Treatment Of Choice Research Articles

Laparoscopic abdominoperineal resection and myocutaneous flap reconstruction for anal fistula cancer arising from complicated anal fistula: two case reports.

Anal fistula cancer is rare and definitive treatment has not yet been established. Laparoscopic abdominoperineal resection is generally the first choice of treatment if the cancer is determined to be resectable. However, complicated anal fistula cancer often requires extensive resection. Using a myocutaneous flap for reconstruction after resection in such cases, radical resection can be performed regardless of the size of the anal fistula cancer. We report two cases in which we performed laparoscopic abdominoperineal resection with extensive buttock resection and myocutaneous flap reconstruction for widespread anal fistula cancer. One of the cases was reconstruction with a posterior thigh flap, the other was with a bilateral expanded gluteus maximus flap. Both cases were anal fistula cancers that developed from complicated anal fistulas. If the size of anal fistula cancer is large and extended buttock resection is necessary, radical resection of anal fistula cancer is possible using myocutaneous flap for reconstruction after extended abdominoperineal resection.

Retrospective Analysis Comparing the Efficacy of GLP-1 Receptor Agonists Dulaglutide and Semaglutide

Background: Glucagon-like peptide-1 receptor agonists have gained popularity in recent years because of their well-established benefits of increased glycemic control, weight loss, cardiovascular protection, and renal protection, with minimal adverse effects, and low risk for hypoglycemia in patients with type 2 diabetes. This study explored the effectiveness of the GLP-1 receptor agonist semaglutide and dulaglutide on body weight and hemoglobin A1c in patients with type 2 diabetes. Methods: In this retrospective cohort study, 244 patients diagnosed with type 2 diabetes and prescribed semaglutide or dulaglutide were identified through Lourdes Hospital electronic medical records. Over a 12-month period, in set intervals every 3 months, patients were assessed for changes in their hemoglobin A1c and body weight measured as a reduction in their body mass index (BMI). These primary outcomes were compared using linear mixed models from the lme4 package in R (v. 4.2.2). Results: Semaglutide and dulaglutide showed comparable effectiveness in reducing hemoglobin A1c compared with baseline. Both medications also led to a reduction in BMI. However, semaglutide showed statistically significant improvements in weight loss compared with dulaglutide at 3-6 months ( P = 0.01), 6-9 months ( P = 0.01), and 9-12 months ( P = 0.01). Conclusions: These findings suggest that in type 2 diabetes, semaglutide and dulaglutide show comparable effectiveness in reducing hemoglobin A1c. However, semaglutide was shown to be more effective in promoting weight loss. While these findings may be beneficial when treating patients with type 2 diabetes and obesity, treatment should be individualized to the patient, considering all factors before treatment choice.

Computational Drug Design Approaches for the Identification of Novel Antidiabetic Compounds from Natural Resources through Molecular Docking, ADMET, and Toxicological Studies.

Type 2 diabetes mellitus (T2DM) is usually depicted by relative insulin deficiency, raised blood glucose levels, and the predominant risk factor, insulin resistance. Hence, the development of insulin sensitizer drugs targeting PPAR-γ receptors has expanded enormous interest as an attractive choice for T2DM treatment. Thiazolidinediones (TZD) enhance insulin sensitivity either by directly functioning on gene transcription of the PPARγ receptor related to glucose homeostasis or by systemic sensitization of insulin and, therefore, improved hyperglycemia in a wide range of patients. However, severe complications and adverse effects of TZDs necessitate the development of an efficacious and reliable insulin sensitizer from alternative resources. On the contrary, Nature is a rich source of anticipated effective and safer medicine; more than fifty percent of drugs on the market are developed from natural products. Hence, searching for a new PPAR-γ agonist from bioactive secondary compounds of medicinal plants along with greater efficacy and safety is a recognized and consistent tactic for developing novel antidiabetic agents. Pulicaria jaubertii is a fragrant perennial aromatic plant with anti-inflammatory, antidiabetic, antimicrobial, antimalarial, and insecticidal properties. The current study was designed to use a computer-aided drug design to explore the best antidiabetic compounds from P. jaubertii. Herein, the molecular docking study of 80 investigated ligands against the PPAR-γ receptor identifies the highest docking score for five ligands ranging from -8.9 kcal/mol to 8.0 kcal/mol, which is also more significant than the standard drug pioglitazone (-7.7 kcal/mol) determined by the PyRx 8.0 virtual screening software. GLN286, CYS285, SER289, TYR473, MET364, ARG288, ILE341, and LEU333 residues are found to be significant contributors to the non-bonded interaction between ligands and receptors. Molecular electrostatic potential (MEP), DFT, molecular orbital (MO), ADMET, and toxicological analyses were performed on the selected five high-scored ligands of P. jaubertii. Results documented that all investigated ligands, especially L4, show considerably excellent profiles in molecular docking, MEP, DFT, MO, ADMET, and toxicological predictions, suggesting our drug-designing approaches may contribute to the development of a novel antidiabetic drug for the treatment of T2DM from natural resources.

Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost.

Azole antifungals are the main drugs used to treat fungal infections. Amino acid substitutions in the drug target Erg11 (Cyp51) are a common resistance mechanism in pathogenic yeasts. How many and which mutations confer resistance is, however, largely unknown. Here we measure the impact of nearly 4,000 amino acid variants of Candida albicans Erg11 on the susceptibility to six clinical azoles. This was achieved by deep mutational scanning of CaErg11 expressed in Saccharomyces cerevisiae. We find that a large fraction of mutations lead to resistance (33%), most resistance mutations confer cross-resistance (88%) and only a handful of resistance mutations show a significant fitness cost (9%). Our results reveal that resistance to azoles can arise through a large set of mutations and this will probably lead to azole pan-resistance, with little evolutionary compromise. This resource will help inform treatment choices in clinical settings and guide the development of new drugs.

An instantly applicable machine learning model for extraprostatic extension prediction in prostate cancer: A post-hoc analysis of the RAPID 68Ga-PSMA PET/MRI trial

Radical prostatectomy (RP) is a common first-line treatment for patients with localized prostate cancer (PCa), with nerve-sparing techniques recommended to minimize adverse effects on quality of life. Accurate pre-operative detection of extraprostatic extension (EPE) remains difficult, often resulting in suboptimal treatment choices. Machine learning (ML) has the potential to improve pre-operative EPE detection through the integration of multimodal data, but its clinical adoption is hindered by implementation complexities and explainability issues. This study conducted a post-hoc analysis of a prospective clinical trial (NCT02659527) involving patients who underwent [68Ga]Ga-PSMA-11 PET/MRI from 2014 to 2019. Only the clinically used parameters were collected, including PET-derived features, blood-based markers, histology-derived parameters, and patient demographics. ML models were developed using either only non-invasive features or a combination of non-invasive and invasive features for EPE detection and were compared to conventional PET image readings. Among the 77 patients included in the study, 44 (57%) had EPE based on post-surgical findings. The ML models outperformed traditional PET image readings in diagnostic accuracy, with the explainable boosting machine (EBM) model achieving an AUC of 0.88. The ML model incorporating invasive features showed superior predictive ability for EPE compared to visual clinical assessments (AUC 0.88 vs. 0.71, p 0.02), while the difference between the ML model with non-invasive features and clinical assessments was not significant (AUC 0.83 vs. 0.71, p 0.34). Explainable ML models utilizing routinely acquired clinical data can greatly enhance the pre-operative detection of EPE in PCa patients, potentially leading to more accurate clinical staging, better treatment decisions, and improved patient outcomes. Please click on the 'PDF' for the full abstract!

GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer

BackgroundThere are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib...

Role of Suprachoroidal versus Intravitreal injection of triamcinolone: In diabetic macular edema.

Objective: To assess the efficacy of suprachoroidal versus intravitreal injection of triamcinolone in diabetic macular edema. Study Design: Randomized Controlled Trial. Setting: Department of Ophthalmology, Ziauddin Hospital Kemari, Karachi. Period: 1st November 2022 and 30th October 2023. Methods: The study observed 71 eyes of 59 patients diagnosed with Diabetic macular edema. All patients that met the inclusion criteria were divided into two groups, Group A Suprachoroidal Triamcinolone and Group B Intravitreal Triamcinolone. Results: This research encompasses 71 eyes from 59 patients diagnosed with diabetic macular edema, divided into two groups based on their chosen treatment. Group A consisted of 34 patients, whereas Group B comprised 37 patients. The average age of patients in both groups was 43.6±6.2. Baseline visual acuity and macular thickness were recorded in both groups and compared after treatment. Significant improvement was observed in both groups, particularly notable in the 3rd month. The suprachoroidal triamcinolone injection exhibited a more stable response, accompanied by lower complication rate. Conclusion: In conclusion, the comparative analysis of Suprachoroidal Triamcinolone acetate and Intravitreal Triamcinolone Acetate showed a more significant improvement in IOP and CMT in the suprachoroidal group as compared to intravitreal. Hence Suprachoroidal injection was seen as the treatment of choice in treatment of Diabetic Macular Edema.

