Catecholamine Levels Research Articles

Sympathetic nerve activity and response to physiological stress in Takotsubo syndrome.

The prevailing hypothesis posits that Takotsubo syndrome (TTS) is caused by massive sympathetic activation, yet supporting evidence remains inconsistent. The objectives of the present study were to determine whether sympathetic activity and reactivity are enhanced in the recovery phase of TTS, and to evaluate the effect of selective β1-receptor blockade on sympathetic reactivity. We conducted a case-control study that included 18 female patients with TTS and 13 age- and sex-matched controls. Muscle sympathetic nerve activity was measured through microneurography of the peroneal nerve at rest and during the cold pressor test. In the TTS group, recordings were repeated after randomisation to intravenous metoprolol or placebo. In 10 TTS patients, cardiac sympathetic activity was assessed using iodine123-metaiodobenzylguanidine scintigraphy. Blood samples were collected during hospitalisation. Microneurography was performed a median of 27.5days after patient admission. There were no significant differences in burst incidence, burst frequency, burst height or burst area between the TTS patients and the controls at rest, during stress or after administration of intravenous metoprolol. Iodine123-metaiodobenzylguanidine scintigraphy was performed a median of 12.5days after admission, revealing decreased early 1.54 ± 0.13 and late 1.40 ± 0.13 heart-to-mediastinum ratios, and an increased washout rate of 41.8 ± 12.1%. Catecholamine metabolites were comparable between the study groups. General sympathetic hyperactivity or hyperreactivityunlikelycontributesto TTS, as catecholamine levels and muscle sympathetic nerve activity at rest and during stress were similar between the TTS patients and the controls.As scintigraphy showed increased cardiac sympathetic activity, a pathological cardiac adrenergic response and vulnerability to sympathetic activationmay be crucial for the development of the syndrome.

High specificity and sensitivity of spot urine normetanephrine-to-creatinine ratios in the diagnosis of canine pheochromocytoma.

To evaluate the specificity/sensitivity and predictive values of urine spot metanephrines-to-creatinine ratios to diagnose canine pheochromocytomas and to determine whether there is a correlation between urine catecholamine levels and tumor volume. In a retrospective study, 32 client-owned dogs with adrenal tumors were identified (13 nonpheochromocytoma and 19 pheochromocytoma). Medical records were evaluated for patients undergoing adrenalectomy between August 2020 and August 2023. Patients were divided into groupings of pheochromocytoma and other adrenal tumor diagnosis on the basis of histopathology. Urine spot normetanephrine concentrations were significantly elevated in dogs with pheochromocytomas compared to dogs with other adrenal tumors. Sensitivity was 78.9%, specificity 76.9%, positive predictive value 83.3%, and negative predictive value 71.4% for discriminating between pheochromocytoma and nonpheochromocytoma. Spot urine metanephrine concentrations were not significantly different between the 2 groups. Only 5 of 19 pheochromocytoma patients had urine normetanephrine concentrations > 4 times the upper reference limit, which is the previously established diagnostic cutoff. Median tumor volume did not correlate with normetanephrine values, nor did those values correlate to patients that experienced intraoperative complications. Twenty-one percent of cases were biochemically silent pheochromocytomas. Urine normetanephrine-to-creatinine levels but not metanephrine-to-creatinine levels can potentially differentiate a pheochromocytoma from a nonpheochromocytoma. Previously published guidelines of 4 times the upper reference limit in spot urine metanephrines testing used to diagnose pheochromocytomas will lead to a significant number of missed diagnoses.

IMMU-09. REVERSING SYSTEMIC T CELL DYSFUNCTION TO LICENSE IMMUNOTHERAPY IN INTRACRANIAL TUMORS

Abstract Intracranial tumors present unique challenges for immunotherapy. These can include both local and systemic modes of immune suppression, the mechanistic underpinnings of which are incompletely understood. Our work reveals that intracranial tumors elicit systemic increases in circulating catecholamine levels, and that this chronic sympathetic hyperactivity results in T cell dysfunction that impedes immunotherapeutic efficacy. We show that treatment with b-adrenergic blockade can partially overcome the negative impacts of chronic sympathetic hyperactivity by increasing NF-kB activity in immune cells, restoring T cell polyfunctionality, favorably modifying the tumor microenvironment, and extending survival in murine models of glioblastoma treated with immune-based therapies. Furthermore, we demonstrate that extended survival is also observed in glioblastoma patients receiving b-adrenergic blockade, as well as in patients with melanoma and lung cancer brain metastases who received b-blockade alongside concomitant immune checkpoint inhibition. Importantly, while local sympathetic hyperactivity in the tumor microenvironment and b-blockade also impact the anti-tumor immune response in the context of extracranial disease, these effects are markedly more pronounced in intracranial disease. Taken together, these data reveal that sympathetic hyperactivity facilitates systemic immune dysfunction in the setting of intracranial tumors and highlight a novel role for the application of b-adrenergic blockade to license immunotherapy in intracranial malignancies.

