Effectiveness and safety of continuous subcutaneous hydrocortisone infusion in managing adrenocortical insufficiency in adult patients: a systematic review.

Oral hormone replacement therapy has been and continues to be the cornerstone of adrenocortical insufficiency management. However, the introduction of continuous subcutaneous hydrocortisone infusion (CSHI) shows great potential for advancing the management of adrenocortical insufficiency. It resembles the circadian rhythm of physiological cortisol secretion and was shown to have a promising outcome in terms of quality of life (QOL) and clinical outcomes in the literature. We conducted a systematic search strategy including MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and the online trials registers at ClinicalTrials.gov without geographic restrictions. Research investigations where self-reported quality of life (QOL) was assessed as a variable in adult individuals with confirmed adrenal disease, treated by CSHI, and results were presented in English. All articles included were published between 2014 and 2023, even though we had no timeframe limitations in our inclusion criteria. A total of six studies were included, with 63 subjects enrolled, and the average age was 40 years, a study showed a significant reduction in the average total daily dose of HC from 47.5 mg to 31.4 mg on CSHI, while other two studies estimated a reduction in the hospitalization rate due to adrenal crisis from 2.6 to 1.3 admissions per year on CSHI. Most of the studies on subjective well-being and quality of life have shown significant improvement. Overall, CSHI shows great potential as a treatment method for Adrenal insufficiency. It improves the quality of life and lowers hospitalization rates, resulting in increased patient satisfaction and acceptance. Additional comprehensive research is necessary to strengthen these discoveries, gain a deeper understanding of the effectiveness and safety of this treatment approach, and provide guidance for medical practitioners.

Isolated Adrenocorticotropic Hormone Deficiency Diagnosed After the Cessation of Glucocorticoid Therapy for Eosinophilic Esophagitis: A Case Report.

Isolated adrenocorticotropic hormone deficiency (IAD) is a rare pituitary disorder that can cause adrenal insufficiency. However, due to its nonspecific symptoms, its diagnosis is often difficult and may be delayed. Patients with IAD require lifelong glucocorticoid (GC) replacement therapy. Contrastingly, GC-induced secondary adrenal insufficiency is a reversible condition that arises when patients receiving GC therapy reduce their GC dosage or discontinue therapy. Differentiating between IAD and GC-induced secondary adrenal insufficiency is clinically crucial. We report a unique case that required differentiation between these two conditions. A 71-year-old Japanese woman presented with symptoms of adrenal insufficiency after discontinuation of GC therapy for eosinophilic esophagitis. We conducted detailed interviews and repeated the endocrinological examinations. We concluded that her symptoms were owing to IAD rather than GC-induced secondary adrenal insufficiency. She began a lifelong hydrocortisone replacement therapy. This case suggests that when caring for patients undergoing GC therapy, it is important to consider the possibility of coexisting IAD and arrange endocrinological examinations if signs of adrenal insufficiency arise during the gradual reduction of GC treatment.

Atypical Presentation and Successful Management of Combined Hyperthyroidism and Adrenal Insufficiency in a Young Male.

This case report details the unusual presentation and successful management of a 25-year-old male diagnosed with both hyperthyroidism and adrenal insufficiency. The patient initially presented with symptoms of fatigue, weight loss, and palpitations, with no significant past medical history. Further evaluation revealed elevated thyroid hormone levels and decreased cortisol levels, confirming the diagnosis of concurrent hyperthyroidism and adrenal insufficiency. The complexity of managing these coexisting endocrine disorders required a multidisciplinary approach. Techniques utilized included detailed hormonal assays, imaging studies, and dynamic endocrine testing. The therapeutic regimen involved the administration of antithyroid medications, beta-blockers for symptom control, and glucocorticoid replacement therapy. This report underscores the importance of considering multiple endocrine disorders in patients with nonspecific systemic symptoms and highlights the need for individualized treatment plans to address the unique challenges presented by such comorbidities.

Adrenal gland haemangioma, a rare entity difficult to differentiate from malignancy.

