[A rare cause of hypercorticism: ACTH-secreting pheochromocytoma (a case report)]. / Une cause rare d'hypercorticisme: un phéochromocytome sécrétant l'ACTH (à propos d'un cas).

Ectopic ACTH-secreting pheochromocytoma is a very rare cause of Cushing´s syndrome, posing diagnostic and therapeutic challenges. We here report the case of a female patient with suspected severe Cushing´s syndrome associated with melanoderma, arterial hypertension resistant to triple therapy and unbalanced diabetes treated with insulin therapy. Biologically, urinary ethoxylated, 24-hour urinary free cortisol and ACTH were very high. Imaging showed a 3.5 cm left adrenal mass. The patient underwent left adrenalectomy after medical preparation, with good clinico-biological outcome. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. This case study highlights the importance of measuring methoxylated derivatives in any patient with ACTH-dependent Cushing´s syndrome associated with an adrenal mass. The aim is to ensure early treatment and avoid life-threatening complications.

Giant Bilateral Adrenal Myelolipomas in a Non-Compliant Patient with Congenital Adrenal Hyperplasia.

BACKGROUND 21-hydroxylase deficiency, an essential enzyme for glucocorticoid and mineralocorticoid synthesis, is the cause of congenital adrenal hyperplasia (CAH) in more than 95% of cases. It is an autosomal recessive disorder encoded by the CYP21A2 gene, categorized into classical forms, which encompass the salt-wasting (SW) and simple virilizing (SV) forms, as well as the nonclassical form (NC). The aim of medical treatment is to replace missing glucocorticoids and, if necessary, mineralocorticoids, while also reducing elevated adrenal androgens. CASE REPORT We present the case of a 42-year-old woman with CAH who discontinued therapy during adolescence and was admitted to hospital with fatigue, nausea, and severe abdominal pain. A CT scan showed an extreme enlargement of the adrenal glands. Laboratory tests revealed elevated levels of 17-hydroxyprogesterone and other adrenal androgens, along with normal plasma metanephrine levels. Decreased morning cortisol levels suggested partial adrenal insufficiency requiring glucocorticoid replacement therapy. Due to the development of several serious complications and clinical deterioration, the multidisciplinary team recommended bilateral removal of masses measuring 300×250×200 mm on the right side and 250×200×200 mm on the left side. Histological and immunochemical examination confirmed the presence of giant myelolipomas with adrenal cortex hyperplasia. CONCLUSIONS Adrenal tumors, particularly myelolipomas, have a higher prevalence in patients with CAH. Our case report provides further evidence of the suspected link between non-compliant CAH therapy and the development of myelolipomas, along with promotion of their pronounced growth.

Elevated IL-6 levels in a patient with pheochromocytoma.

Pheochromocytoma is a chromaffin cell-derived adrenal medullary tumour and usually presents with paroxysms of hypertension, palpitations, sweating and headache due to excessive catecholamine release. These tumours can also secrete a variety of bioactive neuropeptides and hormones other than catecholamines, resulting in unusual clinical manifestations. We report a female in her mid-30s who presented with fever, anaemia, thrombocytosis and markedly elevated inflammatory markers. The fever profile, including cultures, was negative. Contrast-enhanced CT of abdomen showed a large solid-cystic right adrenal lesion with elevated plasma-free normetanephrine levels suggestive of pheochromocytoma. The fever persisted despite empirical antibiotics and antipyretics. Interleukin-6 (IL-6) levels were elevated (41.2 pg/mL (3-4 pg/mL)). She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively.

Anastomosing haemangioma of adrenal gland: an unusual vascular tumour.

