Time-of-Day Adrenal Modulation of Corticosterone Synthesis is Affected by Sex and Diet but Not by Proanthocyanidins in Rat.

SCOPE: The aim of this study is to investigate the effect of time-of-day on serum hormones and gene expression in adrenal glands, studying the impact of sex, obesogenic diet, and timing of proanthocyanidins administration, with a focus on glucocorticoids synthesis by this gland. METHODS AND RESULTS: Female and male rats, assigned to a standard chow or a cafeteria diet-fed group, receive a daily oral dose of a grape seed proanthocyanidin extract (GSPE), or a vehicle (when light is turned on, or when light is turned off). Corticosterone, estradiol, and testosterone serum levels, and the expression analysis of clock genes and genes related to corticosterone synthesis pathway, are assessed. Serum hormone levels exhibited a marked time-of-day effect also see in the expression of scavenger receptor class B member 1 (Scarb1) and cyp11b genes. The correlation between these two genes and period circadian regulator 2 (Per2) is also extended to other clock genes, although to a lesser extent: cryptochrome (Cry) and nuclear receptor subfamily 1 group D member 1 (Rev-erba). CONCLUSION: The strong correlations found suggest an important role of local Per2 (but also of Cry and Rev-erbA) in regulating the expression of the enzymes involved in the corticosterone synthesis pathway. The expression of clock genes in adrenals is influenced by sex and diet but not by GSPE.

[Pseudocyst of adrenal gland. Case report]. / Pseudoquiste de glándula suprarrenal. Reporte de un caso.

Background: Adrenal gland cysts are a rare entity, with a reported incidence in post-mortem series of 0.06-0.18%. However, the incidence seems to be increasing in recent years. The presentation of adrenal gland cysts is usually asymptomatic, but those cases in which symptoms are present are usually non-specific, which makes adrenal cysts generally recognized as incidentalomas. The finding is mainly made by computed tomography. The main objective of this article was to describe the clinical course of a patient with an adrenal gland pseudocyst, which is accompanied by symptoms of compression and persistent pain of long evolution in the left flank. Clinical case: A 65-year-old female patient attended the emergency room of a second-level hospital due to an increase in volume of the abdominal region with a sensation of fullness, heartburn, vomiting and pain. Computed tomography was performed, which reported a cystic mass and, later, exploratory laparotomy plus adrenalectomy were carried out. The pathology analysis reported a diagnosis of a 10 x 15 x 14 cm solid, cystic, and adherent tumor, coinciding with a pseudocyst of the adrenal gland. Conclusions: Adrenal gland cysts are rare. Computed tomography is recommended for its diagnosis and the standard of treatment is surgical intervention in the presence of symptoms.

Introducción: los quistes de glándula suprarrenal son una entidad rara, con un reporte en la incidencia de series post mortem de 0.06-0.18%. Sin embargo, la incidencia parece ir en aumento en los últimos años. La presentación de los quistes de glándula suprarrenal es habitualmente asintomática, pero en aquellos casos en que se presentan síntomas, estos suelen ser inespecíficos, lo cual hace que los quistes suprarrenales generalmente sean reconocidos como incidentalomas. El hallazgo se hace principalmente mediante tomografía computarizada. El objetivo principal de este artículo fue describir el curso clínico de una paciente con un pseudoquiste de glándula suprarrenal, que se acompaña de síntomas de compresión y dolor persistente de larga evolución en el flanco izquierdo. Caso clínico: mujer de 65 años que acudió a urgencias de un hospital de segundo nivel por aumento de volumen de región abdominal con sensación de plenitud, pirosis, vómito y dolor. Se realizó tomografía computarizada que reportó masa quística; posteriormente se realizó laparotomía exploradora y adrenalectomía. El análisis de patología reportó diagnóstico de tumor de 10 x 15 x 14 cm, sólido, quístico y adherido, coincidente con pseudoquiste de glándula suprarrenal. Conclusiones: los quistes de glándula suprarrenal son raros. Para su diagnóstico se recomienda realizar tomografía computarizada y el estándar de tratamiento es la intervención quirúrgica ante la presencia de sintomatología.

