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BJOG : An International Journal of... Jul 2021Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child.
BACKGROUND
Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child.
OBJECTIVE
To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL.
SEARCH STRATEGY
Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French.
SELECTION CRITERIA
Case reports containing a predefined minimum of clinical data on PPGL and pregnancy.
DATA COLLECTION AND ANALYSIS
Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni- and multivariable logistic regression analysis.
MAIN RESULTS
Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42-fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67-370, P = 0.0003). Offspring mortality was 2.6-fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38-6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12-4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29-7.63, P = 0.014) and a history of PPGL, a known PPGL-associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89-41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52-20.5, P < 0.0001), initial diagnosis of pre-eclampsia (OR 6.34, 95% CI 2.60-15.5, P < 0.0001), admission for obstetric care (OR 10.71, 95% CI 2.70-42.45, P = 0.0007) and maternal tachycardia (OR 2.72, 95% CI 1.26-5.85, P = 0.011) were independent factors of postpartum diagnosis.
CONCLUSION
Several clinical clues can assist clinicians in considering an antenatal diagnosis of PPGL in pregnancy, thus potentially improving outcome.
TWEETABLE ABSTRACT
Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis.
Topics: Adrenal Gland Neoplasms; Early Diagnosis; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Paraganglioma; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prenatal Diagnosis; Prognosis; Risk Factors
PubMed: 33342020
DOI: 10.1111/1471-0528.16635 -
The Lancet. Diabetes & Endocrinology Jan 2021Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We...
BACKGROUND
Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy.
METHODS
We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression.
FINDINGS
The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery).
INTERPRETATION
Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes.
FUNDING
US National Institutes of Health.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Cohort Studies; Female; Fetal Diseases; Humans; Incidence; Infant, Newborn; Infant, Newborn, Diseases; Male; Middle Aged; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Retrospective Studies; Young Adult
PubMed: 33248478
DOI: 10.1016/S2213-8587(20)30363-6 -
The Journal of Clinical Endocrinology... Jan 2021Evidence on follow-up duration for patients with sporadic pheochromocytomas is absent, and current guidelines of the European Society of Endocrinology, American... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence on follow-up duration for patients with sporadic pheochromocytomas is absent, and current guidelines of the European Society of Endocrinology, American Association of Clinical Endocrinologists and Endocrine Surgeons, and the Endocrine Society are ambiguous about the appropriate duration of follow-up. The aim of this systematic review and meta-analysis is to evaluate the recurrence rate of sporadic pheochromocytomas after curative adrenalectomy.
MATERIALS AND METHODS
A literature search in PubMed, Embase, and the Cochrane Library was performed. A study was eligible if it included a clear report on the number of sporadic patients, recurrence rate, and follow-up duration. Studies with an inclusion period before 1990, <2 years of follow-up, <10 patients, and unclear data on the sporadic nature of pheochromocytomas were excluded. A meta-analysis on recurrence was performed provided that the heterogeneity was low (I2 < 25%) or intermediate (I2 26-75%). Hozo's method was used to calculate weighted mean follow-up duration and weighted time to recurrence with combined standard deviations (SDs).
RESULTS
A total of 13 studies, including 430 patients, were included in the synthesis. The meta-analysis results describe a pooled recurrence rate after curative surgery of 3% (95% confidence interval: 2-6%, I2 = 0%), with a weighted mean time to recurrence of 49.4 months (SD = 30.7) and a weighted mean follow-up period of 77.3 months (SD = 32.2).
CONCLUSIONS
This meta-analysis shows a very low recurrence rate of 3%. Prospective studies, including economical and health effects of limited follow-up strategies for patients with truly sporadic pheochromocytomas should be considered.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Humans; Neoplasm Recurrence, Local; Pheochromocytoma; Prognosis
PubMed: 33125073
DOI: 10.1210/clinem/dgaa794 -
JBI Evidence Synthesis Mar 2021The purpose of this systematic review and meta-analysis was to determine the effectiveness of intravenous magnesium sulfate when used to attenuate hemodynamic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this systematic review and meta-analysis was to determine the effectiveness of intravenous magnesium sulfate when used to attenuate hemodynamic fluctuations associated with the creation of pneumoperitoneum in adults undergoing laparoscopic surgery.