Case report of laparoscopic adrenalectomy for a giant pheochromocytoma: medical and surgical challenge

Pheochromocytomas are rare adrenal tumors that can pose significant clinical challenges due to their potential for catecholamine release and hypertensive crises. We present a case of a large pheochromocytoma managed successfully through a laparoscopic adrenalectomy. A 66-year-old male presented with adrenal incidentaloma. Imaging revealed a sizable left adrenal mass (9.5 cm) consistent with a pheochromocytoma. Preoperative alpha- and beta-adrenergic blockade was initiated to optimize hemodynamic control. The patient underwent a laparoscopic adrenalectomy, with meticulous dissection and adrenal vein ligation to minimize catecholamine release during surgery. Post operatively, blood pressure and catecholamine levels normalized. Histopathological evaluation confirmed the diagnosis of pheochromocytoma with high pheochromocytoma of the adrenal gland scaled score (PASS) and grading of adrenal pheochromocytoma and paraganglioma (GAPP) scoring. Laparoscopic adrenalectomy proved to be a safe and effective approach for managing this large pheochromocytoma, resulting in improved blood pressure control and quality of life for the patient. This case underscores the importance of a multidisciplinary approach, including preoperative medical optimization and close postoperative monitoring, in the management of pheochromocytomas, and contributes to the growing body of evidence supporting laparoscopic techniques for these adrenal tumors.

Autonomic Modulation in Parkinson’s Disease Using Whole-Body Cryostimulation: A Pilot Study

Background: Parkinson’s disease (PD) is a multifaceted neurodegenerative disorder that progressively affects both the central and peripheral nervous systems. This pilot study aimed to examine the effects of repeated whole-body cryostimulation (WBC) sessions on the sympathovagal balance in PD patients and correlate heart rate variability (HRV) indexes with peripheral biomarkers of the autonomic nervous system (ANS). Methods: Seventeen PD patients with mild to moderate motor severity underwent a 10-session WBC cycle over 5 consecutive days. Thirteen patients (6 males, 7 females; mean age 64.5 ± 9.01 years; mean disease duration 5.4 ± 2.3 years) completed the protocol. Cardiac autonomic activity was assessed through HRV measures including RR interval variability (RR mean, RR min, RR max), power density of high and low frequencies (HF, LF), RMSSD, and the LF/HF ratio. Systemic sympathetic activity was evaluated via circulating blood catecholamine levels. Results: Significant increases were observed in RR mean, RR min, RR max, RMSSD, and HF spectrum, indicating enhanced parasympathetic activity. Blood pressure remained stable, suggesting safety. Conclusions: These findings provide initial support to WBC as a potential “rehabilitation booster” in PD, enhancing sympathovagal balance. Further research is needed to explore the long-term benefits of WBC in PD management.

Ringer’s lactate administered at 15 °C leads to a greater and more prolonged increase in blood pressure compared to 37 °C

18 Participants were randomized to receive 30 ml/kg bodyweight Ringer’s Lactate at 37° or 15 °C over 30 min. In a second session, participants were crossed over. Over a 120 min period after starting the fluid bolus we measured mean arterial pressure (MAP), cardiac output, systemic vascular resistance, and catecholamine levels. After infusion with cold fluids, the absolute increase in MAP at 45 min was significantly higher at + 6.5 mmHg (95% CI 4.8–8.2) compared with warm fluids (+ 0.6 mmHg, 95% CI, − 1.6 to 2.8; p < 0.001). This increase in MAP was longer-lasting after cold fluids (81.7 min, 95% CI 62.5–100.9) than after warm fluids (19.2, 95% CI 3.4–35; p < 0.001). While cardiac output was similar, systemic vascular resistance increase was greater after cold fluids (159 dyn s/cm5, 95% CI 9.5–309) compared to warm fluids (− 66 dyn s/cm5, 95% CI − 191 to 57; p = 0.012). Moreover, noradrenaline increased by up to 246% during cold fluids, and decreased with warm fluids (p < 0.001). Fluid bolus given at 15 °C, compared to 37 °C, leads to a greater and more prolonged increase in MAP accompanied by release of intrinsic noradrenaline and vasoconstriction. These results suggest that fluid temperature rather than volume is predominantly responsible for any increase in MAP.Trial Registration: EudraCT-nummer 2022-002137-34 and clinicaltrials.gov NCT05610254 (first registration 09/11/2022).

