Association of adrenal steroids with metabolomic profiles in patients with primary and endocrine hypertension.

Introduction: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT. Methods: Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus. Results: After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites - 18 in PPGL, 15 in CS, and 23 in PA - were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites. Discussions: Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL's metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.

Feocromocitoma y paraganglioma en un hospital pediátrico de Argentina. Serie de casos / Pheochromocytoma and paraganglioma at a children's hospital in Argentina. A case series

El feocromocitoma y el paraganglioma son tumores neuroendocrinos secretores de catecolaminas. Los feocromocitomas se originan en la médula suprarrenal, mientras que los paragangliomas son extraadrenales. Se describe una serie de casos de niños con diagnóstico anatomopatológico de feocromocitoma o paraganglioma que consultaron en un hospital pediátrico de alta complejidad de Argentina. Se incluyeron 21 pacientes, 14 varones, con una mediana de edad de 11,4 años; 8 casos con feocromocitoma y 13 casos con paraganglioma. Se presentaron con hipertensión arterial 14/21. La mayoría de los paragangliomas tuvieron localización paraaórtica (9/13). Debido a que representan una causa potencialmente curable de hipertensión arterial, la sospecha clínica es muy importante. El diagnóstico temprano y la instauración de un tratamiento antihipertensivo adecuado, que permita afrontar la cirugía con normotensión arterial, aseguran la curación en la mayoría de los casos si la resección tumoral es completa.

Pheochromocytomas and paragangliomas are neuroendocrine tumors producing catecholamines. Pheochromocytomas occur in the adrenal medulla, while paragangliomas are those that occur outside the adrenal gland. Here we describe a case series of children with a pathological diagnosis of pheochromocytoma or paraganglioma who consulted at a tertiary care children's hospital in Argentina. A total of 21 patients (14 males) were included; their median age was 11.4 years; 8 children had pheochromocytoma and 13, paraganglioma. Arterial hypertension was observed in 14/21. Most paragangliomas were para-aortic (9/13). Since they are a potentially curable cause of hypertension, clinical suspicion is very important. An early diagnosis and the initiation of an adequate antihypertensive treatment, which allows the patient to undergo surgery with normal blood pressure, ensure a cure in most cases if tumor resection is complete.

Clinical diagnosis of pheochromocytoma and paraganglioma-induced secondary hypertension through UPLC-MS/MS analysis of plasma catecholamines and their metabolites.

This study aimed to elucidate the clinical diagnostic value of plasma catecholamines and their metabolites for pheochromocytoma and paraganglioma (PPGL)-induced secondary hypertension using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). The study population included 155 patients with PPGL that were divided into the PPGL with hypertension (n = 79) and a PPGL without hypertension (n = 76) groups, and 90 healthy volunteers and 90 patients with primary hypertension as the control groups. UPLC-MS/MS was performed to detect plasma levels of catecholamines and their metabolites, including dopamine, vanillylmandelic acid (VMA), norepinephrine, metanephrine, and normetanephrine. Receiver operating characteristic curves were generated to analyze the diagnostic value of the plasma levels of catecholamines and their metabolites in PPGL-induced secondary hypertension. Patients in the primary hypertension and PPGL without hypertension groups had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal group (all p < .05). On the other hand, patients in the PPGL with hypertension group had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal, primary hypertension, and PPGL without hypertension groups (all p < .05). Collectively, our findings showed that dopamine, VMA, norepinephrine, metanephrine, and normetanephrine are all effective biomarkers for the diagnosis of PPGL and PPGL-induced secondary hypertension.

Cannabinoid hyperemesis and pheochromocytoma hypertensive urgency: a case report.

