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Secondary adrenal insufficiency is the most common subtype of adrenal insufficiency; it is caused by certain medications and pituitary destruction (pituitary masses, inflammation, or infiltration) and is rarely associated with certain germline variants. In this review, we discuss the etiology, epidemiology, and clinical presentation of secondary adrenal insufficiency and focus on the diagnostic and management challenges. We also review the management of selected special populations of patients and discuss patient-important outcomes associated with secondary adrenal insufficiency.
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Insuficiência Adrenal , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Humanos , HidrocortisonaRESUMO
PURPOSE OF REVIEW: Pheochromocytoma and paraganglioma (PPGL) in pregnancy is a rare entity and management of these patients is fraught with uncertainty. Our objective is to review current literature and discuss diagnosis and management of these patients. RECENT FINDINGS: Outcomes of PPGL in pregnancy have improved in recent years. The greatest risk for adverse maternal and fetal outcomes is the diagnosis of PPGL after delivery. Alpha- and beta-adrenergic blockade is well tolerated and is associated with less adverse outcomes. Antepartum surgery is not associated with improved maternal or fetal outcomes. Biochemical testing and cross-sectional imaging should be performed prior to conception for patients with a known germline variant associated with PPGL. CONCLUSIONS: Medical therapy should be initiated when PPGL is diagnosed in pregnancy. Antepartum surgery should be reserved for special circumstances. Case detection testing in high-risk patients can identify PPGL before pregnancy.
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Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Feminino , Humanos , Paraganglioma/diagnóstico por imagem , Paraganglioma/cirurgia , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , GravidezRESUMO
OBJECTIVE: Comprehensive data about patients with bilateral pheochromocytoma are limited. We aimed to describe the clinical presentation, genetic analysis, treatment and outcomes of patients with bilateral pheochromocytoma. DESIGN: A retrospective study at a tertiary care centre. PATIENTS: All patients with bilateral pheochromocytoma evaluated at Mayo Clinic in Rochester, Minnesota between January 1951 and December 2015. MEASUREMENTS: Tumour size, genetic testing, plasma/urine metanephrines and catecholamines. RESULTS: A total of 94 patients (51% women) were diagnosed with bilateral pheochromocytoma at a median age at first presentation of 31 years (range, 4-70). Bilateral disease was noted in 8.0% of pheochromocytoma patient overall and 37.5% of patients 18 years of younger. Most patients presented with synchronous tumours (80%). Median time to metachronous tumours was 4.5 years (range, 1-38). Genetic disease was identified in 75 (80%) patients, including MEN 2A (42.6%), VHL (19.1%), MEN 2B (9.6%) and NF1 (8.5%). Excess catecholamines were present in 97% of patients. Patients with synchronous pheochromocytoma commonly underwent simultaneous bilateral adrenalectomy (99%), and 18 (24%) had cortical-sparing surgery. Multicentric tumours were reported in 23 of 77 (30%) patients with available data. Recurrent disease was found in 9.6% of patients, and 8.5% developed metastatic disease. Median follow-up was 8.5 years. At the study conclusion, 4 patients had died due to pheochromocytoma or adrenalectomy. CONCLUSIONS: Bilateral pheochromocytoma occurred in 7.0% of adults with pheochromocytoma and 37.5% of paediatric patients. Genetic disease was identified in 80% of patients, predominantly MEN2A. Multicentric tumours were common, but most were still cured following adrenalectomy.