Sympathetic activity markers in patients with resistant hypertension with renal dysfunction

Aim. To study the informativeness of sympathetic activity markers and perirenal adipose tissue (PRAT) in assessing renal function decline in patients with resistant hypertension (RH).Material and methods. The study included 63 patients with RH of both sexes aged 40-80 years. The main group included 19 patients with chronic kidney disease (CKD). The control group consisted of 44 patients with RH without CKD. All patients were assessed for uric acid, blood lipid profile, beta-adrenergic reactivity of erythrocyte mem­branes, free metanephrine and normetanephrine in plasma and 24-hour urine. The renal function was assessed by the glomerular filtra­tion rate calculated using the CKD-EPI equation. Twenty-four hour blood pressure monitoring was performed on the brachial artery of one arm at intervals of 15 minutes during the day and 30 minutes at night. Kidney size and PRAT were calculated based on the magnetic reso­nance imaging.Results. In both groups of patients, a significant increase in blood normetanephrine and beta-adrenergic reactivity of erythrocyte mem­branes relative to the reference values was shown. Blood and 24-hour urine metanephrine were within the reference intervals. No differences were found between the sympathetic activity indices in the main and control groups. In the main group patients, the PRAT thickness was greater (p=0,013), and the kidney diameter was smaller (p=0,046) than in the control group patients.Conclusion. CKD in RH patients is not accompanied by additional significant changes in sympathetic regulation, assessed by the blood and 24-hour urine catecholamine levels, the degree of beta-adrenergic receptor desensitization and variability of blood pressure. PRAT increase according to magnetic resonance imaging in patients with RH is associated with a decrease in renal filtration function.

Clinical analysis of robotic-assisted surgery in the treatment of large pheochromocytoma/paraganglioma: a study of 29 cases

This study aimed to compare the safety and clinical efficacy of Da Vinci robotic surgery (control group) versus traditional laparoscopic surgery in the treatment of large (tumor size >6 cm) pheochromocytomas/paragangliomas. The evaluation was based on intraoperative metrics such as operative time, blood loss, conversion to open surgery rates, postoperative drain duration, and length of postoperative hospital stay. A retrospective analysis was conducted on 29 patients (14 males and 15 females) who underwent Da Vinci robotic surgery for large (greater than 6 cm) pheochromocytomas/paragangliomas from October 2019 to September 2023. The average maximum tumor diameter was (7.2±1.6) cm. During the same period, 32 patients underwent laparoscopic resection of challenging pheochromocytomas/paragangliomas.Data showed no significant differences between the two groups, except for the norepinephrine levels. Operative time, blood loss, conversion rate, postoperative drainage duration, and length of hospital stay were recorded and compared between the two groups. The differences between the groups were analyzed using the t-test, and the conversion rates were compared using the chi-square (χ²) test. All surgeries were successfully performed. One patient underwent a one-stage bilateral tumor resection. In the Da Vinci robotic surgery group, the average operative time was (76±32) minutes, compared to (106±45) minutes in the control group (P=0.003). The average intraoperative blood loss was (95±75) ml, compared to (160±90) ml in the control group (P=0.019). The conversion rate to open surgery was 2 cases (6.9%) in the robotic group compared to 5 cases (15.6%) in the control group (P=0.031). The average postoperative drainage duration was (3.0±1.0) days, compared to (3.5±1.5) days in the control group (P=0.128). The average length of hospital stay was (4.5±1.2) days, compared to (4.7±2.2) days in the control group (P=0.657). Postoperative pathological diagnosis confirmed pheochromocytoma or paraganglioma. Blood pressure normalized within 1 to 3 months postoperatively, with an average systolic blood pressure of (116±13) mmHg(1 mmHg=0.133 kPa）and diastolic blood pressure of (73±5) mmHg in the robotic surgery group. Follow-up for 3 to 40 months showed normal levels of blood catecholamines and no recurrence or metastasis on follow-up imaging studies, including chest, abdominal, and pelvic CT scans. The average levels of 3-methoxy-norepinephrine, 3-methoxy-epinephrine, and 3-methoxy-tyramine were (0.42±0.21) nmol/L (normal value≤1.05 nmol/L), (0.11±0.07) nmol/L (normal value≤0.32 nmol/L), and (0.017±0.006) nmol/L (normal value≤0.036 nmol/L), respectively. This study demonstrates that for the treatment of large pheochromocytomas/paragangliomas, the Da Vinci robotic technique offers advantages such as high-definition visualization, precise operation, and flexibility. These advantages enable the safe and efficient completion of surgeries, as evidenced by shorter operative times, less blood loss, and lower conversion rates.