The effect of obesity on the outcomes of laparoscopic adrenal surgery in patients with Cushing syndrome.

Purpose: The aim of this study is to investigate the effect of obesity on the results of laparoscopic adrenal surgery in patients with Cushing syndrome. Methods: This retrospective study was performed in Department of General Surgery at Erciyes University School of Medicine between January 2010 and January 2023. Our analysis included Cushing syndrome patients who underwent unilateral laparoscopic adrenalectomy (LA) with the transabdominal lateral approach. All patients were evaluated in terms of age, sex, tumor diameter, body mass index (BMI), American Society of Anesthesiologists physical status classification, morbidities, surgery history, tumor side, operative time, conversion to open surgery, complications, and length of hospital stay. Results: A total of 90 patients (75 females and 15 males) underwent a transperitoneal LA. Patients were divided into 2 groups according to their BMI: obese group (≥30 kg/m2; n = 53, 58.8%) and nonobese group (<30 kg/m2; n = 37, 41.2%). All patients were classified into 3 subgroups: obese patient group, BMI ≥30-39 kg/m2 (n = 23); morbidly obese patient group, BMI ≥40 kg/m2 (n = 14); and nonobese patient group, BMI <30 kg/m2 (n = 53). There was no significant difference in intraoperative complications, conversion to open surgery, operative time, or length of hospital stay between the groups. Only conversion to open surgery was a risk factor for postoperative complications in univariate and multivariate analyses (odds ratio, 15.4; 95% confidence interval, 1.277-185.599; P = 0.031). Conclusion: Our results showed that LA is safe and effective in patients with Cushing syndrome with morbid obesity, allowing acceptable morbidity and length of hospital stay.

Bilateral Infiltrating Ductal Carcinoma With Adrenal Metastasis: A Rare Case Report.

Adrenal gland metastasis is rare, often associated with invasive lobular carcinoma (ILC) rather than infiltrating ductal carcinoma (IDC). This report presents a case of a 43-year-old female with bilateral breast IDC and metastasis to the adrenal gland, with bilateral axillary and supraclavicular node involvement. Initial symptoms included a nipple discharge and a palpable lump. Diagnostic imaging and biopsy confirmed IDC, grade 2, with positive estrogen receptor (ER) and progesterone receptor (PR) status and negative human epidermal growth factor receptor 2 (HER2) status. The patient is undergoing chemotherapy and radiotherapy, with adrenalectomy planned post chemotherapy. The case underscores the need for early diagnosis and rapid treatment to improve outcomes, highlighting the paucity of data on managing solitary adrenal metastasis from IDC. Further research and clinical trials are essential to develop standardized treatment protocols.

Robot-assisted laparoscopic adrenalectomy: Extended application in children.

BACKGROUND: Minimally invasive surgery for paediatric adrenal tumours has evolved, but robot-assisted laparoscopic adrenalectomy (RALA) in children remains poorly studied. The current prospective study aims to demonstrate the safety and efficacy of RALA in treating children with adrenal tumours. METHODS: A prospective institutional analysis of children presenting with neuroblastic and endocrine tumours treated with RALA was undertaken over a six year-period. For each child, clinical parameters were collected relating to diagnosis, surgery and outcomes. RESULTS: A total 50 RALA were performed; 23 for unilateral neuroblastic tumours (87 % neuroblastomas) and 27 for endocrine tumours. Eight neuroblastic tumours (35 %) had image-defined risk factors (all due to tumour invading the renal pedicle). Median length of stay was two days. Resection margins were macroscopically clear in all cases. After median follow-up of 2.9 years (1.6-3.9), two children are under treatment for metastatic relapse (high-risk disease) and three died due to refractory disease. Sixteen children had endocrine tumours: pheochromocytoma (n = 13), or bilateral nodular adrenocortical hyperplasia with Cushing's syndrome (n = 14). One child required non-emergent conversion, and one complication occurred (grade IIIb) after median follow-up of 3.3 years (1.0-5.7). CONCLUSIONS: The current study is the largest reported experience in the literature and confirms the safety and effectiveness of RALA in carefully selected children with adrenal tumours. Through an iterative process and in the setting of a dedicated paediatric robotic surgical team indications have been clarified and extended. The current study confirms RALA has particularly utility in patients with severe disease (IDRF + metastatic neuroblastomas) or genetic predisposition syndromes.

