Hormones-International Journal of Endocrinology and Metabolism最新文献

Purpose: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent disease with limited treatment options. The aim of this study was to evaluate the preventive effects of a sodium-glucose co-transporter (SGLT)-2 inhibitor, empagliflozin, on a dietary mouse model of MASLD.

Methods: In total, 24 C57BL/6 J mice of both sexes were randomly allocated to three groups, as follows: the fast food diet (FFD) group (eight mice, receiving a high-fat, high-cholesterol, high-fructose diet, FFD), the EMPA group (eight mice, fed a FFD with 10 mg/kg/d empagliflozin), and the chow diet (eight mice, CD) group. The mice were weighed and blood samples were drawn every 4 weeks; after 25 weeks the mice were euthanized, at which point liver tissues were histologically evaluated.

Results: After 25 weeks, there was no significant difference in body weight between the three groups, whereas liver-to-body weight ratio was greater in the EMPA compared to the CD group (p = 0.002). Hepatic fibrosis was marginally different between the three groups (p = 0.045). Fibrosis stage 1 was present in five mice on FFD (62.5%), in one mouse on EMPA (12.5%), and in one mouse on CD (12.5%). Lipogenic, inflammatory, and fibrogenic genes did not differ between the EMPA and FFD groups. Interestingly, mRNA encoding for SGLT-1 and SGLT-2 was detected in the mouse livers.

Conclusions: Empagliflozin treatment in mice on a FFD did not result in any significant effects on morphological, biochemical, or histological features or on expression of hepatic genes associated with MASLD compared to those fed a FFD without empagliflozin. The observed effects on mild hepatic fibrosis warrant validation, possibly via studies of longer duration.

Hashimoto's thyroiditis (HT) is the most common autoimmune endocrine disease worldwide with an annual incidence of 0.3-1.5 per 1000 people and a prevalence of 8% of the general population. At least nine terms appear in the literature denoting HT, which are used as synonyms or are terms describing disorders closely related to HT. Moreover, the definitions of HT vary, and the role of several parameters in making a diagnosis remains unclear. Furthermore, the term "thyroiditis" is often used among experts to describe the triphasic evolution in thyroid status (thyrotoxicosis, hypothyroidism, and euthyroidism) that can occur not only after some forms of HT but also in other causes of thyroid inflammation. The present work proposes novel approaches for the nomenclature problems. Firstly, we should abandon the eponym "Hashimoto" in keeping with recent trends. The void left can be replaced by the terms "autoimmune thyroiditis" or "autoimmune thyroid disease", which are already in use. In communicating among ourselves and with patients, it is imperative and good practice to provide, whenever possible, context to these terms by specifying whether they apply to thyroid status, presence or absence of goiter, thyroid autoantibodies, imaging, cytology/histology, epidemiology, or etiology. Secondly, the considerable potential harm associated with treating euthyroid people with thyroid hormones could be curtailed by avoiding testing for thyroid autoantibodies or performing thyroid imaging in asymptomatic euthyroid patients following the current guidelines and by discouraging the use of the word "disease" when the evidence is based only on results of investigations, such as positive antibodies, or imaging.

Purpose: Metabolic syndrome (MS) and obstructive sleep apnea-hypopnea syndrome (OSAHS) are associated with an increased risk of cardiometabolic disease. The coexistence of OSAHS and metabolic disorders is common, but research on how to recognize OSAHS and how OSAHS risk exacerbates metabolic disorders is limited. This study aimed to analyze the correlations of the ZJU index and triglyceride‒glucose (TyG) index with OSAHS in MS patients and to investigate the ability to use the ZJU index and TyG-related indices to assess the presence and severity of OSAHS in MS patients.

Methods: This retrospective study included 216 MS patients with perfect polysomnographic monitoring (PSG), who were categorized into MS combined with OSAHS (n = 142) and MS alone (n = 74) groups according to the sleep monitoring results. The MS combined with OSAHS group was further categorized into mild (n = 55), moderate (n = 34), and severe (n = 53) groups according to the apnea hypopnea index (AHI). The general clinical data, clinical biochemical indices, AHI, mean oxygen saturation (MSaO₂), lowest oxygen saturation (LSaO₂), and longest apnea duration were collected from all the included subjects. Composite indices such as the ZJU, TyG, and TyG-BMI indices were calculated. The differences in each metabolic index among the different groups were analyzed; logistic regression analysis was used to compare the correlations between each parameter and OSAHS, and the efficacy of each parameter in identifying OSAHS in the MS population was evaluated by receiver operating characteristic (ROC) curves.