RNA m6A methyltransferase activator affects anxiety-related behaviours, monoamines and striatal gene expression in the rat.

Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N6 (m6A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m6A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt's test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m6A methylation has potential for neuropsychiatric drug development.

7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma

Abstract Disclosure: R.C. Attah: None. I. Sirisena: None. Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref &amp;lt;30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref &amp;lt;1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg &amp;lt;205 pg/mL), normetanephrine 244.1 (ref &amp;lt;210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (&amp;gt;4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases. Presentation: 6/1/2024

6365 An Atypical Case Of Large Metastatic Pheochromocytoma With Negative Catecholamine Secretion

Abstract Disclosure: D. Caesario: None. J.K. Fernandes: None. Introduction: Pheochromocytomas (PCCs) are rare tumors arising from chromaffin cells of the adrenal medulla. Diagnosis is suggested by clinical presentations and confirmed by biochemical hypersecretion of metanephrines (MN) and catecholamines (CA). We report an atypical case of large metastatic PCC with normal MN and CA. Case Report: A 61-year-old female presented with uncontrolled HTN despite taking amlodipine, losartan, and carvedilol. No other symptoms reported. She had presented 12 years prior with an 8.7 cm left adrenal mass (AdM) that was incidentally found on CT scan, but she was lost to follow-up. Repeat imaging for her current presentation revealed enlargement of left AdM to 15 cm, centrally necrotic, with absolute washout of 63%. There was extensive local regional involvement, including possible invasion of the pancreas; abutment to left kidney, left renal vein, left hepatic lobe, and stomach; encasement and possible invasion of the splenic vein; and formation of perisplenic collateral vessels. Metastatic lesions were also seen in the liver, bones, and lungs. DOTATATE PET/CT scan showed variable uptake, not a definitive pattern for PCC or neuroendocrine tumor (NET). Labs showed normal levels of plasma fractionated MN and CA, dopamine, renin, aldosterone, cortisol, ACTH, and DHEA-S. Chromogranin A (CgA) was elevated to &amp;gt;8000 ng/dL. Biopsy taken from one of the liver lesions was consistent with metastatic PCC. No family history of NET. Genetic testing was offered, but was deferred. Due to the large tumor burden, she was determined to be nonsurgical and started on systemic therapy with sunitinib. Doxazosin was also added, which better controlled her BP. After 9 months of sunitinib therapy, a repeat CT scan showed overall stable metastatic lesions, but the left AdM had enlarged to 16 cm. Given the slowly worsening disease, patient was switched to temozolomide. She is still actively being treated and monitored today. Discussion: The clinical features of PCC result from excessive CA secretion. HTN is the hallmark of CA release, but the amount, type, and pattern of CA secretion is extremely variable, leading to varied clinical presentations. CgA secretion is also elevated in PCC, but is generally a non-specific marker as its level is also increased in multiple NETs and non-endocrine medical conditions. About 9% of patients with PCC may have normal biochemical workup, with this being even rarer in malignant cases. In general, the amount of CA, MN, and CgA released by the tumor is also positively correlated with the tumor size. The case above is unique in that despite the large tumor burden the patient only presented with HTN and had normal MN and CA levels. Her CgA was significantly elevated, which could correlate with the tumor size, but was interestingly the only marker elevated. It appears that CgA could be a useful adjunct in the diagnosis of PCC, especially in cases where PCC appeared to be non-secretory. Presentation: 6/3/2024

