共找到 20 条结果
暂无摘要（点击查看详情）
Hyperglycemia is very common in critical care and is the focus of intense clinical research. To date, more than 24,000 patients have been enrolled in interventional randomized trials. The pioneering studies by the Louvain group reported remarkable benefits of intensive insulin therapy in intensive care units; however, subsequent large multicenter trials failed to confirm these findings. Recent evidence suggests that pre-admission glycemic status should be taken into account in defining glucose targets, through new parameters such as the stress hyperglycemia ratio and relative hypoglycemia, which include pre-admission glycemic control. Continuous glucose monitoring and individualization of glycemic targets according to these new parameters and the patient's clinical context are likely to bring major advances in the management of hyperglycemia in critically ill patients.
暂无摘要（点击查看详情）
Primary aldosteronism (PA) represents the leading cause of secondary hypertension, resulting from autonomous aldosterone production driven in the majority of cases by a lateralized aldosterone-producing adenoma or by bilateral adrenal hyperplasia. Its frequency increases in parallel with hypertension severity, reaching a prevalence of up to 25% of patients with treatment resistant hypertension. Advances in our understanding on the genetic causes of PA have reshaped our understanding of the pathogenesis of the disease, revealing a broad spectrum of somatic and inherited mutations across most aldosterone-producing adenomas as well as familial forms of the disorder. More recently, susceptibility loci shared between unilateral and bilateral PA, and overlapping with known blood-pressure associated variants, have been identified, highlighting genetic susceptibility that extends beyond PA to hypertension in the general population. Associated with clinical and biochemical evidence of a continuum of aldosterone dysregulation in hypertension, these discoveries suggest that common genetic variants may drive aldosterone dysregulation in a large fraction of hypertensive subjects leading, in extreme cases, to overt PA.
暂无摘要（点击查看详情）
Adult growth hormone deficiency (GHD) is associated with increased adiposity, reduced lean mass, adverse lipid profile, decreased bone density and impaired quality of life. Growth hormone (GH) replacement therapy provides significant metabolic, cardiovascular, musculoskeletal and psychological benefit. Traditional stimulation tests, such as the insulin tolerance and glucagon tests, are gold standards for diagnosis, but the oral macimorelin test offers a safe, reliable and well-tolerated alternative. GH replacement should be titrated to achieve age-appropriate insulin-like growth factor 1 (IGF-1) levels. Monitoring should address potential side effects, including glucose intolerance and fluid retention. Long-acting growth hormone (LAGH) formulations, such as somapacitan, lonapegsomatropin and somatrogon, now enable weekly administration, improving adherence while maintaining efficacy and safety comparable to daily therapy. Early evidence suggests enhanced patient satisfaction and similar metabolic outcomes. Ongoing longitudinal studies are essential to clarify long-term safety.
Ectopic ACTH-secreting pituitary adenoma, arising outside the sella turcica from residual cells of Rathke's pouch, is an exceptionally rare cause of Cushing's syndrome. Diagnosis is often challenging and may be late despite extensive clinical and biochemical work-up. We report here an ectopic corticotroph tumor of the maxillary sinus, which was finally localized by 18F-FDG PET/CT and somatostatin receptor scintigraphy. A 38-year-old woman was referred for suspicion of ACTH-dependent Cushing's syndrome. Biological testing was indicative of ectopic ACTH secretion; however, extensive investigation failed to identify any culprit tumor. In contrast, pituitary MRI revealed a doubtful 4-mm right-side pituitary lesion, leading to hypophysectomy, without clinical or biochemical remission. After pituitary surgery, medical therapy was initiated but had limited efficacy, and bilateral adrenalectomy was subsequently performed. Following the adrenalectomy, the patient developed hyperpigmentation due to elevated ACTH levels. 18F-FDG PET/CT and somatostatin receptor scintigraphy (Octreoscan®), years after initial diagnosis, revealed a hypermetabolic lesion in the maxillary sinus. Surgical resection identified an ectopic ACTH-secreting pituitary adenoma expressing ACTH and T-Pit; a marked decrease in plasma ACTH was observed postoperatively. In conclusion, we report a case of ACTH-dependent Cushing's syndrome, caused by an ectopic corticotroph adenoma located in the maxillary sinus. This case illustrates the diagnostic challenges in localizing ectopic ACTH-secreting pituitary adenomas and highlights the value of nuclear medicine imaging in identifying these unusual lesions.