With only 15 reported cases, anastomosing haemangioma of adrenal is a rare entity and usually presents as adrenal incidentaloma. A hypertensive, diabetic, non-smoker man in his late 60s presented with irritative voiding symptoms. On evaluation, he was found to have a urinary bladder mass and left adrenal incidentaloma measuring 8 cm. Metabolic evaluation confirmed it to be non-functional.The patient underwent transurethral resection of bladder tumour with left laparoscopic adrenalectomy. Intraoperatively, the adrenal tumour was highly vascular with multiple feeder vessels. Grossly it was soft, encapsulated with focal grey-brown areas. Microscopically, most of adrenal gland was replaced by anastomosing proliferating capillary vessels within framework of non-endothelial supporting cells reminiscent of splenic sinusoids. The tumour was positive for CD-31, CD-34, Glut-1 and SMA.Anastomosing haemangioma is a benign entity but it must be differentiated from angiosarcoma. Characteristic imaging features are not yet defined and is, therefore, difficult to diagnose preoperatively.

[Clinical features of patients with metastatic pheochromocytoma/paraganglioma].

Objective: To analyze the clinical features of patients with metastatic pheochromocytoma/paraganglioma (PPGL). Methods: A follow-up study. The clinical data of 250 patients with metastatic PPGL treated at Peking Union Medical College Hospital from January 2018 to August 2023 were retrospectively analyzed, including 124 males and 126 females. The clinical features and treatment status of patients with metastatic PPGL were summarized and analyzed. Kaplan-Meier survival curve was used to evaluate patients' prognosis. Results: The age of onset, age of diagnosis, and age of tumor metastasis in patients with metastatic PPGL were (33.1±14.2) years, (35.4±15.2) years, and (40.7±15.3) years, respectively. Metastasis occurred in 26.4%(66/250) of patients at the time of initial diagnosis. Among patients without metastases at the time of initial diagnosis, the time from primary tumor resection to metastasis[M(Q1, Q3)] was 5.0 (3.0, 9.0) years, among which 20.1%(37/184) of patients had metastases more than 10 years after surgery. Most patients showed increased 24-hour urinary norepinephrine and plasma normetanephrine, accounting for 78.2%(176/225) and 78.7%(85/108), respectively. 42.3%(69/163) of patients had increased neuron specific enolase (NSE)levels. Germline mutations were screened in 201 patients, of which 55.2%(111/201) had germline pathogenic mutations. In patients with gene mutations, 76.5%(85/111) had SDHB mutations. 52.0%(130/250) of metastatic PPGL patients had primary sites outside the adrenal gland, with the Ki-67 index of 5% (3%, 8%). There were 85.6%(214/250) patients had multisystem metastasis, with bone metastasis being the most common site of metastasis, accounting for 60.8%(152/250). In terms of treatment, 32.8%(75/229) of patients underwent two treatment regimens and 8.7%(20/229) of patients underwent three treatment regimens. Most patients had a good prognosis, with a 5-year and 10-year survival rate of 88.0% and 84.0%, respectively. However, some patients had rapid disease progression, and as of August 2023, 30 patients died, and the time from diagnosis to death in deceased patients was 2.0 (1.0, 4.0) years. Conclusions: Patients with metastatic PPGL have a high rate of germline mutations, especially those with SDHB mutations. The metastatic PPGL is usually multisystem metastasis with the characteristics of mostly paraganglioma, large lesion diameter and high Ki-67 index.

A 14-year-old girl with premature ovarian insufficiency but with a positive pregnancy test.

OBJECTIVES: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test. CASE PRESENTATION: A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17 bèta-estradiol: hCG levels normalized. CONCLUSIONS: The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.

Patient-reported burden associated with pheochromocytoma/paraganglioma diagnosis.