8623 Atypical VHL Genetic Variant Causing Paraganglioma

Abstract Disclosure: G. Mangu: None. J.J. Faria Briceno: None. R. Yatavelli: None. Abstract: Pheochromocytomas and paragangliomas (PPGLs) are rare chromaffin cell tumors that originate from the adrenal medulla and extra-adrenal paraganglia respectively. Previous studies have shown that incidental PPGLs are seen in older patients with mild symptoms. They have lower levels of plasma catecholamines and lower incidence of malignancy than patients with nonincidental PPGLs. We report a case of an incidental paraganglioma in a young female with atypical pathogenic variant in the VHL gene which is known to cause familial erythrocytosis but NOT VHL syndrome or PPGL. Case Presentation: A 33-year-old African American female with no significant medical history presented to the emergency room with the chief complaint of right lower quadrant pain for 2 days, which started with her menstruation. The vitals were BP 128/67, pulse 67 and physical examination was unremarkable. CT showed a 4.0 x 3.0 cm heterogenous enhancing left adrenal mass and MRI with adrenal protocol revealed 3.4 x 3.1 cm mass consistent with pheochromocytoma. Labs revealed elevated plasma nor metanephrines and 24-hour urine normetanephrines were 1020 mcg. She was asymptomatic without hypertension, palpitations, or chest pain. She underwent laparoscopic left adrenalectomy after appropriate alpha blockade. The pathology report showed left periadrenal paraganglioma with immunohistochemistry staining significant for Carbonic anhydrase IX (CAIX) membranous expression which is mostly seen in paragangliomas associated with von Hippel-Lindau syndrome. Clinically, she did not have any stigmata for hereditary PPGL syndrome. Her genetic testing revealed a pathogenic heterozygous variant in the VHL gene, Exon 3, c.598C.T (pArg200Trp), which is a missense variant expected to disrupt VHL protein function. Although she has a germline mutation in VHL, it is not the garden variant which is associated with classic VHL syndrome. It has been reported to cause autosomal recessive erythrocytosis but not PPGL. Conclusion: The pathogenic heterozygous variant in VHL gene, Exon 3, c.598C.T (pArg200Trp) is known to cause autosomal recessive familial erythrocytosis type 2 in the Chuvash population, termed as Chuvash Polycythemia. Our patient did not have polycythemia but had iron deficiency anemia from menorrhagia. Several studies have reported that this variant does not cause VHL syndrome, however it has been reported in a single family with VHL syndrome but WITHOUT pheochromocytoma. To our knowledge, incidental adrenergic paraganglioma associated with this mutation has not been reported in the literature. Presentation: 6/3/2024

12325 Adrenocortical Carcinoma Masquerading As Pheochromocytoma In A Patient With Congenital Adrenal Hyperplasia

Abstract Disclosure: E.M. Niedzialkowska: None. A.A. Banka: None. Introduction: The development of adrenocortical carcinoma (ACC) in patients with congenital adrenal hyperplasia (CAH) is rare. The patients with CAH are at increased risk of adrenal tumors which is attributed to ACTH stimulation of adrenal gland if the disease is not appropriately treated. ACC cases mistaken for pheochromocytomas have been reported in the literature and are attributed to the variety of immunohistochemical markers expressed by the tumors. Case description:59 y.o female with salt-wasting CAH diagnosed at the age of 2 (21-hydroxylase deficiency) on hydrocortisone supplementation reported to the hospital due to episodes of sweating, tachycardia and hypertension. Work up revealed mildly elevated plasma normetanephrine 1 nmol/l (N &amp;lt;0.9), urine normetanephrine 1762 mcg (N&amp;lt;899), VMA 11.2 mcg/24hr (N 3.3-7.2). MRI of the abdomen revealed 2 left adrenal masses of 3.7 and 2.4 cm, right adrenal gland hyperplasia and low T1 and T2 enhancement. I-123 MIBG revealed increased activity and thickness of the right adrenal gland and no significant uptake on the left with nodular masses. The patient underwent left adrenalectomy with pathological report consistent with pheochromocytoma due to positive chromogranin and synaptophysin staining and moderate Ki activity. A year later follow up imaging showed an enhancing mass up to 7 cm at the suprarenal fossa invading the left kidney that was positive for nodular adrenocortical hyperplasia per pathology report. The patient continued to have elevated 17-OH- progesterone (2740 ng/l, N &amp;lt;51) despite compliance with her steroid therapy and suppressed ACTH. She underwent mass resection along with nephrectomy, splenectomy, partial colectomy and partial pancreatectomy. Pathology report was positive for adrenocortical carcinoma (positive chromogranin, synaptophysin, CAM 5.2, polycystic cytokeratin, Ki positive in greater than 10% of the tumor cells) with renal and regional lymph node invasion and colonic metastases. The patient was started on mitotane therapy but a year later PET scan was positive for liver and omental metastases and was subsequently started on carboplatin/etoposide followed by streptozocin/adriamycin with initial good response, however repeat PET a year afterwards showed progression of the liver lesions, metastases to omentum and metastatic lesion to calvarium and the patient expired soon afterwards. Discussion: CAH predisposes patients to adrenal tumors which is attributed to increased ACTH stimulation of the adrenal gland but ACC in this population is extremely rare. In very rare cases ACC can present clinically as pheochromocytoma with elevated catecholamine levels and positive synaptophysin and chromogranin staining which poses a clinical challenge. Both CAH and ACC can lead to increased androgen levels and ACTH levels can help to differentiate the origin of the hyperandrogenemia. Presentation: 6/2/2024