Adrenal haemangioma is a rare benign vascular lesion, which is usually asymptomatic and it is typically discovered incidentally on radiographic imaging. Differential diagnosis from other benign or malignant adrenal neoplasms may be challenging, and in many cases, the diagnosis is only possible after surgical resection. We present a case of a 39-year-old female with abdominal pain in the upper right quadrant, who was referred to our hospital after incidentally discovering a mass above the right kidney on abdominal ultrasonography. MRI revealed an adrenal mass, with features not indicative of adenoma and suggestive of adrenal haemangioma, without ruling out other possible diagnoses such us phaeochromocytoma and adrenal cortical carcinoma. Biochemical tests did not reveal any endocrine dysfunction. The patient underwent adrenalectomy, and histopathological analysis confirmed a venous haemangioma. Adrenal gland haemangioma is an unusual vascular lesion, typically diagnosed incidentally during abdominal imaging. Certain radiologic features may raise suspicion for malignancy, making it difficult to distinguish them from a primary adrenal cortical carcinoma. They may also grow large, compressing surrounding structures and causing abdominal pain, or may rupture, leading to retroperitoneal haemorrhage. For these reasons, some authors recommend excision of all suspected adrenal haemangiomas, and in many cases, the final diagnosis is made only after surgical removal.

Androgens suppress corticosteroid binding globulin in male mice, affecting the endocrine stress response.

Biological sex affects the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, how androgen deprivation affects this axis remains largely unknown. In this study, we investigated the effect of androgen status on different components of the HPA axis in male mice. Two weeks of androgen deprivation did not affect total plasma corticosterone levels but led to increased pituitary adrenocorticotropic hormone (ACTH) levels. Stress-induced total plasma corticosterone levels were increased, while the suppression of corticosterone after dexamethasone treatment under basal conditions was attenuated. Androgen-deprived mice displayed a 2-fold increase in plasma levels of corticosteroid binding globulin (CBG). A similar increase in CBG was observed in global androgen receptor (AR) knock-out animals, compared to wild-type litter mates. Androgen deprivation was associated with a 6-fold increase in CBG mRNA in the liver and enhanced transcriptional activity at CBG regulatory regions, as evidenced by increased H3K27 acetylation. We propose that the induction of CBG as a consequence of androgen deprivation, together with the unaltered total corticosterone levels, results in lower free corticosterone levels in plasma. This is further supported by mRNA levels of androgen-independent GR target genes in the liver. The reduction in negative feedback on the HPA axis under basal condition would suffice to explain the enhanced stress reactivity after androgen deprivation. Overall our data demonstrate that, in mice, tonic AR activation affects CBG levels, in conjunction with effects on gene expression and HPA-axis reactivity.

Molecular Analysis of Renal/Adrenal Angiosarcomas Reveals High Frequency of Recurrent Genetic Alterations.

Angiosarcomas of the kidney and adrenal gland are rare, highly aggressive vascular neoplasms. Their genomic profile has not been systematically studied to date. We report the clinicopathologic and molecular features of six angiosarcomas centered in the kidney/adrenal gland. All patients were male adults, ranging from 58 to 77 years of age. Tumor sizes ranged from 2.5 to 22.5 cm. Half of the cases demonstrated hot spot mutations in the KDR gene, while one-third demonstrated mutations in the PIK3CA gene; both of these gene alterations being previously described, preferentially in breast angiosarcomas. In addition, two cases each demonstrated BRIP1 gene amplification, CTNNB1 and ETV6 mutations, which have not been previously reported in angiosarcoma. Notably, molecular studies were critical in establishing the correct diagnoses in three cases: one was an epithelioid angiosarcoma originally misdiagnosed as metastatic adenocarcinoma to the adrenal gland, the second was a vasoformative angiosarcoma that mimicked hemangioma, and the third was a collision tumor between a high-grade angiosarcoma and a chromophobe renal cell carcinoma which was originally diagnosed as a sarcomatoid renal cell carcinoma. In summary, angiosarcomas of the kidney and adrenal gland have a high frequency of recurrent genetic alterations, some of them being shared with other angiosarcoma subtypes, while other appear to be novel. In particular, activating hot spot KDR and PIK3CA mutations represent potential therapeutic targets for these highly aggressive cancers.

Adrenal ganglioneuroma with nodal metastases on 123I-MIBG SPECT/CT and 18F-FDG PET/CT.

Ganglioneuroma is a well-differentiated tumor originating from neural crest cells of the sympathetic nervous system. Although benign, a few cases have been reported that ganglioneuroma can metastasize to other sites. We report a case of adrenal ganglioneuroma with para-aortic nodal metastases with low FDG and MIBG uptake. In order to avoid unnecessary wide excision or aggressive medication, it is important to consider the possibility of ganglioneuroma preoperatively even if with metastases.

A case of adrenal cavernous hemangioma resected due to tumor growth accompanied by intratumoral hemorrhage.

