Clinical Medicine Insights-Endocrinology and Diabetes最新文献

Background: It is still unelucidated how hormonal alterations affect developing organisms and their descendants. Particularly, the effects of androgen levels are of clinical relevance as they are usually high in women with Polycystic Ovary Syndrome (PCOS). Moreover, it is still unknown how androgens may affect males' health and their descendants.

Objectives: We aimed to evaluate the multigenerational effect of prenatal androgen excess until a second generation at early developmental stages considering both maternal and paternal effects.

Design and methods: This is an animal model study. Female rats (F0) were exposed to androgens during pregnancy by injections of 1 mg of testosterone to obtain prenatally hyperandrogenized (PH) animals (F1), leading to a well-known animal model that resembles PCOS features. A control (C) group was obtained by vehicle injections. The PH-F1 animals were crossed with C males (m) or females (f) and C animals were also mated, thus obtaining 3 different mating groups: Cf × Cm, PHf × Cm, Cf × PHm and their offspring (F2).

Results: F1-PHf presented altered glucose metabolism and lipid profile compared to F1-C females. In addition, F1-PHf showed an increased time to mating with control males compared to the C group. At gestational day 14, we found alterations in glucose and total cholesterol serum levels and in the placental size of the pregnant F1-PHf and Cf mated to F1-PHm. The F2 offspring resulting from F1-PH mothers or fathers showed alterations in their growth, size, and glucose metabolism up to early post-natal development in a sex-dependent manner, being the females born to F1-PHf the most affected ones.

Conclusion: androgen exposure during intrauterine life leads to programing effects in females and males that affect offspring health in a sex-dependent manner, at least up-to a second generation. In addition, this study suggests paternally mediated effects on the F2 offspring development.

Background: The Republic of the Marshall Islands (RMI) faces a high prevalence of type 2 diabetes (T2DM).

Objectives: The aim of the study is to document the health of Marshallese with and without a T2DM diagnosis to inform future interventions.

Design: Data are from screenings collected in preparation for a diabetes education intervention. Data, including HbA1c, random glucose, cholesterol, weight, and self-rated health, were collected.

Methods: Kruskal-Wallis and Fisher's exact tests were used to identify differences in participants with and without T2DM diagnosis.

Results: There were significant differences in both HbA1c level (P ⩽ .0001) and glucose level (P ⩽ .0001) between the diagnosed T2DM and non-diagnosed T2DM groups, as well as diastolic blood pressure (P = .0179), systolic blood pressure (P = .0003), and pulse pressure (P = .0023). There were no differences in weight, body mass index (BMI), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol, or self-rated health. Marshallese without a T2DM diagnosis have signs of insulin resistance, including elevated glucose and triglyceride levels.

Conclusion: The results indicate a need for a socioecological approach to T2DM interventions, and interventions in the RMI should consider inclusion of blood pressure and cholesterol management. There is a need for interventions to prevent prediabetes and its progression to T2DM.

Graves' disease (GD) is the most common cause of hyperthyroidism in children. A common GD symptom is a goiter. The usual biochemical profile in children with GD is a decreased thyroid hormone stimulating hormone (TSH) level and high free thyroxine (FT4) and free triiodothyronine (FT3) concentrations. The presence of thyroid receptor antibodies (TRAb) is the most important specific immunological sign for diagnosing GD. The treatment choices for pediatric GD are anti-thyroid drugs (ATDs), radioiodine, and thyroidectomy, but the risks and benefits of each modality are different. Management recommendations include the first-line use of a prolonged course of ATDs for at least 3 years and potentially 5 years or more. Rituximab and Teprotumumab are new novel alternative medications for the treatment of adult patients with GD and Graves' orbitopathy respectively, but evidence of the efficacy and safety of these drugs in pediatric patients with GD is lacking.

Background: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder. The aim of the present investigation was to identify gene signature specific to T2DM.

Methods: The next generation sequencing (NGS) dataset GSE81608 was retrieved from the gene expression omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) between T2DM and normal controls. Then, Gene Ontology (GO) and pathway enrichment analysis, protein-protein interaction (PPI) network, modules, miRNA (micro RNA)-hub gene regulatory network construction and TF (transcription factor)-hub gene regulatory network construction, and topological analysis were performed. Receiver operating characteristic curve (ROC) analysis was also performed to verify the prognostic value of hub genes.

