Aberrant hormone receptors regulate a wide spectrum of endocrine tumors.

Aberrant G-protein coupled receptor (GPCR) expression is highly prevalent in cortisol-secreting primary bilateral macronodular adrenal hyperplasia (PBMAH) and unilateral adenomas. The aberrant expression of diverse GPCRs and their ligands play an important role in the over-function of various endocrine tumours. Examples include aberrant expression of MC2R, 5-HT4R, AVPR1A, LHCGR, and GnRHR in primary aldosteronism; GCGR, LHCGR, and 5-HT4R in phaeochromocytomas and paragangliomas; TRHR, GnRHR, GIPR, and GRP101 in pituitary somatotroph tumours; AVPR2, D2DR, and SSTR5 in pituitary corticotroph tumours; GLP1R, GIPR, and somatostatin receptors in medullary thyroid carcinoma; and SSTRs, GLP1R, and GIPR in other neuroendocrine tumours.

Usefulness of the Upright Posture Test in the Diagnosis of Primary Aldosteronism.

Objective: To assess the usefulness of the upright posture stimulation test (UPT) in the confirmation of primary aldosteronism (PA) in patients in whom saline tests (ST) were inconclusive.

Methods: One hundred eighty-seven adult patients with possible PA were retrospectively included and compared to 25 control subjects. Blood samples were obtained after a 1-hour supine posture and during 2 hours of ambulation.

Diagnosis and management of secondary adrenal crisis.

Adrenal crisis (AC) is a life threatening acute adrenal insufficiency (AI) episode which can occur in patients with primary AI but also secondary AI (SAI), tertiary AI (TAI) and iatrogenic AI (IAI). In SAI, TAI and IAI, AC may develop when the HPA axis is unable to mount an adequate glucocorticoid response to severe stress due to pituitary or hypothalamic disruption. It manifests as an acute deterioration in multi-organ homeostasis that, if untreated, leads to shock and death.

Sex-Related Differences in Self-Reported Symptoms at Diagnosis in Pheochromocytomas and Paragangliomas.

Context: Biological sex can play a role in the severity of certain diseases.

Objective: Our objective was to evaluate whether sex-related differences affect the signs and symptoms of pheochromocytomas and paragangliomas (PPGLs) at presentation.

Methods: We reviewed the records of patients with PPGLs at our center from 1995 to 2022.

ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans.

Background: Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II).

Results: We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time.

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study.

Background: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence.

Methods: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries.

Role of Adrenal Vein Sampling in Guiding Surgical Decision in Primary Aldosteronism.

Adrenal vein sampling (AVS) is recommended for subtyping primary aldosteronism (PA) to identify lateralized or bilateral sources of aldosterone excess, allowing for better decision-making in regard to medical or surgical management on a case-by-case basis. To date, no consensus exists on protocols to be used during AVS, especially concerning sampling techniques, the timing of sampling, and whether or not to use adrenocorticotropic hormone (ACTH) stimulation. Interpretation criteria for selectivity, lateralization, and contralateral suppression vary from one expert center to another, with some favoring strict cut-offs to others being more permissive.

Regional differences in stage distribution and rates of treatment for adrenocortical carcinoma across United States SEER registries.

Background: We tested for regional differences across United States (US) in rates of adrenalectomy, systemic therapy, and adrenalectomy and systemic therapy combination for adrenocortical carcinoma (ACC) patients. We hypothesized that no differences exist, especially after accounting for baseline patient and tumor characteristics.

Methods: Within Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), 1275 ACC patients were identified.

African American vs Caucasian race/ethnicity in adrenocortical carcinoma patients.

In some primaries, African American race/ethnicity predisposes to higher stage and worse survival. We tested for differences in cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with adrenocortical carcinoma (ACC) according to African American vs Caucasian race/ethnicity. We hypothesized that African Americans present with higher tumor stage and grade, do not receive the same treatment, and experience worse oncological outcomes than Caucasians.

Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches.

Central Hypothyroidism is Frequent During Mitotane Therapy in Adrenocortical Cancer Patients: Prevalence and Timeline.

Context: Central hypothyroidism was described previously in mitotane-treated patients but data on its prevalence and time of occurrence are limited.

Objective: To better characterize thyroid hormone insufficiency in patients exposed to mitotane.

Methods: We reviewed medical records of patients from 2 academic centers in Montreal (Canada) and Toulouse (France) with exposure to mitotane therapy for adrenocortical cancer between 1995 and 2020.

Clinical, Pathophysiologic, Genetic, and Therapeutic Progress in Primary Bilateral Macronodular Adrenal Hyperplasia.

Patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) usually present bilateral benign adrenocortical macronodules at imaging and variable levels of cortisol excess. PBMAH is a rare cause of primary overt Cushing's syndrome but may represent up to one-third of bilateral adrenal incidentalomas with evidence of cortisol excess. The increased steroidogenesis in PBMAH is often regulated by various G protein-coupled receptors (GPCRs) aberrantly expressed in PBMAH tissues; some receptor ligands are ectopically produced in PBMAH tissues, creating aberrant autocrine/paracrine regulation of steroidogenesis.

Contemporary conditional cancer-specific survival rates in surgically treated adrenocortical carcinoma patients: A stage-specific analysis.

Background And Objectives: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in surgically treated adrenocortical carcinoma (ACC) patients.

Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2018), 867 ACC patients treated with adrenalectomy were identified. Conditional survival estimates at 5-years were assessed based on DFI duration and according to stage at presentation.

Hispanic Caucasian Race/Ethnicity in Adrenocortical Carcinoma Patients.

Background/aim: In primaries other than adrenocortical carcinoma (ACC), Hispanic race/ethnicity may predispose to higher stage at initial diagnosis and may result in worse survival. We tested the association between Hispanic race/ethnicity and cancer specific mortality (CSM) in ACC patients in addition to testing for differences in other-cause mortality (OCM) rates between Hispanics and Caucasians.

Patients And Methods: Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 1,060 ACC patients: 167 (15.

Genetic Dissection of Primary Aldosteronism in a Patient With MEN1 and Ipsilateral Adrenocortical Carcinoma and Adenoma.

Background: Adrenal tumors are found in up to 40% of patients with multiple endocrine neoplasia type 1 (MEN1). However, adrenocortical carcinomas (ACC) and primary aldosteronism (PA) are rare in MEN1.

Case: A 48-year-old woman known to have primary hyperparathyroidism and hypertension with hypokalemia was referred for a right complex 8-cm adrenal mass with a 38.

Successful Adrenal Vein Sampling Using Dexamethasone Premedication in Patients With Iodine Contrast Media Allergy.

Context: Preparation of patients with iodine contrast media (ICM) allergy who require adrenal vein sampling (AVS) to establish source of aldosterone excess of their confirmed primary aldosteronism (PA) is controversial. Usual premedication with high-dose prednisone can interfere with cortisol determinations, possibly altering the aldosterone to cortisol ratios for the identification of lateralized aldosterone excess.

Objective: We aimed to evaluate the efficacy and safety of premedication with high-dose dexamethasone to perform AVS in patients with ICM.

Postoperative Recurrences in Patients Operated for Pheochromocytomas and Paragangliomas: New Data Supporting Lifelong Surveillance.

At least 10% of pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs) may recur after the initial surgery. Guidelines recommend annual screening for recurrence in non-metastatic tumors for at least 10 years after the initial surgical resection and lifelong screening in high-risk patients. However, recent data suggest that a shorter follow-up might be appropriate.

ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia.

ARMC5 is implicated in several pathological conditions, but its function remains unknown. We have previously identified CUL3 and RPB1 (the largest subunit of RNA polymerase II (Pol II) as potential ARMC5-interacting proteins. Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1.

Endogenous Cushing's syndrome during pregnancy.

Endogenous Cushing's syndrome (CS) is rare during pregnancy, probably because hypercortisolism induces anovulation and infertility. To date, slightly above 200 cases have been reported in the literature. The most frequent etiology of CS diagnosed during gestation is from primary adrenal causes, namely adrenal adenomas and an entity called pregnancy-induced CS.

Characterization of hyperlipidemia secondary to mitotane in adrenocortical carcinoma.

Background: This study examined the magnitude of changes and the time required to observe maximal changes in LDL-c, HDL-c, triglycerides (Tg) and non-HDL-c after the introduction of mitotane.

Methods: Retrospective study of 45 patients with adrenocortical carcinoma who were treated at the Centre hospitalier de l'Université de Montréal. Clinical and biochemical data were collected, including lipid profiles before and during the first year of treatment with mitotane.

Genetic spectrum in a Canadian cohort of apparently sporadic pheochromocytomas and paragangliomas: New data on multigene panel retesting over time.

Objective: Pheochromocytomas (PHEOs) and paragangliomas (PGLs), collectively known as PPGLs, are tumours with high heritability. The prevalence of germline mutations in apparently sporadic PPGLs varies depending on the study population. The objective of this study was to determine the spectrum of germline mutations in a cohort of patients with apparently sporadic PPGLs over time.