bluuebunny/crossref_metadata_2025 huggingface dataset:
High-density Lipoprotein Over Midlife and Future Cognition in Women: The SWAN HDL Ancillary Study
Authors: Qi Meiyuzhen , Billheimer Jeffrey , Chang Chung-Chou H , Janssen Imke , Brooks Maria M , Orchard Trevor , Karlamangla Arun S , Barinas-Mitchell Emma , Derby Carol A , McConnell Dan , Crawford Sybil , El Khoudary Samar R
Published: October 2024

Context

Limited data provides evidence-based insights on the association between the comprehensive metrics of high-density lipoproteins (HDL) and cognitive performance, especially in midlife women for whom the benefit might be the greatest.

Objective

To assess the associations of serum HDL metrics including HDL lipid content [HDL cholesterol, phospholipid (HDL-PL), triglyceride], proteins/subclasses [apolipoprotein A-1 (apoA-1); small, medium, large, total HDL particle (HDL-P); and HDL size], and cholesterol efflux capacity with cognitive performance in midlife women.

Methods

This prospective cohort study was conducted among 503 midlife women (1234 observations) from the Study of Women's Health Across the Nation HDL ancillary study. Joint models were applied to examine associations of HDL metrics assessed at midlife (50.2 ± 2.9 years, baseline of the current study) and their changes over midlife (6.1 ± 3.9 years of duration) with subsequent cognitive performance [working memory (Digit Span Backward Test), processing speed (Symbol Digit Modalities Test), and episodic memory immediate and delayed recall (East Boston Memory Test)] assessed repeatedly (maximum 5 times) 1.5 ± 1 years later over 7.72 ± 4.10 years of follow-up.

Results

Higher total HDL-P and smaller HDL size at midlife were associated with a better subsequent immediate recall, delayed recall, and/or processing speed. Greater increase in HDL-PL, apoA-1, medium HDL-P, and total HDL-P and less increase in HDL size over midlife were associated with a better subsequent immediate and/or delayed recall.

Conclusion

Enhancing specific serum HDL metrics during midlife could be promising in cognitive restoration, particularly memory, the initial and predominant symptom of Alzheimer's disease.
6613 Liver and Spleen Linked in Hepatic Steatosis during Weight Reduction in Type 2 Diabetes
Authors: Han K , MIN K
Published: October 2024

Disclosure: K. Han: None. K. Min: None.

Splenectomy increased serum lipids, except triglyceride (TG) and high-density lipoprotein (HDL), significantly accelerating hepatic steatosis in animal study. Recently, the concept of a liver-spleen axis has been proposed in nonalcoholic fatty liver disease. The purpose of this study was to investigate change of the liver Hounsfield Units (HU), reflecting the hepatic steatosis, and its relation to spleen HU, central, or peripheral and ectopic adipose tissue during weight reduction in type 2 diabetes. Total 187 women with type 2 diabetes were educated on lifestyle modification. We assessed liver Hounsfield Units(HU) and spleen HU with total abdominal fat(ATAF) , visceral adipose tissue (AVAT), subcutaneous adipose tissue(ASAT) at mid-abdomen level, and total adipose tissue (TTAT)and intramuscular adipose tissue(TIMAT) at midthigh level using nonenhanced computed tomography, at baseline and 12 weeks. We investigated whether changes in liver HD were related to fat in other regions, serum triglycerides, free fatty acids, and adiponectin-leptin ratio (ALR). The participants’ age was 55.2±7.3 years, BMI was 27.3±2.7 kg/m2, Body Weight (BW) 66.8±6.9kg). Baseline liver HU was 54.7±11.5, and spleen HU was 48.5±8.5. At 12 weeks, BW lost 2.4±2.2kg. Liver HU changed with spleen HU (r=0.357, p<0.001, ATAT(r=-0.343, p<0.0001), AVAT (r=0.220, p=.011), ASAT(r=-0.339, p<0.001) and adiponectin-leptin ratio (ALR) (r=-0.174, p=0.047), but no significant relations with TTAT, TIMAT, triglyceride, and free fatty acid. Linear regression analysis showed the best model for change of liver HU (Model R2=0.209, p<0.001) was as follows: Change of Liver HU=0.534 +0.038* change of spleen HU - 0.290* change of ATAF. Higher spleen HU (p<0.001) and lower abdominal fat (p<0.001) predicted higher liver HU (less steatosis). These results suggested that the liver might be metabolically linked to the spleen in hepatic steatosis of type 2 Diabetes.

Presentation: 6/2/2024
7769 Natural plant extract alleviates high-fat diet-induced obesity through enhancing PLIN5 expression
Authors: Shin Su-Kyung , Jang Hisue , Kwon Eun-Young
Published: October 2024

Disclosure: S. Shin: None. H. Jang: None. E. Kwon: None.