The discovery of RET as the primary driver of hereditary medullary thyroid cancer in multiple endocrine neoplasia syndrome drastically changed the diagnosis, management, and prognosis of patients with this rare endocrine tumor. First, from a diagnostic viewpoint, RET testing within families became possible, ruling out unnecessary follow-up for negative patients and proposing an adapted surveillance protocol for positive patients. Second, large-scale epidemiological studies paved the way for early "prophylactic" thyroidectomy, rendering a historically fatal disease curable. RET identification also allowed for proper screening of pheochromocytoma and primary hyperparathyroidism. Lastly, RET identification enabled the synthesis of new, highly effective, and well-tolerated specific inhibitors, which changed the outcome for patients with metastatic disease. The RET discovery is thus a perfect example of how gene discovery can transform the fate of a rare syndrome, and this is what will be described in this short review.
McCune-Albright syndrome MAS is a rare mosaic disorder caused by post-zygotic GNAS activating mutations. MAS is characterized by fibrous dysplasia (FD) of the skeleton, café-au-lait skin macules, and hyperfunctioning endocrinopathies such as precocious puberty, thyroid disease, growth hormone excess, and FGF23-mediated phosphate wasting. Mosaicism leads to marked clinical heterogeneity and complicates molecular diagnosis. We retrospectively analyzed clinical and genotyping data of patients referred for suspected or clinically diagnosed MAS in a single French center (2014-2025). GNAS R201C and R201H mutations were detected by digital droplet PCR using peripheral blood as first-line samples, with additional testing of circulating cell-free, saliva, or tissue when indicated. We included 405 patients, from which 89 (22%) carried a GNAS mutation (52 R201C, 37 R201H). No significant clinical differences were observed between R201C and R201H. Among 578 analyzed samples, mutation detection varied by sample type, with the highest rates in tissue. Mutant allele frequency (MAF) in blood DNA was higher in patients with polyostotic than in monostotic FD (P=0.0055), but was not associated with the overall MAS-related lesion number. No correlation was found between MAF and age at diagnosis. MAS shows substantial clinical and molecular heterogeneity without clear genotype-phenotype differences between R201 variants. Mutation detection strongly depends on sample type, reflecting disease mosaicism. A multimodal diagnostic strategy and larger collaborative cohorts are needed to optimize molecular diagnosis and refine genotype-phenotype correlations in MAS patients.
Growth hormone deficiency (GHD) is a rare endocrine disorder responsible for growth failure. In the absence of an identified secondary cause, a genetic etiology can be identified, affecting genes involved in hypothalamo-pituitary growth hormone (GH) regulation or in pituitary development itself. The anterior pituitary gland arises from the oral ectoderm and is regulated by neuroectodermal signaling and transcription factors that ensure proper differentiation of hormone-producing cells. GH secretion is stimulated by growth-hormone-releasing hormone (GHRH) and ghrelin, with mutations in their respective receptors (GHRHR, GHSR) contributing to isolated GHD (IGHD). Mutations in GH1, encoding GH itself, are the main genetic cause of IGHD. GHD can also arise from mutations in transcription factor genes such as POU1F1, PROP1, IGSF1 or TBX19 or in genes involved in early brain development such as GLI2, LHX3 or HESX1, potentially leading to syndromic presentations with multi-organ involvement. Understanding the genetic basis of GHD is essential to improving diagnostic strategies, genetic counseling and the development of targeted therapies. Although animal models have been fundamental for understanding pituitary ontogenesis, emerging tools such as human pituitary organoids now offer the promise of dissecting human-specific regulatory mechanisms that cannot be fully captured in traditional animal models. This review aims to provide a comprehensive overview of all known genetic causes of GHD, with a particular focus on the underlying molecular mechanisms and their associated phenotypes.
