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Background: Uteroplacental insufficiency in fetuses with growth restriction (FGR) leads to chronic hypoxia and stress, predominantly affecting the adrenal glands. However, the mechanisms of impact remain unclear. Objectives: This study is aimed at comparing the Doppler indices of the adrenal artery and the adrenal gland sizes between FGR and those with normal growth. Materials and Methods: A multicenter, cross-sectional study was conducted from February to December 2023. We compared 34 FGR to 34 with normal growth in terms of inferior adrenal artery (IAA) Doppler indices and adrenal gland volumes. Results: The IAA peak systolic velocity (PSV) in the FGR group was 14.9 ± 2.9 cm/s compared to 13.5 ± 2.0 cm/s in the normal group, with a mean difference of 1.4 cm/s (95% confidence interval [CI]: 0.27-2.65; p value = 0.017). There were no significant differences between groups in terms of IAA pulsatility index (PI), resistance index (RI), or systolic/diastolic (S/D), with p values of 0.438, 0.441, and 0.658, respectively. The volumes of the corrected whole adrenal gland and the corrected neocortex were significantly larger in the FGR group, with p values of 0.031 and 0.020, respectively. Conclusion: Both increased IAA PSV and enlarged volumes of the corrected whole adrenal gland and neocortex were found in fetuses with FGR, suggesting significant adrenal gland adaptation in response to chronic intrauterine stress.
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Glándulas Suprarrenales , Retardo del Crecimiento Fetal , Ultrasonografía Doppler , Ultrasonografía Prenatal , Humanos , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/fisiopatología , Femenino , Embarazo , Estudios Transversales , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/embriología , Ultrasonografía Prenatal/métodos , AdultoRESUMEN
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Neoplasias de las Glándulas Suprarrenales , Ultrasonografía , Humanos , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/patología , Ultrasonografía/métodos , Linfoma/diagnóstico por imagen , Linfoma/patología , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/patología , Masculino , Femenino , Persona de Mediana EdadRESUMEN
The adrenal gland is a player in the Ominous Octet of obesity, which lists eight endocrine contributors to the development of obesity. Baro-adrenal axis describes the bidirectional, multifaceted link between weight homoeostasis and adrenal function, in health and disease. This communication lists the various ways in which adrenal function influences, and is impacted by, obesity.
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Glándulas Suprarrenales , Obesidad , Humanos , Obesidad/fisiopatología , Glándulas Suprarrenales/fisiología , Glándulas Suprarrenales/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/fisiologíaRESUMEN
BACKGROUND: Hypocholesterolemia hallmarks critical illness though the underlying pathophysiology is incompletely understood. As low circulating cholesterol levels could partly be due to an increased conversion to cortisol/corticosterone, we hypothesized that glucocorticoid treatment, via reduced de novo adrenal cortisol/corticosterone synthesis, might improve cholesterol availability and as such affect adrenal gland and skeletal muscle function. METHODS: In a matched set of prolonged critically ill patients (n = 324) included in the EPaNIC RCT, a secondary analysis was performed to assess the association between glucocorticoid treatment and plasma cholesterol from ICU admission to day five. Next, in a mouse model of cecal ligation and puncture-induced sepsis, septic mice were randomized to receive either hydrocortisone (1.2 mg/day) (n = 17) or placebo (n = 15) for 5 days, as compared with healthy mice (n = 18). Plasma corticosterone, cholesterol, and adrenocortical and myofiber cholesterol were quantified. Adrenal structure and steroidogenic capacity were evaluated. Muscle force and markers of atrophy, fibrosis and regeneration were quantified. In a consecutive mouse study with identical design (n = 24), whole body composition was assessed by EchoMRI to investigate impact on lean mass, fat mass, total and free water. RESULTS: In human patients, glucocorticoid treatment was associated with higher plasma HDL- and LDL-cholesterol from respectively ICU day two and day three, up to day five (P < 0.05). Plasma corticosterone was no longer elevated in hydrocortisone-treated septic mice compared to placebo, whereas the sepsis-induced reduction in plasma HDL- and LDL-cholesterol and in adrenocortical cholesterol was attenuated (P < 0.05), but without improving the adrenocortical ACTH-induced CORT response and with increased adrenocortical inflammation and apoptosis (P < 0.05). Total body mass was further decreased in hydrocortisone-treated septic mice (P < 0.01) compared to placebo, with no additional effect on muscle mass, force or myofiber size. The sepsis-induced rise in markers of muscle atrophy and fibrosis was unaffected by hydrocortisone treatment, whereas markers of muscle regeneration were suppressed compared to placebo (P < 0.05). An increased loss of lean body mass and total and free water was observed in hydrocortisone-treated septic mice compared to placebo (P < 0.05). CONCLUSIONS: Glucocorticoid treatment partially attenuated critical illness-induced hypocholesterolemia, but at a cost of impaired adrenal function, suppressed muscle regeneration and exacerbated loss of body mass.
