-
European Journal of Endocrinology Oct 2023To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; >... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test).
DESIGN
Systematic review and meta-analysis.
METHODS
Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs).
RESULTS
In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy.
CONCLUSIONS
The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities.
Topics: Humans; Adrenal Gland Neoplasms; Hydrocortisone; Cross-Sectional Studies; Hypertension; Dyslipidemias
PubMed: 37801655
DOI: 10.1093/ejendo/lvad134 -
The Journal of Clinical Endocrinology... Aug 2023Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess. (Meta-Analysis)
Meta-Analysis
CONTEXT
Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess.
OBJECTIVE
To increase knowledge about AMH by reviewing the reported cases of this disorder.
DESIGN
Systematic review and meta-analysis of the genotype/phenotype relationship in all reported cases of AMH.
SETTING
Literature review and analysis.
PATIENTS OR OTHER PARTICIPANTS
All cases of AMH published to date.
MAIN OUTCOME MEASURE(S)
Characteristics of AMH cases and genotype-phenotype relationships.
RESULTS
A total of 66 patients, median age of 48 years, were identified from 29 reports. More than one-half were male (n = 39, 59%). The majority had unilateral (73%, n = 48) disease; 71% (n = 47) were sporadic and 23% (n = 15) were associated with the MEN2. Most (91%, n = 60) displayed signs and symptoms of excess catecholamine secretion, particularly hypertension. Elevated catecholamine concentrations (86%, n = 57) and adrenal abnormalities on imaging were common (80%, n = 53). More than one-half (58%, n = 38) had concurrent tumors: pheochromocytoma (42%, n = 16/38); medullary thyroid cancer (24%, n = 9/38); and adrenocortical adenoma (29%, n = 11/38). Most (88%, n = 58) underwent adrenalectomy with 45/58 achieving symptom resolution. Adrenalectomy was less common in patients under 40 years and those with bilateral disease (both P < .05).
CONCLUSION
AMH may be sporadic or associated with MEN2, most have catecholamine excess and imaging abnormalities. Unilateral involvement is more common. Most reported patients have been treated with adrenalectomy, which is usually curative with regard to catecholamine hypersecretion.
Topics: Male; Humans; Female; Hyperplasia; Adrenal Gland Neoplasms; Pheochromocytoma; Adrenal Medulla; Adrenalectomy; Catecholamines
PubMed: 36896586
DOI: 10.1210/clinem/dgad121 -
Journal of Clinical Medicine Jul 2023To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and... (Review)
Review
To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Systematic literature review. We performed a search in the PubMed database using search terms: 'abscess and adrenal glands', 'adrenalitis', 'infection and adrenal gland', 'adrenal abscess', 'adrenal infection' and 'infectious adrenalitis'. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia ( = 0.048). Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.
PubMed: 37510716
DOI: 10.3390/jcm12144601 -
Annals of Anatomy = Anatomischer... Jun 2024The aim of this systematic review is to study the subdiaphragmatic anatomy of the phrenic nerve. (Review)
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.
Topics: Phrenic Nerve; Humans; Diaphragm; Animals
PubMed: 38692333
DOI: 10.1016/j.aanat.2024.152269 -
Endocrine-related Cancer Jul 2023Core needle biopsy (CNB) has been used with caution in pheochromocytoma and paraganglioma (PPGL) due to concerns about catecholamine-related complications. While it is... (Meta-Analysis)
Meta-Analysis
Core needle biopsy (CNB) has been used with caution in pheochromocytoma and paraganglioma (PPGL) due to concerns about catecholamine-related complications. While it is unclear what scientific evidence supports this claim, it has limited the acquisition of biological samples for diagnostic purposes and research, especially in metastatic PPGL. We performed a systematic review and individual patient meta-analysis to evaluate the risk of complications after CNB in PPGL patients. The primary and secondary objectives were to investigate the risk of death and the occurrence of complications requiring intervention or hospitalization, respectively. Fifty-six articles describing 86 PPGL patients undergoing CNB were included. Of the patients (24/71), 34% had metastases and 53.4% (31/58) had catecholamine-related symptoms before CNB. Of the patients (14/41), 34.1% had catecholamine excess testing prior to the biopsy. No CNB-related deaths were reported. Four patients (14.8%, 4/27) experienced CNB-related complications requiring hospitalization or intervention. One case had a temporary duodenal obstruction caused by hematoma, two cases had myocardial infarction, and one case had Takotsubo cardiomyopathy. Eight patients (32%, 8/25) had CNB-related catecholamine symptoms, mainly transient hypertension, excessive diaphoresis, tachycardia, or hypertensive crisis. The scientific literature does not allow us to make any firm conclusion on the safety of CNB in PPGL. However, it is reasonable to argue that CNB could be conducted after thorough consideration, preparation, and with close follow-up for PPGL patients with a strong clinical indication for such investigation.