Patients with primary bilateral macronodular adrenal hyperplasia, recently reclassified as bilateral macronodular adrenal disease (BMAD), have bilateral benign large adrenocortical nodules and variable cortisol excess. BMAD is considered a rare cause of overt Cushing's syndrome but a more frequent cause of bilateral adrenal incidentalomas. Initially considered a sporadic disease, the bilateral nature of the adrenal nodules and familial aggregation suggested a genetic origin. Indeed, genomic studies have improved our understanding of BMAD pathogenesis and identified several genetic events responsible for BMAD. As rare syndromic presentations were described, non-syndromic etiologies were also identified, suggesting distinct molecular backgrounds among BMAD cases. Firstly, germline heterozygous inactivating mutations of the ARMC5 gene, discovered in 2013, are now known to account for around 20-25% of sporadic cases and most familial cases. A second molecular group was later identified, characterized by germline heterozygous pathogenic variants and loss of heterozygosity of the lysine demethylase 1A gene (KDM1A, or LSD1) in familial and sporadic GIP-dependent BMAD, representing less than 5% of BMAD cases. Similarly to ARMC5, the stepwise inactivation of KDM1A, an epigenetic regulator gene, supports a tumor suppressor model of tumorigenesis. The latter, more heterogeneous, molecular group remains globally unelucidated, with the exception of reports of pathogenic variants in genes involved in the PKA and cAMP signaling pathways. In all cases, genetic counseling should be offered to identify affected members and to screen for BMAD.
Since the mid-1980s, the combination of clinical research into rare diseases and rapid advances in molecular genetics has led to major breakthroughs in the molecular diagnosis and management of these conditions, which sometimes affect only a small number of patients. These advances have been made possible by considerable investment in understanding the structure of the genome. Techniques have been greatly simplified over the past 20 years, and whole genome sequencing is now performed as part of patient care. Major advances have thus been made in the interest of patients, but new challenges have also emerged. The limiting factor is no longer knowing the sequence of a patient's genome, but rather confirming the link between a specific DNA variant and the phenotype. The more we advance in this understanding, the more we realize that the simplest situations are now well understood. The purpose of this article is to briefly review the organization of the human genome and the difficulties encountered in confirming the pathogenicity of a variant, using the example of congenital gonadotropin deficiency.
Imprinting disorders result from (epi)genetic abnormalities affecting genomic regions whose expression depends on parental origin. Among these, multilocus imprinting disturbances (MLID) constitute a specific entity characterised by simultaneous alterations in several imprinted regions, often leading to complex phenotypes. In recent years, the identification of maternal genetic factors, particularly within the maternal subcortical complex (SCMC), has led to a better understanding of the origin of certain cases of MLID. At the same time, rapid advances in molecular analysis - methylation arrays, targeted NGS panels, and long-read sequencing approaches - have profoundly renewed diagnostic capabilities. Together, these advances now offer a more integrated view of the mechanisms, phenotypes, and genetic determinants of imprinting-related diseases.
The incidence of thyroid cancer has risen in recent decades, largely due to the widespread use of increasingly sensitive imaging techniques that have enhanced the detection of thyroid nodules. Fine-needle aspiration cytology remains the diagnostic gold standard; however, 15-25% of samples fall into indeterminate Bethesda categories (III and IV), for which the traditional approach often involves diagnostic surgery, despite around 75% of these nodules ultimately prove to be benign. Advances in the genetic characterization of thyroid tumors, together with the development of next generation sequencing (NGS) technologies, have enabled the introduction of molecular tests aimed at improving preoperative risk stratification. Key genetic alterations include mutations in BRAF, the RAS family, the TERT promoter, and rearrangements involving RET, NTRK, and ALK, all of which have diagnostic and prognostic implications. Several commercial assays have been developed, employing methodologies including NGS, RNA sequencing, microRNA profiling, and qPCR. These tests demonstrate good sensitivity and high negative predictive value, helping to reduce unnecessary surgeries and better guide therapeutic decisions. Alongside commercial platforms, the high cost and limited accessibility of such tests have stimulated the development of increasingly robust in-house panels. Integrating molecular profiling with clinical and ultrasound findings now enables a more personalized approach to the management of indeterminate thyroid nodules, including surgery, mini-invasive treatments or active surveillance. Future perspectives include multi-omic and artificial intelligence approaches, which may further enhance diagnostic accuracy and cost-effectiveness.