Obesity is one of the metabolic diseases caused by excessive differentiation and excessive accumulation of adipose tissue due to an imbalance between energy intake and consumption. Various drugs have been developed to effectively treat obesity, but the side effects often outweigh the benefits. Therefore, alternative weight loss supplements that can minimize side effects are needed. In this study, the effects of natural plant extract (NPE) on the high-fat diet (HFD)-induced obesity mice were confirmed to discover new anti-obesity material.After acclimating C57BL/6J mice for 1 week, they were divided into two groups: a normal diet (ND) group and an HFD group. After inducing obesity over 4 weeks, the HFD group was divided into HFD and HFD+NPE and reared together with the ND group for an additional 10 weeks. After a 12-hour fasting period, observations were made on weight, adipose tissue mass, morphological changes in adipocytes, and the expression differences in genes and proteins related to fatty acid oxidation (FAO) in the epididymal white adipose tissue, particularly focusing on the PLIN5 protein.The increase in body weight and epididymal fat mass induced by the HFD was reduced by the administration of NPE. Morphological analysis of the epididymal fat revealed a significant increase in adipocyte size in the HFD group, whereas the NPE group showed a reduction in adipocyte size. The expression of FAO-related genes (PPARa, PGC1a, CPT1, and CPT2) and TCA cycle-related genes (PDHb, ACO, DIST, SUCLG, SDHC, and MDH2) decreased in the epididymal fat due to the HFD, but significantly increased with the administration of NPE. The NPE induced the breakdown of intracellular stored triglycerides by upregulating ATGL, LIPE, and MGL mRNA expression. The resulting liberated fatty acids were translocated to the mitochondria and oxidized through the TCA cycle, ultimately leading to a reduction in body fat. Furthermore, PLIN5 expression exhibited a significantly higher level in the NPE group compared to the other two groups. In other words, elevation in PLIN5 expression, induced by the NPE, appears to enhance lipid breakdown, activate FAO pathways, and stimulate the TCA cycle. Consequently, lipid combustion is increased, improving the weight gain and fat accumulation induced by the HFD.If additional experimental results on human application align with the above findings, NPE holds the potential as a low-side-effect ingredient for weight loss supplements.

Presentation: 6/1/2024
9210 Nephron specific ATP6AP2 knockout reduces renal fat accumulation in mice consuming high fat diet
Authors: Allen Culver Silas , Lois Balugo Jamie Lynne , Jansen Maurits , Harris Thurl , Siragy Helmy M
Published: October 2024

Disclosure: S.A. Culver: None. J. Balugo: None. M. Jansen: None. T. Harris: None. H.M. Siragy: None.

Diet induced obesity causes increased renal fat accumulation in both humans and mice which contributes to obesity related kidney injury. We have previously shown that mice with nephron specific ATP6AP2 knockout (KO) consuming high fat diet (HFD) are resistant to weight gain due to increased urinary excretion of glucose, albumin, and fatty acids. Magnetic resonance imaging (MRI) is a useful imaging modality for quantifying organ fat content in live animals though there are few reports of its use quantifying fat in murine kidney. We hypothesized that nephron specific ATP6AP2 knockout inhibits renal fat accumulation with HFD and that we would be able to detect this using MRI. Eight-week-old male wild type (WT) or inducible nephron specific ATP6AP2 KO mice underwent either induction with oral doxycycline or received sucrose water as controls before being placed on either normal diet (ND) (12% fat) or HFD (45% fat) for 3 months. Mice were then imaged using a 9.4 Tesla Bruker BioSpin MRI to determine both liver and kidney cortex fat content. The mean weight of WT HFD mice was 36.03 g compared to 29.03 g in WT ND controls. ND fed and HFD fed KO mice weighed 22.74 g and 23.03 g respectively. MRI showed significant 67% (p<0.05) increase in liver fat content in WT HFD compared to WT ND fed controls, confirming the ability of our MRI technique to detect expected differences in organ fat content. In renal cortex, MRI detected a 54% (p<0.05) increase in lipid content for WT HFD mice compared to WT ND controls. Nephron specific ATP6AP2 KO on HFD demonstrated reduced renal cortical lipid content by 36% (p<0.05) compared to WT HFD controls. These results indicate that ATP6AP2 KO is associated with reduced renal fat accumulation that is measurable with in vivo MRI. MRI therefore represents a valuable tool for studying renal sequelae of obesity in live murine models. Future investigation should examine whether ATP6AP2 KO prevents renal lipotoxicity and kidney injury in the setting of obesity.

Presentation: 6/3/2024
12418 Patient- And Caregiver-reported Experiences Of Hunger, Weight, And Energy In Acquired Hypothalamic Obesity Before And During Setmelanotide Treatment
Authors: Roth C L , Shoemaker A H , Ervin C , Norcross L , Fehnel S , Huber C , Scimia C , Abuzzahab M J
Published: October 2024

Disclosure: C.L. Roth: Advisory Board Member; Self; Rhythm Pharmaceuticals, Inc. A.H. Shoemaker: Advisory Board Member; Self; Saniona, Rhythm Pharmaceuticals, Inc. Speaker; Self; Saniona, Rhythm Pharmaceuticals, Inc. C. Ervin: Other; Self; Rhythm Pharmaceuticals, Inc. L. Norcross: Other; Self; Rhythm Pharmaceuticals, Inc. S. Fehnel: Other; Self; Rhythm Pharmaceuticals, Inc. C. Huber: Employee; Self; Rhythm Pharmaceuticals, Inc.. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. C. Scimia: Employee; Self; Rhythm Pharmaceuticals, Inc.. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. M.J. Abuzzahab: Consulting Fee; Self; Rhythm Pharmaceuticals, Inc., Ascendis, Novo Nordisk, Lumos, Soleno, Pfizer, Inc.. Speaker; Self; Rhythm Pharmaceuticals, Inc., Ascendis, Novo Nordisk, Lumos, Soleno, Pfizer, Inc..

