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Journal of Obstetrics and Gynaecology... Aug 2022Pheochromocytoma during pregnancy is a rare cause of secondary hypertension with lethal consequences to both mother and fetus. As patients are young, the possibility of...
INTRODUCTION
Pheochromocytoma during pregnancy is a rare cause of secondary hypertension with lethal consequences to both mother and fetus. As patients are young, the possibility of syndromic associations like MEN-2, VHL, NF-1, etc., needs to be considered.
METHODOLOGY
Three primigravida were diagnosed before the 20th week of gestation when they presented with classical triad of pheochromocytoma.
RESULTS
Diagnosis of pheochromocytoma was confirmed by 24 h urinary metanephrine/normetanephrine or epinephrine/norepinephrine levels. Non-contrast MRI abdomen could localize the tumor. One patient had medullary thyroid carcinoma with hyperparathyroidism, indicative of MEN-2A. Another patient had brain stem hemangioblastoma, pancreatic cysts and family history of spinal hemangioblastoma, so diagnosed to have Von Hippel-Lindau (VHL) syndrome. Whereas, the third patient had sporadic pheochromocytoma. Preoperatively, they required antihypertensive medications including prazosin and metoprolol. They underwent laparoscopic/open adrenalectomy between 19th and 21st week of gestation without complication. Histopathology in all the three patients revealed low-grade pheochromocytoma by pheochromocytoma of the adrenal gland scaled score. None required antihypertensive medications after surgery. All the three newborns were small for gestational age, while one neonate expired due to intra-cardiac rhabdomyoma. So, the timely evaluation and surgical intervention for pheochromocytoma avoid lethal consequences.
CONCLUSIONS
Pregnancy leads to unmasking of pheochromocytoma as it is physiological stress. The syndromic association is more frequent as the population is younger. A poor fetal outcome like IUGR can be explained by endovascular changes in uterine vessel or due to the associated manifestations of MEN-2A, VHL syndromes. Family members should be screened for associated syndromic feature.
PubMed: 35928058
DOI: 10.1007/s13224-021-01532-8 -
Endocrine-related Cancer Feb 2023The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131...
The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine in patients with advanced pheochromocytoma or paraganglioma. Biomarker status was assessed and post-treatment responses were analyzed for catecholamines, metanephrines, and serum chromogranin A. Complete biomarker response (normalization) or partial response, defined as at least 50% reduction from baseline if above the normal range, was evaluated at specified time points over a 12-month period. These results were correlated with two other study objectives: blood pressure control and objective tumor response as per RECIST 1.0. In this open-label, single-arm study, 68 patients received at least one therapeutic dose (~18.5 GBq (~500 mCi)) of high-specific-activity I-131 meta-iodobenzylguanidine. Of the patients, 79% and 72% had tumors associated with elevated total plasma free metanephrines and serum chromogranin A levels, respectively. Best overall biomarker responses (complete or partial response) for total plasma free metanephrines and chromogranin A were observed in 69% (37/54) and 80% (39/49) of patients, respectively. The best response for individual biomarkers was observed 6-12 months following the first administration of high-specific-activity I-131 meta-iodobenzylguanidine. Biochemical tumor marker response was significantly associated with both reduction in antihypertensive medication use (correlation coefficient 0.35; P = 0.006) as well as objective tumor response (correlation coefficient 0.36; P = 0.007). Treatment with high-specific-activity I-131 meta-iodobenzylguanidine resulted in long-lasting biomarker responses in patients with advanced pheochromocytoma or paraganglioma that correlated with blood pressure control and objective response rate. ClinicalTrials.gov number: NCT00874614.
Topics: Humans; Pheochromocytoma; 3-Iodobenzylguanidine; Iodine Radioisotopes; Chromogranin A; Paraganglioma; Adrenal Gland Neoplasms; Biomarkers, Tumor; Metanephrine
PubMed: 36472300
DOI: 10.1530/ERC-22-0236 -
International Journal of Molecular... Feb 2021The aim of our study was to assess the sympathetic nervous system's involvement in the evolution of gastric carcinoma in patients by analyzing the mediators of this...