Introduction: We describe a case of an adrenal cavernous hemangioma that was surgically resected because of tumor growth and intratumoral hemorrhage. Case presentation: A 73-year-old woman presented with an enlarged adrenal tumor and intratumoral hemorrhage during the follow-up of an incidental adrenal tumor. A computed tomography showed that the left adrenal tumor had grown from 23 to 44 mm over 1 year. Blood tests revealed a normal metabolic profile. Paragangliomas and metastatic tumors were suspected on imaging. Laparoscopic adrenalectomy was performed to prevent tumor rupture due to further bleeding. No adhesions or bleeding were observed around the tumor during surgery. Pathological diagnosis was adrenal cavernous hemangioma. Conclusion: Adrenal cavernous hemangioma is difficult to distinguish preoperatively from other adrenal tumors, including malignant tumors. The intraoperative findings of this case suggest that laparoscopic adrenalectomy is a safe treatment option for relatively small adrenal cavernous hemangioma.

Presentation, Management, and Outcomes of Patients with Giant Pheochromocytoma: Retrospective Cohort Study.

CONTEXT: Data on giant pheochromocytomas (PHEO), defined based on size ≥ 10 cm, are scarce. OBJECTIVE: to compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs. DESIGN: retrospective cohort study, 2000-2023. SETTING: referral center. PATIENTS: consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at a 1:6 ratio. OUTCOMES: perioperative complications, metastases, mortality. RESULTS: Of 828 patients with PHEO, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe catecholamine excess (76% vs 30%, P<.0001).Adrenalectomy was performed in 94% of patients with giant PHEOs and 100% referents. In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a higher perioperative complication rate (31% vs 10%, P=.004).During a median follow-up of 3 years, metastases developed at a higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease-specific mortality was 7% in patients with giant PHEOs and 0% in referents (P=.02). CONCLUSION: Patients with giant PHEO as compared to referents were more symptomatic, had a higher degree of catecholamine excess, and had a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up.

Management of patients with adrenal myelolipoma: experience from a tertiary referral centre.

BACKGROUND: Adrenal myelolipomas are rare, benign, tumours of the adrenal cortex. AIMS: This study reports the experience of a tertiary adrenal surgery referral centre's approach to the management of patients with adrenal myelolipoma. METHODS: A retrospective observational cohort study was conducted on all adult patients (> 18 years age) diagnosed with adrenal myelolipoma from January 1, 2014, to December 30, 2022. Demographics, imaging characteristics, histological diagnosis (where applicable) and follow-up data were compared between patients undergoing surgery and those referred to surveillance. Indications for operative intervention were recorded at the time of multidisciplinary team discussion, consisting of surgeons, endocrinology physicians, radiologists, pathologists and specialist nursing representatives. RESULTS: Of the 522 patients with an adrenal lesion discussed in adrenal tumour meeting between 2014 and 2022, n = 15 (2.8%) were diagnosed with adrenal myelolipoma. Of the 15 patients, 4 underwent adrenalectomy at first presentation (27%), while 1 patient underwent adrenalectomy after interval follow-up. Indications for operative intervention were as follows: 'indeterminate lesion' (n = 3), 'abdominal pain and size (> 4 cm)' (n = 1) and 'mass effect on adjacent organs' (n = 1). The mean rate of lesion growth in patients referred for surveillance (n = 10) was 0.13 cm/year. Histology confirmed adrenal myelolipoma as the diagnosis in all resected tumours. CONCLUSIONS: For patients with adrenal myelolipoma, the presence of symptoms and/or indeterminate features on imaging may be more clinically useful indications for operative intervention over size alone. The surveillance of adrenal myelolipomas, even in patients with adrenal lesions > 4 cm, is a safe clinical strategy, provided the imaging characteristics are benign and patients remain asymptomatic.

Adrenal tumours in patients with pathogenic APC mutations: a retrospective study.

BACKGROUND: Adrenal tumours are associated with familial adenomatous polyposis (FAP). In the literature, most studies use the clinical definition of FAP (more than 100 adenomatous polyps found in endoscopic studies). However, not all patients that meet clinical criteria for FAP carry pathogenic mutations in the adenomatous polyposis coli (APC) gene, as there is genetic heterogeneity responsible for FAP with the polyposis sometimes explained by genetic and environmental factors other than pathogenic APC mutations. Reciprocally, not all the patients with pathogenic APC variants will fulfil the classic criteria of FAP. OBJECTIVE: This study aims to investigate the characteristics of adrenal tumours in patients with pathogenic or likely pathogenic APC variants and explore the hormonal function of these patients. METHOD: This is a retrospective cohort study. Patients with pathogenic or likely pathogenic APC variants were recruited and their radiological assessments were reviewed. Patient demographic data, APC variants, adrenal mass characteristics and hormonal testing results were collected. RESULT: The prevalence of adrenal mass was 26.7% (24/90) among patients with pathogenic or likely pathogenic APC variants. Using the classic definition, the prevalence was 32.4% (22/68). Four patients had adrenal hormone testing, two of which had Conn's syndrome and two had nonspecific subclinical results. CONCLUSION: In our cohort, the prevalence of adrenal tumours among patients with pathogenic and likely pathogenic APC mutations is at least twice to three times higher than the general population prevalence reported from international population-based studies. The hormonal functions of patients with pathogenic APC variants and adrenal tumours can be investigated with routine testing in further research.