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Glándulas Suprarrenales , Colesterol , Enfermedad Crítica , Glucocorticoides , Músculo Esquelético , Animales , Enfermedad Crítica/terapia , Humanos , Ratones , Glucocorticoides/uso terapéutico , Glucocorticoides/farmacología , Colesterol/sangre , Colesterol/análisis , Masculino , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/fisiopatología , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Femenino , Anciano , Hidrocortisona/análisis , Hidrocortisona/uso terapéutico , Hidrocortisona/sangre , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Sepsis/complicaciones , Modelos Animales de EnfermedadRESUMEN
The distribution of CYP11B2-positive or aldosterone producing adrenocortical cells in human fetuses and children and their age-dependent changes has not been studied. We aimed to explore the changes of aldosterone biosynthesis and age-related histological alterations of the zona glomerulosa in human adrenal gland during fetal and pediatric periods. We first reviewed 125 fetal and pediatric autopsy cases and retrieved 78 adrenals from 70 cases. CYP11B2 immunohistochemistry and quantitative image analysis of its results were performed in all adrenal glands. The ratio of the definitive zone (DZ) or zona glomerulosa (ZG) / the whole adrenocortical areas started to increase in the 2nd trimester, subsequently decreased in the 3rd, increased after birth, peaked in infancy, and then gradually decreased. The ratio of CYP11B2-positive / whole adrenocortical areas remained low during the fetal period but increased after birth, peaked at infancy, and then decreased. The ratio of CYP11B2-positive / DZ or ZG areas and CYP11B2-positive areas / depth of DZ or ZG demonstrated a distinctive bimodal pattern, with one peak in the fetal period and another in the neonatal period to infancy. This is the first study to perform quantitative analysis of the distribution of CYP11B2-positive cells, the histological DZ or ZG, and the development of aldosterone biosynthesis in human adrenal glands during fetal and pediatric periods.
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Aldosterona , Citocromo P-450 CYP11B2 , Feto , Zona Glomerular , Humanos , Citocromo P-450 CYP11B2/metabolismo , Citocromo P-450 CYP11B2/genética , Aldosterona/biosíntesis , Aldosterona/metabolismo , Lactante , Zona Glomerular/metabolismo , Femenino , Preescolar , Feto/metabolismo , Masculino , Recién Nacido , Niño , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/embriología , Adolescente , EmbarazoAsunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1 , Colesterol , Colesterol/metabolismo , Colesterol/biosíntesis , Animales , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Humanos , Glándulas Suprarrenales/metabolismo , Esteroides/biosíntesis , Esteroides/metabolismo , RatonesRESUMEN
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3ß-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.