INTRODUCTION
Laparoscopic surgery has gained popularity as a result of improved patient outcomes postoperatively, but pneumoperitoneum alters the patient's physiology and hemodynamic profile during the intraoperative period. Magnesium sulfate is a nonopioid agent known for its ability to blunt the physiologic sympathetic response associated with exposure to noxious stimuli. Magnesium sulfate may be efficacious in promoting anesthetic management that optimizes a patient's cardiopulmonary function while minimzing opioid use.
INCLUSION CRITERIA
Studies with participants at least 18 years old undergoing any elective laparoscopic surgery using pneumoperitoneum with CO2 insufflation were included. Studies were excluded if patients were being treated for pheochromocytoma. Studies eligible for inclusion employed any intravenous dosing strategy of magnesium sulfate, administered at any point in the perioperative period for the purpose of blunting the sympathetic response to creation of a pneumoperitoneum. The comparator utilized was normal saline.
METHODS
A systematic search of MEDLINE, CINAHL, Cochrane Library, Google Scholar, Trip Database, MedNar, Grey Literature Report, ClinicalTrials.gov, and ProQuest Dissertations and Theses was conducted to identify both published and unpublished studies. The search was limited to studies written in the English language and performed on human subjects. Studies were selected for review based on inclusion criteria and were appraised by two reviewers using the appropriate JBI standardized appraisal tool. Data extraction was performed for all outcome variables. Data were pooled using the JBI System for the Unified Management, Assessment and Review of Information. Mean differences (95% confidence interval) were calculated for all continuous variables. Meta-analysis using a fixed effects model was performed at various time points for heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Standard GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) evidence assessment was also reported.
RESULTS
A total of six randomized controlled trials were included in the review. Meta-analysis of data for biophysical parameters (heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure) at five minutes, 10 to 15 minutes, 30 minutes after pneumoperitoneum, and at the end of surgery showed a consistent reduction in the magnesium groups compared to placebo. Support for all outcome variables was determined to be high using the GRADE criteria.
CONCLUSION
The administration of magnesium sulfate consistently demonstrated improved hemodynamic measurements during laparoscopic surgery. All doses administered in the included studies proved beneficial compared to placebo. Magnesium sulfate should be considered as an adjunct agent in laparoscopic surgery to blunt the sympathetic nervous system response to surgical stimulation. The quality of the included studies was high, but small sample sizes and selection of healthy participants may limit the generalizability of the results. The use of magnesium sulfate may have improved effects on patients with significant health comorbidities, but the limitations of the included studies related to sample demographics make the evidence inconclusive.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO (CRD42019139991).
Topics: Administration, Intravenous; Adolescent; Adult; Hemodynamics; Humans; Insufflation; Laparoscopy; Magnesium Sulfate
PubMed: 33074990
DOI: 10.11124/JBISRIR-D-19-00414 -
Endocrine, Metabolic & Immune Disorders... 2021Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma...
BACKGROUND
Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed.
METHODS
This study reports 5 Chinese pedigrees with 5 individuals harboring germline RETM918T, and systematically reviewed previous Chinese literature reported.
RESULTS
All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, a total of 32 MEN 2B patients from literature were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms, respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at the mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage III and others in IV. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B.
DISCUSSION & CONCLUSION
The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.
Topics: Adolescent; Adult; Asian People; Biomarkers, Tumor; Calcitonin; Child; China; DNA Mutational Analysis; Early Detection of Cancer; Female; Genetic Predisposition to Disease; Heredity; Humans; Lymph Node Excision; Male; Middle Aged; Multiple Endocrine Neoplasia Type 2b; Mutation; Pedigree; Predictive Value of Tests; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Risk Factors; Thyroidectomy; Treatment Outcome; Young Adult
PubMed: 32914730
DOI: 10.2174/1871530320666200910112230 -
The Journal of Urology Jan 2021Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of...