Management of undifferentiated adrenal gland metastases from malignant melanoma: case report.

Adrenal gland metastases from malignant melanoma are a common but poorly characterised condition. Their lack of consistent clinical features and poor response to immune checkpoint inhibitors pose a significant diagnostic and therapeutic challenge to practitioners. This case report describes a 78-year-old male with no prior history of melanoma presenting with nonspecific abdominal symptoms and unintentional weight loss who was found to have undifferentiated bilateral adrenal gland metastases from malignant melanoma. Despite ongoing investigations, the primary site of the adrenal gland metastases remained unknown, prompting the consideration of primary adrenal melanoma as a diagnosis. The patient underwent four cycles of treatment with immune checkpoint inhibitors, nivolumab and ipilimumab, followed by maintenance therapy and subsequent adrenal metastasectomy. Despite therapeutic efforts, the patient's tumour was resistant to treatment and became undifferentiated. The patient continued with palliative care until his death, more than three years after the onset of symptoms. The clinical features, pathophysiology, diagnosis, treatment, and prognosis of this patient's disease are discussed in detail to help inform the management of similar cases.

A Novel Steroidogenic Acute Regulatory Protein (StAR) Mutation Causing Adrenal Insufficiency in a Neonate: A Case Report of a Rare Medical Condition.

Congenital lipoid adrenal hyperplasia is a very rare and severe cause of adrenal insufficiency. It occurs due to a mutation of the steroidogenic acute regulatory protein (StAR), disrupting adrenal steroid biosynthesis. Here, we report a case of a three-week-old female infant with vomiting, failure to thrive, electrolyte imbalance, and generalized hyperpigmentation. The hormonal assay and genetic diagnosis confirmed a mutation in the StAR protein, leading to adrenal insufficiency. Appropriate replacement therapy resulted in the resolution of clinical and biochemical abnormalities. This case is being reported for its rare etiology and diagnostic clues. It can guide clinicians to keep adrenal insufficiency as a differential diagnosis in a neonate presenting with hyperpigmentation and electrolyte disturbance to save lives.

Serum steroid profiling in the diagnosis of adrenocortical carcinoma: a prospective cohort study.

CONTEXT: Guidelines suggest performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of adrenocortical carcinoma (ACC). However, urine steroid profiling is not widely available. OBJECTIVE: To determine the accuracy of clinically available serum 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC. METHODS: We conducted a prospective single-center cohort study of patients with adrenal masses evaluated between 2015-2023. Serum was analyzed by liquid chromatography-mass spectrometry for 17OH-pregnenolone, 17OH-progesterone, 11-deoxycortisol. Reference standard for adrenal mass included histopathology, imaging characteristics, imaging follow up of 2 years, or clinical follow up of 5 years. Localized Generalized Matrix Learning Vector Quantization (LGMLVQ) analysis was used to develop serum steroid score and assessed with area under receiver operating curve (AUROC). RESULTS: Of 263 patients with adrenal masses, 44 (16.7%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. Hounsfield unit (HU) ≥ 20 was demonstrated in all ACCs, in all but one other adrenal malignancy, and in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs non-ACCs, including when comparing ACCs with functioning ACAs, and with ACAs with HU ≥ 20 (P<0.0001 for all). LGMLVQ analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed AUROC of 0.823. CONCLUSIONS: We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice.

Ruptured triple hormone-secreting adrenal cortical carcinoma with hyperaldosteronism, hypercortisolism, and elevated normetanephrine: a case report.