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Encefalomielitis Autoinmune Experimental , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Animales , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Femenino , Masculino , Sistema Hipófiso-Suprarrenal/metabolismo , Ratas , Sistema Hipotálamo-Hipofisario/metabolismo , Corticosterona/sangre , Hormona Adrenocorticotrópica/sangre , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Caracteres Sexuales , Progesterona/sangreRESUMEN
OBJECTIVE: This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. METHODS: Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. RESULTS: The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p < 0.001). The rates of clinical success and biochemical success after adrenal artery ablation were 63.2% (43/68) and 39.7% (27/68), respectively. Overall, there were significant reductions in daily defined doses (DDD), aldosterone/renin ratio (ARR), and plasma aldosterone levels (p < 0.001). Plasma renin levels increased by a mean value of 10.4 ± 39.0 pg/mL (p = 0.049), and potassium levels increased by 0.40 ± 0.63 mmol/L (p < 0.001). No significant adverse events were reported during SAAE or the follow-up period of up to one year. Additionally, no abnormalities were detected by adrenal 68Ga-Pentixafor PET/CT scans before or after SAAE. CONCLUSION: Bilateral SAAE appears to lead to sustained improvements in blood pressure and biochemical parameters in patients with bilateral PA, with minimal adverse effects. This suggests that bilateral SAAE could serve as an effective alternative approach for treating bilateral IHA, potentially curing this condition.
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Glándulas Suprarrenales , Embolización Terapéutica , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/terapia , Hiperaldosteronismo/cirugía , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/sangre , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Embolización Terapéutica/métodos , Resultado del Tratamiento , Adulto , Glándulas Suprarrenales/irrigación sanguínea , Estudios de Seguimiento , Aldosterona/sangreRESUMEN
BACKGROUND: Adrenal gland injury (AGI) associated with trauma is an uncommon and often overlooked condition. This study aimed to evaluate the frequency of AGI in individuals with severe trauma injuries and investigate the outcomes of patients with AGI. METHODS: All patients admitted to a tertiary trauma referral center under the trauma protocol who had a computed tomography (CT) scan between January 2012 and January 2023 were analyzed retrospectively. Patients who were dead on arrival and patients with incomplete data were excluded. They were classified into two main groups, adult and pediatric, and further subcategorized by the presence or absence of radiologically evident AGI. Demographic data, mechanism of injury, injury severity scores (ISS), presence of concurrent abdominal injury, and 30-day mortality rates were compared. A separate analysis was performed for factors affecting mortality rates. RESULTS: A total of 1,253 patients were included: 950 adults and 303 pediatric patients. In the adult group, AGI was detected in 45 (4.7%) patients and was more commonly associated with the following mechanisms of injury: motor vehicle accidents (26.7% vs. 14.3%) and pedestrian accidents (37.8% vs. 15.5%). Injury to the right side was more common (55.6%). Patients with AGI had higher rates of concurrent liver (17.8% vs. 3.9%), spleen (11.1% vs. 3.6%), and kidney injuries (15.6% vs. 1.3%). In the pediatric population, AGI was detected in 30 patients (14.8%), a significantly higher rate compared to the adult group. Similar to the adult group, AGI was more commonly associated with concurrent abdominal injuries and had a right-sided dominance (60%), but the rate of concurrent abdominal injuries was higher in the pediatric group (80% vs. 46%). The 30-day mortality was significantly higher in both adult and pediatric AGI groups compared to patients without AGI (adult: 15.6% vs. 2.9%, pediatric: 10% vs. 1.8%). In patients with AGI, major head and neck injuries and chest injuries were associated with mortality. CONCLUSION: Adrenal gland injuries due to trauma are not uncommon. They are usually associated with blunt trauma and other concurrent abdominal organ injuries. The major contributors to mortality in patients with AGI were major head and neck injuries and chest injuries.