Background: Acquired hypothalamic obesity (HO) is a rapid-onset, severe obesity caused by hypothalamic injury that may impair melanocortin-4 receptor (MC4R) pathway signaling and lead to hyperphagia, decreased energy expenditure, and severe obesity, for which no approved therapies exist. We describe experiences or caregiver observations of hunger, weight, and energy in patients with HO before and after investigational treatment with the MC4R agonist setmelanotide. Methods: In-depth qualitative interviews were conducted via Zoom by 2 members of the study team with patients or caregivers of patients who completed a Phase 2 trial of setmelanotide (NCT04725240) and enrolled in the open-label long-term extension (NCT03651765). Eligible patients were aged ≥12 years and eligible caregivers were aged ≥18 years and full-time caregivers of patients aged <12 years or unable to self-report. Interview transcripts were analyzed using a thematic approach. Results: Five participants (3 patients, 2 caregivers) completed interviews. After hypothalamic damage (before setmelanotide), all participants described unrelenting hunger, drastically reduced energy or physical activity, and substantial weight gain negatively impacting self-esteem, emotions, and family dynamics. With setmelanotide, all participants reported reduced weight or body mass index, and 4 reported reduced hunger, which was accompanied by improved food-seeking behaviors, sleep (eg, not waking at night for food), self-confidence, and mood. Participants identified reduced hunger and weight and improved emotions or mood as the most important treatment benefits. Additional benefits were improved social engagement, physical activity, and school/work performance. All reported satisfaction and a desire to continue setmelanotide. Conclusions: Patients experienced negative consequences of hypothalamic damage on hunger, weight, and energy that were alleviated by setmelanotide, resulting in broad benefits for patients and caregivers.

Presentation: 6/1/2024
7358 Profile of Circulating miRNAs Associated with Body Weight Reduction in Type 2 Diabetes Patients Treated with GLP-1 Receptor Agonist Dulaglutide: Secondary Analysis of AWARD-7 Trial
Authors: Satake Eiichiro , McFarlin Brandon E , Cin Tye Sok , Ricca Joseph , Matthew Wilson Jonathan , Duffin Kevin L , Krolewski Andrzej S
Published: October 2024

Disclosure: E. Satake: None. B.E. McFarlin: Employee; Self; Eli Lilly & Company. S.C. Tye: None. J. Ricca: None. J.M. Wilson: Employee; Self; Eli Lilly & Company. K.L. Duffin: Employee; Self; Eli Lilly & Company. A.S. Krolewski: Grant Recipient; Self; Novo Nordisk, NNF14OC0013659.

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to have beneficial effects on reducing body weight, such as appetite control, reducing fat accumulation, and improving metabolic parameters. However, the underlying mechanism remains unclear, and no biomarker has been established to predict or monitor the effects of GLP-1 receptor agonists. Circulating microRNAs (miRNAs) are short, non-coding RNA molecules known to regulate proteins. In this study, we investigated the effect of the GLP-1 receptor agonist Dulaglutide (DULA) treatment on longitudinal changes in plasma concentrations of circulating miRNAs. We analyzed the correlation with body weight change in patients enrolled in the AWARD-7 trial. Methods: Plasma samples were obtained from patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) stages 3-4 who were treated with Dulaglutide 1.5 mg (n=29) or insulin Glargine (n=31) for 52 weeks. Using the HTG edgeSeq platform, we measured 2,079 miRNAs at baseline, 26 weeks, and 52 weeks. As a sub-cohort of the study, we divided patients receiving DULA treatment into two categories: patients who lost 3 kg of weight during the first 26 weeks of treatment (n=11) and those who did not (n=18). Fold change (FC) values were calculated for each patient and each miRNA by dividing the concentration of miRNA at 26 weeks by its concentration at baseline. Results: Body weight at 26 weeks in the DULA treatment group was significantly reduced compared to the placebo group (p=7.6x 10-4). Among the patients who received DULA treatment and lost 3 kg of body weight during this period, 31 miRNAs were found to be significantly up/downregulated at baseline compared to those who did not lose weight. Out of these miRNAs, 18 showed a significant correlation with the change in body weight between baseline and 26 weeks. Further analysis of the changes in miRNAs from baseline to 26 weeks (delta) revealed that 102 miRNAs differed significantly between the patients who lost body weight and those who did not. Among these miRNAs, 47 were found to be correlated with delta body weight at 26 weeks. Conclusion: This study demonstrated circulating miRNAs associated with body weight reduction in T2D patients treated with a GLP-1 agonist. These miRNAs have the potential to serve as biomarkers to predict or monitor the effect of DULA on body weight in T2D patients and may provide a mechanistic understanding of physiological processes associated with weight reduction.

Presentation: 6/3/2024
8515 Role of Insulin Receptor in Trpv1-positive Adipocyte Progenitor Cellsin Adipocyte Differentiation and Metabolic Function
Authors: Sahin C , Camara H , Shamsi F , Lynes M , Tseng Y H
Published: October 2024

Disclosure: C. Sahin: None. H. Camara: None. F. Shamsi: None. M. Lynes: None. Y. Tseng: None.

Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, is an important endocrine organ in the regulation of energy balance. Stimulating BAT activation and beiging of white adipose tissue (WAT) are new strategies to combat metabolic diseases, such as obesity and diabetes. Traditionally, thermogenic adipocytes are known to originate from mesenchymal Pdgfrα-expressing adipocyte progenitor cells (APCs). A previous study conducted by our lab identified vascular smooth muscle cells as a novel cellular origin of APCs. These cells are characterized by the expression of transient receptor potential cation channel subfamily V member 1 (Trpv1+). With cold exposure, the Trpv1+ APC-derived adipocytes are increased in BAT and WAT and differentiated into highly thermogenic adipocytes. These findings indicate that the Trpv1+-APCs may play an important role in the development of brown and beige adipocytes in response to cold. This study was designed to explore the function of the Trpv1+ APC-derived adipocytes in thermogenic adipocyte differentiation and metabolic regulation. We generated a mouse model in which insulin receptor (IR), a well-known player in adipocyte differentiation, was deleted in the Trpv1+ APCs to impair their adipogenic potential. Trpv1-Cre::mTmG::IRflox transgenic and IRwt control mice were housed at cold temperature (5°C) for 7 days. Because the lineage tracing mTmG system was included, we were able to trace the fate of Trpv1+ APCs in the presence or absence of IR. We first examined the adipogenic capacity of the IR-deficient Trpv1+ cells in BAT and WAT tissues using whole-mounted adipose tissue imaging. In control mice, approximately 30% of all mature adipocytes were derived from Trpv1+ APCs in adipose tissue in response to cold. With ablation of IR in Trpv1+ APCs, this contribution was significantly reduced in BAT (by 11.7 % in females; 6.1% in males), inguinal WAT (by 16.8% in females; 19.3% males), and perigonadal WAT (by 11.4% in females; 14.8% in males) in transgenic mice compared to control mice. These results showed that IR-deficiency in the Trpv1-expressing cells impaired their adipogenesis in both male and female mice. In contrast, thermogenic genes (e.g., Ucp1, Pparγc1a, Cox7a1) were not significantly altered in BAT and inguinal WAT of the IR-deficient Trpv1+ APCs mice. Despite the changes in the adipocyte populations, we observed that deletion of IR in Trpv1+ APCs has no impact on body weight, food intake, fat mass, glucose tolerance, and insulin sensitivity relative to control mice. Taken together, blocking the contribution of Trpv1+ APCs to the mature adipocyte population results in no metabolic changes in mice, suggesting that the other APCs, such as PdgfRα+ APCs, may potentially compensate for impaired adipogenesis in different adipose tissues.

Presentation: 6/1/2024
8729 Role of PARP1 in Macrophage-dependent Regulation of Adipose Tissue Inflammation, Adipogenesis, and Diet-induced Obesity
Authors: Zhu J , Gupte R , Nandu T S , Kraus W L , Huang D
Published: October 2024

Disclosure: J. Zhu: None. R. Gupte: None. T.S. Nandu: None. W.L. Kraus: None. D. Huang: None.

Adipose tissue macrophages play a significant role in maintaining adipose tissue homeostasis, as well as promoting chronic low-grade inflammation during the development of obesity and metabolic dysfunction. However, the crosstalk between macrophages and adipocytes, especially how macrophages affect adipogenesis in obese adipose tissue, are still poorly understood. We have investigated the function of PARP1 in the control of adipogenesis by using an adipocyte precursor-specific Parp1 knockout mouse model. Here, to investigate the role of macrophage PARP1 in regulating adipogenesis, we deleted Parp1 in the myeloid lineage by crossing Parp1loxp/loxp mice with LysMCre mice (Parp1 cKOLysMCre). Macrophages-specific knockout of Parp1 dramatically reduced LPS-induced pro-inflammatory gene expression in bone marrow-derived macrophages (BMDMs). To explore whether macrophage-specific Parp1 knockout affects adipocyte differentiation, we treated the primary preadipocytes from stromal vascular fraction (SVF) of white adipose tissue with the conditioned medium from LPS-stimulated control or Parp1 cKOLysMCre BMDMs throughout a 6-day period of differentiation. We observed that exposure of preadipocytes to the conditioned medium of Parp1 cKOLysMCre macrophages promoted adipogenesis by Oil Red O staining, as well as by monitoring the expression of key proadipogenic marker genes (e.g., Adipoq and Fabp4) by RT-qPCR. To further investigate the role of macrophage-specific deletion of Parp1 in metabolic outcomes, we fed the Parp1 cKOLysMCre mice with a high fat diet for 12 weeks. The knockout mice exhibited a significant increase in body weight compared to the control mice. Interestingly, we observed a reduction of the total number of macrophages resident in the adipose tissue from macrophage-specific Parp1 knockout mice. To explore the underlying mechanism, we performed single cell RNA-seq for adipose tissue macrophages using sorted SVF cells collected from HFD-fed mice. The results demonstrated dramatic reductions in macrophage M1 marker genes and pro-inflammatory transcription factors in Parp1 cKOLysMCre mice. Taken together, our study suggests that Parp1 knockout in macrophages selectively affects the recruitment and pro-inflammatory activation of macrophages, as well as adipocyte differentiation in adipose tissue. Importantly, despite the decreased adipose tissue inflammation, macrophage-specific Parp1 knockout enhanced adipogenesis, which leads to obesity in mice.This work was supported by a grant from the NIH/NIDDK (R01 DK069710) and funds from the Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment, to W.L.K., and a grant from NSFC (82270929) to D.H.

Presentation: 6/1/2024
12394 "Sugar And Tumors: A Case Report On New-onset Diabetes In Metastatic Pheochromocytoma With Elevated Dopamine Levels"
Authors: Agrawal Bhavika , mehta vidhi , naseem rabia , Renzu Mahvish , rashid rakin
Published: October 2024

Disclosure: B. Agrawal: None. V. mehta: None. R. naseem: None. M. Renzu: None. R. rashid: None.