We report a case of a ruptured triple hormone-secreting adrenal mass with hyperaldosteronism, hypercortisolism, and elevated normetanephrine levels, diagnosed as adrenal cortical carcinoma (ACC) by histology. A 53-year-old male patient who initially presented with abdominal pain was referred to our hospital for angiocoagulation of an adrenal mass rupture. Abdominal computed tomography revealed a heterogeneous 19×11×15 cm right adrenal mass with invasion into the right lobe of the liver, inferior vena cava, retrocaval lymph nodes, and aortocaval lymph nodes. Angiocoagulation was performed. Laboratory evaluation revealed excess cortisol via a positive 1-mg overnight dexamethasone suppression test, primary hyperaldosteronism via a positive saline infusion test, and plasma normetanephrine levels three times higher than normal. An adrenal mass biopsy was performed for pathological confirmation to commence palliative chemotherapy because surgical management was not deemed appropriate considering the extent of the tumor. Pathological examination revealed stage T4N1M1 ACC. The patient started the first cycle of adjuvant mitotane therapy along with adjuvant treatment with doxorubicin, cisplatin, and etoposide, and was discharged. Clinical cases of dual cortisol- and aldosterone-secreting ACCs or ACCs presenting as pheochromocytomas have occasionally been reported; however, both are rare. Moreover, to the best of our knowledge, a triple hormone-secreting ACC has not yet been reported. Here, we report a rare case and its management. This case report underscores the necessity of performing comprehensive clinical and biochemical hormone evaluations in patients with adrenal masses because ACC can present with multiple hormone elevations.

Long COVID and pituitary dysfunctions: a bidirectional relationship?

Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome.

Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.

BACKGROUND: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited. METHODS: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques were employed. RESULTS: Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC-MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data. CONCLUSION: This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans.

Typing diagnostic value of 68Ga-pentixafor PET/CT for patients with primary aldosteronism and unilateral nodules.

PURPOSE: Our goal was to compare the lateralization of 68Ga-pentixafor PET/CT with adrenal vein sampling (AVS) in primary aldosteronism (PA) patients with unilateral lesions. METHODS: We retrospectively enrolled 61 patients with PA and all patients showed unilateral nodular lesions on CT and underwent 68Ga-Pentixafor PET/CT. The general clinical data, imaging and AVS results were collected. The diagnostic efficiency of 68Ga-Pentixafor PET/CT imaging in PA patients was calculated by visual and semi-quantitative analysis to compare the consistency with AVS, and the correlation between CXCR4 express and 68Ga-Pentixafor uptake was performed. RESULTS: The study included 42 unilateral PA (UPA) and 19 bilateral PA (BPA). The area under curve (AUC) of 68Ga-Pentixafor PET/CT to diagnosis UPA with 10 min maximum standardized uptake value (SUVmax) > 8.17 was 0.82 ([0.70-0.90], P < 0.001), and the sensitivity and specificity were 0.64 and 0.90, respectively. The maximal AUC of 68Ga-pentixafor PET/CT for the diagnosis UPA in patients with nodules with a diameter ≥1 cm was 0.87 ([0.73-0.95],P both <0.001,[10 min SUVmax=8.17 and 10 min mean standardized uptake value (SUVmean)=5.57]), and the sensitivity and specificity were 0.73 and 0.93, respectively. Unilateral adrenalectomy and significant CXCR4 expression were present in 32 UPA, including 27 aldosterone-producing adenoma and 5 idiopathic adrenal hyperplasia. Additionally, 68Ga-pentixafor uptake in adrenal lesions was significantly correlated with CXCR4 expression, and statistical differences in 68Ga-pentixafor uptake among IRS subgroups. CONCLUSIONS: 68Ga-Pentixafor PET/CT can be helpful for subtyping diagnosis of PA patients with unilateral adrenal nodular, showing significant potential in non-invasive PA classification.

Critical illness-related corticosteroid insufficiency: latest pathophysiology and management guidelines.

Intensive care unit (ICU) admissions in the United States exceed 5.7 million annually, often leading to complications such as post-intensive care syndrome and high mortality rates. Among these challenges, critical illness-related corticosteroid insufficiency (CIRCI) requires emphasis due to its complex, multiple-cause pathophysiology and varied presentations. CIRCI, characterized by adrenal insufficiency during critical illness, presents in up to 30% of ICU patients and may manifest as an exaggerated inflammatory response. Factors such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, tissue corticosteroid resistance, and drug-induced suppression contribute to CIRCI. Diagnosis is a complex process, relying on a comprehensive assessment including clinical presentation, laboratory findings, and dynamic stimulatory testing. Treatment involves intensive medical care and exacting glucocorticoid therapy. Recent guidelines advocate for individualized approaches tailored to patient presentation and etiology. Understanding the pathophysiology and treatment of CIRCI is vital for clinicians managing critically ill patients and striving to improve outcomes. This research paper aims to explore the latest developments in the pathophysiology and management of CIRCI.

Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022.

Background: It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Aim: Study temporal trends of AI related AE in the I-CAH Registry. Methods: In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019. Results: In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02). Conclusion: The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.