bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSAT051 Posterior Reversible Leukoencephalopathy Syndrome Associated With Cushing's Syndrome
Authors: Ferri-Guerra Juliana , Sacco Susana Barreiro , Manzano Alex J 
Published: November 2022

Abstract

Background
Corticosteroids can induce hypertension through a variety of mechanisms such as vasoconstriction, increased hepatic production of angiotensinogen, sympathetic activity, and possible direct cardiotoxic effect. Posterior reversible leukoencephalopathy syndrome (PRES), a syndrome with unclear pathogenesis, can be the consequence of blood pressure elevation in these patients, which can present with headaches, altered consciousness, visual disturbances, or seizures. CASE REPORTA 57-year-old African American woman with a history of hypertension on Lisinopril 40mg as an outpatient, who was brought to the emergency department (ED) by family members due to altered mental status (AMS). Daughter reports that a day prior to the admission the patient has complained of feeling unwell, with mild shortness of breath and anxiety. On admission, she was found to be on sinus tachycardia with heart rate between 100-140bpm and severely hypertensive at 203/107mmHg. Toxicology screen was positive for cannabinoids, which the patient admitted to vapping the night prior. At the ED, Stroke alert was called due to altered mentation and weakness, however CT brain showed no large infarct or hemorrhage. MRI was obtained and showed patchy t2/flair hyperintense signal abnormality predominantly of the subcortical white matter in the bilateral frontoparietal lobes, most conspicuous at the vertex. Findings could reflect acute hypertensive encephalopathy (PRES). The patient had a Cushingoid appearance, with truncal obesity, moon face and reported easy bruising. Given the clinical findings and severe hypertension, serum cortisol was obtained at night and was found to be elevated at 34. 08UG/DL (3.44 - 16.76 ug/dl). ACTH was mildly low at 5 pg/mL (6-50pg/mL). 24-hour urine cortisol was then ordered and also found to be elevated at 818mcg/24h (4-50mcg/24h). Blood pressure was controlled with antihypertensive medications (nifedipine 60mg and carvedilol 12.5mg), AMS resolved and patient was discharged home with follow up with endocrinology for further Cushing's workup.

Conclusion
Cushing Syndrome is a known cause of secondary hypertension that should not be neglected. Patients that present with severe or resistant hypertension regardless of age should be worked up for possible secondary cases. Patients with Cushing syndrome are at elevated cardiovascular risk and the sooner the diagnosis is made, the better, so they can receive appropriate treatment. Hypertensive crisis can present as PRES syndrome and patients with clinical suspicion for Cushing should be worked up for the condition.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT052 Iatrogenic Cushing's Syndrome With a Remote History of Synthetic Glucocorticoid Use in the Setting of a CYP3A4 Inhibitor – Location Matters
Authors: Hand Jane , Shah Kajal , Chang Alan 
Published: November 2022

Abstract

Introduction
The most common cause of Cushing's syndrome is iatrogenic due to the exogenous administration of glucocorticoids (GCs). Exogenous GCs disrupt the hypothalamic-pituitary-adrenal (HPA) axis by reducing ACTH production, thereby suppressing cortisol production by the adrenal gland. The degree of HPA axis suppression and recovery varies by the formulation, dose, duration, frequency, timing, and location of GC administration. It is also well known that the clearance of GCs is delayed by inhibitors of cytochrome P450 (CYP) 3A4 isoenzyme. Here we report a case in which a patient on cobicistat developed iatrogenic Cushing's syndrome (ICS) even with a remote history of GC use.