Introduction: Metastatic pheochromocytoma is a rare neuroendocrine tumor with potential complication of new-onset diabetes mellitus (DM). We present a case highlighting the challenges in managing a patient with metastatic pheochromocytoma and concurrent DM. Case presentation: A 66-year-old male with a history of hypertension and gout initially presented in 2010 with an adrenal mass, later identified as pheochromocytoma and resected. In 2018, he presented with bilateral leg pain, revealing metastatic disease-causing spinal cord compression along with metastatic lung nodules and metastasis in adrenalectomy bed. Despite interventions including T6,7,8 laminectomy in 2020 and radiation therapy, metastases persisted. In 2024, he presented with polyuria, polydipsia, and hyperglycemia (blood glucose >500 mg/dL). Laboratory findings showed elevated a1c of 15 in addition to elevated normetanephrines, metanephrines, and dopamine with levels of 3880, 48 and 488 respectively. He was diagnosed with new-onset DM and started on insulin therapy in addition to metformin and jardiance. Discussion: Secondary diabetes mellitus (DM) in secretory pheochromocytoma occurs in approximately 50% of cases, manifesting from mild insulin resistance to severe presentation like DKA. Epinephrine-secreting tumors contribute to glucose intolerance by activating beta receptors, thereby stimulating gluconeogenesis. Patients with higher levels of epinephrine and preoperative glucose intolerance were more prone to developing postoperative hypoglycemia, requiring close monitoring during the postoperative period. Additionally, research by DiSalvo et al. Epinephrine-secreting tumors have a more significant impact on hyperglycemia by impairing insulin secretion and stimulation GLP-1. Tumor resection has been found to be more effective effective in restoring normal glucose homeostasis in these patients. Dopamine-secreting pheochromocytomas are rare neoplasms characterized by the presence of immature catecholamine vesicles that inhibit dopamine conversio owing to localized dopamine beta hydroxylase. Typically presenting around the age of 48, these tumors often lack excess catecholamines, leading to atypical symptoms such as local discomfort or pain from tumor compression. These neoplasms are less detectable on metaiodobenzylguanidine (MIBG) scans, necessitating positron emission tomography (PET) for accurate diagnosis. Surgical resection is the treatment, with preoperative management involving metyrosine instead of alpha blockers. These tumors are frequently diagnosed late, often in a malignant stage, contributing to poor prognosis Conclusion: Overall, understanding the complex interplay between catecholamines and glucose metabolism is crucial for the comprehensive management of patients with pheochromocytoma and secondary DM.

Presentation: 6/1/2024
7328 A case of Adrenal Calcifications in a Patient with Familial Cerebral Cavernous Malformations
Authors: Dorin Richard I , Aguirre Lina E , Bomgardner Magdalena
Published: October 2024

Disclosure: R.I. Dorin: None. L.E. Aguirre: None. M. Bomgardner: None.

Background: Familial syndromes of cerebral cavernous malformation (fCCM) having autosomal dominant inheritance and variable penetrance and expression have been linked to loss of function mutations at three genetic loci. The association of small focal adrenal calcifications with fCCM was only recently recognized in a New Mexican cohort of subjects predominately carrying the founder common Hispanic mutation in the CCM1 locus (stop codon Q455X in the Krev1 interaction trapped gene 1 [KRIT1]). We report a case of bilateral, focal adrenal calcifications in a patient affected by fCCM. Clinical Case: A 72-year-old Hispanic male with past medical history of intracranial CCM was referred for osteoporosis and hyperthyroidism due to multinodular goiter. Small focal calcifications of the adrenal glands were incidentally noted on prior imaging studies. There was no history of anticoagulant use, adrenal hemorrhage, or systemic/adrenal infection. The patient was without clinical manifestations of adrenal insufficiency, morning cortisol and plasma ACTH concentrations were normal, and exam was negative for hyperpigmentation or cutaneous vascular malformations. Brain MRI revealed the presence of over 100 parenchymal CCM lesions. A family history of CCM was reported in multiple family members, including 7/10 siblings. Conclusion: In addition to cutaneous malformations, small focal adrenal calcifications are now recognized as one of the extra-neurological manifestations of fCCM, particularly in patients harboring the common Hispanic CCM1/KRIT1 mutation. Whether adrenal calcifications are observed in fCCM patients having other mutations of KRIT1 or other genetic loci of fCCM (CCM2 or PDCD10) remains to be determined. The focal adrenal calcifications are believed to be result of dyssynchronous, subclinical hemorrhagic events related to vascular malformations in the adrenal gland. These findings implicate a role for KRIT1 in endothelial development in the adrenal gland in addition to established role in CNS, spinal cord, and skin. Our patient appeared had normal adrenocortical function, as expected for the focal nature of the adrenal lesions. Though adrenal function has not been evaluated in fCCM patients, there are no reports of primary adrenal insufficiency in fCCM in the literature. Adrenal calcifications may be considered to represent an imaging biomarker for fCCM, and fCCM should be included in the differential diagnosis of adrenal calcifications. The incidental recognition of characteristic small, focal adrenal calcifications in either bilateral or unilateral adrenal glands should prompt evaluation for fCCM. References: Strickland CD, Eberhardt SC, et al. Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Radiology. 2017; 284(2):443-450.

Presentation: 6/2/2024
7412 A Case of Exogenous Cushing Syndrome in a Patient with History of Acromegaly Status Post Transsphenoidal Resection Complicated by Panhypopituitarism Requiring Glucocorticoid Replacement
Authors: Capozza Alexandria , Heluey Camila , Chaidarun Sushela S
Published: October 2024

Disclosure: A. Capozza: None. C. Heluey: None. S.S. Chaidarun: None.

