European Journal of Endocrinology最新文献

Objective: We aim to investigate the association between bone mineral density (BMD) measurement and fragility fractures and assess the predictive value of combining BMD measurement and frailty for fracture risk assessment.

Methods: This retrospective cohort study analyzed data from 5126 rural Koreans in the Chungju Metabolic Disease Cohort study. Frailty was defined using Fried's frailty phenotype. Fractures were assessed via structured medical interviews. Adjusted odds ratios (ORs) were calculated considering age, sex, body mass index, behavior, BMD, handgrip strength, medications, and comorbidities.

Results: The study cohort consisted of 5126 participants comprising 1955 (38.1%) males and 3171 (61.9%) females. Osteoporosis significantly increased the fracture risk across all types, except vertebral fracture, with adjusted OR (95% CI) of 1.89 (1.23-3.47) for any fracture, 2.05 (1.37-2.98) for hip fracture, 2.18 (1.06-4.50) for other fracture, and 1.71 (1.03-3.63) for major osteoporotic fracture (MOF). Frail individuals exhibited significantly increased risk for any fracture (OR 2.12; 95% CI, 1.21-3.71), vertebral fracture (2.48; 1.84-3.61), hip fracture (2.52; 1.09-3.21), other fracture (2.82; 1.19-8.53), and MOF (1.87; 1.01-3.47). The combination of frailty and BMD further increased the risks, with frail individuals demonstrating elevated ORs across BMD categories. In subgroup analyses, men showed a significant association between frailty with osteoporosis in hip fracture and MOF. Frail women with osteoporosis exhibited the highest risks for all fractures, particularly vertebral (OR 5.12; 95% CI, 2.07-9.68) and MOF (OR 5.19; 95% CI, 2.07-6.61). Age-specific analysis revealed that individuals aged 70 and older exhibited markedly higher fracture risks compared with those under 70. The combination of frailty and low BMD further elevated the fracture risk. Frailty was applied with BMD and demonstrated superior risk prediction for MOF compared with that with either score alone (area under the curve 0.825; P = .000).

Conclusions: Combining frailty with BMD provides a more accurate fracture risk assessment for individuals over 50 years.

Objective: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs).

Design: This is a single-center cohort study.

Methods: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016.

Results: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 μg/dL, P = .002).

Conclusions: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.

Propensity score methods are popular to control for confounding in observational biomedical studies of risk factors or medical treatments. This paper focused on aspects of propensity score methods that often remain undiscussed, including unmeasured confounding, missing data, variable selection, statistical efficiency, estimands, the positivity assumption, and predictive performance of the propensity score model.

Background: Most pituitary adenomas (PAs), also termed pituitary neuroendocrine tumors, are benign in nature and can be treated effectively by surgical resection, medical treatment, and in special cases by radiotherapy. However, invasive growth can be an important feature of a more aggressive behavior and adverse prognosis. The extension of PAs into the cavernous sinus can be categorized according to the Knosp criteria on magnetic resonance imaging (MRI). Comparative analyses of MRI features and intraoperative findings of invasive growth regarding different clinical factors are still scarce.

Materials and methods: We performed a retrospective single-center analysis of 764 PAs that were surgically treated between October 2004 and April 2018. Invasive growth was assessed according to the surgical reports and preoperative MRI (Knosp criteria). Clinical data, such as patient age at diagnosis and gender, histopathological adenoma type, and extent of resection, were collected.

Results: Invasive features on MRI were seen in 24.4% (Knosp grades 3A-4, 186/764) of the cases. Intraoperatively, invasion was present in 42.4% (324/764). Complete resection was achieved in 80.0% of adenomas and subtotal resection, in 20.1%. By multivariate analysis, invasion according to intraoperative findings was associated with the sparsely granulated corticotroph (SGCA, P = .0026) and sparsely granulated somatotroph (SGSA, P = .0103) adenoma type as well as age (P = .0287). Radiographic invasion according to Knosp grades 3A-4 correlated with age (P = .0098), SGCAs (P = .0005), SGSAs (P = .0351), and gonadotroph adenomas (P = .0478). Both criteria of invasion correlated with subtotal resection (P = .0001, respectively).

Conclusions: Both intraoperative and radiographic signs of invasive growth are high-risk lesions for incomplete extent of resection and occur more frequently in older patients. A particularly high prevalence of invasion can be found in the SGCA and SGSA types. Cavernous sinus invasion is also more common in gonadotroph adenomas. Usage of the Knosp classification is a valuable preoperative estimation tool.