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
Radiofrequency ablation (RFA) has emerged as a minimally invasive alternative to surgery for secondary hyperparathyroidism (SHPT), but efficacy and safety are still under evaluation. This meta-analysis assesses the effectiveness and complications of ultrasound-guided RFA in SHPT. We searched PubMed, Scopus, Web of Science, and the Cochrane Library from inception to February 10, 2025, for studies enrolling dialysis patients with SHPT treated by ultrasound-guided RFA. We included observational cohorts and case series (≥10 patients) with ≥6 month's follow-up, reporting changes in intact parathyroid hormone (iPTH), serum calcium or phosphorus; conference Abstracts, case reports, non-human studies, and non-English-language publications were excluded. Random-effects models were used to pool standardized mean differences (SMDs) and complication rates; heterogeneity was assessed using I2. Eight retrospective studies (n=349) were included. RFA was associated with significant reductions in iPTH at 1 day (SMD=-2.64, 95% CI -3.72 to -1.56; P<0.00001), 6 months (SMD=-2.09, 95% CI -2.54 to -1.64; P<0.00001), 12 months (SMD=-1.76, 95% CI -2.17 to -1.35; P<0.00001), and at final follow-up (SMD=-1.47, 95% CI -1.85 to -1.09; P<0.00001). Serum calcium decreased at 1 day (SMD=-1.26, 95% CI -2.22 to -0.30; P=0.010), 6 months (SMD=-0.98, 95% CI -1.35 to -0.61; P<0.00001), 12 months (SMD=-1.15, 95% CI -1.49 to -0.82; P<0.00001), and final follow-up (SMD=-1.24, 95% CI -2.21 to -0.28; P=0.010). Serum phosphorus also decreased at 1 day (SMD=-1.25, 95% CI -2.21 to -0.30; P=0.010), 6 months (SMD=-0.77, 95% CI -1.03 to -0.51; P<0.00001), 12 months (SMD=-0.73, 95% CI -0.95 to -0.50; P<0.00001), and final follow-up (SMD=-0.75, 95% CI -1.01 to -0.49; P<0.00001). Pooled complication rates included hypocalcemia (0.447, 95% CI 0.211-0.682), hoarseness (0.056, 95% CI 0.019-0.093), and recurrent laryngeal nerve injury/paralysis (0.027, 95% CI 0.000-0.066), with substantial heterogeneity in outcomes. RFA is an effective and safe alternative to parathyroidectomy for SHPT, with significant biochemical improvements and low risk of permanent complications. Long-term clinical trials are needed before drawing solid conclusions.
Adrenocortical carcinoma (ACC) is a rare malignancy with limited therapeutic options and poor prognosis in advanced stages. Clinico-pathological markers, such as Ki67 and ENSAT stage remain insufficient to fully predict recurrence or treatment response, highlighting the need for molecular characterization. Omic approaches, including transcriptomics, DNA methylation and chromosomal alteration profiling have consistently identified two distinct ACC subtypes "C1A" and "C1B". C1A tumors, overexpressing proliferation genes, are associated to poorer outcomes. C1B tumors however, are characterized by their immune signature and are of better prognosis. Single-cell analyses have helped understanding the mechanisms underlying these differences, hinting at a central role of intratumoral steroid differentiation in shaping the immune microenvironment. Transcriptome sequencing from paraffin-embedded samples are bringing molecular classification closer to routine care, with ongoing prospective trials evaluating its feasability. Genomic classification represents a major step in ACC management and understanding, offering improved prognostic stratification and orienting future therapeutic strategies.