Introduction: Exogenous Cushing syndrome is a complication of long-term glucocorticoid therapy. Frequency of Cushingoid features such as truncal obesity, buffalo hump, moon faces, weight gain, striae, ecchymosis, and skin thinning increases as the glucocorticoid dose increases. Here we present a case of exogenous Cushing syndrome in a patient with history of acromegaly status post transsphenoidal resection of adenoma complicated by panhypopituitarism requiring glucocorticoid replacement. Clinical Case: A 37-year-old female with history of acromegaly status post transsphenoidal resection of somatotroph/thyrotroph adenoma in 2019 complicated by panhypopituitarism, diabetes insipidus, and type 2 diabetes was admitted after presenting with diarrhea and electrolyte derangements. At home, the patient was on desmopressin 0.1 mg nightly, dexamethasone 1.5 mg daily, levothyroxine 175 mcg nightly, and estradiol 1 mg daily. Her dexamethasone dose had been increased from 0.75 mg-1 mg daily to 1.5 mg daily over the years due to hypoglycemia. At time of admission, labs were significant for free T4 of 2.20 (0.93-1.70 ng/dL), free T3 1.7 (2-4.4 pg/mL), sodium 130 (135-145 mmol/L), potassium 2.8 (3.5-5 mmol/L), calcium 7.4 (8.5-10.5 mg/dL), phosphorous 1.0 (2.5-4.5 mg/dL), PTH 237 (15-65 pg/mL), 25-OH vitamin D 39 (21-100), 1,25 vitamin D 31 (18-78 pg/mL), and glucose 207 (65-199 mg/dL). On physical exam, she had signs of acromegaly including large tongue, thick lips, large nose, prognathism, frontal bossing, and deep voice. She also appeared Cushingoid with rounded face, thin skin, multiple areas of ecchymosis, wide purple striae over the abdomen and upper arms, posterior cervical hump, supraclavicular fullness, and trunk obesity. Long-term, supra-physiologic dose glucocorticoids were thought to be the cause of her Cushingoid appearance. Glucocorticoids were also contributing to hyperglycemia and reduced conversion of free T4 to free T3. Conclusion: Glucocorticoids have numerous adverse effects such as hyperglycemia, exogenous Cushing syndrome, osteoporosis to name a few. Higher doses and longer duration of glucocorticoids carry a higher risk of adverse effects. This case illustrates the importance of thorough physical exam and frequent assessment for adverse effects in patients on glucocorticoids. Both acromegaly and Cushing syndrome render poor health outcomes, so optimal treatment and long-term care of post-surgical hypopituitarism is important.

Presentation: 6/3/2024
7469 A Case of Severe Transient Hypercortisolism In a Patient With Bacterial Meningitis
Authors: Harxhi Rea , Valentin Mihailescu Dan , Pilati Stamatoula
Published: October 2024

Disclosure: R. Harxhi: None. D.V. Mihailescu: None.

Background: Increased cortisol levels are known to occur in states of significant stress caused by acute illness. This may be attributed to stress leading to a rise in the corticotrophin releasing hormone thereby increasing adrenocorticotrophic hormone levels. This may consequently result in severe transient hypercortisolism and bilateral adrenal structural changes.Clinical case:A 55-year-old female with a past medical history of HTN and pre-diabetes presented to the hospital with a headache and altered mental status starting the day prior to admission. On arrival, she was found to be hypertensive, confused and was diagnosed with acute bacterial meningitis caused by streptococcus pneumoniae. Initial labs were notable for a potassium level of 2.5 mEq/L (normal 3.5-5 mEq/L). Work-up of persistent hypokalemia revealed a cortisol of 54.83 ug/dL (normal 6.7-22.6 ug/dL), ACTH 166 pg/mL (normal 9-50 pg/mL), aldosterone < 1 ng/dL (normal 3-16 ng/dL), and renin 0.57 (normal 0.25-5.82). CT of the abdomen showed bilateral periadrenal fat stranding, larger on the left with no adrenal nodules. On physical exam, patient did not exhibit any cushingoid features. Significantly elevated AM cortisol levels persisted despite treatment with high dose dexamethasone as part of the meningitis regimen (20 mg) resulting in unsuppressed AM cortisol of 9.22 ug/dL. An MRI of the brain showed a partially empty sella rendering a pituitary adenoma unlikely. Patient’s clinical status improved rapidly, and hypokalemia resolved. A low dose dexamethasone suppression test performed 9 days post admission produced an appropriately suppressed cortisol (1.0 ug/dL) and ACTH (14 pg/mL) levels, thus confirming a functional response to acute illness. Conclusion: This is a rare case of severe transient hypercortisolism with periadrenal congestion (“fat stranding”) resulting in hypokalemia (likely due inappropriate activation of mineralocorticoid receptors) in the setting of acute illness. There have been a very limited number of similar cases reported in literature, particularly with respect to CNS infections. It is important to recognize the response to acute stress could produce significant elevation of cortisol levels leading to the activation of mineralocorticoid receptors, therefore mimicking primary hyperaldosteronism.

Presentation: 6/1/2024
8045 A Case Report of Primary Adrenal Insufficiency Due to a Novel Pathogenic Variant in NR0B1 (Dax 1) Gene
Authors: de Lemos Manuela Nascimento , de Oliveira Martins Graziela , Richter Cicogna Julia Isabel , Scalissi Nilza Maria , Lima-Jr Jose Viana
Published: October 2024

Disclosure: M.N. Lemos: None. G.D. Martins: None. J.R. Cicogna: None. N.M. Scalissi: None. J.V. Lima-Jr: None.