7439 Mercury toxicity presenting as Pheochromocytoma

Abstract Disclosure: A. Ansar: None. K. McNerney: None. B.A. Marshall: None. Background: Mercury intoxication is a rare cause of hypertension in children and can mimic other endocrinopathies such as pheochromocytoma. Mercury affects catecholamine metabolism and can cause elevated catecholamine levels, thereby incorrectly suggesting a catecholamine-secreting tumor. Clinical Case: An 8-year-old girl presented to the ED with progressive night sweats, intractable migratory myalgias, hypertension and tachycardia. Patient was in her usual state of health until 2 weeks before presentation when she started to have worsening intermittent pains in her chest, arms, back, and knees. She also experienced restlessness and inability to sleep. On presentation she was hypertensive, with blood pressure of 146/116 mm Hg while calm, heart rate 125 bpm, afebrile. She was anxious, irritable, and seemed uncomfortable. Her skin was dry and rough with a scaly eczematous rash on the arms and legs. She had persistently elevated blood pressure in upper and lower extremities, unremarkable echocardiogram and electrocardiogram, and a normal result on fundoscopic examination. Her initial electrolytes, creatinine, and urinalysis were all normal and remained so on serial evaluations. Urine drug screen was negative. Thyroid function panel showed normal TSH with slightly elevated Free T4 2.28 ng/dL (0.9-1.7), but a normal Free T3 3.9 pg/mL (2.0-4.4) and Free T4 by equilibrium dialysis 1.8 ng/dL (0.8 - 2.0). CT of the chest, abdomen and pelvis was negative and did not show any lesions. Plasma renin activity was 4.6 ng/mL/hour, supine, (&amp;lt;2.0) and plasma aldosterone level &amp;lt; 4.0 ng/dL (&amp;lt; 40 supine) were normal. 24-hour urinary norepinephrine was 90 μg/24h (13-65), epinephrine 37 μg/24h (0.2-10), urine metanephrines 195 μg/24h (18-144), urine normetanephrines 305 μg/24h (29-145), all elevated. Further history taking revealed that patient was taking Ayurvedic supplements prepared by hand by medicinal personnel in India for 3 months prior to presentation. These were stopped 2 weeks prior to her presentation, when she first became symptomatic. Her blood mercury level was 11 ng/mL (n &amp;lt;9), and urinary mercury excretion 67 μg/24 hours (n&amp;lt;10), both obtained 3 weeks after stopping supplementation. She was started on oral chelation therapy with succimer 10 mg/kg/day. Her hypertension was controlled with doxazosin. One week after initiation of therapy, her symptoms improved, and she became normotensive. Her acrodynia and irritability resolved. Urine metanephrine levels will be repeated at upcoming clinic follow up. Conclusion: Mercury toxicity should be considered in the differential of pheochromocytoma to avoid extensive diagnostic testing and morbidity associated with it. Lead, mercury, and arsenic have been detected in traditionally prepared Ayurvedic supplements. A careful history of intake of supplements can be important in cases with unusual symptomatology. Presentation: 6/3/2024

Differential involvement of central and peripheral catecholamines between Alzheimer's disease and vascular dementia