BACKGROUND: This report presents a case of cannabinoid-induced hyperemesis syndrome causing repeated violent retching in a patient with a large (8 cm) adrenal pheochromocytoma resulting in hypertensive urgency. CASE PRESENTATION: A 69-year-old white male patient with a previously diagnosed pheochromocytoma presented to the emergency department with nausea and vomiting and was found to have hypertensive urgency. Computed tomography scan did not show any acute abdominal pathology and history was inconsistent with a gastrointestinal etiology. Patient had a history of daily cannabinoid use for many years and repeated self-limited hyperemesis episodes, and thus a diagnosis of cannabinoid-induced hyperemesis syndrome was made. It was concluded that the likely explanation for the hypertensive urgency was from physical compression of his adrenal tumor during the episodes of retching resulting in a catecholamine surge. The patient was given antiemetics and admitted to the intensive care unit for blood pressure management. Blood pressure was initially controlled with phentolamine and a clevidipine infusion, then transitioned to oral doxazosin and phenoxybenzamine. Hyperemesis and abdominal pain resolved after 24 hours, and his blood pressure returned to baseline. The patient was discharged with the recommendation to stop all cannabis use. On follow-up, his blood pressure remained well controlled, and he subsequently underwent adrenalectomy for tumor removal. CONCLUSION: Hyperemesis can cause hypertensive events in patients with pheochromocytoma by increasing abdominal pressure, leading to catecholamine release.

[Spontaneous retroperitoneal hematoma]. / Spontaan retroperitoneaal hematoom.

Spontaneous retroperitoneal hematoma refers to bleeding of the retroperitoneal space without prior trauma or iatrogenic injury. Its diagnosis is often delayed due to a nonspecific clinical presentation. This case-series presents three patients with spontaneous retroperitoneal bleeding. Patient A presented with a spontaneous bleeding around the right iliopsoas muscle due to antiplatelet medication and was managed conservatively. Patient B had a spontaneous arterial bleeding near the right kidney, subsequently determined to be associated with a pheochromocytoma. Endovascular treatment successfully stopped the bleeding. The pheochromocytoma was resected during follow-up. Patient C had a spontaneous rupture of the left iliac vein with a concomitant deep vein thrombosis. She underwent emergent laparotomy, but unfortunately did not survive. This case-series emphasize the diverse presentation, varied causes, and different treatment strategies for spontaneous retroperitoneal hematoma. Timely diagnosis is hard, but crucial to enable an individualized treatment.

[Headache and hypertension as a form of presentation of pheochromocytoma and simulating a post-COVID-19 syndrome]. / Cefalea e hipertensión como forma de presentación de un feocromocitoma y simulando un síndrome post-COVID-19.

Post-COVID-19 syndrome is a set of symptoms and signs that persist for more than 12 weeks after COVID-19 infection and currently lacks a standardised clinical definition. Only one case has been reported in which a pheochromocytoma was mistaken for post-COVID-19 syndrome. The symptomatology of this syndrome is variable and ranges from headache and fatigue to persistent dyspnoea and neurocognitive disturbances. In addition, SARS-CoV-2 can affect the autonomic nervous system, contributing to symptoms resembling those of pheochromocytoma. The importance and need to discern between COVID-19-related symptoms and other conditions is emphasised, as the specificity of the clinical manifestations of post-COVID-19 syndrome is very low and can be confused with other vital pathologies. A case is presented in which a pheochromocytoma was mistaken for post-COVID-19 syndrome in a patient with no medical history.

Ectopic pheochromocytomas in the third trimester: A case report and literature review.

INTRODUCTION: To investigate the clinical features, pregnancy care, timing, and approaches of pregnancy termination as well as the perinatal management of pregnant women with ectopic pheochromocytomas (EPCC) (paragangliomas, PGL). METHODS: We report the diagnosis and treatment of a pregnant women with EPCC which was confirmed in the third trimester in our hospital. Literature in relation to EPCC during pregnancy both in and outside China was searched for data analysis such as maternal clinical features and maternal and fetal prognosis. RESULTS: A total of 20 papers including 21 cases (plus ours) were retrieved. The average age of pregnant patients was 28 years old (from 21 to 37). Two patients presented no hypertension. Nineteen had hypertension in various extent with the accompany of headache (11 cases, 57.9%), palpitations (8 cases, 42.1%), sweating (6 cases, 31.6%), nausea (6 cases), abdominal pain (2 cases), etc. The tumor was found in the chest in 3 patients, in the upper abdomen in 1 patient, in the middle abdomen in 10 patients, between the lower abdomen and pelvic cavity in 3 patients and in the pelvic cavity in 3 patients. Five patients had a surgical removal of the tumor before delivery, 3 during cesarean section and 10 after giving birth. CONCLUSION: EPCC (PGL) during pregnancy is a rare extra-adrenal tumor, whose manifestations are often confused with those of pregnancy-induced hypertension. It is extremely hard to diagnosis the disease before surgery. Patients still have an opportunity of undergoing spontaneous delivery if their tumors have been removed before labor. However, for patients whose pheochromocytomas is localized before labor, it is better to terminate their pregnancy via cesarean section in a proper time according to their obstetric conditions, while under the supervision of multidisciplinary specialists. The preparations of both α and ß adrenergic receptor blocker treatment that is normally carried out before PGL removal surgery are unnecessary to be overemphasized before the cesarean section.