The aim of our study was to assess the sympathetic nervous system's involvement in the evolution of gastric carcinoma in patients by analyzing the mediators of this system (epinephrine and norepinephrine), as well as by analyzing the histological expression of the norepinephrine transporter (NET). We conducted an observational study including 91 patients diagnosed with gastric carcinoma and an additional 200 patients without cancer between November 2017 and October 2018. We set the primary endpoint as mortality from any cause in the first two years after enrolment in the study. The patients were monitored by a 24-h Holter electrocardiogram (ECG) to assess sympathetic or parasympathetic predominance. Blood was also collected from the patients to measure plasma free metanephrine (Meta) and normetanephrine (N-Meta), and tumor histological samples were collected for the analysis of NET expression. All of this was performed prior to the application of any antineoplastic therapy. Each patient was monitored for two years. We found higher heart rates in patients with gastric carcinoma than those without cancer. Regarding Meta and N-Meta, elevated levels were recorded in the patients with gastric carcinoma, correlating with the degree of tumor differentiation and other negative prognostic factors such as tumor invasion, lymph node metastasis, and distant metastases. Elevated Meta and N-Meta was also associated with a poor survival rate. All these data suggest that the predominance of the sympathetic nervous system's activity predicts increased gastric carcinoma severity.
Topics: Electrocardiography; Epinephrine; Gene Expression Regulation, Neoplastic; Heart Rate; Humans; Metanephrine; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Normetanephrine; Prognosis; Stomach Neoplasms
PubMed: 33670813
DOI: 10.3390/ijms22042042 -
Frontiers in Endocrinology 2022Adrenal hemorrhage is a rare, usually life-threating complication. The most common neoplasm resulting in spontaneous adrenal bleeding is pheochromocytoma and it accounts...
BACKGROUND
Adrenal hemorrhage is a rare, usually life-threating complication. The most common neoplasm resulting in spontaneous adrenal bleeding is pheochromocytoma and it accounts for nearly 50% of cases. Currently, the recommendations for the diagnosis and management of patients with adrenal bleeding due to pheochromocytoma are unavailable.
MATERIALS AND METHODS
We performed a database search for all pheochromocytoma patients, diagnosed and treated from 2005 to 2021 in tertiary endocrinology center. 206 patients were identified, 183 with complete data were included in the analysis. We investigated clinicopathological characteristics, treatment and outcomes of hemorrhagic pheochromocytoma cases and characterize our approach to perioperative diagnosis and medical management. Finally our experiences and data from previously published articles concerning adrenal hemorrhage were analyzed to propose a diagnostic and therapeutic algorithm for hemorrhagic pheochromocytomas.
RESULTS
In the whole group, seven patients (4 men and 3 women) with adrenal bleeding were found, (3.8%). Median patient's age was 49 years (range: 36-78 years). The most common manifestation of adrenal bleeding was acute abdominal pain (5/7). Two patients developed shock. Hormonal assessment was performed in five patients, based on 24-hour urinary fractionated metanephrines with urinary 3-methoxytyramine. Normetanephrine was elevated in all patients, metanephrine and 3-methoxytyramine - in four cases (4/5). Most patients (6/7) had symptoms suggesting pheochromocytoma before hemorrhage - most commonly paroxysmal hypertension (4/7). One patient died, before the diagnosis of adrenal bleeding was made. Diagnostic imaging performed in six out of seven patients revealed adrenal tumor, with median largest diameter equal to 7.4 cm (range: 5-11 cm). Five patients had elective surgery, in one case an urgent surgery was performed. In all cases the diagnosis of pheochromocytoma was confirmed in postoperative histopathology or in autopsy. The perioperative survival rate was 85.7%.
CONCLUSIONS
Diagnosis of pheochromocytoma should be always considered in patients with adrenal bleeding, especially with accompanying abdominal pain, hemodynamic shock and previous history of pheochromocytoma-associated symptoms. Lack of proper diagnosis of pheochromocytoma before surgery is associated with an additional perioperative risk. To improve the decision making in this life-threatening clinical situation, based on our results and literature data, we proposed a diagnostic and treatment algorithm.
Topics: Abdominal Pain; Adrenal Gland Neoplasms; Adult; Aged; Algorithms; Female; Hemorrhage; Humans; Male; Middle Aged; Pheochromocytoma
PubMed: 35992110
DOI: 10.3389/fendo.2022.908967 -
Cureus Aug 2023A 23-year-old female presented to the emergency department (ED) after sustaining a motor vehicle accident and subsequent loss of consciousness. In the ED, the...