Results: The ZJU, TyG, and TyG-BMI indices were associated with OSAHS after adjusting for sex, age, history of hypertension, history of diabetes, and history of smoking (all P < 0.05). The odds ratios for the ZJU, TyG, and TyG-BMI indices were 1.472 (1.293-1.674), 9.811 (3.916-24.582), and 1.032 (1.020-1.044), respectively. The ZJU, TyG, and TyG-BMI indices are effective predictors of the occurrence of OSAHS in MS patients, and their cutoff values could be used for early screening of OSAHS. The ZJU index was the strongest predictor of OSAHS, (area under the curve 0.829, 95% CI 0.771-0.888), with an optimal cutoff value of 38.940.

Conclusions: The ZJU, TyG, and TyG-BMI indices are novel, valid, and practical indicators for early screening of OSAHS risk in MS patients.

Aromatase enzyme deficiency (AED) is a rare autosomal recessive disorder caused by mutations in the CYP19A1 gene. This disorder causes an inability to convert androgens into estrogens, resulting in excess androgens and estrogen deficiency. AED is typically diagnosed in female infants, but diagnosis in men is often delayed until adulthood due to late-onset skeletal and metabolic issues. We report the case of a 31-year-old male referred for increased height and bone discomfort. Over the past 6 years, his height had increased by 5 cm, accompanied by leg cramps and bone pain. He had a height of 193 cm, weighed 103 kg, and presented with a eunuchoid body habitus. The patient's height was above/at + 2 SD from target height. Laboratory findings revealed elevated FSH, LH, and testosterone, with undetectable estrogen levels. Serum osteocalcin and alkaline phosphatase were elevated. X-rays showed incomplete epiphyseal fusion. Bone densitometry revealed Z scores of -2 (lumbar spine) and - 2.6 (femoral neck). Genetic testing confirmed a homozygous exon 6 deletion in CYP19A1. The patient was treated with transdermal estradiol (25 µg twice weekly), which normalized estradiol, testosterone, and gonadotropin levels. Epiphyseal fusion occurred within 6 months. Aromatase deficiency in men frequently goes undiagnosed until adulthood. Timely diagnosis is crucial to initiating estrogen treatment early after puberty to prevent skeletal problems linked to this disorder.

Objective: This study aimed to investigate the relationship between ACE2 expression in peripheral blood and the prognosis of patients with adrenal adenoma and hypertension.

Methods: We recruited 80 patients with adrenal adenoma and hypertension (47 males, 33 females) treated between March 2021 and September 2022. Patients were divided into high ACE2 expression (n = 26) and low ACE2 expression (n = 54) groups. General patient data, blood pressure, serum potassium, creatinine, and hormone levels (cortisol, aldosterone, catecholamines) were compared. The frequency of hypertensive episodes with palpitations was recorded. Correlations between ACE2 expression and prognosis were analyzed using Pearson correlation and Cox regression models.

Results: The ACE2 high expression group had significantly lower blood pressure, serum creatinine, and hormone levels (P < 0.001), but higher serum potassium (P < 0.001) compared to the low expression group. Over 3 months, the incidence of hypertensive episodes with palpitations was lower in the high expression group (7.69%) compared to the low expression group (24.07%) (P = 0.002). The frequency of episodes was also lower in the high expression group (P = 0.016). Pearson correlation analysis showed a negative correlation between ACE2 expression and poor prognosis (P < 0.001). Multivariate Cox regression confirmed low ACE2 expression as an independent risk factor for poor prognosis (P < 0.001).

Conclusion: High ACE2 expression is associated with improved cardiovascular and renal function and lower incidence of hypertensive episodes in patients with adrenal adenoma and hypertension, suggesting a protective role of ACE2 in mitigating hypertension-related complications.

Clinical trial number: Not applicable.

Background: Aldosterone plays a critical role in sodium homeostasis by binding to the mineralocorticoid receptor promoting sodium retention. It increases the expression of epithelial sodium channels (ENaC) and sodium-potassium ATPases in the renal distal tubules and collecting ducts. Defects in aldosterone synthesis lead to hyponatremia, hyperkalemia, hyperreninemia, metabolic acidosis, and hypovolemia.

Patient: We present a 7-year-old boy with holoprosencephaly, dysmorphic features, and short stature presenting with persistent hyponatremia since birth and occasional hypokalemia and hyporeninemia. Initial whole exome sequencing (WES) identified a novel in-frame SHH variant, NM_000193.4:c.755_757del (p.Phe252del); possible aldosterone deficiency due to adrenocortical hypoplasia caused by the SHH variant did not fully explain the patient's clinical presentation, prompting further investigation.