Background: X-linked adrenal hypoplasia congenita caused by a pathogenic variant in NR0B1/DAX-1 is a rare inherited disorder. Patients with adrenal hypoplasia congenita are usually diagnosed with primary adrenal insufficiency in infancy or early childhood and usually present hypogonadotropic hypogonadism during adolescence. Clinical Case: Our male patient first presented with adrenal crisis at the age of 11 years, managed with glucocorticoids (prednisolone) and mineralocorticoids (fludrocortisone) in a local hospital at Bahia state, Brazil. He was referred to our reference service in Sao Paulo at the age of 14, in regular use of those medications. In this time, he brought some laboratorial analysis from the time of diagnosis, and it showed hyponatremia (sodium 99 mEq/L; NR 135 - 150) and hyperkalemia (potassium 6,7 mEq/L; NR 3,5 - 5), ACTH 23,2 pg/mL (NR < 45) and basal cortisol 6,6 mcg/dL (NR 5 - 18). In addition, we had from this time some additional laboratorial data from our admissional analysis, that found S-DHEA 10,1 mcg/dL (NR: 23,8 - 267,7), total testosterone 472 ng/dL (NR: 240 - 816), FSH 3,05 mUI/L (NR: < 10), LH 2,63 mUI/L (NR: <10), aldosterone 1,9 ng/dL (NR: 5 - 23) and renin > 500µIU/mL (NR: 2,8 - 39,9). Over the years, he started to present hyperpigmented skin lesions, due to primary adrenal insufficiency, resulting in great psychological suffering. We have screened hypogonadism many times during follow-up, but it was never found. The Genetics analysis by next generation sequence (NGS) identified in homozygosity, in gene NR0B1 (DAX1) on X chromosome, a variant of normality (chrX:30.309.248 C>T) were amino acid tryptophan was replaced by a stop codon. The patient does not have any brother, no other similar cases in the family and their parents deny consanguinity. Our case differs from others previously described because of the absence of associated hypogonadism, which is very common in NR0B1 variants. Clinical lesson/Conclusion: This case report shows that the absence of hypogonadism does not exclude the possibility of primary adrenal insufficiency caused by NR0B1(DAX 1) gene variants, and encourages genetic testing to patients living with this disease.

Presentation: 6/2/2024
6516 A Curious Case of Cushing Syndrome
Authors: Bellavia Lauren , Pignanelli Marcelle , Aqbal Daliha
Published: October 2024

Disclosure: L. Bellavia: None. M. Pignanelli: None. D. Aqbal: None.

Background: Cushing Syndrome (CS) from iatrogenic steroid administration is a well- established consequence of steroid use. It is important to recognize the potential of this condition even after a 1-time intraarticular steroid injection received months earlier. Clinical Case: A 40-year-old woman presented for evaluation of rapid weight gain, abdominal stretch marks and excess hair growth. Work-up was consistent with an ACTH-independent etiology of CS, suggestive of exogenous steroid use: ACTH undetectable (< 5 pg/mL, n6-50 pg/mL), 24 hr urinary free cortisol undetectable (< 2 ug/24 hrs, n6-42 ug/24hr), morning cortisol undetectable (< 0.5 mcg/dL, n4-22 mcg/dL). Historical review with patient included thorough review of medications and products without noted steroids. CT Abdomen pelvis completed 12 months prior for unrelated symptoms showed unremarkable adrenal glands without any masses. MRI Brain pituitary was normal. The source of her steroid exposure was still unclear, so a serum synthetic glucocorticoid screen was sent, which revealed elevated levels of Triamcinolone Acetonide (TCA) at 0.22 mcg/dL (n<0.10 mcg/dL). Her pharmacy and her providers were contacted to assess for any TCA exposures, which revealed that she received 40mg of TCA intraarticular injection via ultrasound guided technique into her right hip bursa for hip bursitis 6 months prior to presentation. No other exposures to TCA were found on review. Two months after presentation (8 months after TCA exposure), she began to develop nausea, vomiting, fatigue, and weakness and was thus started on Hydrocortisone 10mg daily for developing adrenal insufficiency. Repeat testing at that time revealed a suppressed adrenal axis, with repeat morning cortisol <0.5 mcg/dL, ACTH < 5 pg/mL and TCA levels of 0.15 mcg/dL. The pharmacokinetics of TCA following intraarticular injections is not well established with variable reports of synovial half-life ranging from 1 day to greater than 3 weeks, with the maximum effect of TCA on cortisol suppression observed with TCA serum levels of >0.19 mcg/dL. No other documented cases of TCA induced CS have demonstrated lasting clinical effects 8 months after TCA exposure. Conclusion: It is important to recognize the potential of rare adverse events that are attributable to the systemic absorption of intraarticular corticosteroids as their pharmacokinetics are not well known. This case raises the need for early general medical education for clinicians and patients about the potential risks of corticosteroids, administered from any route, even after isolated exposures. Reference: Dickson RR, Reid JM, Nicholson WT, Lamer TJ, Hooten WM. Corticosteroid and Cortisol Serum Levels Following Intra-articular Triamcinolone Acetonide Lumbar Facet Joint Injections. Pain Pract. 2018 Sep;18(7):864-870. doi: 10.1111/papr.12686. Epub 2018 Mar 23. PMID: 29436106.

Presentation: 6/3/2024
6853 A Curious Case of MACS
Authors: Dillon Martha , Syeda Asma , Kantorovich Vitaly
Published: October 2024

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
8358 A Diagnostic Challenge: Occult Paraganglioma Misdiagnosed as Pheochromocytoma Leading to Unnecessary Adrenalectomy
Authors: Kasireddy A R , Alshami S , Gummalla S , Balasubramaniapandian C , Henske J A , Albashaireh A
Published: October 2024

Disclosure: A.R. Kasireddy: None. S. Alshami: None. S. Gummalla: None. C. Balasubramaniapandian: None. J.A. Henske: None. A. Albashaireh: None.