PURPOSE
Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines.
MATERIALS AND METHODS
PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria.
RESULTS
There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years.
CONCLUSIONS
After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.
Topics: Adenoma; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Adrenergic alpha-Antagonists; Biopsy; Endocrinology; Humans; Magnetic Resonance Imaging; Medical Oncology; Patient Preference; Pheochromocytoma; Positron-Emission Tomography; Practice Guidelines as Topic; Radiology; Tomography, X-Ray Computed; Urology; Watchful Waiting
PubMed: 32856984
DOI: 10.1097/JU.0000000000001342 -
Gland Surgery Jun 2020Pheochromocytomas (PHEOs) are neural crest cell tumors producing catecholamines. PHEOS need to be early diagnosed and adequately managed. Adrenalectomy is the gold... (Review)
Review
Pheochromocytomas (PHEOs) are neural crest cell tumors producing catecholamines. PHEOS need to be early diagnosed and adequately managed. Adrenalectomy is the gold standard treatment of these type of tumors. There has been major improvement of surgical technologies with the development of laparoscopic and robotic systems these past several years. We conducted a review of the literature to evaluate the robotic approach for adrenalectomy for patients with PHEO.
PubMed: 32775278
DOI: 10.21037/gs-2019-ra-05 -
BMC Surgery Jul 2020Surgical resection is the main treatment for pheochromocytoma (PHEO). Although open surgery (OS) has been shown to be safe and feasible, the safety and efficacy of... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Surgical resection is the main treatment for pheochromocytoma (PHEO). Although open surgery (OS) has been shown to be safe and feasible, the safety and efficacy of laparoscopic surgery (LS) for PHEO remain controversial due to the uncertain effects of pneumoperitoneum on haemodynamics and the complexity of the tumour itself. This study was performed to compare the treatment outcomes of OS with those of LS for patients with PHEO.
METHODS
A systematic search through November 11, 2019, was conducted. All studies comparing outcomes of LS and OS for PHEO were included according to eligibility criteria. This meta-analysis was conducted using Review Manager Software, version 5.3, and STATA software, version 12.0. The quality of the included studies was assessed using the Newcastle-Ottawa scale.
RESULTS
Fourteen studies involving 626 patients were included in this meta-analysis. LS was associated with lower rates of intraoperative haemodynamic instability (IHD) [odds ratio (OR) = 0.61, 95% CI: 0.37 to 1.00, P = 0.05], less intraoperative blood loss [weighted mean difference (WMD) = - 115.27 ml, 95% confidence interval (CI): - 128.54 to - 101.99, P < 0.00001], lower blood transfusion rates [OR = 0.33, 95% CI: 0.21 to 0.52, P < 0.00001], earlier ambulation (WMD = - 1.57 d, 95% CI: - 1.97 to - 1.16, P < 0.00001) and food intake (WMD = - 0.98 d, 95% CI: - 1.36 to - 0.59, P < 0.00001), shorter drainage tube indwelling time (WMD = - 0.51 d, 95% CI: - 0.96 to - 0.07, P = 0.02) and postoperative stay (WMD = - 3.17 d, 95% CI: - 4.76 to - 1.58, P < 0.0001), and lower overall complication rates (OR = 0.56, 95% CI: 0.35 to 0.88, P = 0.01). However, no significant differences in operative time, postoperative blood pressure control, rates of severe complications, postoperative hypotension or cardiovascular disease (CVD) were found between the two groups.
CONCLUSIONS
LS is safe and effective for PHEO resection. Compared with OS, LS caused less IHD, providing an equal chance to cure hypertension while also yielding a faster and better postoperative recovery.