Background and aimThe important role of catecholamines has been gradually emphasized in the pathogenesis of neurodegenerative process. As the most prevalent form of cognitive dysfunction, Alzheimer's disease (AD) and vascular dementia (VaD) have the distinct pathological features and pathogenic mechanisms, however, the differential involvement of central and peripheral catecholamines between AD and VaD was still unclear. MethodsTriple-transgenic AD (3 × Tg-AD) mice and chronic cerebral hypoperfusion (CCH) in rats induced by two-vessel occlusion (2VO) were used as the AD and VaD model in this study, respectively. The concentrations of catecholamines (dopamine, epinephrine and norepinephrine) and their metabolites (3-methoxytyramine, metanephrine and normetanephrine) in serum and five brain regions (hippocampus, cortex, corpus striatum, thalamus and pons) from 3 × Tg-AD mice and 2VO rats were quantitatively determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. ResultsHigh expression and distribution of hippocampal dopamine, and epinephrine and norepinephrine in the cortex and thalamus were found in the early 3 × Tg-AD model, whereas chronic cerebral hypoperfusion induced by 2VO mainly affected the central noradrenergic and noradrenergic system, but not dopaminergic system. The increased serum levels of catecholamines were investigated in the 2VO rats, but not in the 3 × Tg-AD mice. ConclusionThe differential expression and distribution of central catecholamines and their metabolites suggests the distinct catecholamines-related pathogenesis between AD and VaD. Peripheral catecholamine surge may be involved in the development of VaD, and the treatment strategy to prevent or reverse the effects of peripheral catecholamines may be protective for VaD.

Preparation of Platinum Nanoparticles of Biophytum reinwardtii and Evaluation of Neuroprotective Activity of MPTP-induced Parkinson’s Disease in Zebra Fish

Aim: To evaluate the Neuroprotective activity of Biophytum reinwardtii Platinum nanoparticles Methods: Biophytum reinwerdtii platinum nanoparticles were subjected to evaluation of the neuroprotection activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced zebra fishes. Experimental fishes are divided into 5 groups, each containing 8 fishes. Group I is considered a normal group; Group II is a toxic group means treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 225 mg/kg, i.p. for 5 days; Group III, IV, and V are treatment groups means treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (225 mg/kg) with 0.3 µmol, 0.4µmol, and 0.5 µmol of Biophytum reinwardtii Platinum nanoparticles respectively for 5 days. Results: In the in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine group, locomotor activity and complex I activity are decreased, Malondialdehyde levels increased, antioxidants, and catecholamines levels decreased, whereas Biophytum reinwardtii Platinum nanoparticles treated fishes exhibit significant locomotor and increased levels of antioxidants and catecholamines. Conclusion: These results suggest that Biophytum reinwardtii Platinum nanoparticles. Showed significant neuroprotection activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -induced Parkinson’s zebra fishes.

Hipertensão refratária em paciente jovem: Um relato de caso

Introduction: Pheochromocytoma, a rare tumor originating from the chromaffin tissue of the adrenal medulla, has a prevalence of about 0.1-0.6% in patients with hypertension. Usually benign, its surgical removal can be curative. However, delays in diagnosis and inadequate treatment can lead to high mortality and morbidity rates. Case Report: A 23-year-old man with a history of resistant hypertension since December 2022 presented with symptoms of headache, palpitation, sweating, and anxiety. Tests revealed elevated levels of metanephrines and catecholamines, leading to the suspicion of pheochromocytoma. An MRI of the abdomen identified an expansive lesion in the right adrenal gland. Treatment included clinical management with alpha- and beta-blockers, followed by successful adrenalectomy, resulting in improvement of symptoms and hypertension. Discussion: The case illustrates the complexity inherent in the diagnosis of pheochromocytoma, a condition that often manifests surreptitiously in hypertensive patients. Resistance to conventional antihypertensive therapy, combined with symptoms such as headache, palpitations, and sweating, should raise suspicions of secondary hypertension and, consequently, pheochromocytoma. This case underlines the importance of a meticulous diagnostic evaluation in patients with refractory hypertension. Conclusion: Pheochromocytoma, despite being a rare cause of hypertension, represents a crucial differential diagnosis in secondary hypertension. Early diagnosis and appropriate surgical intervention are essential to prevent associated morbidity and mortality. This case reinforces the need for clinical surveillance for suggestive symptoms and the importance of appropriate diagnostic investigations in patients with resistant hypertension, particularly in young people.