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Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Doença de von Hippel-Lindau , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Feocromocitoma/genética , Feocromocitoma/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: Individuals with neurofibromatosis type 1 (NF1) are at an increased risk of developing a pheochromocytoma or paraganglioma (PHEO/PGL). However, the best case detection strategy is unknown. Our objectives were to describe the prevalence, clinical presentation and outcomes of PHEO/PGL associated with NF1 and formulate case detection testing recommendations for PHEO/PGL. DESIGN: A retrospective cohort study from 1959 to 2015, Tertiary medical centre. PATIENTS AND MEASUREMENTS: We studied 41 patients with NF1 and PHEO/PGL who were identified using the PHEO/PGL and NF1 databases: 3289 and 1415 patients, respectively. Our main outcome measures were prevalence of PHEO/PGL in NF1 and occurrence of bilateral, recurrent, or metastatic disease and method of PHEO/PGL detection (symptoms vs incidental vs biochemical case detection testing). RESULTS: The prevalence of PHEO/PGL in patients with NF1 was 2·9%. The 41 patients included 23 men (56%) and 18 women. The median age at diagnosis was 41·0 years (range 14-67). The median tumour size was 3·4 cm (range 0·8-9·5). Bilateral PHEO was identified in 17% (n = 7) of patients, all women. Metastatic or recurrent disease occurred in 7·3% (n = 3). In the last 25 years, PHEO/PGL was diagnosed after incidental finding on computed imaging in 31% of patients (n = 11). Only three patients (7·3%) had PHEO/PGL discovered because of biochemical case detection testing. CONCLUSION: We recommend patients with NF1 have biochemical case detection testing for PHEO/PGL every 3 years starting at age 10 to 14 years. Biochemical case detection testing should also be carried out prior to elective surgical procedures and conception.
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Neurofibromatose 1/complicações , Paraganglioma/etiologia , Feocromocitoma/etiologia , Adolescente , Adrenalectomia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Paraganglioma/epidemiologia , Feocromocitoma/epidemiologia , Feocromocitoma/cirurgia , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: We aim to evaluate the incidence of venous thromboembolism (VTE) following adrenalectomy. METHODS: A retrospective analysis of the Collaborative Endocrine Surgery Quality Improvement Program was performed to assess incidence for VTE, including pulmonary embolism or deep vein thrombosis, in adults undergoing adrenalectomy (2014-2022). RESULTS: 2567 patients undergoing adrenalectomy were included. Surgical approach was 10% open and 90% minimally invasive. Pathology was 13% malignant and 87% benign; 19% had hypercortisolism. VTE developed in 0.27% at a median of 8 days from surgery. The incidence was higher in primary adrenal malignancy compared to benign or metastases to the adrenals, p â< â0.01. VTE was associated with longer hospital stay, longer operative time, readmission, and mortality. VTE rates were similar for hypercortisolism vs no hypercortisolism and between patients with clinical vs subclinical hypercortisolism. CONCLUSION: Although VTE following adrenalectomy is rare, it is more common in cases of primary adrenal malignancy, those with longer operations, or those requiring prolonged hospitalization.
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Neoplasias das Glândulas Suprarrenais , Síndrome de Cushing , Embolia Pulmonar , Tromboembolia Venosa , Adulto , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Incidência , Estudos Retrospectivos , Adrenalectomia/efeitos adversos , Síndrome de Cushing/complicações , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Neoplasias das Glândulas Suprarrenais/cirurgiaRESUMO
Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.
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BACKGROUND: PIT1 is a pituitary transcription factor that is associated with either growth hormone (GH), prolactin (PRL), or thyroid-stimulating hormone (TSH) production. However, PIT1-positive pituitary neuroendocrine tumors (PitNETs) are occasionally immunonegative for GH, PRL, and TSH. This paper describes the clinical presentation of PIT1 positive however immunonegative PitNETs. METHODS: We conducted a retrospective analysis, identifying 228 PIT1-positive PitNET patients between 2017 and 2022. Out of these, ten (4%) tested negative for GH, PRL, and TSH. Functioning PitNETs were defined as those causing hormonal excess symptoms or hormonal overproduction. RESULTS: As for 10 patients immunonegative for all three hormones however PIT1-positive, the mean ( ± standard deviation) age was 46 ± 13 years with 70% women. Six patients exhibited signs of excess GH or PRL, and three had visual problems. Additionally, one patient had secondary hypothyroidism and adrenal insufficiency resulting from the mass effect. All tumors were macroadenoma, with a median volume of 2.1 cm3 (range, 0.8-17.5 cm3). Gross total resection was attained in six patients by trans-sphenoidal surgery. Postoperatively, eight patients experienced clinical improvement: three in vision, two in amenorrhea, two in headache, and one in acromegaly symptoms. Biochemical improvement was observed in six patients, with all experiencing remission in hormonal excess and one showing improvement in secondary hypothyroidism. Stereotactic radiosurgery was performed in three patients. CONCLUSIONS: Patients with functioning PitNETs may exhibit PIT1 staining without GH, PRL, or TSH staining. Hormonally active tumors exist in this patient population; therefore, close endocrine follow-up is necessary despite the lack of staining for GH, PRL, and TSH.
