, hyperphagia, obesity, altered body composition, cognitive impairment, behavioral disturbances, short stature, and multiple endocrinopathies, including growth hormone (GH)/IGF-I axis dysfunction.

Areas covered: This narrative review addresses the current state-of-the-art of recombinant human GH therapy (rhGHT) in adults with PWS, focusing on its effects on body composition, muscle strength and exercise capacity, cardiovascular and respiratory function, endocrine and metabolic parameters, bone health, and psychological aspects.

Expert opinion: Available data demonstrated the positive effects of rhGHT on the body composition of GH-treated subjects. This observation is significant, as improving body composition has been shown to increase muscle strength and exercise tolerance. Overall, rhGHT appears to improve both cardiorespiratory function and psychological outcomes. However, most of the studies are uncontrolled and short-term. Therefore, longitudinal trials evaluating the long-term effects of rhGHT are recommended to confirm these findings. Since the beneficial effects of rhGHT appear to be independent of the presence of GH deficiency, we believe that its approval should be considered in adults with genetically confirmed PWS without testing for GH secretion.

Background: DPP-4 inhibitors have anti-diabetic effects in T2DM, but their impact on pancreatic function and underlying mechanisms remain unclear. This study aimed to evaluate the effects of sitagliptin on pancreatic function and glucose regulation, focusing on the roles of IL-18, IL-1, and IL-6 in T2DM patients.

Research design and methods: A 12-week clinical trial included 60 T2DM patients, randomly assigned to receive either metformin (2000 mg/day) or sitagliptin + metformin (100 mg and 2000 mg/day, respectively). Metabolic indices (fasting blood sugar [FBS], hemoglobin A1c [HbA1c], triglycerides [TG], cholesterol [Chol]), biochemical parameters, and vitamin D3 levels were measured at baseline and after 12 weeks. IL-1, IL-6, IL-18, and insulin levels were also evaluated.

Results: Sitagliptin + metformin group showed a greater reduction in FBS (p = 0.005), blood sugar (p = 0.011), and improvements in cholesterol (p = 0.001), TG-G index (p = 0.017), and pancreatic efficiency (p = 0.003) compared to metformin alone. Reductions in IL-1, IL-6, and IL-18 levels were observed (p = 0.00). Sitagliptin significantly reduced IL-1 levels (p = 0.034) compared to metformin alone. No significant changes were seen in HbA1c or vitamin D3.

Conclusion: Sitagliptin plus metformin improved pancreatic function, glucose homeostasis, and reduced IL-1, IL-6, and IL-18 levels in T2DM patients with inadequate glycemic control on metformin alone, offering cardiovascular benefits (Clinical Trial Registration: https://www.irct.ir/trial/44061).

Objectives: Raised asprosin may be related to the development of postmenopausal osteoporosis. This study aimed to determine the role of asprosin in oxidative stress in postmenopausal osteoporosis and its relation with estrogen, osteoprotegerin (OPG), and bone mineral density (BMD).

Methods: A case-control study included 80 women, aged 42-65, presenting at Shalamar Hospital, Lahore, Pakistan. Informed consent was taken, and single blinding was done. Demographic details and a bone mineral density scan were done. Three ml of venous blood sample was taken to measure asprosin, glutathione (GSH), osteoprotegerin, and estrogen levels.

Results: Women with osteoporosis had significantly higher levels of serum asprosin and lower levels of OPG than those without osteoporosis. (p < 0.05) Asprosin was negatively correlated with BMD, OPG, and GSH, and positively with body mass index (p < 0.05). The cutoff value of serum asprosin for screening postmenopausal osteoporosis by area under the curve was > 27.4 ng/ml with a sensitivity of 75% and a 1-specificity of 14%.

Conclusion: Higher serum asprosin and oxidative stress biomarkers are related to decreased bone mineral density in postmenopausal women. Asprosin may be used as a potential biomarker for early screening of postmenopausal osteoporosis. Small sample size and observational study design were the key limitations of this study.