[Robotic adrenalectomy-current evidence]. / Robotische Nebennierenchirurgie ­ aktuelle Evidenzlage.

Laparoscopic adrenalectomy is worldwide currently considered the gold standard technique for patients suffering from benign lesions. There has been an increasing number of robotic-assisted adrenalectomies in the last decade due to the systematic further development of minimally invasive surgery resulting in the implementation of robot-assisted surgery. Interestingly, the available studies show some perioperative advantages for robotic surgery but overall the current evidence is weak and there are economic aspects that are not negligible. Therefore, further high-quality studies about robotic-assisted adrenalectomy are mandatory to strengthen the current evidence.

More efficient adaptation of cardiovascular response to repeated restraint in spontaneously hypertensive rats: the role of autonomic nervous system.

We hypothesized that sympathetic hyperactivity and parasympathetic insuficiency in spontaneously hypertensive rats (SHR) underlie their exaggerated cardiovascular response to acute stress and impaired adaptation to repeated restraint stress exposure compared to Wistar-Kyoto rats (WKY). Cardiovascular responses to single (120 min) or repeated (daily 120 min for 1 week) restraint were measured by radiotelemetry and autonomic balance was evaluated by power spectral analysis of systolic blood pressure variability (SBPV) and heart rate variability (HRV). Baroreflex sensitivity (BRS) was measured by the pharmacological Oxford technique. Stress-induced pressor response and vascular sympathetic activity (low-frequency component of SBPV) were enhanced in SHR subjected to single restraint compared to WKY, whereas stress-induced tachycardia was similar in both strains. SHR exhibited attenuated cardiac parasympathetic activity (high-frequency component of HRV) and blunted BRS compared to WKY. Repeated restraint did not affect the stress-induced increase in blood pressure. However, cardiovascular response during the post-stress recovery period of the 7th restraint was reduced in both strains. The repeatedly restrained SHR showed lower basal heart rate during the dark (active) phase and slightly decreased basal blood pressure during the light phase compared to stress-naive SHR. SHR subjected to repeated restraint also exhibited attenuated stress-induced tachycardia, augmented cardiac parasympathetic activity, attenuated vascular sympathetic activity and improved BRS during the last seventh restraint compared to single-stressed SHR. Thus, SHR exhibited enhanced cardiovascular and sympathetic responsiveness to novel stressor exposure (single restraint) compared to WKY. Unexpectedly, the adaptation of cardiovascular and autonomic responses to repeated restraint was more effective in SHR.

Co-administration of xylo-oligosaccharides produced by immobilized Aspergillus terreus xylanase with carbimazole to mitigate its adverse effects on the adrenal gland.

Carbimazole has disadvantages on different body organs, especially the thyroid gland and, rarely, the adrenal glands. Most studies have not suggested any solution or medication for ameliorating the noxious effects of drugs on the glands. Our study focused on the production of xylooligosaccharide (XOS), which, when coadministered with carbimazole, relieves the toxic effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity. This XOS produced by Aspergillus terreus xylanase was covalently immobilized using microbial Scleroglucan gel beads, which improved the immobilization yield, efficiency, and operational stability. Over a wide pH range (6-7.5), the covalent immobilization of xylanase on scleroglucan increased xylanase activity compared to that of its free form. Additionally, the reaction temperature was increased to 65 °C. However, the immobilized enzyme demonstrated superior thermal stability, sustaining 80.22% of its original activity at 60 °C for 120 min. Additionally, the full activity of the immobilized enzyme was sustained after 12 consecutive cycles, and the activity reached 78.33% after 18 cycles. After 41 days of storage at 4 °C, the immobilized enzyme was still active at approximately 98%. The immobilized enzyme has the capability to produce xylo-oligosaccharides (XOSs). Subsequently, these XOSs can be coadministered alongside carbimazole to mitigate the adverse effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity.