Triad of cluster-like headaches, hypertension and hypercoagulability a pointer to pheochromocytoma.

We report the case of a middle-aged hypertensive woman presenting to the neurology department with short-lasting episodic headaches for 4 years. She was initially diagnosed and treated with cluster headaches for one year. Following this, she presented with right lower limb arterial claudication. Arterial Doppler of lower limbs showed thrombosis of the bilateral common femoral arteries. Further computed tomography (CT) angiogram of the lower limbs confirmed extensive arterial thrombosis in bilateral lower limbs. The CT angiogram incidentally detected a left adrenal lesion. She had elevated urinary vanillylmandelic Acid and 24-hour metanephrines suggesting the presence of a pheochromocytoma. She was initially medically managed and later underwent left open adrenalectomy. Histopathology examination of the sections proved pheochromocytoma. Postsurgery, the patient's symptoms improved remarkably. This case highlights the importance of diagnosing pheochromocytoma when you encounter a patient with refractory short-lasting headaches, hypertension and hypercoagulability.

Rare and aggressive metastatic pheochromocytoma recurrence in a patient with MEN 2A syndrome.

An adult male in his early 30s diagnosed with multiple endocrine neoplasia type 2A syndrome, confirmed through genetic testing, presented as bilateral pheochromocytoma in a metachronous fashion, primary hyperparathyroidism and medullary thyroid carcinoma. Left and right adrenalectomy was done 9 years and 3 years ago, respectively. He was also subjected to total thyroidectomy with neck dissection and left inferior parathyroidectomy. During surveillance monitoring, 24-hour total urine metanephrines were elevated 13.977 mg (Normal value 0-1 mg) 1 year after right adrenalectomy. Adrenal CT scan demonstrated a 2.1 cm ovoid focus in the right suprarenal region, and functional imaging (131I meta-iodobenzylguanidine (MIBG scan) showed an avid uptake on the right frontal bone. Excision of the right adrenal bed and the right frontal bone tumour was performed, and metastatic pheochromocytoma was confirmed histologically. The patient achieved clinical and biochemical remission postoperatively and is currently receiving steroid and thyroxine replacement.

Adrenalectomy for the treatment of hypotension in a cat with phaeochromocytoma associated with caudal vena cava syndrome.

An 11-year-old spayed female, Persian cat was referred to the Jeonbuk Animal Medical Center for evaluation of a 2-month history of lethargy and anorexia. Physical examination revealed tachycardia and hypotension. Abdominal imaging via sonography and CT identified a right adrenal gland mass causing severe deviation and compression of the caudal vena cava. After stabilising the blood pressure and heart rate through positive inotropes and fluid therapy, right adrenalectomy was performed. Surgery confirmed the adrenal gland mass was severely compressing the caudal vena cava. Histopathological examination revealed that the mass was a pheochromocytoma. After adrenalectomy, blood pressure and heart rate stabilised and remained unaffected 8 months postsurgery. This report describes a rare case of an adrenal pheochromocytoma leading to caudal vena cava compression in a cat presenting with hypotension.

Risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas.