A Study to Assess the Effectiveness of Video Assisted Teaching Programme on Knowledge, Attitude and Practice Regarding Renal Rehabilitation among Patients with Chronic Kidney Disease Who are Admitted in the Mamata General and Super Specialty Hospital, at Khammam, Telanagana

ABSTRACT Background: Kidneys are one of the vital organs in the human body. Kidneys perform vital functions like excretion of waste products, maintenance of water balance, thus maintaining the homeostasis. In addition, kidneys perform many other functions such as role in Homeostasis, Production of Erythrocyte, Endocrine function, Regulation of Blood Sugar and regulation of Blood Calcium level. Because the kidney performs a wide variety of functions, the effects of loss of renal function not only in kidney but also in other organ systems.Hemo dilaysis is used for clients with acute or irreversible renal failure and fluid and electrolyte imbalances. It is usually the treatment of choice when toxic agents, such as barbiturates after an over dose need to be removed quickly. The availability of the treatment for clients with end stage renal failure (ESRF) has become more prevalent. The population receiving hemo dilaysis now represents a wide cross-section of age rehabilitative potential of socio-economic status. Materials and Methods: For the present study, quantitative Evaluative Approach ,Pre – Experimental research design, one group pretest and one group post test design.The study was conducted in the Mamata General and super specialty Hospital at Khammam, Telangana. Results: The above table shows that the pre test mean knowledge score is 10.05 and standard deviation is 3.77 where as post test mean score is 18.02 and standard deviation is 3.36 and mean difference is 7.97, the paired ‘t’ test calculated value is 14.89, which is greater than table value with df value of 79at (p<0.05) level. Conclusion: The main study was conducted in Mamata general and super specialty hospital, at Khammam, Telanagana . The sample sizes 30. The sample was selected by using non probability of convenient sampling technique among those fulfill the criteria.

Minimally invasive caries treatment

The development of minimally invasive caries treatment has dramatically changed dentistry. Instead of traditional, often invasive methods that resulted in significant loss of healthy dental tissue, this approach focuses on preserving the vitality of the pulp and minimizing tissue loss by delaying and scaling back restorative treatments. This involves the use of modern methods, with selective caries removal with or without indirect (pulp) capping being the norm for treating extensive lesions. The philosophy of minimal intervention goes beyond treatment choices to include a holistic approach from diagnosis to follow-up care, emphasizing personalized care based on risk profiles. This paradigm shift has greatly improved the standard of care, but continued attention to the risks of overdiagnosis and overtreatment is necessary to ensure optimal oral health.

6457 You Are Never Too Old For Pheo

Abstract Disclosure: M. Masumy: None. B. McAdams: None. P. Mikkilineni: None. Introduction: Pheochromocytomas (PCC) are a rare neuroendocrine tumor derived from chromaffin cells. The incidence is estimated at 8 in 1 million individuals with no sex or ethnic predilection. It is estimated that 0.05-0.2% of hypertensives may have PCC. Its incidence generally peaks between the third and fifth decades of life. The classic PCC symptoms are headaches, hypertension, palpitations, pallor and tachycardia. However, most patients may not present with these symptoms, and may go undiagnosed. Untreated PCC can have significant morbidity and mortality such as MI, CVA, and hypertensive crises. The current standard of evaluation for PCC includes obtaining serum metanephrines, then if significantly elevated, obtaining CT imaging. Oftentimes, surgical resection is the treatment of choice, but PCC may recur, thus regular follow up is needed. We present a case of PCC in an elderly patient who developed symptoms over a year. Case presentation: A 72-year-old Caucasian female with diabetes presented to the emergency department with palpitations, severe headache, flushing and hypertension. She began experiencing these spells several months earlier with increasingly difficult to manage hypertension. She also had a CVA and NSTEMI earlier in the year. Her blood pressure regimen included amlodipine 20 mg, valsartan 160 mg, and carvedilol 12.5 mg bid. Despite this her blood pressure was uncontrolled. She also had palpitations and unease up to an hour after taking valsartan. Due to her symptoms; PCC was suspected. Serum metanephrines were obtained with her normetanephrines measured at 3334.7 pg/ml and metanephrines were 475.6 pg/ml, these were significantly elevated and thus an abdominal CT scan was done. On CT, she was found to have a 4.9 cm x 4.4 cm left adrenal mass with a density of 31 Hounsfield units. Her symptoms, labs and imaging were strongly indicative of PCC and she was referred to surgery. Her previous blood pressure medications were discontinued, and doxazosin was titrated to a goal SBP of 120 mmHg. Then metoprolol was added to attain a goal heart rate below 70 bpm. She then underwent a successful laparoscopic left adrenalectomy. She is now on 5mg of amlodipine for her blood pressure and metformin for her diabetes. She will be having regular follow ups to monitor for pheochromocytoma recurrence. Conclusion: Though pheochromocytoma is a rare entity that affects individuals primarily in the third and fourth decade of life, it may also occur in elderly patients. In patients with difficult hypertension, screening with metanephrines may be indicated if these are significantly elevated CT imaging should be obtained. When obtaining CT imaging, Hounsfield units are important in characterizing PCC. Achieving adequate alpha blockade before beta blockade is also essential pre-surgery for the best outcome. Even after surgery, patients will require lifelong follow up to monitor for recurrence. Presentation: 6/1/2024