Topics: Humans; Pheochromocytoma; Biopsy, Large-Core Needle; Paraganglioma; Catecholamines; Adrenal Gland Neoplasms; Retrospective Studies
PubMed: 37185155
DOI: 10.1530/ERC-22-0354 -
World Journal of Clinical Cases Oct 2023Ewing sarcoma (ES) is a malignant neoplasm of neuroectodermal origin and is commonly observed in children and young adults. The musculoskeletal system is the main body...
BACKGROUND
Ewing sarcoma (ES) is a malignant neoplasm of neuroectodermal origin and is commonly observed in children and young adults. The musculoskeletal system is the main body system impacted and ES is rarely seen in the visceral organs particularly the adrenal gland.
AIM
To present a comprehensive review of primary adrenal ES, with emphasis on diagnosis, therapy and oncological outcomes.
METHODS
A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020. PubMed/ MEDLINE, EMBASE and Google Scholar bibliographic databases were searched to identify articles from 1989 to 2022 and included patients with ES/primitive neuroectodermal tumor (PNET) of the adrenal gland. PubMed, Google Scholar and EMBASE medical databases were searched, combining the terms "adrenal", "ES" and "PNET". Demographic, clinical, pathological and oncological data of patients were analyzed by SPSS version 29.0.
RESULTS
A total of 52 studies were included for review (47 case reports and 5 case series) with 66 patients reported to have primary adrenal ES. Mean age at diagnosis was 26.4 ± 15.4 years (37.9% males, 57.6% females, sex not reported in 3 cases). The most frequent complaint was abdominal/flank pain or discomfort (46.4%) followed by a palpable mass (25.0%), and the average duration of symptoms was 2.6 ± 3.1 mo. The imaging modality of choice was computed tomography scan (81.5%), followed by magnetic resonance imaging (20.4%). Preoperative staging revealed that 17 tumors (27.9%) were metastatic and 14 patients had inferior vena cava or renal vein neoplastic thrombus at initial diagnosis. Open adrenalectomy was performed in the majority of cases (80.0%), of which 27.9% required more extensive resection. Minimally invasive surgery was attempted in 8.2% of tumors. Complete surgical resection was achieved in 89.4% of the patients. Adjuvant therapy was administered to 32 patients, in the form of chemotherapy (62.5%), radiotherapy (3.1%) or combination (34.4%). Median overall survival was 15 mo and 24-mo overall survival was 40.5%. Median disease-free survival was 10 mo and 24-mo disease-free survival was 33.3%.
CONCLUSION
The significant progress in molecular biology and genetics of ES does not reflect on patient outcomes. ES remains an aggressive tumor with a poor prognosis and high mortality.
PubMed: 37900999
DOI: 10.12998/wjcc.v11.i28.6782 -
Life (Basel, Switzerland) Sep 2023Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the... (Review)
Review
Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the suprachiasmatic nucleus (SCN), which receives information from the short-wavelength-sensitive intrinsically photosensitive retinal ganglion cells. The SCN synchronizes local clocks throughout the body affecting sleep/wake routines and the secretion of neuroendocrine-linked hormones such as melatonin from the pineal gland and cortisol via the hypothalamic pituitary adrenal (HPA) axis. Although the effects of light parameters on melatonin have been recently reviewed, whether the experimental variation of the spectral power distribution and intensity of light can induce changes in cortisol rhythms remains unclear. Thus, this systematic review evaluated the effects of daytime exposure to lights of different spectral wavelength characteristics and luminance intensity on the cortisol levels in healthy individuals. A search of the PubMed, Web of Science, EMBASE, CINAHL, Medline, PsycINFO and Cochrane Library databases on 19 June 2023 identified 3418 articles, of which 12 studies (profiling 337 participants) met the inclusion and risk of bias criteria. An analysis of the literature indicated that exposure to bright lights of any colour during the late night or early morning can induce significant increases in cortisol secretion relative to time-matched dim light comparison conditions. Furthermore, exposure to bright lights with stronger short-wavelength (blue/green) components in the early morning typically induced greater increases in cortisol relative to lights with stronger long-wavelength (red) components. Thus, the circadian regulation of cortisol is sensitive to the wavelength composition of environmental lighting, in line with the more commonly studied melatonin. As such, wavelength characteristics should be optimized and reported in light intervention studies (particularly for the investigation of cortisol-associated disorders and HPA axis function), and exposure to short-wavelength light during sensitive periods should be carefully considered in constructed environments (e.g., bedroom and classroom lighting and device screens).