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Glándulas Suprarrenales , Puntaje de Gravedad del Traumatismo , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Glándulas Suprarrenales/lesiones , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/patología , Estudios Retrospectivos , Adulto , Niño , Persona de Mediana Edad , Adolescente , Traumatismos Abdominales/mortalidad , Traumatismos Abdominales/complicaciones , Traumatismos Abdominales/epidemiología , Preescolar , Adulto Joven , Anciano , Turquía/epidemiologíaRESUMEN
We studied the effect of enteral administration of GABA on the gastric mucosa in male Wistar rats (n=47) with modeled metabolic stress (food deprivation for 9 days with free access to water). The relative weights of the adrenal glands and thymus were determined, and histological examination of the stomach was performed. In control rats, modeling the metabolic stress was accompanied by the development of erosive damage to the gastric mucosa related to blood supply disturbances. Administration of GABA prevented erosions and exhibited a pronounced gastroprotective effect. Thus, administration of GABA can be a promising method for the prevention and treatment of erosive gastric lesions associated with metabolic stress.
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Mucosa Gástrica , Ratas Wistar , Estrés Fisiológico , Ácido gamma-Aminobutírico , Animales , Masculino , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacología , Ratas , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Estrés Fisiológico/efectos de los fármacos , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Timo/efectos de los fármacos , Timo/patología , Timo/metabolismo , Privación de Alimentos , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Úlcera Gástrica/prevención & control , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
Adrenal gland-induced hypertension results from underlying adrenal gland disorders including Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These adrenal disorders are a risk for cardiovascular and renal morbidity and mortality. Clinically, treatment for adrenal gland-induced hypertension involves a pharmaceutical or surgical approach. The former presents very significant side effects whereas the latter can be ineffective in cases where the adrenal disorder reoccurs in the remaining contralateral adrenal gland. Due to the limitations of existing treatment methods, minimally invasive treatment options like microwave ablation (MWA) have received significant attention for treating adrenal gland disorders. A precise comprehension of the dielectric properties of human adrenal glands will help to tailor energy delivery for MWA therapy, thus offering the potential to optimise treatments and minimise damage to surrounding tissues. This study reports the ex vivo dielectric properties of human adrenal glands, including the cortex, medulla, capsule, and tumours, based on the data obtained from four patients (diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma) who underwent unilateral adrenalectomy at the University Hospital Galway, Ireland. An open-ended coaxial probe measurement technique was used to measure the dielectric properties for a frequency range of 0.5-8.5 GHz. The dielectric properties were fitted using a two-pole Debye model, and a weighted least squares method was employed to optimise the model parameters. Moreover, the dielectric properties of adrenal tissues and tumours were compared across frequencies commonly used in MWA, including 915 MHz, 2.45 GHz, and 5.8 GHz. The study found that the dielectric properties of adrenal tumours were influenced by the presence of lipid-rich adenomas, and the dielectric properties of Cushing's syndrome tumour were lowest in comparison to the tumours in patients diagnosed with Conn's syndrome and Pheochromocytoma. Furthermore, a notable difference was observed in the dielectric properties of the medulla and cortex among patients diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These findings have significant implications for the diagnosis and treatment of adrenal tumours, including the optimisation of MWA therapy for precise ablation of adrenal masses.
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Neoplasias de las Glándulas Suprarrenales , Glándulas Suprarrenales , Síndrome de Cushing , Hipertensión , Microondas , Feocromocitoma , Humanos , Neoplasias de las Glándulas Suprarrenales/cirugía , Microondas/uso terapéutico , Glándulas Suprarrenales/cirugía , Glándulas Suprarrenales/patología , Hipertensión/terapia , Feocromocitoma/cirugía , Síndrome de Cushing/cirugía , Técnicas de Ablación/métodos , Femenino , Masculino , Hiperaldosteronismo/cirugía , Hiperaldosteronismo/terapia , Adrenalectomía , Persona de Mediana EdadRESUMEN
BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome due to ectopic expression of the GIP receptor (GIPR) typically harbor inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied. METHODS: We investigated a woman with a large, heterogeneous adrenal mass and severe adrenocorticotropic hormone-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents. RESULTS: Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of 4 representative nodules detected KDM1A germline variants, benign NM_001009999.3:c.136G > A:p.G46S, and likely pathogenic NM_001009999.3:exon6:c.865_866del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA sequencing of a representative nodule showed low/absent KDM1A expression and increased GIPR expression compared with 52 unilateral sporadic adenomas and 4 normal adrenal glands. Luteinizing hormone/chorionic gonadotropin receptor expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7 and mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess. CONCLUSIONS: We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A.