Clinical Case
A 34-year-old male with Human Immunodeficiency Virus (HIV) on cobicistat and a history of a motor vehicle accident was referred for evaluation of ICS. The patient was started on triamcinolone epidural injections after the accident and developed a ruddy face, weight gain, posterior neck fat redistribution, and purple abdominal striae. He received a total of nine injections over three months at an unknown dose with the last injection being given two years ago. His symptoms improved after stopping the regimen. He received no GCs again until four months prior to presentation when he completed a 4 mg methylprednisolone taper and the cushingoid phenotype returned. Biochemical workup was consistent with HPA axis suppression: morning cortisol &lt;0.5 mcg/dL (4-22 mcg/dL), ACTH &lt;5 pg/mL (6-50 pg/mL), and DHEAS 18 mcg/dL (106-464 mcg/dL). Synthetic glucocorticoid screen was positive for methylprednisolone 5.3 mcg/dL (n &lt;0.10 mcg/dL) and triamcinolone 0.29 mcg/dL (n &lt;0.1 mcg/dL). The patient denied any surreptitious GC use. We concluded the patient still had unmetabolized triamcinolone even after two years due to drug interactions from cobicistat, which is a CYP3A4 inhibitor. Moreover, epidural triamcinolone has the longest half-life, 523 hours, compared to oral or intraarticular injections.
Clinical Lesson: GCs are primarily metabolized in the liver by CYP3A4. Very few cases have been reported with the use of cobicistat and the cushingoid phenotype typically appears within 3-6 months of the GC use. However, our patient had detectable triamcinolone and return of ICS two years after epidural injections. It is not enough to know whether a patient received GCs; it is also essential to know how it was given and the location of the injection as the half-lives vary depending on said location. This case reinforces the importance of pharmacovigilance and performing a thorough medication reconciliation, as even a remote history of steroid use in the setting of CYP3A4 inhibitors could lead to ICS.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT072 Clinical Features of Patients with 21-Hydroxylase Deficiency and Testicular Adrenal Rest Tumors
Authors: Bachega Tânia A S S , Costa Fernanda C , Madureira Guiomar , Mendonca Berenice B , Miranda Mirela C 
Published: November 2022

Abstract

Testicular adrenal rest tumors (TARTs) are one of the most frequent comorbidities in males with 21-hydroxylase deficiency (CAH) and different prevalence rates have been reported. TART still present difficult control and frequently lead to infertility. Since it is also observed in patients with adequate hormonal control, its predictors factors are not yet well-known.

Objective
To evaluate TARTs prevalence in a significant CAH male cohort and to correlate with the long-term predictors and their impact on patients’ gonadal function. Patients and methods: Data of 53 males (24 salt wasters, 10 non-classical) were retrospectively evaluated. Hormonal control quality, assessed through long-term (last 5 years) mean ACTH, 17OHP, androstenedione (D4), testosterone (T), FSH, LH, inhibin B and renin levels were analyzed as well as sperm analysis. Mean glucocorticoid doses were evaluated and converted into cortisol equivalent. Genotypes, determined through entire CYP21A2 sequencing, were classified according to predicted impairment on residual enzymatic activity: null and severe groups. Data of patients with/without TARTs by scrotal ultrasound (US) were compared. Student's t and Chi-square tests were used.

Results
TARTs were observed in 18 (42%) of classical patients, all of them presented with bilateral lesions. None of the non-classical males presented with TART. The mean age of TART diagnosis was 21.32±5.2 years, the youngest patient with TART was 12y6mo old. Ten patients with TART underwent sperm analysis and all of them presented with altered results, while 3/10 patients without TART presented with abnormal sperm count. On the other hand, only 4 (22%) TART patients developed hypergonadotropic hypogonadism. Despite late diagnosis of the SV form in our cohort, the frequency of TARTs was significantly higher in SW patients (54% vs 37%); interestingly, similar frequencies of genotype groups were observed in patient with/without TARTs. Mean glucocorticoid doses did not differ in patients with and without TARTs as well as fludrocortisone doses in SW patients with and without TARTs (p&gt;0.05 for both). Mean 17OHP, D4 and T levels did not differ in both patient groups; mean ACTH levels were 305.3+/-282 vs. 103.2+/-81.9pg/ml in patients with and without TART, respectively (p&gt;0.05). Mean renin levels were significantly higher in patients with TARTs than in those without (152.4+/-116.8 vs. 93.8+/-96.4mIU/ml). Testicular function parameters (mean inhibin B, FSH, LH levels and frequency of abnormal sperm analysis) were worse in the TART group vs without TART (p&lt;0.05).