PubMed: 37895351
DOI: 10.3390/life13101968 -
Biomedicines Apr 2024This systematic review article aims to investigate the clinical and radiological imaging characteristics of adrenal abnormalities in patients with thrombocytopenia,... (Review)
Review
This systematic review article aims to investigate the clinical and radiological imaging characteristics of adrenal abnormalities in patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. We searched the literature in PubMed, the Cochrane Library, and the Web of Science Core Collection. Ultimately, we analyzed 11 studies with 22 patients plus our 1 patient, totaling 23 patients. The mean age was 47.0 ± 12.6 years. There were 20 male and 3 female patients, respectively. The histopathological analysis of lymph nodes was conducted in 15 patients (65.2%), and the diagnosis was consistent with TAFRO syndrome in all 15 patients. Among the 23 patients, 11 patients (18 adrenal glands) showed adrenal ischemia/infarction, 9 patients (13 adrenal glands) showed adrenal hemorrhage, and 4 patients (7 adrenal glands) showed adrenomegaly without evidence of concurrent ischemia/infarction or hemorrhage. One patient demonstrated unilateral adrenal hemorrhage and contralateral adrenomegaly. In patients with adrenal ischemia/infarction, the adrenal glands displayed poor enhancement through contrast-enhanced computed tomography (CT). In patients with adrenal hemorrhage, the adrenal glands revealed high attenuation through non-enhanced CT and hematoma through magnetic resonance imaging. Adrenomegaly, with or without adrenal ischemia/infarction or hemorrhage, was observed in all patients (23/23, 100%). The subsequent calcification of the affected adrenal glands was frequently observed (9/14, 64.3%) when a follow-up CT was performed. Abdominal pain was frequent (15/23, 65.2%), all of which occurred after the disease's onset, suggesting the importance of considering TAFRO syndrome as a cause of acute abdomen. Given the absence of evidence of adrenal abnormalities in non-TAFRO-idiopathic multicentric Castleman disease (iMCD), they may serve as diagnostic clues for differentiating TAFRO syndrome from non-TAFRO-iMCD.
PubMed: 38672191
DOI: 10.3390/biomedicines12040837 -
Lung Cancer (Amsterdam, Netherlands) Dec 2023For diagnosing left adrenal gland metastasis in lung cancer, clinical guidelines recommend to perform EUS, but EUS-B (EUS using an EBUS-scope) is increasingly being... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
For diagnosing left adrenal gland metastasis in lung cancer, clinical guidelines recommend to perform EUS, but EUS-B (EUS using an EBUS-scope) is increasingly being used. We evaluated the diagnostic performance of both procedures.
MATERIALS AND METHODS
We did a systematic review (PROSPERO, CRD42023416205) and searched MEDLINE and EMBASE on 04-July-2023 for studies evaluating EUS and/or EUS-B in diagnosing left adrenal gland metastases in adults with (suspected) lung cancer. Outcomes were: (1) ability to visualize the left adrenal gland, (2) ability to sample (in those with successful visualization and in whom sampling was attempted), (3) ability to obtain adequate material (in those with successful sampling), (4) malignancy detection rate (in those with successful sampling), and (5) remaining risk of malignancy (in those with a negative EUS(-B)-FNA and undergoing a reference standard). We performed random-effects meta-analyses.
RESULTS
We included 19 studies (EUS: n = 11, EUS-B: n = 6, both: n = 2), covering 1712 patients. All studies had high (n = 18) or unclear (n = 1) risk of bias (QUADAS-2). Average ability to visualize the left adrenal gland was 0.94 (95 %CI 0.82-0.98; n = 7 studies). Average ability to sample was 1.00 (95 %CI 0.99-1.00; n = 9). Average ability to obtain adequate material was 0.96 (95 %CI 0.93-0.98; n = 18). Average malignancy detection rate was 0.42 (95 %CI 0.34-0.49; n = 18). Remaining risk of malignancy was 0.07 (95 %CI 0.04-0.12; n = 8). Ability to visualize was slightly higher for EUS (0.99; 95 %CI 0.90-1.00) than EUS-B (0.84; 95 %CI 0.70-0.92; p = 0.025), but the other performance characteristics were similar. No major complications were reported.
CONCLUSION
Both EUS and EUS-B have good performance and are safe for left adrenal gland analysis in patients with lung cancer, but the number of high-quality studies is limited and further well-constructed prospective studies are needed.
Topics: Adult; Humans; Lung Neoplasms; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endosonography; Sensitivity and Specificity; Adrenal Glands; Adrenal Gland Neoplasms
PubMed: 37827042
DOI: 10.1016/j.lungcan.2023.107391 -
Frontiers in Endocrinology 2024Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease. (Review)
Review
BACKGROUND
Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease.
METHODS
We comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded.
RESULTS
We identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD.
CONCLUSION
IAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.
Topics: Humans; Adrenal Insufficiency; Adrenocorticotropic Hormone; Endocrine System Diseases; Genetic Diseases, Inborn; Hypoglycemia; Immune Checkpoint Inhibitors
PubMed: 38318292
DOI: 10.3389/fendo.2024.1326684