6589 Antisense Oligonucleotides for Reducing ACTH Secretion in a Model of Cushing's Disease

Abstract Disclosure: M.S. Varughese: None. H. Eltumi: None. E.H. Kemp: None. J.D. Newell-Price: None. Antisense Oligonucleotides for Reducing ACTH Secretion in a Model of Cushing’s Disease Background: Cushing’s disease (CD) is a multi-system disorder with high morbidity and mortality characterised by pathologically raised serum cortisol due excess expression of proopiomelanocortin (Pomc) and overproduction of ACTH by a pituitary corticotroph adenoma. Trans-sphenoidal adenomectomy is the treatment of choice, but there is a 30% recurrence rate over time. Advances in medical therapy are needed. Antisense oligonucleotides (ASOs) can silence mRNA translation by specific base-pairing. Locked nucleic acid (LNA) and 2’-O-methyl (OMe) ribose terminals make ASOs more effective by improving affinity and resistance to nuclease degradation. Aims: To investigate the effectiveness of LNA- and OMe-modified anti-Pomc ASOs at reducing ACTH secretion from murine adrenotropic tumour (AtT20) cells. To analyse the nuclease resistance of Pomc ASOs and their ability to drive an immune response. Methods: Two ASOs (ASO2 and ASO3) were designed against Pomc with phosphorothioate backbones modified with either LNA or OMe ribose terminals. These were used in lipofectamine-mediated cell transfections of AtT20 cells and ACTH in the culture medium measured by immunoassay. ASO stability was assessed by nuclease degradation assays and immunogenicity by cytokine ELISAs. Results: When compared with untreated AtT20 cells, LNA- and OMe-modified Pomc ASOs at 1 nM significantly suppressed ACTH secretion for up to 120 h and 96 h, respectively (n = 4; Unpaired t tests, all P values < 0.05). In contrast, control treatments, including scrambled and mismatched ASOs, did not cause a significant reduction. For comparison, 1 nM of ASO2-OMe, ASO2-LNA, ASO3-OMe and ASO3-LNA lowered ACTH at 24 h by 62%, 71%, 63% and 79%, respectively. Modified Pomc ASOs showed 14-31% degradation over a 120-min incubation period with 3’- and 5’-exonucleases, whilst equivalent unmodified Pomc ASOs were completely degraded. No secretion of IFN-α, IFN-β, TNF-α, IL-6 or IL-1β was detected following transfection of AtT20 cells with Pomc ASOs. Conclusions:Pomc ASOs caused significant reduction of ACTH secretion from AtT-20 cells. LNA-modified Pomc ASOs were more effective than those with OMe modifications, with neither stimulating a detectable immune response. These ASOs hold promise as a systemic therapy for Cushing’s disease. Presentation: 6/3/2024