Evolution of metabolic disorders after resection of pheochromocytomas and paragangliomas: a single-center study

Background and aims. Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, responsible for inappropriate secretion of catecholamines, inducing metabolic disorders, increasing basal metabolic rate. Our study aimed to analyze the metabolic profile pre- and post-operatively in patients undergoing surgery for pheochromocytomas and paragangliomas and additionally to determine the predictive factors of metabolic remission. Methods. This was a retrospective, unicentric, descriptive, and analytical study with a duration of 9 years. It includes data from 35 patients followed up for pheochromocytoma or paraganglioma in the Endocrinology-Diabetology and Nutrition Department of a University Hospital Center. All patients underwent surgery for pheochromocytoma or paraganglioma. Results. Among the 35 patients, 51.4% of the patients with pheochromocytomas had diabetes mellitus, and 42.8% had dyslipidemia. We found that high levels of catecholamines were associated with the onset of diabetes. We also noted that patients with a long history of the disease were statistically at greater risk of developing dyslipidemia. After surgery, the body mass index of our patients had statistically increased, and 50% of patients experienced resolution or improvement of their diabetes. Improvement of dyslipidemia was observed in 53% of patients. We also found that the percentage of dyslipidemia was higher in patients who did not resolve their diabetes. Conclusion. Diabetes mellitus and dyslipidemia are metabolic complications that must be investigated in patients with pheochromocytoma. Post-operative monitoring of body mass index and changes in glycemic and lipid levels is essential to adapt therapeutic management.

Boric Acid Functionalized Hypercrosslinked Polymers for Selective Extraction of Trace Catecholamines and Their Metabolites in Rat Serum

ABSTRACTAbnormal levels of catecholamine (CA) neurotransmitters and their metabolites in biological fluids can lead to various neurological disorders. Herein, a boric acid‐functionalized hypercrosslinked polymer was prepared and utilized as a sorbent for the dispersive solid‐phase extraction of CAs and their metabolites in rat serum. By combination with a high‐performance liquid chromatography‐fluorescence detector, the extraction parameters for the seven target analytes were optimized. Under the optimal extraction condition, the methodology for the quantitative analysis of CAs and their metabolites in rat serum samples was established. The limits of detection and limits of quantification were found to be in the ranges of 0.010–0.015 and 0.033–0.050 ng/mL, respectively. The results demonstrated satisfactory recoveries, with values ranging from 88.02% to 113.27%, accompanied by relative standard deviations within the range of 2.69%–9.59%. In addition, the method showed good anti‐interference ability (matrix effect ranged from 2.64% to 18.07%). The developed method was validated for the determination of CAs and their metabolites in normal and Alzheimer's disease model rats’ serum, which proved the promising application of the method for CAs neurotransmitter analysis in biological samples.

Impact of Dexmedetomidine on Hemodynamics, Plasma Catecholamine Levels, and Delirium Incidence Among Intubated Patients in the ICU--A Randomized Controlled Trial.

To investigate the impact of various sedative medications on hemodynamics and plasma levels of epinephrine (E) and norepinephrine (NE) in mechanically ventilated patients postoperatively in the intensive care unit (ICU). Ninety-seven patients admitted to the ICU undergoing postoperative mechanical ventilation with tracheal intubation and continuous analgesic sedation following general anesthesia were randomly assigned to either the observation group (dexmedetomidine) (n = 49) or the control group (propofol) (n = 48) in this randomized controlled trial. Upon transfer to the ICU, vital signs (heart rate [HR], respiratory rate [RR], mean arterial pressure [MAP]) were recorded prior to the initiation of the sedation treatment (T0), at one-hour post sedation (T1) and two hours following tracheal extubation (T2), plasma levels of epinephrine (E) and norepinephrine (NE) were measured at these time points. The incidence of delirium was recorded in both groups. MAP between the two groups at both T0 and T1 At T2 plasma NE and HR were found to be lower in the observation group compared to the control group (P < 0.001). Among the patients receiving antihypertensive medication in the ICU, NE levels were significantly lower in the observation group compared to the control group (P = 0.019) Among the patients not receiving antihypertensive medication, both NE (P < 0.001) and MAP (P = 0.001) levels were lower in the observation group compared to the control group. The incidence of delirium in the observation group (dexmedetomidine) was not significantly different from that in the control group (propofol). With dexmedetomidine sedation, blood pressure fluctuated less, plasma catecholamine levels were lower, and sympathetic inhibition was stronger in patients before and after extubation. However, it did not significantly reduce the incidence of postoperative delirium.