Background: Pheochromocytomas and paragangliomas are rare neuroendocrine tumors. Catecholamine-secreting paragangliomas, like pheochromocytomas, can present with hypertension, sweating and episodic headaches. Thoughtful consideration must be given to distinguish between the two and potentially avoid a critical misdiagnosis. Case: A 61-year-old woman with hypertension and diabetes presented for evaluation of glomus jugulare discovered on CT of the head during evaluation of worsening hearing loss and tinnitus. She reported a longstanding history of episodic headaches, palpitations, anxiety spells and excessive sweating with more recent onset of ear fullness. When symptoms first presented, she had a left adrenalectomy 3 years prior. CT abdomen at that time showed 1.8 x 2.2 cm left adrenal nodule with a density of 12.2 HU and early contrast washout. Plasma metanephrines were normal but normetanephrines were elevated at 5.1 nmol/L (nl: less than 0.9 nmol/L). 24-hour urine metanephrines were normal but normetanephrines were elevated to 892mcg/24h (nl: 122-676 mcg/24h). MIBG scan was done and showed increased activity in the left adrenal nodule. Decision was made to proceed with left adrenalectomy. Surgical pathology was benign. Present evaluation after discovery of the glomus tumour with worsening symptoms showed normal plasma metanephrines, elevated plasma normetanephrines at 1529.9 pg/ml (0- 285.2 pg/ml), elevated plasma norepinephrine at 3280 pg/ml (0-874 pg/ml), with normal dopamine and epinephrine levels. CT head showed a 3 x 2.7 x 2.1 cm lytic destructive mass within the petrous temporal bone at the left skull base containing multiple internal calcifications. Given the lab and imaging findings, paraganglioma was diagnosed. Genetic testing revealed SDHB mutation. Neurosurgery consultants determined that the tumour was not amenable to resection. She was treated with radiation therapy, alpha blockade, and close blood pressure monitoring. Discussion: This case highlights the importance of reviewing the degree of hormonal elevations as well as the pattern of elevation to obtain a correct diagnosis. Paragangliomas commonly secrete normetanephrines rather than metanephrines and are often not immediately localized. Understanding the most likely genetic mutations when a paraganglioma is suspected can direct appropriate choice of radionuclide scanning agents. In this case, an earlier diagnostic scan may have prevented unnecessary adrenalectomy and facilitated earlier discovery of the paraganglioma.

Presentation: 6/2/2024
8097 A Rare Case of a Renal Cell Carcinoma and Pheochromocytoma Collision Tumor
Authors: Daas Rana , Logan Sarah , Sexton Wade , Chumbalkar Vaibhav , McGettigan Melissa , Veloski Colleen
Published: October 2024

Disclosure: R. Daas: None. S. Logan: None. W. Sexton: None. V. Chumbalkar: None. M. McGettigan: None. C. Veloski: None.

Background: Collision tumors are neoplasms comprised of two or more distinct tumors. A collision tumor consisting of a renal cell carcinoma and pheochromocytoma is extremely rare with less than five cases reported in the literature. Clinical Case: A 64-year-old male with a history of hypertension and type 2 diabetes presented with hematuria. The patient was on 4 anti-hypertensive medications at the time. He noted increased road rage, anxiety, tremors, and insomnia. A CT abdomen/pelvis revealed an exophytic 8.6 x 7.9 cm left upper pole renal mass and a 7.5 x 6.2 cm left adrenal mass. Contrast-enhanced MRI abdomen showed a left upper/interpolar renal mass with heterogenous peripheral enhancement, restricted diffusion, and areas of central necrosis along with a heterogenous, enhancing left adrenal mass with associated restricted diffusion and areas of cystic necrosis. Both masses had associated areas of hyperintense signal on T1 fat-suppressed MRI suggestive of hemorrhage. Lab work revealed ACTH 26.6 pg/mL (7.2-63.3), cortisol 13 ug/dL (3.7-19.4), aldosterone 23.1 ng/dL (4-31), renin 4 ng/mL/hr (0.5-4), dopamine 136 pmol/L (<240), epinephrine 121 pmol/L (<330), norepinephrine 23,666 pmol/L (1050-4800), plasma normetanephrines 12.3 nmol/L (0-0.89), plasma metanephrines <0.10 nmol/L (0-0.49), 24-hour urine normetanephrines 4,178 mcg (122-676) and 24-hour urine metanephrines 4,233mcg (224-832). The patient was treated with alpha blockade prior to left radical nephrectomy, left adrenalectomy and infrahilar paraaortic lymph node dissection. Despite aggressive preoperative alpha blockade with maximal doses of doxazosin, addition of metyrosine and other anti-hypertensives, he developed acute hypertension with adrenal mass manipulation during the procedure and then hypotension following removal. He was admitted to the ICU for management of hypotension with pressors and fluid resuscitation and did well. Post-operative labs showed plasma normetanephrines 0.98 nmol/L (0.00-0.89) and plasma metanephrines 0.11 nmol/L (0.00-0.49). Pathology revealed clear cell renal cell carcinoma (RCC) of the kidney. The adrenal gland showed 2 tumors; one consistent with pheochromocytoma and another intimately associated with the former consistent with metastatic RCC, morphology diagnostic of a collision tumor. Following surgical resection, the patient was referred for genetic testing, surveillance imaging and lab testing, and treated with pembrolizumab adjuvant therapy for stage IV RCC. Conclusion: Although collision tumors are rare, biochemical testing to rule out a pheochromocytoma must be performed for all indeterminate adrenal masses and presumed adrenal metastases of active malignancies.

Presentation: 6/2/2024