[Endocrine side effects of tumor treatment]. / Endokrine Nebenwirkungen von Tumortherapien.

Targeted and immune-based treatments represent significant innovations in oncology and impressively improve the prognosis of many tumor diseases. Their now widespread use as a standard treatment for several malignant diseases increasingly requires knowledge of how to deal with new adverse events (AE) induced by oncological agents in centers and routine practice [12, 13]. For example, the blockade of specific checkpoints of the inhibitory immune system by immune checkpoint inhibitors (ICI) causes the loss of immune tolerance to the body's own tissue with the occurrence of endocrine immune-related AE (irAE) in approximately 10% of patients treated with ICI [3, 11]. Targeted treatments, such as with tyrosine kinase inhibitors (TKI), mammalian target of rapamycin (mTOR) and phosphoinositide 3­kinase (PI3K) inhibitors often lead to disorders of glucose metabolism and thyroid gland dysfunction. The challenges of maintaining bone health during endocrine therapy in patients with prostate and hormone receptor-positive breast cancer and in the endocrine follow-up care of childhood cancer survivors are well-known and are becoming increasingly more important for the long-term prognosis and quality of life [5, 20]. However, although the recommendations for a systematic management of endocrine side effects of these relatively new tumor therapies can be found in guidelines, they are not yet established in routine clinical care [15, 19]. A close interdisciplinary cooperation is required for optimal care of people with cancer [7]. The development of such interdisciplinary cross-sectoral treatment structures is important as tumor treatment is primarily carried out by hematologists or oncologists, while the management of AE induced by oncological agents increasingly involves primary care physicians including internists and in the case of endocrine AE requires the specific expertise of endocrinologists and diabetologists.

A Case Report of Bilateral Adrenal Gland Stereotactic Body Radiotherapy to Manage Hypercortisolemia in a Patient With Ectopic Adrenocorticotropic Hormone (ACTH) Production From a Metastatic Pancreatic Neuroendocrine Tumor.

A 63-year-old woman presented with hypokalemia, hypertension, weight gain, limb edema, and tremors. She was diagnosed with Cushing syndrome, with a 24-hour urine cortisol level of 41,013 nmol/day. Investigations revealed a grade 2 pancreatic neuroendocrine tumor with extensive hepatic metastases. Owing to excessive adrenocorticotropic hormone production from her disease, her hypercortisolemia and Cushing symptoms worsened despite ketoconazole, somatostatin analogs, and right liver lobe chemoembolization. Stereotactic body radiotherapy (SBRT) at a dose of 39 Gy in three fractions was administered to her bilateral adrenal glands in the hope of reducing her cortisol levels and improving her symptoms. Her 24-hour urine cortisol levels decreased following SBRT, but not rapidly enough; her clinical condition continued to deteriorate, and she died 21 days after treatment. SBRT was not effective as an urgent intervention in this setting; a greater latency to realize a response is likely necessary.

Subdiaphragmatic phrenic nerve supply: A systematic review.

OBJECTIVE: The aim of this systematic review is to study the subdiaphragmatic anatomy of the phrenic nerve. MATERIALS AND METHODS: A computerised systematic search of the Web of Science database was conducted. The key terms used were phrenic nerve, subdiaphragmat*, esophag*, liver, stomach, pancre*, duoden*, intestin*, bowel, gangli*, biliar*, Oddi, gallbladder, peritone*, spleen, splenic, hepat*, Glisson, falciform, coronary ligament, kidney, suprarenal, and adrenal. The 'cited-by' articles were also reviewed to ensure that all appropriate studies were included. RESULTS: A total of one thousand three hundred and thirty articles were found, of which eighteen met the inclusion and exclusion criteria. The Quality Appraisal for Cadaveric Studies scale revealed substantial to excellent methodological quality of human studies, while a modified version of the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias Tool denoted poor methodological quality of animal studies. According to human studies, phrenic supply has been demonstrated for the gastro-esophageal junction, stomach, celiac ganglia, liver and its coronary ligament, inferior vena cava, gallbladder and adrenal glands, with half of the human samples studied presenting phrenic nerve connections with any subdiaphragmatic structure. CONCLUSIONS: This review provides the first systematic evidence of subdiaphragmatic phrenic nerve supply and connections. This is of interest to professionals who care for people suffering from neck and shoulder pain, as well as patients with peridiaphragmatic disorders or hiccups. However, there are controversies about the autonomic or sensory nature of this supply.