Conclusion
in our series, a high frequency of TARTs was observed, leading to male fertility impairment. An additive renin stimulatory effect, instead of long-term hormonal control or genotype, seemed to be the major role in TARTs development.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT096 Development and Validation of Mitotane Determination in Plasma Samples by LC-DAD
Authors: Lima-Valassi Helena P , Marques Anna Sylvia Ferrari , Alves Atecla Nunciata Lopes , Mendonca Berenice B 
Published: November 2022

Abstract

Introduction
Mitotane (o,p'–DDD) is the drug of choice for adrenocortical carcinomas (ACC) and its measurement in plasma is essential to control drug administration.

Objective
To develop and validate a simple, reliable and straightforward method for Mitotane determination in plasma samples.

Method
Drug free plasma samples were collected in potassium-ethylenediamine tetraacetate (K-EDTA) tubes and spiked with 1.0, 2.5, 10.0, 25.0 and 50.0 µg/mL of DDD. p,p´-DDD was used as internal standard and was added at 25.0 µg /mL to each sample, standards and controls. Samples were submitted to protein precipitation with acetonitrile and than centrifuged and 50 uL sobrenadant was injecting into a 1260 Infinity II liquid chromatography system (Agilent Technologies) and DDD and IS were detected at 230 nm by diodo array detector (DAD) in a 12 minutes isocratic mode with a solvent mixture of 60% acetonitrile and 40% formic acid in water 0.1% pump mixed, at 0.6 mL/min flow rate. Chromatography column Waters Acquity HSS T3 was kept at 28°C. We evaluated sensitivity, precision, presence of carry-over, recovery, linearity and the accuracy of this method.

Results
Our method resulted in a symmetrical peak shape and good baseline resolution for DDD (mitotane) and 4,4´-DDD (internal standard) with retention times of 6.0min, 6.4mim, respectively, with resolution higher than 1.5. Endogenous plasma compounds did not interfere with the evaluated peaks when blank plasma and spiked plasma with standards were compared. Linearity was assessed over the range of 1.0 to 50.0 µg/mL for DDD (R2 &gt; 0.9987 and a 97.8% - 105.5% extraction efficiency). Analytical sensitivity was 0.98 µg/mL, functional sensitivity was 1.00 µg/mL, intra-assay and inter-assay coefficient of variation were less than 9. 98%, carry-over was not detected, recovery ranged from 98% to 117% and high accuracy was observed (89.4% to 105.9%) with no matrix effects for mitotane measurements. Patient's samples results were compared with previous measurement by GC-MS method with a high correlation (r=0.88 and bias=-10.2%) showed that our method is usefull for routine mitotane measurement.

Conclusion
DDD determination in plasma samples by our developed and validated method is simple, robust, efficient and sensitive for therapeutic drug monitoring and dose management in order to achieve therapeutic index of mitotane in patients with adrenocortical cancer.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN12 Change of Computed Tomography-Based Body Composition After Adrenalectomy in Patients with Pheochromocytoma: Importance of Sympathetic Activity on Human Fat Metabolism
Authors: Kim Beom-Jun , Kim Kyung Won , Ko Yousun 
Published: November 2022

Abstract

Context
Despite potential biological importance of sympathetic nervous system on fat and skeletal muscle metabolism in animal and in vitro experiments, its impact in humans remains questionable.

Objective
To clarify the influence of catecholamine excess on human body composition

Design
Retrospective longitudinal cohort study

Patients
313 consecutive patients with histologically confirmed pheochromocytoma who underwent repeat abdomen computed tomography (CT) scans before and after adrenalectomy were included.
Measurements: Changes in CT-determined visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle area (SMA), and skeletal muscle index (SMI) measured at the level of third lumbar vertebra

Results
The mean age was 50.6X ± 13.6 years and 171 (54.6%) were women. A median follow-up duration of repeat CT was 25.0 months. VFA and SFA were 14.5% and 15.8% higher, respectively, after adrenalectomy, whereas SMA and SMI remain unchanged. Consistently, patients with visceral obesity significantly increased from 103 (32.9%) at baseline to 138 (44.1%) following surgery; however, the prevalence of sarcopenia was equivalent. Furthermore, higher baseline levels of blood metanephrine and urine normetanephrine were related to greater increases in SFA, but not in muscle parameters, after adrenalectomy.