Results: Deep analysis of the WES data revealed a second variant of unknown significance in the SCNN1G gene affecting the γ-ENaC subunit, namely NM_001039.4.1904 C > T (p.Ala635Val), which was previously unreported in association with a clinical phenotype. Electrophysiological studies of the amiloride-sensitive current before and after trypsin exposure showed that the γ-ENaC-A635V mutation reduced the amiloride-sensitive sodium current by approximately 30%. The trypsin experiments suggested a lower channel open probability and a reduced inward sodium current through the ENaC.

Conclusions: These findings indicate that the A635 residue participates in channel function, with γ-Α635V leading to decreased sodium reabsorption. This case underscores the importance of reevaluating genetic data to understand complex clinical presentations and identifies a new potential pathogenic variant affecting sodium homeostasis. The case illustrates how genetic variants with contrasting effects on a physiological loop along with functional changes due to development and age may be hard to interpret.

Purpose: Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard for localizing ACTH-dependent Cushing's syndrome (CS). While corticotropin-releasing hormone (CRH) was initially used for stimulation, desmopressin has become a common alternative. This research evaluates desmopressin's effectiveness in lateralizing Cushing's disease (CD) during BIPSS compared to CRH stimulation.

Methods: The study included 33 individuals with ACTH-dependent CS who underwent BIPSS and had diagnoses confirmed by endoscopic endonasal transsphenoidal pituitary surgery (EETPS). Fourteen participants underwent BIPSS with CRH and 19 with desmopressin. A comparative analysis was conducted.

Results: BIPSS accurately lateralized 76% of cases, specifically, 71% with CRH and 79% with desmopressin (p = 0.2). For tumors < 6 mm on MRI, overall accuracy was 82%, namely, 75% with CRH and 90% with desmopressin (p = 0.4). IPSS achieved 100% accuracy in the four cases with no lesion on preoperative MRI.

Conclusion: This study demonstrates no significant difference in lateralization accuracy between desmopressin and CRH for IPSS. In challenging cases, especially those with microadenomas or non-lesional CD, desmopressin with IPSS aids in preoperative lateralization.

Graves' disease is the most common form of hyperthyroidism, especially in younger people. Current European guidelines recommend antithyroid drugs as initial treatment for a period limited to 12-18 months. Definitive treatment such as surgery or radioactive iodine is proposed in the case of contraindication to antithyroid drugs or in the case of recurrence after medical treatment. However, more recent studies show that long-term antithyroid treatment is associated with reduced risk of recurrence without an increase in adverse effects. Such data support the option of long-term treatment of Graves' disease with antithyroid drugs and suggest the necessity for a change to long-standing practices in the field. Herein, after reviewing some general knowledge on Graves' disease treatment, we discuss the evidence regarding long-term treatment of Graves' disease with antithyroid drugs for endocrinologists, internists, and other specialists involved in the management of these patients. We consider the main studies in the field, outline their respective strengths and limitations, and, finally, present our opinion on when, in the light of this new evidence, endocrinologists should consider long-term treatment with antithyroid drugs.

Purpose: Canada has experienced a ten-fold increase in referrals for gender-affirming care. Clinical guidelines emphasize the importance of a comprehensive and systematic approach to outcome measurement for gender-affirming hormonal care. However, research is lacking on the investigation of outcomes of Canadian gender-affirming hormonal treatments.

Methods: In total, five databases were searched, as follows: MEDLINE, Embase, PsycINFO, Scopus, and CINAHL on December 26, 2023. To meet inclusion criteria, each study needed to be an original article including patients identifying as transgender or gender diverse (TGD) who were receiving gender-affirming hormonal care in Canada. The Critical Appraisal Skills Programme (CASP) and Joanna Briggs Institute (JBI) tools were used to assess the methodological quality of the study. Descriptive frequencies were calculated for demographic information and a narrative synthesis was conducted to summarize outcomes organized for different treatments.

Results: A total of 3315 articles were identified, with 34 articles being included, representing 3990 patients. Physiologic parameters were reported in 62% of the studies and patient-reported outcomes (PROs) in 50%, although only 32% utilized standardized patient-reported outcome measures (PROMs). In studies reporting quantitative results, testosterone treatments showed 80% effectiveness in achieving desired physical changes, while several studies demonstrated that estrogen and antiandrogen treatments improved mental health in 85% of patients. The narrative synthesis of the results reveals positive outcomes and limited adverse effects of gender-affirming hormone therapy; however, it also underscores the need for standardized, consistent outcome measurement tools, particularly PROMs.

Conclusion: The present systematic review highlights the need for standardized outcome reporting in gender-affirming hormone therapy, underscoring the need for measurement of the patient's perspective through PROMs. Resolving these issues can improve evidence-based practices and support high-quality, patient-centered gender-affirming hormone care.