PURPOSE: To identify presurgical and surgical risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas (PGLs) (PPGLs). METHODS: Retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. Intraoperative hypertensive crisis was defined as systolic blood pressure (SBP) greater than 200 mmHg lasting more than 1 min and postoperative hypertensive crisis as SBP greater than 180 mmHg or diastolic blood pressure (DBP) greater than 110 mmHg. RESULTS: A total of 296 surgeries were included. Alpha presurgical blockade was employed in 93.2% of the cases and beta-adrenergic in 53.4%. Hypertensive crisis occurred in 20.3% ( n  = 60) of the surgeries: intraoperative crisis in 56 and postoperative crisis in 6 cases (2 cases had both types of crises). We identified as risk factors of intraoperative hypertensive crisis, absence of presurgical glucocorticoid therapy (odds ratio [OR] 3.48; 95% confidence interval [CI] 1.19-10.12) higher presurgical SBP (OR 1.22 per each 10 mmHg, 95% CI 1.03-1.45), a larger tumor size (OR 1.09 per each 10 mm, 95% CI 1.00-1.19) and absence of oral sodium repletion (OR 2.59, 95% CI 1.25-5.35). Patients with hypertensive crisis had a higher rate of intraoperative bleeding ( P  < 0.001), of intraoperative hemodynamic instability ( P  < 0.001) and of intraoperative hypotensive episodes ( P  < 0.001) than those without hypertensive crisis. CONCLUSION: Intraoperative hypertensive crisis occurs in up to 20% of the PPGL resections. Patients not pretreated with glucocorticoid therapy before surgery, with larger tumors and higher presurgical SBP and who do not receive oral sodium repletion have a higher risk for developing hypertensive crisis during and after PPGL surgery.

Pheochromocytoma and paraganglioma at a children's hospital in Argentina. A case series. / Feocromocitoma y paraganglioma en un hospital pediátrico de Argentina. Serie de casos.

Pheochromocytomas and paragangliomas are neuroendocrine tumors producing catecholamines. Pheochromocytomas occur in the adrenal medulla, while paragangliomas are those that occur outside the adrenal gland. Here we describe a case series of children with a pathological diagnosis of pheochromocytoma or paraganglioma who consulted at a tertiary care children's hospital in Argentina. A total of 21 patients (14 males) were included; their median age was 11.4 years; 8 children had pheochromocytoma and 13, paraganglioma. Arterial hypertension was observed in 14/21. Most paragangliomas were para-aortic (9/13). Since they are a potentially curable cause of hypertension, clinical suspicion is very important. An early diagnosis and the initiation of an adequate antihypertensive treatment, which allows the patient to undergo surgery with normal blood pressure, ensure a cure in most cases if tumor resection is complete.

El feocromocitoma y el paraganglioma son tumores neuroendocrinos secretores de catecolaminas. Los feocromocitomas se originan en la médula suprarrenal, mientras que los paragangliomas son extraadrenales. Se describe una serie de casos de niños con diagnóstico anatomopatológico de feocromocitoma o paraganglioma que consultaron en un hospital pediátrico de alta complejidad de Argentina. Se incluyeron 21 pacientes, 14 varones, con una mediana de edad de 11,4 años; 8 casos con feocromocitoma y 13 casos con paraganglioma. Se presentaron con hipertensión arterial 14/21. La mayoría de los paragangliomas tuvieron localización paraaórtica (9/13). Debido a que representan una causa potencialmente curable de hipertensión arterial, la sospecha clínica es muy importante. El diagnóstico temprano y la instauración de un tratamiento antihipertensivo adecuado, que permita afrontar la cirugía con normotensión arterial, aseguran la curación en la mayoría de los casos si la resección tumoral es completa.

A Patient with Partial 17α-Hydroxylase Deficiency Initially Diagnosed with Asherman Syndrome and Pheochromocytoma.

This study present a case of a 49-year-old woman who suffered from resistant hypertension, hypokalemia, hypomenorrhea, and infertility. She was hospitalized 6 years earlier for hypomenorrhea and abdominal pain at the Xiamen Maternity and Child Health Hospital, where she was diagnosed with Asherman syndrome. During hospitalization, a computed tomography examination revealed an adrenal mass. She was referred to Xiamen University Affiliated Zhongshan Hospital for pheochromocytoma and underwent surgical resection of the left adrenal gland. The adrenal cortex adenoma was confirmed by pathological biopsy. Six years later, the patient also presented with hypertension and hypokalemia to our emergency department. A diagnosis of 17α-hydroxylase deficiency was established through the analysis of clinical and laboratory characteristics. The genetic analysis of CYP17A1 revealed compound heterozygous mutations, 1 of which was a mutation of c.1226 C>G, and the other c.297+2T>C.

Giant left pheochromocytoma with vascular anomalies and pelvic horseshoe kidney: a case report.