Conclusion
This study provides important clinical evidence that sympathetic hyperactivity can contribute to lipolysis in both visceral and subcutaneous adipose tissues, while its impact on human skeletal muscle is less clear.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN15 Recurrence of Benign Pheochromocytoma
Authors: Manas F N U , Jagan Suchetha , Mols-Kowalczewski Barbara 
Published: November 2022

Abstract
INTRODUCTION: Pheochromocytoma is a rare, usually benign, tumor of adrenal medulla. The prevalence is about 4.5-6.5%. The common presenting symptoms are headache, palpitations, diaphoresis, flushing, hypertension, and tachycardia. The high catecholamine levels can also result in arrhythmias, cardiomyopathy, stroke, and even death. It can also be asymptomatic and diagnosed as an adrenal incidentaloma on routine imaging. Due to its diverse and non-specific presentation, it is often called a great mimic in medicine. It is diagnosed both biochemically with plasma or urine metanephrines and by imaging (CT or MRI). The first line treatment is surgical resection of adrenal gland, adrenalectomy. Resected tumors should be pathologically confirmed for absence of malignancy. The recurrence of benign pheochromocytoma after adrenalectomy is rare. Recurrence rate following adrenalectomy is 6.5-16.5%. There are no identified predictors of recurrence but usually it occurs after 2-3 years. Annual imaging and biochemical testing for plasma and urinary metanephrines is recommended for early diagnosis of recurrence. CASE PRESENTATION: A middle aged female with past medical history of uncontrolled hypertension and uncontrolled diabetes mellitus underwent CT scan for abdominal pain, fatigue, and unintentional weight loss. She also complained of intermittent palpitations, chest heaviness, sweating, facial flushing, and headaches. Family history was negative for endocrinopathies or endocrine malignancies. CT showed 12 cm right adrenal mass. Plasma metanephrines were ordered given the imaging findings and they were elevated at more than 13000 pg/nl (normal &lt; 60 pg/ml). All other adrenal hormones were within normal range. She was diagnosed with pheochromocytoma and underwent right adrenalectomy. The tumor was confirmed to be benign by histopathology. Post-surgery her symptoms resolved, and biochemical tests normalized with plasma metanephrine at 35 pg/ml. She presented again 4 years later with similar symptoms. Patient experienced palpitation and noted to have high blood pressure at home. She had also been experiencing flushing and having a sense of impending doom. On examination the patient was diaphoretic and review of systems was positive for heat intolerance, polydipsia and polyuria. EKG revealed sinus tachycardia and blood glucose was elevated. Labs revealed elevated plasma metanephrine and normetanephrine levels. Renin activity and plasma aldosterone levels were normal. CT scan confirmed soft tissue masses, 2. 0 x4. 0 cm posteriorly and 2. 0 x3.2cm laterally, in the pararenal space surrounding the right kidney, suggestive of local recurrence of pheochromocytoma. CONCLUSION: Even though rare, the recurrence of pheochromocytoma can occur, usually after 2-3 years. Annual imaging and biochemical testing is recommended to diagnose recurrent pheochromocytoma, especially in patients with large tumors (&gt;5cm).
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN16 Sublethal Hyperthermia Decreases Cellular Proliferation and Transiently Disrupts Steroidogenesis in Adrenal Cells
Authors: Mullen Nathan , Donlon Padraig T , Duffy Katen , Feely Sarah , Warde Kate M , Prakash Punit , Dennedy Michael Conall , O’Halloran Martin 
Published: November 2022

Abstract

Introduction
Primary Aldosteronism is the most common cause of secondary hypertension. First-line treatment; adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone producing adenomas, while preserving adjacent normal adrenal cortex. Ablation involves heating tissue &gt;50°C to induce cellular necrosis. Outside the core ablation zone, the transitional zone is an area exposed to variable temperatures between 37°C – 50°C. To understand the feasibility of precision ablation in the adrenal gland, we examined the effect of applying these temperatures to adrenocortical cells to identify i) the required temperature to effectively ablate adrenal cells ii) the extent of damage that may occur to surrounding healthy adrenal cells with exposure to transitional zone temperatures.