8275 Recurrent Retroperitoneal Paraganglioma

Abstract Disclosure: J. Kang: None. V. Gupta: None. J.S. Subauste: None. Paragangliomas are rare, highly vascular neuroendocrine neoplasms that may originate from sympathetic or parasympathetic paraganglia and may secrete catecholamines. They are closely related to pheochromocytomas which are considered to be their intra-adrenal counterparts. A 65-year-old African American male with type 2 diabetes and tobacco use presented to his primary care physician with night sweats and unintentional weight loss of about 30 pounds in 3 months. Review of systems and laboratory workup was unremarkable. CT Chest/Abdomen/Pelvis with contrast showed a homogenous, well-circumscribed 4.6cm retroperitoneal mass causing mass effect on portal vein, Inferior vena cava, and right renal artery. Interventional radiology performed fine needle aspiration with intra-procedural blood pressure rising to 201/70 mmHg. Pathology showed paraganglioma, staining positive for synaptophysin, chromogranin A, CD 56 and S-100 protein. Plasma metanephrines were elevated at 2818 pg/mL, plasma normetanephrines at 1247 pg/mL with consistent 24-hour urine results. Workup for other adrenal hormones was negative. No family history of pheochromocytoma/paraganglioma or any clinical manifestations of Von-Hippel-Lindau syndrome or Neurofibromatosis were present. He was started on alpha blockade followed by beta blocker and surgical resection was planned. In the interim, escalating requirements of insulin were noted. Intra-operative course was complicated by systolic blood pressure rising to 290s which resolved after mass was removed. Immunohistochemical studies sent to Mayo, Rochester showed retained cytoplasmic SDHB expression in tumor cells. Hence, no further genetic testing was performed. Post excision, plasma-free metanephrines normalized with significant improvement in blood pressure and diabetes. He was followed with yearly plasma-free metanephrines for surveillance. Although asymptomatic, a three-fold rise of plasma metanephrines was noted five years later. CT Abdomen was concerning for recurrence. Dotate/PET scan showed dotate-avid para-aortic soft tissue lesion measuring 2.3 cm between the celiac artery and the superior mesenteric artery which was surgically excised with pathology consistent with paraganglioma (Ki67<1%). Diagnosis of paragangliomas is often in 3rd - 5th decade. About 30% are hereditary and associated with Von-Hippel-Lindau, Neurofibromatosis-1, MEN2A/B among other syndromes. They are mostly benign but SDHB pathogenic variants are likely to be malignant. Genetic testing should be considered in all paraganglioma patients to screen for germline pathogenic variants in SDH and other genes. Diagnosis of secretory paraganglioma is by urinary and/or plasma fractionated metanephrines and catecholamines. Treatment of choice is surgery when amenable to resection with preoperative medical blockade to prevent perioperative complications. Presentation: 6/1/2024

EXCISÃO DE MUCOCELE EM LÁBIO INFERIOR: RELATO DE CASO

Mucocele is the phenomenon of mucin leakage into soft tissues. The most common benign lesion of the oral cavity, of traumatic etiology, pseudocyst that appears after rupture of the duct of a minor salivary gland, with a predilection for the lower lip, floor of the mouth, belly of the tongue, followed by the buccal mucosa. It is worth mentioning that mucoceles can be self-limiting, that is, they rupture leaving shallow, painful ulcers and then heal on their own. However, there are mucoceles of a chronic nature, which require surgical excision and microscopic evaluation. In this sense, the present work aims to carry out a literature review as well as describe a clinical case report of mucocele in the lower lip, whose treatment of choice was surgical excision. In short, the chosen procedure is considered by many authors to be atraumatic, safe and effective.

6853 A Curious Case of MACS

Abstract Disclosure: M. Dillon: None. A. Syeda: None. V. Kantorovich: None. Introduction: Mild autonomous cortisol secretion (MACS) is characterized by biochemical evidence of mild hypercortisolemia inducing metabolic comorbidities without any obvious phenotypic stigmata of Cushing’s syndrome (CS). This case highlights the challenges faced in the diagnosis and management of MACS. Case: A 76-year-old female with past medical history of class II obesity (BMI 31.83 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, osteoporosis and chronic kidney disease stage IIIb was diagnosed with MACS after an overnight 1 mg dexamethasone suppression test (DST) showed unsuppressed 8 AM cortisol of 2.4 mcg/dL (<1.8 mcg/dL). Dexamethasone level was appropriate at 355 ng/dL (180-550 ng/dL), ACTH was <5 pg/mL (6-50 pg/mL) and DHEA-S was normal. Late night salivary cortisol (LNSC) levels were elevated to 0.12 mcg/dL (< 0.09 mcg/dL). The 24-hour urine cortisol level was normal. Baseline 8 AM cortisol level was 17 mcg/dL and ACTH was 19 pg/mL. Abdominal CT scan showed a 1 cm left adrenal nodule of 25 HU density and a normal right adrenal with no atrophy. Phaeochromocytoma and primary hyperaldosteronism work up was negative. She started on Mifepristone 300 mg daily and titrated up to 600 mg daily. She presented to our institution one month later with 1 week of nausea, vomiting and muscle weakness. Laboratory studies revealed acute kidney injury with creatinine of 6.69 mg/dL (baseline Cr 1.5 mg/dL) and rhabdomyolysis with creatinine kinase level of 12,819 U/L (24-173 U/L) and urine myoglobin level of 888 ng/mL (0-13 ng/mL). It was evident that her catastrophic presentation was from development of adrenal insufficiency in the setting of Mifepristone glucocorticoid receptor blockade. The drug was discontinued immediately. She was treated with intravenous hydration and intermittent diuretics. Over 10 days, her clinical status gradually improved and creatinine decreased to baseline levels. Discussion: MACS is a challenging diagnosis as cortisol levels are affected by several variables including obesity, drugs, and poorly controlled diabetes. Hence, a meticulous evaluation is mandated before confirming the diagnosis. Our patient’s baseline cortisol and ACTH levels were normal, and her DST and LNSC levels were mildly elevated. Unilateral cortisol producing adenoma causes contralateral gland atrophy due to suppressed ACTH. This was not evident in our patient, thus making the diagnosis questionable. Adrenalectomy is the treatment of choice in MACS with adrenal adenoma. Off label medical management with Mifepristone, a glucocorticoid receptor antagonist, is being pursued in select cases and was trialed due to our patient's age and surgical risk. Mifepristone is approved for the treatment of hyperglycemia due to CS. The data supporting its use in MACS is sparse. Therefore, it is important to be aware of associated risks of Mifepristone when advising patients. Presentation: 6/3/2024