Comparative assessment of CacyBP/SIP, ß-catenin and cannabinoid receptors in the adrenals of hypertensive rats.

Taking into account homeostatic disorders resulting from arterial hypertension and the key importance of CacyBP/SIP, ß-catenin and endocannabinoids in the functioning of many organs, it was decided to assess the presence and distribution of CacyBP/SIP, ß-catenin, CB1 and CB2 in the adrenal glands of hypertensive rats of various aetiology. The study was conducted on the adrenal glands of rats with spontaneous and renovascular hypertension. The expression of CacyBP/SIP, ß-catenin, CB1 and CB2 was detected by immunohistochemistry and real-time PCR method. The results of the present study revealed both lower gene expression and immunoreactivity of CacyBP/SIP in the adrenal glands of all hypertensive groups compared to the normotensive rats. This study demonstrated a reduction in the immunoreactivity and expression of the ß-catenin, CB1 and CB2 genes in the adrenals of 2K1C rats. While in SHR, the reaction showing ß-catenin and CB1 was very weak or negative, and the expression of CB2 in the adrenal glands of these rats increased. The results of this study show, for the first time, marked differences in the expression of CacyBP/SIP, ß-catenin and CB1 and CB2 cannabinoid receptors in the adrenal glands of rats with primary (SHR) and secondary hypertension (2K1C).

Anatomical Variations Encountered during Adrenal Venous Sampling: A Report of Three Case Series and Review of Literature.

Primary aldosteronism is a group of disorders in which the autonomous secretion of aldosterone is associated with hypertension and hypokalemia. It is crucial to determine the laterality of aldosterone hypersecretion because treatment options differ accordingly. Adrenal venous sampling (AVS) is considered the most reliable method for assessing the laterality of primary aldosteronism. This procedure is often technically challenging because of the small size and varied locations of the adrenal veins. A better understanding of anatomical variations and careful review of imaging studies would improve sampling success. This report presents three cases of anatomical variations encountered during AVS.

Impact of endocrine-active compounds on adrenal androgen production in pigs during neonatal period.

This study investigated the impact of neonatal exposure to endocrine-active compounds (EACs): flutamide (antiandrogen), 4-tert-octylphenol (an estrogenic compound), and methoxychlor (an organochlorine insecticide exhibiting estrogenic, antiestrogenic and antiandrogenic activities) on androgen production within porcine adrenal glands. The expression of genes related to androgen synthesis and the level of androgen production were analyzed (i) in the adrenal glands of piglets exposed to EACs during the first 10 days of life (in vivo study), and (ii) in adrenal explants from sow-fed or formula-fed 10-day-old piglets incubated with EACs (ex vivo study). EACs affected the expression of genes linked to adrenal androgen biosynthesis. The prominent effect of methoxychlor on downregulation of StAR, CYP11A1 and HSD3B and upregulation of CYP17A1 and SULT2A1 were demonstrated. Furthermore, our study revealed divergent response to EACs between sow-fed and formula-fed piglets, suggesting that natural feeding may provide protection against adverse EACs effects, particularly those interfering with estrogens action.

Effect of resuscitation of cryopreserved porcine adrenal glands at 26 °C on their recovery and functioning under xenotransplantation.

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.

Dabigatran Etexilate Related Unilateral Adrenal Hemorrhage.