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Adenoma , Hormônio do Crescimento Humano , Hipotireoidismo , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Hormônio do Crescimento , Prolactina , Tireotropina , Estudos Retrospectivos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Adenoma/cirurgiaRESUMO
Mutations that predispose to familial pheochromocytoma and paraganglioma include inherited variants in the four genes (SDHA, SDHB, SDHC and SDHD) encoding subunits of succinate dehydrogenase (SDH), an enzyme of the mitochondrial tricarboxylic acid cycle and complex II of the electron transport chain. In heterozygous variant carriers, somatic loss of heterozygosity is thought to result in tumorigenic accumulation of succinate and reactive oxygen species. Inexplicably, variants affecting the SDHB subunit predict worse clinical outcomes. Why? Here we consider two hypotheses. First, relative to SDH A, C and D subunits, the small SDHB subunit might be more intrinsically 'fragile' to missense mutations because of its relatively large fraction of amino acids contacting prosthetic groups and other SDH subunits. We show evidence that supports this hypothesis. Second, the natural pool of human SDHB variants might, by chance, be biased toward severe truncating variants and missense variants causing more disruptive amino acid substitutions. We tested this hypothesis by creating a database of known SDH variants and predicting their biochemical severities. Our data suggest that natural SDHB variants are more pathogenic. It is unclear if this bias is sufficient to explain clinical data. Other explanations include the possibility that SDH subcomplexes remaining after SDHB loss have unique tumorigenic gain-of-function characteristics, and/or that SDHB may have additional unknown tumor-suppressor functions.
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Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH. Most common presentation was multisystem (34.2%), followed by single-system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (the liver, spleen, or bone marrow) was seen in 8.7% of cases, and 40 of 88 (45.5%) tested cases were BRAFV600E. At a median follow-up of 74 months, 5-year progression-free survival (PFS) was 58.3% and estimated median PFS was 83 months. Median overall survival (OS) was not reached; 5- and 10-year OS rates were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (hazard ratio [HR], 4.5) and OS (HR, 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR], 2.66), specifically among those aged <55 years at diagnosis (SMR, 5.94) and those with multisystem disease (SMR, 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5 years of diagnosis. After 5 years, non-LCH causes of death, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases, predominated. Our study highlights, to our knowledge, for the first time, that adults with LCH experience early and late mortality from non-LCH causes and the need for development of targeted survivorship programs to improve outcomes.
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Histiocitose de Células de Langerhans , Segunda Neoplasia Primária , Neoplasias , Humanos , Adulto , Adolescente , Estudos Retrospectivos , Histiocitose de Células de Langerhans/epidemiologia , BaçoRESUMO
Intrapericardial paragangliomas are rare, highly vascular tumors that frequently adhere to adjacent structures and blood vessels, making surgical resection challenging. In this case series, we discuss the role of multimodality imaging and preoperative embolization in the management of 3 patients presenting with intrapericardial paragangliomas. (Level of Difficulty: Advanced.).
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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.