Current Treatment Approaches for Full-Thickness and Non-Thickness Macula Hole in Pathological Myopia

Full-thickness and non-full-thickness macular holes seen in pathological myopia constitute a special subgroup in terms of vitretoretinal surgery with their formation mechanisms, progression and response to treatment. Compared to idiopathic macular holes, it has different features in that more complex tractional components are involved in its pathogenesis and tissue degeneration and atrophy play a role in pathological myopia. The determination of surgical indications, timing, and the choice of treatment for these cases should be tailored based on the pathology’s characteristics and the potential benefits of the surgery. The aim of surgical treatment is to eliminate tractional forces and restore the anatomical structure. This article aims to evaluate the treatment approaches for full-thickness and non full-thickness macular holes in pathological myopia by reviewing the current literature, thereby contributing to clinical practices in this field.

7553 Thyroid Paraganglioma: A Complex Tale of the Familiar Thyroid Nodule

Abstract Disclosure: V. Moorthy: None. A. Kondapally: None. L.E. Kimball-Ravari: None. Background: Thyroid paragangliomas are rare and often misdiagnosed on fine-needle aspiration (FNA). Clinical Case & Discussion: A 58-year-old female presented with an asymptomatic “cold” thyroid nodule. Ultrasound demonstrated a 2 cm hypoechoic nodule in the isthmus. FNA yielded a follicular lesion of undetermined significance, and genomic sequencing estimated a 50% risk of malignancy prompting the patient to opt for total thyroidectomy. Histopathology and immunohistochemistry (IHC) confirmed the diagnosis of benign paraganglioma (PGL). SDH-B (succinate dehydrogenase subunit B) was notably absent on IHC. Past medical history is significant for hysterectomy for uterine fibroids and obesity, along with a confirmed family history of Hereditary Leiomyomatosis with Renal Cell Cancer (HLRCC). The patient and several family members tested positive for a pathogenic variant of fumarate hydratase (FH) gene implicated in HLRCC and undergo annual MRIs for cancer surveillance. The loss of SDH-B suggests underlying mutation. Germline SDH mutations occur in 20% of patients with pheochromocytoma and PGLs, predisposing to hereditary syndromes. PGLs are catecholamine-secreting neuroendocrine tumors with carotid body and jugular PGLs accounting for 80% of head and neck PGLs (HNPGLs). Thyroid PGLs originate from the inferior laryngeal paraganglia. They are very rare, often non-secretory, and commonly present as asymptomatic solitary nodules. For these reasons, FNA, while contraindicated, is frequently performed. If FNA is considered, pre-procedural alpha-adrenergic blockade is recommended, although catecholamine secretion triggered by FNA is uncommon. Thyroid PGLs are misdiagnosed on FNA as other thyroid neoplasms. Awareness of the more unique cytopathology of thyroid PGLs and a comprehensive IHC can aid in accurate diagnosis. Interestingly, SDH (complex 2) and FH are closely linked enzymes in the Krebs cycle. Emerging evidence correlates germline FH mutations and hereditary pheochromocytoma-paraganglioma. PGLs are less commonly associated with MEN 2A and 2B, NF type 1, VHL, and Carney-Stratakis syndrome and Carney triad. Therefore, additional testing for SDH, RET, VHL and MAX genes was recommended in this case. Total thyroidectomy or lobectomy with or without elective lymph node dissection remains the treatment of choice. Annual 24-hour urine and plasma metanephrine testing will help screen for potential recurrence. Use of GLP1 agonists for weight loss in this patient warrants further genetic and safety evaluation. Clinical Lesson/Conclusion: Often misdiagnosed on FNA, thyroid paragangliomas are rare, with multiple genetic predispositions. FNA is contraindicated and if considered, must be performed after alpha-blockade. Germline SDH mutations are implicated in PGLs and increasing evidence links FH mutations to hereditary PGLs. Presentation: 6/3/2024

