Citations

AbstractObjectiveTo describe the presentation and outcomes of patients with adrenal ganglioneuromas (AGNs).DesignSingle‐centre retrospective cohort study (1 January 1995 to 31 December 2019) and systematic review of literature (1 January 1980 to 19 November 2019).PatientsDiagnosed with histologically confirmed AGN.MeasurementsBaseline clinical, imaging and biochemical characteristics, recurrence rates and mortality. Subgroup analysis was performed on tumours with histologic elements of ganglioneuroma and pheochromocytoma (ie composite tumours).ResultsThe cohort study included 45 patients with AGN, 20 (44%) of which had composite tumours. Compared to pure AGN, patients with composite tumour were older (median age, 62.5 vs. 35 years, p < .001), had smaller tumours (median size, 3.9 vs. 5.7 cm, p = .016) and were discovered incidentally less frequently (65% vs. 84%, p = .009). No recurrences or ganglioneuroma‐specific mortality occurred during follow‐up (range, 0–266 months). The systematic review included 14 additional studies and 421 patients. The mean age of diagnosis was 39 years, and 47% were women. AGNs were discovered incidentally in 72% of patients, were predominantly unilateral (99%) and had a mean diameter of 5.8 cm and an unenhanced computed tomography (CT) attenuation of −118 to 49 Hounsfield units (HU). On imaging, 69% of AGNs were homogenous, 41% demonstrated calcifications, and 40% were lobulated.ConclusionsAGNs are rare benign tumours that present with variable imaging features including large size, unenhanced CT attenuation >20 HU, calcifications and lobulated shape. Imaging characteristics can assist in establishing a diagnosis and avoiding an unnecessary adrenalectomy. The association of pheochromocytomas with AGNs is frequent. Diagnosis should include biochemical testing.

Abstract Context Treatment of pheochromocytoma and paraganglioma (PPGL) requires preintervention titration of alpha- and beta-adrenergic blockade, but patients may still be at risk for complications from catecholamine excess. Metyrosine decreases catecholamine production, making it an attractive therapeutic adjunct for select patients. Evidence Acquisition A systematic literature review was performed (Ovid Medline and Scopus databases) on December 17, 2019, including studies with humans and original data. Studies with 10 or more patients on metyrosine for PPGL were included. Studies were screened for overlapping populations, and the most comprehensive study was included. The references of included studies were reviewed for additional data. Patient data from our institution between 2000 and 2015 were also reviewed. Evidence Synthesis Metyrosine is well tolerated when used for a short course and can improve intraoperative outcomes in PPGL. Metyrosine should be considered when a difficult PPGL resection is expected (eg, pericardiac paraganglioma, abdominal paraganglioma with great vessel involvement), a large release of catecholamines is anticipated (eg, ablative therapy, chemotherapy), or when standard alpha- and beta-adrenergic blockade are not tolerated or cannot adequately control hypertension. Side effects are generally mild and self-limited, with sedation in a majority of patients. Extrapyramidal side effects are rare but can limit use of metyrosine. Because of its expense and limited availability, metyrosine use should be carefully planned and timed in relation to surgery. Conclusions Metyrosine is a safe addition to traditional alpha- and beta-adrenergic blockade and should be considered in those patients with PPGL at high risk for acute release of catecholamines.

Objective Several small studies reported increased prevalence and incidence of asymptomatic vertebral fractures in patients with non-functioning adrenal adenomas and adenomas with mild autonomous cortisol secretion. However, the risk of symptomatic fractures at vertebrae, and at other sites remains unknown. Our objective was to determine the prevalence and incidence of symptomatic site-specific fractures in patients with adrenal adenomas. Design Population-based cohort study, Olmsted County, Minnesota, USA, 1995–2017. Methods Participants were the patients with adrenal adenoma and age/sex-matched referent subjects. Patients with overt hormone excess were excluded. Main outcomes measures were prevalence and incidence of bone fractures. Results Of 1004 patients with adrenal adenomas, 582 (58%) were women, and median age at diagnosis was 63 years (20–96). At the time of diagnosis, patients had a higher prevalence of previous fractures than referent subjects (any fracture: 47.9% vs 41.3%, P = 0.003, vertebral fracture: 6.4% vs 3.6%, P = 0.004, combined osteoporotic sites: 16.6% vs 13.3%, P = 0.04). Median duration of follow-up was 6.8 years (range: 0–21.9 years). After adjusting for age, sex, BMI, tobacco use, prior history of fracture, and common causes of secondary osteoporosis, patients with adenoma had hazard ratio of 1.27 (95% CI: 1.07–1.52) for developing a new fracture during follow up when compared to referent subjects. Conclusions Patients with adrenal adenomas have higher prevalence of fractures at the time of diagnosis and increased risk to develop new fractures when compared to referent subjects.

Background Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing’s disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. Methods A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, cumulative incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28, 2018. Results Data covered definition and cumulative incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). Conclusions We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2–4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission. Conventional radiotherapy or stereotactic radiosurgery should be utilized as second-line treatment for remnant tumor tissue showing extrasellar extension

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

Abstract Context Current evidence on determinants of adverse health outcomes in patients with adrenal insufficiency (AI) is scarce, especially in regards to AI subtypes. Objective To determine predictors of adverse outcomes in different subtypes of AI. Design and Setting Cross-sectional survey study at 2 tertiary centers. Participants A total of 696 patients with AI: primary AI (PAI, 42%), secondary AI (SAI, 32%), and glucocorticoid-induced AI (GIAI, 26%). Intervention Patient-centered questionnaire. Main Outcome Measures Patients’ knowledge, self-management of AI, self-perceived health, and adverse outcomes. Results The incidence rate of adrenal crisis was 24/100 patient-years with 44% experiencing at least 1 adrenal crisis since diagnosis (59% in PAI vs 31% in SAI vs 37% in GIAI, P &lt; .0001). All patients described high degrees of discomfort with self-management and receiving prompt treatment. Patients with PAI were most likely to develop adrenal crises (adjusted OR 2.8, 95% CI 1.9-4.0) despite reporting better self-perceived health (adjusted OR 3.3, 95% CI 2.1-5.3), understanding of their diagnosis (89% vs 74-81% in other subtypes, P = .002), higher comfort with self-management (62% vs 52-61% in other sub types, P = .005), and higher likelihood to receive prompt treatment for adrenal crises in the emergency department (42% vs 19-30% in other subtypes, P &lt; .0001). Conclusions Patients with AI reported high degrees of discomfort with self-management and treatment delays when presenting with adrenal crises. Despite better self-perceived health and understanding of diagnosis, patients with PAI experienced the highest frequency of adrenal crises. A multidimensional educational effort is needed for patients and providers to improve the outcomes of all subtypes of AI.

Abstract Context Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear. Objective To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain. Design Cross-sectional study, 2016-2018. Setting Referral center. Patients Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center. Main outcome measure Diagnosis of OIAI was considered if positive case detection (cortisol &lt; 10 mcg/dL, ACTH &lt; 15 pg/mL, and dehydroepiandrosterone sulfate &lt; 25 mcg/dL), and confirmed after endocrine evaluation. Daily morphine milligram equivalent (MME) was calculated. Results In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P = 0.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P = 0.03). No patient taking &lt;MME of 20 mg/day developed OIAI (sensitivity of 100% for MME &gt; 20 mg); however, specificity of MME cutoff &gt;20 mg was only 19%. After opioid discontinuation, 6/7 patients recovered adrenal function. Conclusion The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg/day and above should be monitored for OIAI.