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Síndrome de Cushing , Histona Demetilasas , Humanos , Femenino , Adulto , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Síndrome de Cushing/genética , Síndrome de Cushing/patología , Síndrome de Cushing/metabolismo , Glucocorticoides , Embarazo , Andrógenos/metabolismo , Glándulas Suprarrenales/patología , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/diagnóstico por imagen , Hiperplasia Suprarrenal Congénita/genética , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperplasia Suprarrenal Congénita/patología , Hiperplasia Suprarrenal Congénita/metabolismoRESUMEN
BACKGROUND: Adrenal vein sampling (AVS), integral to identifying surgically remediable unilateral primary aldosteronism (PA), is technically challenging and subject to fluctuations in cortisol and aldosterone secretion. Intra-procedural adrenocorticotropic hormone (ACTH), conventionally administered as a 250-µg bolus and/or 50 µg per hour infusion, increases cortisol and aldosterone secretion and can improve AVS success, but may cause discordant lateralisation compared to unstimulated AVS. AIMS: To assess if AVS performed with ultra-low dose ACTH infusion causes discordant lateralisation. METHODS: Here, we describe our preliminary experience using an ultra-low dose ACTH infusion AVS protocol. We retrospectively reviewed the results of consecutive AVS procedures (n = 37) performed with and without ultra-low dose ACTH (1-µg bolus followed by 1.25 µg per hour infusion). RESULTS: Bilateral AV cannulation was successful in 70% of procedures pre-ACTH and 89% post-ACTH (p < 0.01). Sixty-nine percent of studies lateralised pre-ACTH and 55% post-ACTH, improving to 79% when both groups were combined. Lateralisation was discordant in 11 cases, including eight in which lateralisation was present only on basal sampling, and three in which lateralisation occurred only with ACTH stimulation. DISCUSSION: Overall, the decrease in lateralisation rates with ACTH was higher than previously reported for some protocols utilising conventional doses of ACTH. Our results suggest that AVS performed with ultra-low dose ACTH can cause discordant lateralisation similar to AVS performed with conventional doses of ACTH. CONCLUSION: Prospective studies directly comparing low and conventional dose ACTH AVS protocols and long-term patient outcomes are needed to help define the optimal ACTH dose for accurate PA subtyping.