8356 Total Hypophysectomy in Cushing’s Disease: Results from a Terciary Center

Abstract Disclosure: M.V. Lopes: None. M.D. Severino: None. J. Rocha: None. C.R. Peixe: None. M.I. Alexandre: None. A. Gomes: None. M.J. Bugalho: None. Introduction: Transsphenoidal surgery (TSS) is the first line treatment for Cushing’s disease (CD), leading to remission in 70-80% of cases. Though selective adenomectomy is the preferred approach, total hypophysectomy may be needed. Objective: To describe 3 CD patients in which total hypophysectomy was performed. Clinical cases 1. A 58-year-old man with a history of type 2 diabetes (T2D) and obesity, was referred to the Endocrinology Clinic due to abdominal purple striae and facial plethora. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, high 24h urinary cortisol and no cortisol suppression in the overnight 1mg dexamethasone suppression test (DST). The CRH test was suggestive of CD but no adenoma was found on pituitary MRI. Inferior petrosal sinus sampling (IPSS) was compatible with CD with right-sided lateralization. Right hypophysectomy was performed but no CD remission was achieved, so the patient underwent total hypophysectomy. Corticotroph hyperplasia was identified in histology. After 9 months of follow-up, he mantains CD remission. 2.A 37-year-old woman was diagnosed with ACTH dependent hypercortisolism after referral to the Endocrinology Clinic for alopecia, amenorrhea, hypertension and hirsutism. Laboratory tests showed severe hypokalemia, high plasma ACTH and 24h urinary cortisol and the MRI showed a right-sided macroadenoma. Nonetheless, considering the clinical severity, an IPSS was performed and definitely excluded an ectopic Cushing’s syndrome (CS) thus confirming the diagnosis of CD with right-sided lateralization. The patient underwent selective TSS, however, for lack of CD remission, total hypophysectomy was performed. Histology revealed an adenocorticotrophic adenoma. Yet, a year later, she maintains persistence of CD, although less severe, and is under treatment with metyrapone. 3.A 58-year-old woman with a history of T2D and class 3 obesity, was evaluated in our Endocrinology Clinic due to obesity. Her physical examination suggested CS, so this hypothesis was investigated. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, elevated 24h urinary cortisol and no cortisol suppression in the overnight 1mg DST. The high dose DST was suggestive of CD but the pituitary MRI didn’t show an adenoma. IPSS was compatible with CD but it was not possible to determine lateralization. So, total hypophysectomy was performed. An adenocorticotrophic adenoma was identified in histology. Postoperative CD remission was achieved and persists 3 months later. Conclusions: These 3 cases highlight the challenge of treating CD and suggest that in certain cases total hypophysectomy may be the treatment of choice to cure or at least improve CD. Although it is associated with more complications than selective TSS, our patients had no complications, only developed panhypopituitarism and diabetes insipidus. Presentation: 6/1/2024

8479 A Challenging Case of Hypercortisolism in an Adult Patient With McCune Albright Syndrome

Abstract Disclosure: P. Kesavan Chary: None. S. Jasim: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder that occurs due to a spontaneous post-zygotic missense mutation in the GNAS gene resulting in activating gain of function mutations in G-proteins. MAS classically presents as a triad of café-au-lait skin pigmentation, fibrous dysplasia of bone, and precocious puberty. However, continuous autonomous stimulation of endocrine glands can also result in various other endocrinopathies. We present a rare case of hypercortisolism due to bilateral multinodular adrenal hyperplasia (BMAH) in an adult patient with MAS. Case Report: A 38 year old female had MAS, clinically manifested by precocious puberty, renal phosphate wasting with rickets and osteomalacia, fibrous dysplasia of bone with history of multiple fractures, growth hormone excess, and multinodular thyroid status-post total thyroidectomy. A surveillance CT abdomen showed bilateral (right 3.8 x 1.3 cm and left 1.0 x 0.9 cm) adrenal adenomas with low intrinsic attenuation and washout. On diagnosis, the patient had an AM cortisol of 32.5 ug/dL (6.2-19.4 ug/dL) after a low-dose dexamethasone suppression test (DST), and an AM cortisol of 27.3 ug/dL after a high-dose DST. Late night salivary cortisol was 0.518 ug/dL (<0.010-0.090 ug/dL), 24-hour urine cortisol was 78 ug/24hrs (6-42 ug/24hrs), and ACTH was <1.5 pg/mL (7.2-63.3 pg/mL). The patient was initially asymptomatic and monitored for a few months, but subsequently developed easy bruising, recurrent skin infections, and irritability. The patient declined surgical intervention and was initiated on Osilodrostat. Shortly after medication initiation, she was hospitalized for perforated diverticulitis, hypokalemia, and hypomagnesemia. During hospitalization, AM Cortisol was 49 mcg/dL (4.8-19.5 mcg/dL) and 24-hour urine cortisol was 1023 mcg/24hrs (normal range 3.5-45 mcg/24hrs; the patient’s level prior to admission was 170-190 mcg/24hrs). Osilodrostat was held and the patient was initiated on Etomidate infusion. Once plasma cortisol levels normalized, she resumed Osilodrostat prior to discharge. The patient subsequently tried multiple medical therapy options before undergoing a bilateral adrenalectomy as a definitive treatment choice. Conclusion: The gain of function mutations in MAS result in autonomous endocrine gland function that can manifest clinically as various endocrinopathies. While the most common endocrinopathies in MAS are precocious puberty, hyperthyroidism, and pituitary dysfunction, active surveillance is critical to monitor for less common presentations such as hypercortisolism. This is the first report of adrenal Cushing’s in an adult patient with MAS. Presentation: 6/3/2024