Pheochromocytoma and paragangliomas (PPGLs) originate from the chromaffin cells of the adrenal medulla or neural crest progenitors outside the adrenal gland, respectively. The estimated annual incidence of PPGL is between 2.0 and 8.0/million adults. Minimal data exist on the impact of PPGL from the patient's perspective. Therefore, a survey was adapted from a previously published study on gastroenteropancreatic neuroendocrine tumors to explore the voice of patients with PPGL and learn ways to improve clinical care while understanding the current gaps to direct future research. A self-reported online survey was available to patients with PPGL and those with genetic predisposition even without PPGL from June to July 2022. Survey questions captured sociodemographic and clinical characteristics, the diagnostic workup, treatment and monitoring, quality and access to care, and financial impact. Here, we report the most relevant findings on patient experience of disease burden following diagnosis. A total of 270 people responded, the majority of whom were from the USA (79%), Caucasian (88%), and female (81%). The results of this survey highlight the burden of disease on a patient's daily life, resulting in moderate to severe financial distress, increased travel time to specialized facilities resulting in loss of work and wages, and significant delays in care. Respondents reported being unheard and unacknowledged. With a median time to diagnosis just over 2 years, the physical, mental, and emotional toll are substantial. Increasing access to PPGL specialists and centers could lead to faster diagnoses and better management, which may reduce the burden on both patients and healthcare centers.

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.

A multidisciplinary approach of a patient with pheochromocytoma presenting as recurrent acute fulminant myocarditis: A rare case report and comprehensive review of literature.

Fulminant myocarditis (FM) is a rare illness characterized by abrupt and severe widespread cardiac inflammation, which frequently results in mortality due to cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Pheochromocytoma is an uncommon and difficult-to-diagnose cause of FM, and it is associated with a significant risk of recurrent acute myocarditis. There is, however, little information on reoccurring acute FM. Herein, we report a rare case of recurrent acute FM due to pheochromocytoma. We present the case of a 22-year-old woman who was admitted to our hospital three days previously with acute dyspnea. Five months prior, the patient was diagnosed with post-acute myocarditis, and a massive tumor on the right adrenal gland was discovered, which lead to pheochromocytoma diagnosis. In this present admission, following the exclusion of infection, autoimmune, and metabolic derangements, pheochromocytoma was presumed to be the reason for the recurrence and more severe acute FM during the current hospitalization. The patient responded favorably to high-dose steroids combined with heart failure therapy regimens. To detect recurrent acute myocarditis related to pheochromocytoma, a multidisciplinary approach was used, including several laboratory biomarkers and imaging findings. Following pheochromocytoma removal and biopsy, the patient recovered satisfactorily. Our findings may provide beneficial contributions to the literature as pheochromocytoma is an uncommon but important cause of recurrent acute myocarditis. A multidisciplinary approach is essential in identifying acute FM and determining the underlying causes of this malady.

Differential diagnosis of rare adrenal cellular schwannomas: A case report.

BACKGROUND: Adrenal cellular schwannomas are exceptionally rare stromal tumors that are often misdiagnosed due to the lack of specific radiological, serological, or clinical features. In this report, we describe the differential diagnosis of a rare adrenal cellular schwannoma. METHODS: A 69-year-old man with a history of persistent hypertension, chronic kidney disease, hypertensive heart disease, and cardiac insufficiency was hospitalized due to bilateral lower extremity edema lasting for 3 months. Plain computed tomography at that time revealed a space-occupying lesion in the right adrenal gland. As serum levels of catecholamines, cortisol, and adrenocorticotropic hormone were within normal ranges, the edema was attributed to the chronic kidney disease and cardiac insufficiency, and the patient was referred to our hospital for surgical treatment. Contrast-enhanced computed tomography revealed heterogeneous enhancement in the adrenal mass indicating pheochromocytoma. An irregularly shaped 5 cm mass with a complete capsule in the right adrenal gland was laparoscopically resected. The postoperative histopathological diagnosis was adrenal cellular schwannoma. RESULTS: The postoperative course was unremarkable and the tumor did not recur during 5 years of follow-up. CONCLUSION: Adrenal cellular schwannoma is a very rare tumor that is extremely difficult to preoperatively diagnose. Histological and immunohistochemical analyses are required for differential diagnosis and confirmation. Cellular schwannomas can transform into malignant peripheral nerve sheath tumors, but not often. Consequently, regular postoperative follow-up is required for such patients, especially imaging.

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.

Clinical features and treatment options for pediatric adrenal incidentalomas: a retrospective single center study.