A 23-year-old female presented to the emergency department (ED) after sustaining a motor vehicle accident and subsequent loss of consciousness. In the ED, the patient was hemodynamically stable and was appropriately discharged with a diagnosis of mild traumatic brain injury. The patient presented 10 days post-injury to the outpatient brain injury clinic with complaints of headache, anxiety, and dizziness, with an elevated blood pressure of 160/100 mmHg. Initial head imaging, drug screen, complete blood count, and complete metabolic panel were unremarkable, however, urine and plasma metanephrines were found to be elevated. Abdominal computed tomography imaging revealed a pheochromocytoma, and the patient was adequately treated with medication and adrenalectomy with complete resolution of symptoms. Existing literature has indicated that stress and physical trauma can contribute to the escalation of pheochromocytoma symptoms in previously asymptomatic individuals; here, the stress and trauma stemming from an automobile accident and mild traumatic brain injury may have precipitated the onset of pheochromocytoma symptoms in the patient. Symptoms of pheochromocytoma can align with those commonly observed after traumatic brain injury (TBI), encompassing headaches, anxiety, and dizziness. Our case demonstrates the need for clinicians to consider the presence of pheochromocytoma in a post-traumatic brain injury patient.
PubMed: 37753024
DOI: 10.7759/cureus.44161 -
Frontiers in Endocrinology 2022The selectivity index (SI) of cortisol is used to document correct catheter placement during adrenal vein sampling (AVS) in patients with primary aldosteronism (PA). We...
BACKGROUND
The selectivity index (SI) of cortisol is used to document correct catheter placement during adrenal vein sampling (AVS) in patients with primary aldosteronism (PA). We aimed to determine the cutoff values of the SIs based on cortisol, free metanephrine, and the free-to-total metanephrine ratio (FTMR) using an adapted AVS protocol in combination with CT.
METHODS
Adults with PA and referred for AVS were recruited in two hypertension centers. The cortisol and free metanephrine-derived SIs were calculated as the concentration of the analyte in adrenal veins divided by the concentration of the analyte in the distal vena cava. The FTMR-derived SI was calculated as the concentration of free metanephrine in the adrenal vein divided by that of total metanephrine in the ipsilateral adrenal vein. The AVS was classified as an unequivocal radiological success (uAVS) if the tip of the catheter was seen in the adrenal vein. The SI cutoffs of each index marker were established using receiver operating characteristic curve analysis.
RESULTS
Out of 125 enrolled patients, 65 patients had an uAVS. The SI cutoffs were 2.6 for cortisol, 10.0 for free metanephrine, 0.31 for the FTMR on the left side, and 2.5, 9.9, and 0.25 on the right side. Compared to free metanephrine and the FTMR, cortisol misclassified AVS as unsuccessful in 36.6% and 39.0% of the cases, respectively.
CONCLUSION
This study is the first to calculate the SIs of cortisol, free metanephrine, and the FTMR indices for the AVS procedure. It confirms that free metanephrine-based SIs are better than those based on cortisol.
Topics: Adrenal Glands; Adult; Aldosterone; Catheters; Humans; Hydrocortisone; Hyperaldosteronism; Metanephrine
PubMed: 35282466
DOI: 10.3389/fendo.2022.842968 -
Frontiers in Endocrinology 2020Multiple endocrine neoplasia type 2 (MEN2) is a neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma,... (Review)
Review
Multiple endocrine neoplasia type 2 (MEN2) is a neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma, hyperparathyroidism, and extra-endocrine features. MEN2 syndrome includes two clinically distinct forms subtyped as MEN2A and MEN2B. Nearly all MEN2 cases are caused by germline mutations of the proto-oncogene. In this review, we propose "5P" strategies for management of MEN2: prevention, prediction, personalization, psychological support, and participation, which could effectively improve clinical outcomes of patients. Based on mutations, MEN2 could be through prenatal diagnosis or preimplantation genetic testing. Identification of pathogenic mutations in can enable early diagnosis of MEN2. Combining mutation testing with measurement of serum calcitonin, plasma or urinary metanephrine/normetanephrine, and serum parathyroid hormone levels could allow risk stratification and accurately of MEN2 progression, thus facilitating implementation of precision treatments to increase disease-free survival and overall survival. Furthermore, increased awareness of MEN2 is needed, which requires of physicians, patients, family members, and related organizations. support is also important for patients with MEN2 to promote comprehensive management of MEN2 symptoms. The "5P" strategies for management of MEN2 represent a typical clinical example of precision medicine. These strategies could effectively improve the health of MEN2 patient, and avoid adverse outcomes, including death and major morbidity, from MEN2.
Topics: Disease Management; Genetic Testing; Humans; Multiple Endocrine Neoplasia Type 2a; Precision Medicine; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret
PubMed: 33071967
DOI: 10.3389/fendo.2020.543246 -
BMC Pulmonary Medicine Mar 2022Although some evidence suggests an association between obstructive sleep apnea (OSA) and gestational diabetes mellitus (GDM), its consequences still remain largely...