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Glándulas Suprarrenales , Hormona Adrenocorticotrópica , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/sangre , Hormona Adrenocorticotrópica/administración & dosificación , Glándulas Suprarrenales/irrigación sanguínea , Persona de Mediana Edad , Femenino , Masculino , Estudios Retrospectivos , Adulto , Infusiones Intravenosas , Venas , Aldosterona/sangre , Aldosterona/administración & dosificación , Anciano , Hidrocortisona/administración & dosificación , Hidrocortisona/sangreRESUMEN
Objective: To evaluate the function of serum dehydroepiandrosterone sulfate (DHEAS) in adult adrenal space-occupying lesions. Methods: In this cross-sectional study, 395 patients with adrenal space-occupying lesions who had their DHEAS levels measured were collected from the First Medical Center of Chinese PLA General Hospital from January 2010 to June 2021. They were divided into the adrenal Cushing syndrome (ACS) group (n=100) and non-ACS group (n=295). The former was divided into the cortisol-producing adrenal adenoma (CPA) group (n=67) and primary bilateral macronodular adrenal hyperplasia (PBMAH) group (n=33). Clinical data of each group were collected and compared among groups by independent samples t-test, chi-square test, and Mann-Whitney U test. Serum DHEAS ratio corrected for age and sex was further constructed to identify the receiver operating characteristic curve and the optimal tangent point value for different adrenal occupation. Results: Patients in the ACS group were younger (44.9±13.7 vs. 49.9±12.5, P=0.001); had a larger proportion of women (79/100 vs.139/295, P=0.001); and had higher cortisol levels [8â¶00Am, 497.31 (343.52, 606.50) vs. 353.11 (267.50, 487.91) nmol/L, P<0.001] than those in the non-ACS group. The serum DHEAS level and ratio in the ACS group were significantly lower than those in the non-ACS group [0.50 (0.40, 1.21) vs. 2.68 (1.56, 4.32) µmol/L, 1.00 (0.43, 1.68) vs. 3.17 (2.21, 4.54), both P<0.001]. When the serum DHEAS ratio cut-off point was 1.29, the sensitivity and specificity for differential diagnosis of ACS and non-ACS were 72.0% and 91.5% respectively. The ratio of DHEAS in the CPA group was lower [0.58 (0.27, 1.05) vs. 1.14 (1.04, 2.40), P<0.001] than that in the PBMAH group. When the serum DHEAS ratio cut-off point was 0.99, the sensitivity and specificity for differential diagnosis of CPA and PBMAH were 64.2% and 81.2% respectively. Conclusion: Corrected age-sex DHEAS ratio can assist in the functional assessment of adrenal space-occupying lesions.
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Neoplasias de las Glándulas Suprarrenales , Síndrome de Cushing , Sulfato de Deshidroepiandrosterona , Humanos , Sulfato de Deshidroepiandrosterona/sangre , Estudios Transversales , Adulto , Síndrome de Cushing/sangre , Síndrome de Cushing/diagnóstico , Persona de Mediana Edad , Neoplasias de las Glándulas Suprarrenales/sangre , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Glándulas Suprarrenales/metabolismo , Hidrocortisona/sangre , Curva ROC , Masculino , FemeninoRESUMEN
The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours. Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular-endothelial cells and cortical-neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/ß-catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single-nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma-specific clusters, each with varying distributions based on steroid profiles and tumour mutational status. Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal-related pathologies.
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Glándulas Suprarrenales , Homeostasis , Transcriptoma , Humanos , Transcriptoma/genética , Glándulas Suprarrenales/metabolismo , Homeostasis/genética , Neoplasias de la Corteza Suprarrenal/genética , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/patología , Adulto , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patologíaRESUMEN
Hypertension affects one-third of the adult population worldwide, with primary aldosteronism (PA) accounting for at least 5-10% of these cases. The aldosterone synthase enzyme (CYP11B2) plays a pivotal role in PA manifestation, as increased expression of CYP11B2 leads to excess aldosterone synthesis. Physiological expression of CYP11B2 in humans is normally limited to cells of the adrenal zona glomerulosa under tight homeostatic regulation. In PA, however, there are CYP11B2-positive lesions in the adrenal cortex that autonomously secrete aldosterone, highlighting the dysregulation of adrenal cortex zonation and function as a key aspect of PA pathogenesis. Thus, this review aims to summarize the development of the adrenal glands, the key regulators of adrenal cortex homeostasis, and the dysregulation of this homeostasis. It also discusses the development of CYP11B2 inhibitors for therapeutic use in patients with hypertension, as well as the current knowledge of the effects of CYP11B2 inhibition on adrenal cortex homeostasis and cell fate. Understanding the control of adrenal cell fate may offer valuable insights into both the pathogenesis of PA and the development of alternative treatment approaches for PA.