12338 Risk Of Retinopathy In Patients With Type 2 Diabetes On Semaglutide

Abstract Disclosure: A. Gupta: None. M. Nassar: None. H. Ghanim: None. Title: Risk of Retinopathy in Patients with Type 2 Diabetes on SemaglutideBackground: The use of semaglutide in patients with diabetic retinopathy (DR) has raised safety concerns. While previous studies, including a meta-analysis and the SUSTAIN trial, suggested an association between rapid HbA1c reduction and retinopathy progression, recent data question the increased risk with semaglutide. Our study investigates this risk of intensive therapy benefits for the prevention of DR. Methods: This retrospective cohort study utilized TriNetX electronic health records, analyzing 117,693,426 patients with type 2 diabetes mellitus (T2DM) on anti-hyperglycemic drugs. We divided patients into those with and without a history of retinopathy, further subdividing them by treatment (Semaglutide, Sitagliptin, and Empagliflozin). After matching for confounders, we analyzed the incidence and progression of retinopathy among 336,338 Semaglutide, 578,117 Sitagliptin, and 434,552 Empagliflozin patients without a history of DR, as well as a cohort with history. Results: In patients without a prior history of DR, semaglutide showed a significant reduction in DR incidence over three years compared to sitagliptin and empagliflozin (p<0.0001). However, in those with a history, the reduction was not statistically significant (p > 0.05). Patients with mild DR on Semaglutide experienced fewer progressions to severe stages (p<0.0001), while outcomes in severe cases were inconclusive.Discussion: Semaglutide may lower the risk of developing DR in patients with T2DM without a prior history of DR and potentially stabilize or improve mild conditions without worsening severe retinopathy. The observed effects could influence treatment choices, emphasizing the need for individualized patient management. Conclusion: Semaglutide appears safe regarding retinopathy risk in patients with T2DM, offering protective benefits in those without history and not exacerbating conditions in those with prior DR. This underscores the drug's potential for comprehensive diabetes management without compromising ocular health. Presentation: 6/3/2024

TCD-Guided management in carotid endarterectomy: a retrospective study

BackgroundːStroke, primarily resulting from ischemic conditions, is the foremost cause of mortality and long-term impairment and is frequently associated with narrowing of the carotid arteries. Although carotid endarterectomy (CEA) is the treatment of choice, it carries the risk of cerebral ischemia and reduced blood flow. Transcranial Doppler (TCD) ultrasound offers a nonintrusive method to assess cerebral blood circulation during CEA, potentially enhancing surgical outcomes. The objective of this study was to assess the clinical utility and safety of TCD monitoring during CEA and to identify factors influencing postoperative complications.MethodsThis retrospective analysis included 158 CEA patients (from January 2021–August 2023) who underwent TCD monitoring and whose data were compared to historical standard care data. The primary outcomes were operation duration and artery occlusion time. Secondary outcomes included carotid shunt usage, seven-day postoperative complications, and six-month carotid artery patency. Logistic regression identified factors linked to adverse reactions, and a predictive model was evaluated with a receiver operating characteristic (ROC) curve.ResultsːComparative analysis indicated significant reductions in both the duration of surgery (113.26 ± 7.29 min) and artery occlusion time (21.85 ± 2.92 min) for patients monitored with TCD (P < 0.001) and an increase in carotid shunt implementation (25% as opposed to traditional care). The observed postoperative complications were minor, with a nonsignificant trend that favored the use of TCD-monitored procedures (1% vs. historical rates). Factors such as patient age and plaque echogenicity were found to be predictive of postoperative issues, with plaque echogenicity emerging as a significant predictive factor (OR = 10.70, 95% CI: 2.14–202, P = 0.02) upon multivariate analysis. The predictive model exhibited high precision (AUC = 0.93).ConclusionThis retrospective evaluation suggested that TCD monitoring in the CEA may reduce procedural time and potentially decrease postoperative complications, supporting its use for personalized surgical planning.