Results: A total of 927 DEGs (461 were up regulated and 466 down regulated genes) were identified in T2DM. GO and REACTOME results showed that DEGs mainly enriched in protein metabolic process, establishment of localization, metabolism of proteins, and metabolism. The top centrality hub genes APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1 were screened out as the critical genes. ROC analysis provides prognostic value of hub genes.

Conclusion: The potential crucial genes, especially APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1, might be linked with risk of T2DM. Our study provided novel insights of T2DM into genetics, molecular pathogenesis, and novel therapeutic targets.

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) use is associated with an increased risk of diabetic ketoacidosis (DKA).

Objective: This study evaluated and compared the DKA characteristics and outcomes of users and non-users of SGLT2i.

Methods: We retrospectively studied patients with type 2 diabetes mellitus (T2DM) admitted with DKA to Tawam Hospital, Al Ain City, UAE between January 2017 and March 2021. Demographic data, clinical, and laboratory findings were extracted from the electronic medical records.

Results: A total of 55 patients with T2DM (62% UAE nationals, 50% women) were admitted with DKA. The average age was 54.0 ± 18.9 years and average diabetes duration of 15.7 ± 15.1 years. Seventeen patients (31%) were using SGLT2i. Infection was the main precipitating factor for DKA in (8 out of 17) SGLT2i users. Compared to non-users, SGLT2i users had lower systolic blood pressure (119.9 vs 140 mmHg; P = .012) and serum glucose levels (16.2 vs 24.9 mmol/L; P < .001) and higher Na level (137.5 vs 132.6 mmol/L; P = .005). Additionally, 56.3% of SGLT2i users had euglycemic DKA compared to 2.6% of nonusers (P < .001). Acute kidney injury (AKI) occurred more in SGLT2i users compared to non-users (94.1% vs 67.6%, P = .043). Further analysis revealed that SGLT2i users were about five times more likely to have prolonged hospital length of stay (⩾14 days) when compared with non-users (adjusted OR: 4.84; P = .035). Overall, there was no difference between the two groups with regards to DKA complications and mortality.

Conclusions: SGLT2i related DKA is associated with lower blood glucose levels, lower SBP, worse hypovolemia, increased risk of AKI, and longer hospital stay when compared to non SGLT2i related episodes. Since the benefits of SGLT2 inhibitors far outweigh potential risks, there is a need to raise healthcare professionals and patients' awareness about this potential association.

Background: Both hormonal and genetic data reveal that the stress hormone cortisol and its regulating genes may affect the level of testosterone in humans. It is uncertain whether type 2 diabetes mellitus would manifest similarly. Furthermore, a genetic strategy to screen out the stress system genes that may contribute to testosterone decline in humans is less understood.

Objectives: In this study, we aimed to elucidate the link between stress and testosterone levels, both hormonally and genetically.

Method: This study comprised 37 individuals with type 2 diabetes mellitus and 50 healthy individuals. For the analysis of hormones and the targeted genes, we used the RIA system and bioinformatics expertise.

Results: The patients had significantly elevated cortisol and lower testosterone readings, according to data from hormonal analyses. The bioinformatics approach reveals that SHBG was intracellularly suppressed by 2 defined stress system genes: FKB5 and CYP17. TCF4/TCF8, ATRX, and AR in skeletal muscle were inversely related to stress system genes. Furthermore, all testosterone regulated genes were positively linked with SHBG in the current study. A strong relationship between GNAS and PKA with CYP17 and FKBP5 reveals that the Gαs-cAMP/PKA signaling pathway may be one of the regulatory pathways through which the suppression of testosterone system genes happens. In conclusion, this study demonstrated that beyond stress, the key stress system genes might affect cortisol levels, which in turn affect testosterone figures via the Gαs-cAMP/PKA signaling pathway.

Lipoid congenital adrenal hyperplasia (LCAH) is characterized by disturbance of adrenal and gonadal steroidogenesis (OMIM:201710). It is caused by mutation in the Steroidogenic Acute Regulatory Protein (StAR). We report a classic case of LCAH in a neonate (46, XY) with phenotypic female genitalia who presented with significant salt loss with a novel homozygous variant mutation c.745-1G>C p. in StAR gene.

Introduction: Patients with primary hyperparathyroidism (PHPT) experience bone mineral density (BMD) loss and trabecular bone score (TBS) alteration, which current guidelines recommend assessing. Considering TBS alongside BMD for a 10-year fracture risk assessment (FRAX) may improve PHPT management.