Asunto(s)
Glándulas Suprarrenales , Aldosterona , Citocromo P-450 CYP11B2 , Hiperaldosteronismo , Humanos , Aldosterona/metabolismo , Aldosterona/biosíntesis , Citocromo P-450 CYP11B2/metabolismo , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patología , Glándulas Suprarrenales/metabolismo , Animales , Corteza Suprarrenal/metabolismo , Corteza Suprarrenal/citología , Hipertensión/metabolismo , Hipertensión/patología , Zona Glomerular/metabolismo , Diferenciación Celular , HomeostasisRESUMEN
RATIONALE: Adrenal infarction (AI) is a rare type of adrenal damage, which is relatively common in systemic lupus erythematosus, antiphospholipid antibody syndrome (APS) and pregnancy. The diagnosis of AI is mainly by computed tomography (CT) and magnetic resonance imaging, but is easily confused with other adrenal disease. Hence, this report details a condition of AI with systemic lupus erythematosus, APS and made a differential diagnosis from imaging. PATIENT CONCERNS: We report a case of a 55-year-old woman with pain in her fossa axillaries and inguinal regions. Then CT scan disclosed bilateral adrenal diseases, and the patient was diagnosed with systemic lupus erythematosus, APS and AI after additional autoimmune examinations. DIAGNOSES: The patient was diagnosed as systemic lupus erythematosus with lupus nephritis, hematological damage and oromeningitis, APS, AI and secondary blood coagulation disorders. INTERVENTIONS: The patient was treated with methylprednisolone, hydroxychloroquine and low molecular heparin. OUTCOMES: The patient relieves and remains well 1 year after treatment. LESSONS SUBSECTIONS: AI can be divided hemorrhagic and non-hemorrhagic, with bilateral lesions more common. In our case, the AI was bilateral, partially involved and non-hemorrhagic, and the "cutoff sign" was first put forward in CT, which might assist the diagnosis.
Asunto(s)
Síndrome Antifosfolípido , Infarto , Lupus Eritematoso Sistémico , Humanos , Femenino , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Persona de Mediana Edad , Lupus Eritematoso Sistémico/complicaciones , Infarto/etiología , Infarto/diagnóstico , Infarto/diagnóstico por imagen , Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/patología , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Enfermedades de las Glándulas Suprarrenales/etiología , Enfermedades de las Glándulas Suprarrenales/diagnóstico por imagen , Enfermedades de las Glándulas Suprarrenales/diagnósticoRESUMEN
Objective: To analyze the anatomical characteristics of the adrenal veins through adrenal venography to improve the success rate of adrenal venography (AVS). Methods: This study was a cross-sectional study. Patients who were diagnosed with primary aldosteronism and underwent AVS from January 2019 to October 2023 at the First Affiliated Hospital of Dalian Medical University were included. Adrenal vein imaging was collected from the enrolled patients. We performed statistical analysis on the adrenal vein orifice position, inflow angle, and adrenal venography morphology. The adrenal venous orifice was defined as the location where the catheter was placed at the end of the calm inhalation. Spearman correlation analysis was used to explore the relationship between the positions of bilateral adrenal vein orifices and body mass index (BMI). Results: A total of 282 patients with successful bilateral AVS and complete bilateral adrenal vein imaging were enrolled, of whom 57.1% (161/282) were male and the age was (53.3±10.7) years old. The orifice of the left adrenal vein was located between the middle segment of the 11th thoracic vertebra and the upper segment of the 2nd lumbar vertebra. The inflow angle relative to the position of the orifice was all leftward and upward. The orifice of the right adrenal vein was located between the upper segment of the 11th thoracic vertebra and the lower segment of the 1st lumbar vertebra, and 91.1% (257/282) had a rightward and downward angle of inflow relative to the position of the orifice. The position of the adrenal vein orifices on both the left (r=0.211, P<0.001) and right (r=0.196, P=0.001) showed positive correlation with BMI. The position of the right adrenal vein orifice also increased with the position of the left adrenal orifice (r=0.530, P<0.001). The most common adrenal venography morphology on the right side was triangular (36.5%, 103/282), while the most common venography morphology on the left side was glandular (66.3%, 187/282). Conclusions: The anatomical morphology of adrenal veins are diverse. Being familiar with the morphological characteristics of the adrenal vein and identifying the adrenal vein accurately during surgery has important clinical value in improving the success rate of AVS.