BACKGROUND: The aim of this study was to investigate the clinical features and treatment options for pediatric adrenal incidentalomas(AIs) to guide the diagnosis and treatment of these tumors. METHODS: The clinical data of AI patients admitted to our hospital between December 2016 and December 2022 were collected and retrospectively analyzed. All patients were divided into neonatal and nonneonatal groups according to their age at the time of the initial consultation. RESULTS: In the neonatal group, 13 patients were observed and followed up, and the masses completely disappeared in 8 patients and were significantly reduced in size in 5 patients compared with the previous findings. Four patients ultimately underwent surgery, and the postoperative pathological diagnosis was neuroblastoma in three patients and teratoma in one patient. In the nonneonatal group, there were 18 cases of benign tumors, including 9 cases of ganglioneuroma, 2 cases of adrenocortical adenoma, 2 cases of adrenal cyst, 2 cases of teratoma, 1 case of pheochromocytoma, 1 case of nerve sheath tumor, and 1 case of adrenal hemorrhage; and 20 cases of malignant tumors, including 10 cases of neuroblastoma, 9 cases of ganglioneuroblastoma, and 1 case of adrenocortical carcinoma. CONCLUSIONS: Neuroblastoma is the most common type of nonneonatal AI, and detailed laboratory investigations and imaging studies are recommended for aggressive evaluation and treatment in this population. The rate of spontaneous regression of AI is high in neonates, and close observation is feasible if the tumor is small, confined to the adrenal gland and has no distant metastasis.

[Xanthogranulomatous adrenalitis : A rare and difficult differential diagnosis of adrenal gland tumors]. / Xanthogranulomatöse Adrenalitis : Seltene und schwierige Differentialdiagnose von Nebennierentumoren.

A radiologically diagnosed tumor in a 29-year-old woman with a fever of around 39 °C was operated on under the suspicion of cholecystitis or a liver abscess. A solid tumor was found in the adrenal gland and resected. The frozen section findings did not reveal a clear diagnosis of entity and assignment. Histologically, the tumor was found to consist of densely clustered large histiocyte-like cells with expression of vimentin, CD68, and CD163 as well as negativity for keratin, langerin, and SMA. We diagnosed xanthogranulomatous adrenalitis and discussed the differential diagnoses (Langerhans cell histiocytosis, Rosai-Dorfman disease, malakoplakia, Erdheim-Chester disease).

Cascaded nanozyme-based high-throughput microfluidic device integrating with glucometer and smartphone for point-of-care pheochromocytoma diagnosis.

The development of point-of-care (POC) diagnostics devices for circulating tumor cells (CTCs) detection plays an important role in the early diagnosis of pheochromocytoma (PCC), especially in a low-resource setting. To further realize the rapid, portable, and high-throughput detection of CTCs, an Au@CuMOF cascade enzyme-based microfluidic device for instant point-of-care detection of CTCs was constructed by combining a smartphone application and a commercial portable glucose meter (PGM). In this microfluidic system, DOTA and norepinephrine (NE) modified Au@CuMOF signal probes and Fe3O4@SiO2 capture probes were used for the dual recognition and capture of rare PCC-CTCs. Then, the targeted binding of the Au@CuMOF cascade nanozymes to the CTCs endowed the cellular complexes with multienzyme mimetic activities (i.e., glucose oxidase-like and peroxidase-like activity) to catalyze glucose reduction as signal output for colorimetric and personal glucose meter (PGM) dual-mode detection of CTCs. The developed method has a linear range of 4 to 105 cells mL-1 and a detection limit of 3 cells mL-1. This method allows the simultaneous detection of six samples and demonstrates good applicability for CTCs detection in whole blood samples. More importantly, the combination of PGM, smartphone app and array microfluidic chips enables the rapid, portable, and high-throughput diagnoses of PCC, and providing provide a convenient and reliable alternative to traditional liquid biopsy diagnosis of various cancers.

[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.

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.

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.