Design: Retrospective, cross-sectional study composed of 49 Caucasian females (62 ± 10.6 years, 27.7 ± 0.87 kg/m²) with PHPT and 132 matched control subjects (61.3 ± 10.5 years, 27.5 ± 0.49 kg/m²) evaluated in 3 years. We assessed lumbar spine (LS) and femoral neck (FN) BMD, T and Z scores (GE Healthcare Lunar Osteodensitometer) and TBS (iNsight 1.8), major osteoporotic fracture (MOF), and hip FRAX.

Results: Patients with PHPT had statistically lower mean values for lumbar spine bone mineral density (LS BMD) (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm², P = .01), LS T-scores (-2 ± 0.2 vs -1.4 ± 0.1 SD, P = .009), LS Z scores (-0.9 ± 0.19 vs -0.1 ± 0.11 SD, P = .009), femoral neck bone mineral density (FN BMD) (0.79 ± 0.02 vs 0.83 ± 0.01 g/cm², P = .02), FN T-scores (-1.8 ± 0.13 vs -1.5 ± 0.07 SD, P = .017), FN Z scores (-0.51 ± 0.87 vs -0.1 ± 0.82 SD, P = .006), and TBS (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm², P = .01) compared with control subjects. 22.4% of patients with PHPT had degraded microarchitecture (TBS < 1.2) vs. 7.6% in control group (χ² = 0.008). PHPT proved to be a covariate with unique contribution (P = .031) alongside LS BMD (P = .040) in a linear regression model [R ² = 0.532, F(4,16) = 4.543] for TBS < 1.2. TBS adjustment elevated MOF FRAX both for PHPT (4.35  ± 0.6% vs 5.25% ± 0.73%, P < .001) and control groups (4.5  ± 0.24% vs 4.7% ± 0.26%, P < .001) compared with BMD-bases FRAX, but also increased differently between the 2 study groups (1.1-folds for PHPT patients and 1.04 for control subjects, P = .034).

Conclusion: Compared with control, TBS-adjusted FRAX provides significantly higher MOF risk than BMD-based FRAX in PHPT women.

Cushing's syndrome and pheochromocytomas (PCCs) are associated with endocrine hypertension. Cortisol-producing adrenal adenomas are a major cause of Cushing's syndrome. Simultaneous occurrence of cortisol-producing adrenal adenomas and PCCs is rare. Additionally, a PCC generally produces catecholamines in proportion to its size; therefore, micro-PCCs are rarely found in clinical practice. It is unknown whether micro-PCCs produce excess catecholamines during the pre-biochemical phase. Herein, we report the case of a 53-year-old woman who was referred to our hospital for further evaluation of left adrenal incidentaloma. She had been suffering from hypertension for 7 years. Endocrine tests indicated autonomous cortisol secretion, and she was diagnosed with cortisol-producing adrenal adenoma. A laparoscopic left adrenalectomy was performed. The final pathological examination revealed an adrenocortical adenoma measuring 26 × 24 mm. In addition, a micro-PCC measuring 3 × 2 mm was incidentally found near the cortisol-secreting adrenal adenoma in the ipsilateral adrenal gland. All catecholamine biosynthetic enzymes, tyrosine hydroxylase, aromatic l-amino acid decarboxylase, dopamine β-hydroxylase, and phenyl ethanolamine N-methyltransferase, were detected in this micro-PCC by immunohistochemical analyses. Although catecholamine levels were not biochemically elevated, the PCC expressed catecholamine biosynthetic enzymes. This is the first immunohistochemical report to show that a micro-PCC produces excess catecholamines in the pre-biochemical phase.

The COVID-19 pandemic has changed many aspects of people's lives, including not only individual social behavior, healthcare procedures, and altered physiological and pathophysiological responses. As a result, some medical studies may be influenced by one or more hidden factors brought about by the COVID-19 pandemic. Using the literature review method, we are briefly discussing the studies that are confounded by COVID-19 and facemask-induced partiality and how these factors can be further complicated with other confounding variables. Facemask wearing has been reported to produce partiality in studies of ophthalmology (particularly dry eye and related ocular diseases), sleep studies, cognitive studies (such as emotion-recognition accuracy research, etc.), and gender-influenced studies, to mention a few. There is a possibility that some other COVID-19 related influences remain unrecognized in medical research. To account for heterogeneity, current and future studies need to consider the severity of the initial illness (such as diabetes, other endocrine disorders), and COVID-19 infection, the timing of analysis, or the presence of a control group. Face mask-induced influences may confound the results of diabetes studies in many ways.