Methods
Steroidogenic adrenocortical cell lines, H295R and HAC15, were treated with hyperthermia (high precision water bath) at temperatures of 37, 42, 45, 48 and 50°C and steroidogenesis was subsequently stimulated using forskolin (10µM) and angiotensin II (10nM). Cell death (Propidium iodide staining by flow cytometry), proliferation (xCELLigence real-time cell analysis), protein expression (Western blot/qRT-PCR), and steroid secretion (HPLC-Mass spectrometry) were analysed immediately and 7-days post-treatment.

Results
Cell death occurred at 48°C and 50°C (p&lt;0.05 vs 37°C control), but not 45°C, or 42°C. Sublethal hyperthermia (42°C and 45°C for 30 minutes) induced a heat shock response demonstrated by upregulation of HSP70 and HSP90. Proliferation was subsequently reduced over 7-days alongside a decrease in aldosterone and cortisol secretion (p&lt;0.05), and reduced expression of steroidogenic enzymes (CYP11B1, CYP11B2, CYP11A1) 18-hours post treatment (p&lt;0.05). Following 7-days sublethal hyperthermia, steroid secretion and steroidogenic enzymatic expression returned to baseline levels.

Conclusion
Hyperthermia at 48°C and 50°C for 15 minutes is required for sustained cell death at 7-days post treatment. Sublethal hyperthermia, equivalent to that produced in the transitional zone during thermal ablation, produces a short-lived unsustained inhibition of steroidogenesis that recovers 7-days post treatment. Therefore, segmental adrenal sparing ablation is possible with recovery of transitional zone following ablation. This underlines the potential for precision technology development for bilateral adrenal ablation as definitive measure to treat PA caused by APA or Micronodular disease.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN21 Adrenal Incidentaloma: Is Interval Scanning Warranted?
Authors: Fryer Antony , Issa Basil , Lea Simon , Powner Gill , Sathiavageeswaran Mahesh , Waldron Julian , Hanna Prof Fahmy , Wachira Lianne , George Cherian , Clark Alex , Golash Anurag , Kempson Wayne , Accreditation Clinical Audit 
Published: November 2022

Abstract

Background
Adrenal incidentaloma (AI) is an increasingly recognised finding, with pressure on healthcare systems. Earlier guidelines recommended interval scanning and testing to ensure stability. However, the recent European guidelines do not recommend the need for repeat scanning if initial assessment is reassuring.

Aim
To explore the utility of this guidance on need for interval scanning of benign AI.

Methods
A retrospective unselected review of AI cases seen in our unit before the launch of the European guidelines was conducted. At that time, a local protocol was in use to characterise scan and test adrenal functions at baseline, and at two years, the scan and endocrine tests were repeated. We compared the baseline scan results with those at two-years.

Results
We collected data on 54 patients initially identified between 2011 and 2016. Of these, 31 had left-sided lesions, 15 had right-sided lesions and 8 bilateral. Of the left-sided lesions, 16 increased in size over the 2.2-year follow-up period, 4 decreased in size and 17 remained the same. Of the right-sided lesions, 3 increased in size over the follow-up period, 6 decreased in size and 13 remained the same. Of those that increased (left- or right-sided), the largest increase was 5mm. Taking 2 mm as the cut-off for a significant change: on the left, 32/37 (86%) had a change ≤2mm (P&lt;0. 001 for no increase). On the right, 21/22 (95%) had a change ≤2mm (P&lt;0. 001). Using a ≤5% increase as cut-off: 28/37 on the left (P=0. 028) and 20/22 on the right (p&lt;. 001) showed ≤5% increase. There was no statistical difference in change in lesion size in terms of laterality, being indeterminate on initial scanning, gender, age or initial size on presentation.

Conclusion
We found that there was no significant change in size after two years. Therefore, our data support the European guidelines that repeat scanning is unnecessary. This should be reassuring to patients and provide a more cost-effective service.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.