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Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Paraganglioma/tratamento farmacológico , Feocromocitoma/tratamento farmacológico , alfa-Metiltirosina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Combinada , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/etiologia , Paraganglioma/complicações , Paraganglioma/epidemiologia , Paraganglioma/patologia , Feocromocitoma/complicações , Feocromocitoma/epidemiologia , Feocromocitoma/patologia , alfa-Metiltirosina/efeitos adversosRESUMO
PURPOSE: Patients with fibromyalgia (FM) may demonstrate low cortisol concentrations during diagnostic evaluation. However, it remains unclear whether low cortisol reflects underlying pituitary dysfunction. We aimed to determine if a subset of patients with FM have concomitant secondary adrenal insufficiency (SAI) and growth hormone deficiency (GH). PATIENTS AND METHODS: This is a retrospective study of all patients with FM diagnosed with SAI based on abnormal insulin tolerance test (ITT) between June 2002 and August 2019. Patients were excluded if they had other reasons for SAI. Measurements include cortisol and GH during ITT in all patients, and peak cortisol during cosyntropin stimulation test in a subset of patients. RESULTS: We identified 22 patients (median age of 38 years (range 19-65), 18 (82%) women) diagnosed with secondary AI based on abnormal ITT (peak median cortisol level of 11 mcg/dL (range 5.4-17)). Concomitant GH deficiency was diagnosed in 19 (86%) patients. Cosyntropin stimulation test was performed in 14 (64%) patients and was normal in 11 (79%) (peak cortisol ≥18 mcg/dL). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology. All patients were started on physiologic glucocorticoid replacement, and 5 patients were started on GH replacement. Of the 13 patients with follow-up, 8 (62%) reported symptom improvement after starting treatment. CONCLUSION: Patients with FM can have concurrent SAI and GH deficiency. Cosyntropin stimulation test should not be used to exclude SAI in patients with FM. Appropriate glucocorticoid and/or GH replacement may improve symptoms in some patients.
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BACKGROUND: Excluding a pheochromocytoma is important when a patient presents with an incidentally discovered adrenal mass. However, biochemical testing for pheochromocytoma can be cumbersome, time consuming, or falsely positive. Our objective was to determine if unenhanced computed tomography (CT) imaging alone can be used to rule out pheochromocytoma. METHODS: We performed a retrospective study of all patients with a pathologically confirmed pheochromocytoma and unenhanced CT imaging who were treated at the Mayo Clinic between 1998 and 2016. Additionally, we performed a systematic review and meta-analysis of original studies published after 2005 with patients who had adrenal masses, more than 10 patients with pheochromocytomas, and reported attenuation on unenhanced CT imaging in Hounsfield units (HU). RESULTS: In the Mayo cohort, we identified 186 patients and 199 pheochromocytomas with unenhanced CT imaging. The mean unenhanced CT attenuation was 35±9 HU (range, 15-62), and only 15 tumors had attenuation ≤20 HU. The systematic review identified 26 studies (1,217 tumors), and 23 studies provided a mean unenhanced CT attenuation. The overall mean unenhanced CT attenuation across the studies was 35.6 HU (95% CI, 22.0-49.1 HU). A cutoff of >10 HU had a 100% sensitivity (95% CI, 1.00-1.00) for pheochromocytoma with low heterogeneity between the 21 qualified studies (I2=0%). Sensitivity for pheochromocytoma was 100% and 99% for an unenhanced CT attenuation cutoff of >15 and >20 HU. CONCLUSIONS: Biochemical testing may not be required to exclude pheochromocytoma if an incidental adrenal mass has low attenuation (<10 HU) on unenhanced CT images.
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CONTEXT: Modern pheochromocytomas (PHEOs) are often discovered by incidental finding on cross-sectional imaging or mutation-based genetic case detection testing. Little is known about how these PHEOs behave. OBJECTIVE: To describe the characteristics and behavior of PHEOs discovered incidentally on imaging or through mutation-based genetic case detection testing. DESIGN: Retrospective study. SETTING: Referral center. PATIENTS: Consecutive patients with pathology-confirmed PHEOs, treated from 2005 to 2016. MAIN OUTCOME MEASURE(S): Tumor size, plasma/urine fractionated metanephrines and catecholamines, and preoperative management. RESULTS: Two hundred seventy-one patients (52% women, median age 52.0 years) presented with 296 PHEOs. Discovery method was most often incidental finding on cross-section imaging (61%) rather than PHEO-related symptoms (27%) or mutation-based case detection testing (12%). Patients with incidentally discovered PHEOs were older than symptomatic and mutation-based case detection testing patients (median age 56.6 vs 43 vs 35 years, P < 0.0001). Mutation-based case detection PHEOs were smaller than those discovered due to symptoms (median size 29.0 vs 50.5 mm, P = 0.0027). Patients with PHEOs discovered due to symptoms had the highest median concentration of 24-hour urinary metanephrines and total plasma metanephrines (P < 0.0001). These patients required a higher cumulative phenoxybenzamine dose than patients with incidental or case detection PHEO (median 450 vs 375 vs 270 mg, P = 0.029). CONCLUSIONS: PHEOs are primarily discovered due to incidental finding on cross-sectional imaging rather than PHEO-related symptoms. PHEOs discovered through mutation-based genetic case detection testing were smaller and required less α-adrenergic blockade preoperatively compared with PHEOs found due to symptoms, which supports routine case detection testing for patients genetically predisposed for PHEOs.