A 29-year-old female, born to consanguineous parents, was found with unmeasurable levels of vitamin D (<10 nmol/L) after routine biochemical screening during her first pregnancy. She did not respond to either oral or intramuscular vitamin D supplementation and was an otherwise healthy young woman, with no signs of rickets, osteomalacia, osteoporosis, or secondary hyperparathyroidism. Western blot analysis revealed total lack of vitamin D binding protein, and next generation sequencing confirmed a novel, pathogenic homozygote loss-of-function mutation in exon 13 of the group-specific component gene, that encodes the poly A tail for vitamin D binding protein. She was therefore diagnosed with hereditary DBP deficiency, and vitamin D supplementation was diminished to life-long regular vitamin D supplementation (25 μg per day). This case is extremely interesting, as it expands our knowledge of vitamin D physiology and supports the free hormone hypothesis, given that the patient was asymptomatic despite no measurable levels of vitamin D.

Objective: Pituitary stalk interruption syndrome (PSIS) is a rare cause of congenital hypopituitarism. Limited data exist on the gonadotropic status and fertility of adult women with PSIS. Our study aims to describe pubertal development and the evolution of gonadotropic function and fertility in adult women with PSIS.

Design: A retrospective multicentric French study.

Methods: We described gonadotropic function in 56 adult women with PSIS from puberty onward. We compared live birth rates per woman with PSIS with age-matched controls from the large French epidemiological cohort (CONSTANCES). Additionally, we assessed height, body mass index (BMI), blood pressure, other metabolic parameters, and socioeconomic status.

Results and conclusions: Among 56 women with PSIS, 36 did not experience spontaneous puberty. Of these, 13 underwent ovarian stimulation, resulting in 7 women having a total of 11 children. In the subgroup with spontaneous puberty (n = 20), 4 had a total of 8 pregnancies, while 6 developed secondary gonadotropic deficiency. Women with PSIS had fewer children than controls (0.33 vs 0.63, P = .04). Median height was also lower (160.5 vs 165.0 cm, P < .0001). Although mean blood pressure was lower in women with PSIS compared with controls (111.3/65.9 ± 11.2/8.1 vs 118.7/72.1 ± 10.1/7.7 mmHg, P < .001), there were no significant differences in other metabolic parameters, notably BMI and lipid profile. Employment/academic status was not different in the 2 groups, but fewer women with PSIS were in relationships (42% vs 57.6% in controls, P = .02). The fertility prognosis in patients with PSIS needs optimization. Patients should be informed about the likelihood of declining gonadotropic function over time.

Objective: Given the previously identified sex differences in cardiovascular (CV) morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex-specific differences in the efficacy of (long-term) GHRT on CV risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men.

Design: Retrospective nationwide cohort study.

Methods: We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to CV risk profile and morbidity at baseline and during follow-up.

Results: Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol, and triglyceride levels was greater in men than in women (all P < .05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardiovascular or cerebrovascular diseases during GHRT.

Conclusions: Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing CV and cerebrovascular morbidity during GHRT.

Objectives: The etiology of central precocious puberty (CPP) has expanded with identification of new genetic causes, including the monogenic deficiency of Makorin-Ring-Finger-Protein-3 (MKRN3). We aimed to assess the prevalence of CPP causes and the predictors of genetic involvement in this phenotype.

Design: A retrospective cohort study for an etiological survey of patients with CPP from a single academic center.

Methods: All patients with CPP had detailed medical history, phenotyping, and brain magnetic resonance imaging (MRI); those with negative brain MRI (apparently idiopathic) were submitted to genetic studies, mainly DNA sequencing studies, genomic microarray, and methylation analysis.

Results: We assessed 270 patients with CPP: 50 (18.5%) had CPP-related brain lesions (34 [68%] congenital lesions), whereas 220 had negative brain MRI. Of the latter, 174 (165 girls) were included for genetic studies. Genetic etiologies were identified in 22 patients (20 girls), indicating an overall frequency of genetic CPP of 12.6% (22.2% in boys and 12.1% in girls). The most common genetic defects were MKRN3, Delta-Like-Non-Canonical-Notch-Ligand-1 (DLK1), and Methyl-CpG-Binding-Protein-2 (MECP2) loss-of-function mutations, followed by 14q32.2 defects (Temple syndrome). Univariate logistic regression identified family history (odds ratio [OR] 3.3; 95% CI 1.3-8.3; P = .01) and neurodevelopmental disorders (OR 4.1; 95% CI 1.3-13.5; P = .02) as potential clinical predictors of genetic CPP.

Conclusions: Distinct genetic causes were identified in 12.6% patients with apparently idiopathic CPP, revealing the genetic etiology as a relevant cause of CPP in both sexes. Family history and neurodevelopmental disorders were suggested as predictors of genetic CPP. We originally proposed an algorithm to investigate the etiology of CPP including genetic studies.