Asunto(s)
Glándulas Suprarrenales , Hiperaldosteronismo , Flebografía , Venas , Humanos , Hiperaldosteronismo/diagnóstico por imagen , Masculino , Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/diagnóstico por imagen , Estudios Transversales , Persona de Mediana Edad , Femenino , Venas/diagnóstico por imagen , Venas/anatomía & histología , Flebografía/métodos , AdultoRESUMEN
SUMMARY: Aging is an inevitable biological process that affects the function of all organs, including the adrenal gland, which is essential for producing steroid hormones that regulate metabolism, stress response, and immune activation. Understanding how aging affects the morphology of this gland is crucial to developing interventions to mitigate its adverse effects. Thus, this study aimed to describe the morphoquantitative alterations of the adrenal gland in senescent Sprague Dawley rats compared to adult rats. Twelve male rats were divided into 6 adult rats aged 6 months (group A) and 6 senescent rats aged 36 months (group S). Histopathological studies, quantification of collagen fibers types I and III, and stereological analysis were performed to determine the volume density (Vv), surface area (Sv), and number (Nv) of the nuclei of the zona fasciculata cells. Adrenal gland tissue from group S presented dysplasia, metaplasia, intracellular fat accumulation, fibrosis, blood vessel dilation, and increased presence of apoptotic cells. Capsule thickening and increased collagen type I were also observed. There was a significant decrease in Vv, Sv, and Nv of zona fasciculata nuclei in group S compared to group A. The results indicate that aging induces significant morphoquantitative changes in the adrenal gland, which could contribute to the decrease in glucocorticoid production and alterations in aldosterone and cortisol secretion observed in senescence. Understanding these alterations is crucial to developing interventions that mitigate the adverse effects of aging on the endocrine system.
El envejecimiento es un proceso biológico inevitable que afecta la función de todos los órganos, incluida la glándula suprarrenal, fundamental para la producción de hormonas esteroides que regulan el metabolismo, la respuesta al estrés y la activación inmunológica. Comprender cómo el envejecimiento afecta la morfología de esta glándula es crucial para desarrollar intervenciones que mitiguen sus efectos adversos. Así, el objetivo de este estudio fue describir las alteraciones morfocuantitativas de la glándula suprarrenal en ratas Sprague Dawley senescentes comparadas con ratas adultas. Se utilizaron 12 ratas macho, divididas en dos grupos: 6 ratas adultas de 6 meses de edad (grupo A) y 6 ratas senescentes de 36 meses de edad (grupo S). Se realizaron estudios histopatológicos, cuantificación de fibras de colágeno tipos I y III y análisis estereológicos para determinar la densidad de volumen (Vv), de superficie (Sv) y de número (Nv) de los núcleos de las células de la zona fasciculada. El tejido de la glándula suprarrenal del grupo S presentó displasia, metaplasia, acumulación de grasa intracelular, fibrosis, dilatación de vasos sanguíneos y mayor presencia de células apoptósicas. También se observó un engrosamiento de la cápsula y un incremento del colágeno tipo I. Hubo una disminución significativa en Vv, Sv y Nv de los núcleos de la zona fasciculada en el grupo S en comparación con el grupo A. Los resultados indican que el envejecimiento induce cambios morfocuantitativos significativos en la glándula suprarrenal, lo que podría contribuir a la disminución en la producción de glucocorticoides y alteraciones en la secreción de aldosterona y cortisol observadas en la senescencia. Comprender estas alteraciones es crucial para desarrollar intervenciones que mitiguen los efectos adversos del envejecimiento en el sistema endocrino.