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Neoplasias das Glândulas Suprarrenais/diagnóstico , Biomarcadores Tumorais/genética , Mutação , Feocromocitoma/diagnóstico , Índice de Gravidade de Doença , Adolescente , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Testes Genéticos , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Feocromocitoma/genética , Feocromocitoma/cirurgia , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Rotavirus vaccine schedules may impact vaccine response among children in low- and middle-income countries (LMICs). Our objective was to review the literature evaluating the effects of monovalent (RV1) or pentavalent rotavirus vaccines schedules on vaccine response. METHODS: We searched PubMed, Web of Science, Embase, and ClinicalTrials.gov for eligible trials conducted in LMICs comparing ≥2 vaccine schedules and reporting immunologic response or efficacy. We calculated seroconversion proportion differences and geometric mean concentration (GMC) ratios with 95% confidence intervals. RESULTS: We abstracted data from 8 eligible trials of RV1. The point estimates for seroconversion proportions difference ranged from -0.25 to -0.09 for the 6/10-week schedule compared with 10/14. The range for the 6/10/14- compared with 10/14-week schedule was -0.02 to 0.10. Patterns were similar for GMC ratios and efficacy estimates. CONCLUSIONS: The commonly used 6/10-week RV1 schedule in LMICs may not be optimal. Further research on the effect of rotavirus schedules using clinical endpoints is essential.
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OBJECTIVE: To determine whether, despite pharmacologic adrenergic receptor blockade, higher preoperative levels of catecholamines and metanephrines (adrenergic activity) are associated with increased intraoperative complications. MATERIALS AND METHODS: Records of patients undergoing paraganglioma and pheochromocytoma (PGL-PCC) resection from January 1, 2000, to June 30, 2015, were reviewed for preoperative levels of adrenergic activity, intraoperative variability in blood pressure and heart rate (range), and postoperative outcomes (hypotension requiring treatment). Patients were categorized by maximum preoperative adrenergic activity by greater degree of abnormality, categorized as normal (≤100%) or 101%-200%, 201%-500%, 501%-1000%, and ≥1001% of upper limit of normal. RESULTS: In total, 258 patients underwent intrathoracic or intra-abdominal PGL-PCC resection, of whom 240 received pretreatment with nonselective α1,2-blockers and 7 received pretreatment with selective α1-blockers. Intraoperative hemodynamic variability was greater with higher preoperative levels of adrenergic activity (P <.001). However, substantial variability was observed even with adrenergic activity levels within the normal range: systolic blood pressure (median [interquartile range], 75 [63-83] mm Hg) and heart rate (34 [26-43] beats per minute). Among patients with preoperative levels of adrenergic activity ≤500% vs ≥501% of the upper limit of normal, higher levels were associated with greater likelihood of postoperative diagnosis of volume overload (8% vs 2%, P = .04) and greater requirement for vasopressor infusions for hypotension (5% vs 1%, P = .01). CONCLUSION: Substantial intraoperative hemodynamic instability was encountered in patients with PGL-PCC resection, regardless of preoperative hormonal activity level; therefore, universal preoperative adrenergic receptor blockade should be recommended. Postoperative hypotension was rare and more prevalent in those with higher preoperative hormonal activity.