BACKGROUND
Although some evidence suggests an association between obstructive sleep apnea (OSA) and gestational diabetes mellitus (GDM), its consequences still remain largely unknown. We sought to determine whether OSA is associated with higher inflammation and sympathetic levels in GDM, and to relate them with insulin resistance and perinatal outcomes.
METHODS
OSA was identified by polysomnography and defined as an apnea-hypopnea index of ≥ 5 h. Plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10), metanephrine, and normetanephrine were determined by immunoassays.
RESULTS
We included 17 patients with GDM and OSA and 34 without OSA. Women with GDM and OSA had higher normetanephrine concentrations [81 IQR (59-134) vs. 68 (51-81) pg/mL]. No differences in the inflammatory profile were found, while IL-1β was higher in patients with mean nocturnal oxyhemoglobin saturation ≤ 94%. We found positive correlations between increased sympathetic activation and IL-1β, with obstructive apneas, while time in REM showed an inverse relationship with IL-1β and metanephrine. Furthermore, IL-10 was inversely related with time in sleep stages 1-2, and with the arousal index, and it was positively related with time in slow-wave sleep. Significant correlations were also found between IL-1β and insulin resistance. There were no significant differences in neonatal characteristics; however, we found inverse relationships between IL-10 and birth weight (BW), and percentile of BW.
CONCLUSIONS
OSA increased sympathetic activity, and IL-1β concentration was higher in patients with GDM with lower nocturnal oxygenation, all of which were related with obstructive events, and time in REM. Moreover, IL-1β was related with insulin resistance, and IL-10 inversely correlated with neonatal BW.
Topics: Diabetes, Gestational; Female; Humans; Infant, Newborn; Inflammation; Insulin Resistance; Polysomnography; Pregnancy; Sleep Apnea, Obstructive
PubMed: 35303833
DOI: 10.1186/s12890-022-01888-1 -
BMJ Case Reports Mar 2021A postpartum patient with acute-onset dyspnoea and hypotention, associated with reduced left ventricular function requiring intensive blood pressure control, was...
A postpartum patient with acute-onset dyspnoea and hypotention, associated with reduced left ventricular function requiring intensive blood pressure control, was initially misdiagnosed as having peripartum cardiomyopathy. Her clinical symptoms rapidly resolved. Echocardiography revealed reversible left ventricular dysfunction with apical ballooning and coronary angiography was normal. Based on these findings, we diagnosed takotsubo syndrome. Over the next two months, the patient experienced repeated bouts of elevated sympathetic activity. On workup, we found an adrenal mass and elevated urine metanephrines. After adrenalectomy, histology confirmed pheochromocytoma. Our patient had the rare diagnosis of postpartum pheochromocytoma-induced takotsubo syndrome.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Female; Humans; Pheochromocytoma; Postpartum Period; Takotsubo Cardiomyopathy
PubMed: 33741570
DOI: 10.1136/bcr-2020-240098 -
BMJ Case Reports Jun 2021We present a 52-year-old woman who was admitted to the emergency department with a short history of palpitations, sweating and nausea. An electrocardiogram (ECG) that...
We present a 52-year-old woman who was admitted to the emergency department with a short history of palpitations, sweating and nausea. An electrocardiogram (ECG) that was performed suggested inferolateral ischaemia with a significant troponin rise. The patient underwent an invasive coronary angiogram that showed mild non-obstructive coronary disease. She was thus given a provisional diagnosis of myocardial infarction with non-obstructive arteries (MINOCA), treated as an acute coronary syndrome (ACS) and subsequently discharged home. The patient represented within 72 hours with a recurrence of symptoms and a further troponin rise. While on the ward severe recurrent orthostatic hypertensive episodes were noted. Further investigations revealed increased urinary and plasma metanephrines, increased plasma catecholamines and imaging revealed a left adrenal 5.7 cm mass, demonstrating probable pheochromocytoma. The patient was treated with curative surgery. This case highlights the importance of thorough history-taking in patients with atypical symptoms for acute coronary syndrome and diagnosed with MINOCA.
Topics: Adrenal Gland Neoplasms; Arteries; Coronary Angiography; Female; Humans; Middle Aged; Myocardial Infarction; Neoplasm Recurrence, Local; Pheochromocytoma
PubMed: 34155005
DOI: 10.1136/bcr-2020-239761