A 63-year-old male presented to our clinic with computed tomography data of a large tumor of the left adrenal gland. The formation is highly suspicious for malignancy with central necrosis and hemorrhage, and a total size of 197/183/201 mm. Due to elevated D-dimer values of 7.17 mg/l (reference range <0.5 mg/l), treatment with dabigatran etexilate 2x150 mg was prescribed following a cardiology consult. On the third day of therapy, the patient noticed a large swelling in the left abdominal flank, which caused discomfort. No additional symptoms were reported. No previous abdominal surgical interventions or trauma were reported. Following a thorough physical examination, the patient was referred for a computer tomography that reported a diagnosis of a tumor of the left adrenal gland. Due to the size of the neoplasm, the suspicion of malignancy, compression of adjacent structures, and significant anemia with an Hb of 112 g/L, operative treatment was chosen as the best treatment modality. The mass was reported as a large organizing adrenal hematoma with no suspicion of malignancy on histology. Following a review of available literature, no other cases of unilateral adrenal hematoma with a size of 201x197 mm, following oral anticoagulant therapy with dabigatran etexilate, without any prior surgery or trauma have been reported. Most clinical cases report bilateral adrenal hemorrhage during the postoperative period, following prophylaxis with heparin and the development of heparin-induced thrombocytopenia. The patient underwent operative treatment, after which the patient recovered normally and was discharged from the clinic without complications.

Ultrasonographic measurements of the normal adrenal glands in guinea pigs (Cavia Porcellus).

Hyperadrenocorticism is an uncommon but important endocrine disease in guinea pigs, but due to its subtle clinical signs and the limited information in veterinary literature, it can be underdiagnosed or misdiagnosed. Ultrasound of the adrenal glands in patients with suspected hyperadrenocorticism can help in identifying adrenomegaly. The purpose of this prospective study was to identify ultrasonographic adrenal gland dimensions in presumed healthy guinea pigs using the same standardized method described for dogs and cats. A conscious ultrasound scan was conducted on twenty client-owned, presumed healthy guinea pigs, and their adrenal glands were measured. A possible correlation between adrenal dimensions with age, sex, and body weight was investigated. The mean length, cranial and caudal pole thickness for the left and right adrenal glands were, respectively, 12.64 ± 2.11 mm and 11.55 ± 1.52 mm; 4.83 mm ± 1.03 mm and 4.69 ± 1.34 mm; 4.8 ± 1.23 mm and 4.04 ± 0.75 mm. The thickness of the left caudal pole was significantly higher than the right (P = 0.02). A significant positive correlation was found between the length of the left adrenal gland and both age (r = 0.46; P = .03) and weight (r = 0.59; P = .01). Statistical correlation between the thickness of each cranial and caudal pole, with age, sex, or weight, was not found. The dimensions provided could prove a useful tool in the clinical evaluation of guinea pigs with suspected hyperadrenocorticism.

Bilateral Adrenal Myelolipoma and Breast Cancer in a Patient With Congenital Adrenal Hyperplasia.

Adrenal myelolipoma is a rare, benign tumor of the adrenal gland, typically non-functional, asymptomatic and unilateral. With the increased use of radiological imaging, it has been discovered more frequently as incidental mass. It is common to occur concurrently with hormonal dysfunction conditions like congenital adrenal hyperplasia. However, there are few previous reported cases of malignancy concomitant with adrenal myelolipoma. We present a case of a 33-year-old patient diagnosed with congenital adrenal hyperplasia since birth. She was diagnosed with giant bilateral adrenal myelolipoma incidentally during the investigation done for staging her breast cancer. To the best of our knowledge, this is the second reported case of breast cancer concomitant with adrenal myelolipoma. Although this entity is very rare, physicians should be familiar with such rare adrenal masses and their associations in order to manage them appropriately.

Phaeochromocytoma and paraganglioma.

Phaeochromocytomas and paragangliomas are rare catecholamine-producing neuroendocrine tumours which can potentially cause catastrophic crises with high morbidity and mortality. This best practice article considers the causes and presentation of such tumours, screening and diagnostic tests, management of these patients and consideration of family members at risk.