BACKGROUND: Pheochromocytoma is a neuroendocrine tumor, and its treatment is dependent on surgical resection. Due to the wide availability of cross-sectional imaging, pheochromocytomas are commonly seen as small tumors less than 10 cm in size and are mostly treated with minimally invasive surgery. Their concomitant presence with horseshoe kidney or other anatomical and vascular anomalies is rare. Herein, we present a surgically complex giant pheochromocytoma case who underwent an open left radical adrenalectomy. CASE PRESENTATION: A 41-year-old Hispanic female presented with a 12 × 8 cm left hypervascular adrenal mass, pelvic horseshoe kidney, and severely dilated large left retro-aortic renal vein which branched into a left adrenal vein, congested left ovarian vein, and left uterine plexus. She was managed with insulin and metformin for uncontrolled diabetes with an A1c level of 9% and doxazosin for persistent hypertension. Clinical diagnosis of pheochromocytoma was confirmed with elevated urine and serum metanephrine and normetanephrine. The pre-operative ACTH was within normal range with a normal dexamethasone suppression test and 24-hour urine free cortisol. The adrenalectomy of the highly aggressive adrenal mass was performed via open approach to obtain adequate surgical exposure. Due to the large size of the tumor and its significant involvement with multiple adjacent structures, coordination with multiple surgical teams and close hemodynamic monitoring by anesthesiology was required for successful patient outcomes including preservation of blood supply to the pelvic horseshoe kidney. The histopathological diagnosis was pheochromocytoma with negative surgical margins. The patient was followed at 1, 4, 12, and 24 weeks postoperatively. She had a normal postoperative eGFR and was able to discontinue antihypertensive and antidiabetic medications at four weeks. She had transient adrenal insufficiency, which resolved at five months. The horseshoe kidney was intact except for a minimal area of hypo-enhancement in the left superior renal moiety due to infarction, which was significantly improved at six months. CONCLUSION: Our patient had a giant pheochromocytoma with anatomical variations complicating an already surgically challenging procedure. Nonetheless, with multiple provider collaboration, detailed pre-operative surgical planning, and meticulous perioperative monitoring, radical resection of the giant pheochromocytoma was safe and feasible with successful postoperative outcomes.

Multiple GISTand pheochromocytoma -A rare associationin neurofibromatosis type 1 / GIST múltipley feocromocitoma -Una asociación raraen neurofibromatosis tipo 1

We describe a case of coexistence of multiple gastrointestinal stromal tumors (GIST) and pheochromocytoma in a 32-year-old patient with neurofibromatosis type 1. The coexistence of these two conditions in patients with this syndrome is extremely rare.(AU)

Successful treatment of acute respiratory failure following hypertensive crisis in a dog with presumed pheochromocytoma or paraganglioma.

Background: Acute respiratory failure has been reported as one of the manifestations of hypertensive crisis in pheochromocytoma in human medicine. In dogs, no reports have been described as acute respiratory failure following hypertensive crisis. Here, we report the clinical presentation, course, and treatment of acute respiratory failure following the hypertensive crisis in a dog with presumed pheochromocytoma or paraganglioma. Case Description: A 12-year-old neutered male toy poodle was referred for the diagnostic evaluation of a right adrenal gland mass. The dog suddenly exhibited severe dyspnea with abnormal hypertension (systolic blood pressure >200 mmHg) 15 minutes after recovery from the anesthesia for the computed tomography (CT) examination. Pulmonary CT and ultrasonography findings suggested acute onset of severe pulmonary edema. Pulmonary edema was treated with mechanical ventilation (pressure-support ventilation with continuous positive airway pressure) and negative fluid balance after the administration of furosemide. Weaning from mechanical ventilation was successful 24 hours after the onset of respiratory failure. Finally, the dog was discharged 3 days after weaning from ventilation without complications. Conclusion: This report outlines a case of acute respiratory failure following a hypertensive crisis requiring mechanical ventilatory management in a dog. The onset and progression of pulmonary edema were extremely rapid. However, improvement in pulmonary edema was also rapid. Hemodynamic stability, in addition to prompt diagnosis and aggressive therapeutic intervention, including mechanical ventilation, may have contributed to the good prognosis of pulmonary edema following hypertensive crisis in a dog, which we attribute to a catecholamine storm.