Topics: Adrenal Gland Neoplasms; Humans; Laparoscopy; Laparotomy; Length of Stay; Operative Time; Pheochromocytoma; Retrospective Studies; Treatment Outcome
PubMed: 32711496
DOI: 10.1186/s12893-020-00824-6 -
The Journal of Clinical Endocrinology... Jan 2021The characteristics of catecholamine-secreting pheochromocytomas have been well studied. However, less is known about the characteristics, management and outcome in... (Meta-Analysis)
Meta-Analysis
CONTEXT
The characteristics of catecholamine-secreting pheochromocytomas have been well studied. However, less is known about the characteristics, management and outcome in patients with ectopic adrenocorticotropic hormone (ACTH) and/or corticotrophin-releasing hormone (CRH)-secreting pheochromocytomas.
OBJECTIVE
To review the characteristics and outcomes of ACTH- and/or CRH-secreting pheochromocytomas.
DATA SOURCE
A systematic search of PubMed/MEDLINE and Web of Science, identifying relevant reports published up to 10 February 2020.
STUDY SELECTION
Original articles, including case reports and case series, reporting individual patient data from patients with ACTH- and/or CRH-secreting pheochromocytomas.
DATA EXTRACTION
Information on sex, age, symptoms at presentation, comorbidities, biochemistry, imaging, histopathology, and outcomes was extracted.
DATA SYNTHESIS
We identified 91 articles reporting on 99 cases of ACTH- and/or CRH-secreting pheochromocytomas (CRH-secreting n = 4). Median age at diagnosis was 49 years (interquartile range 38-59.5) with a 2:1 female to male ratio. Most patients presented with clinical Cushing syndrome (n = 79; 81%), hypertension (n = 87; 93%), and/or diabetes (n = 50; 54%). Blood pressure, glucose control, and biochemical parameters improved in the vast majority of patients postoperatively. Infections were the most common complication. Most cases (n = 70, 88%) with reported long-term outcome survived to publication (median follow-up 6 months).
CONCLUSION
Ectopic ACTH- and/or CRH-secreting pheochromocytoma should be considered in patients presenting with ACTH-dependent Cushing syndrome and adrenal mass. Despite the challenge in diagnosis, patient outcomes appear favorable.
Topics: Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Biomarkers; Corticotropin-Releasing Hormone; Humans; Pheochromocytoma; Prognosis
PubMed: 32710791
DOI: 10.1210/clinem/dgaa488 -
Journal of Endocrinological... Oct 2020Endocrine neoplasms are generally slow-growing tumors that can show hormonal activity and give metastases. In most cases they are benign and clearly malignant forms are...
BACKGROUND
Endocrine neoplasms are generally slow-growing tumors that can show hormonal activity and give metastases. In most cases they are benign and clearly malignant forms are easy to diagnose. However, borderline forms may occur and be, for the pathologists, very difficult to classify. In these cases, there is a strong need to identify factors that may aid. Official classification systems for endocrine neoplasms are based on the evaluation of proliferation and, in most cases, they rely on mitotic count. In support, the study of Ki67 is carried out which, however, has not yet been included in any official classification system, except for neuroendocrine neoplasms of the gastro-entero-pancreatic tract.
PURPOSE
The aim of the present study was to investigate the proven or unproven role of Ki67 in endocrine neoplasms, in different districts, in order to bring to light the substantial differences, in terms of proliferation, existing between neoplasms so similar, but at the same time, so different.
METHODS
A thorough search of English language literature was performed, looking for articles concerning Ki67 in five endocrine neoplasms (pituitary adenomas, thyroid neoplasms, adrenocortical neoplasms, pheochromocytomas and paragangliomas).
RESULTS
From 2170, 236 articles were selected and it was seen that the endocrine neoplasm in which Ki67 was most studied was the pituitary, where it still shows a controversial role. In other neoplasms different roles were identified.
CONCLUSION
The pathologist should be aware of the contribution that this proliferative marker can give to the diagnosis and, sometimes, to the therapy selection, for the clinician.
Topics: Biomarkers, Tumor; Cell Count; Cell Proliferation; Endocrine Gland Neoplasms; Humans; Ki-67 Antigen; Monitoring, Physiologic; Prognosis; Treatment Outcome
PubMed: 32415572
DOI: 10.1007/s40618-020-01275-9