bluuebunny/crossref_metadata_2025_split huggingface dataset:
6766 Cortisol Pumps: Hospitalizations And Quality Of Life
Authors: Tiwari Apoorv , Berry Ryan , Mokbel Ali , Abotouk Ammar , Rahman Alrifai Abdul , Waleed Jumana , Alzohaili Opada 
Published: October 2024

Abstract
Disclosure: A. Tiwari: None. R. Berry: None. A. Mokbel: None. A. Abotouk: None. A.R. Alrifai: None. J. Waleed: None. O. Alzohaili: None.
Introduction: Oral regimens of exogenous cortisol fail to mimic physiologic levels. The discrepancy leads to complications, notably nausea, hyperglycemia, and susceptibility to infection. Finer control over cortisol delivery may be achievable with infusion pumps. While international groups have published their experiences with cortisol pumps, these studies often include less than ten patients. We share the largest, single-center cohort ever documented and the first from an American clinic. Methods: We conducted a retrospective cohort study. Through chart review, we identified all patients who received a cortisol pump at a private clinic; these pumps were originally designed to deliver insulin, but we repurposed them for patients with adrenal insufficiency. Clinic notes allowed collection of cortisol dosing pre- and post-exposure to the cortisol pump. We supplemented this information with telephone and digital surveys on the frequency of hospitalization, symptoms, and quality of life; patients provided verbal consent before participation. A Wilcoxon signed rank test and Fisher exact test evaluated significant differences between groups. Results: We identified thirty patients who received a cortisol infusion pump. Our study revealed a statistically significant decrease in hospitalization rate after exposure to a cortisol pump (n=26, mean difference = -5.94 hospitalizations per year, p=0.003), a decrease in the frequency of fatigue (n=25, p=0.0001) and a decrease in the frequency of hypotension (n=25, p=0.005). A validated, quality of life survey corroborated these findings with improvement in twenty-seven out of twenty-eight questions (n=22, p&lt;0.05). However, we did not detect a statistically significant difference in the frequency of eighteen other symptoms nor cortisol dosing between pre- and post-exposure groups. Conclusion: Infusion pumps can better mimic physiological variations in cortisol than oral dosing regimens. We show the extent to which cortisol dosing may reduce hospitalization rate - and therefore cost - as well as improve quality of life. We hope our findings encourage the availability of infusion pumps for adrenal insufficiency, a smaller market that may not otherwise attract commercial investment for a dedicated, randomized trial.
Presentation: 6/3/2024
7243 COVID-19 Associated Primary Autoimmune Adrenal Insufficiency: A New Clinical Entity
Authors: Naredo Rojas Jessica , Udegbe Beverly , Remba-Shapiro Ilan , Stockman Sara L , Nachtigall Lisa B 
Published: October 2024

Abstract
Disclosure: J. Naredo Rojas: None. B. Udegbe: None. I. Remba-Shapiro: None. S.L. Stockman: None. L.B. Nachtigall: None.
Background: The adrenal glands express angiotensin converting enzyme and transmembrane serine protease 2 receptors for SARS-CoV-2 protein S, facilitating viral entry. Cortisol levels are decreased in COVID-19 infection in correlation with disease severity. A number of potential mechanisms could relate autoimmune adrenal insufficiency (AI) to COVID-19, but whether or not SARS-CoV-2 infection plays a direct role in the autoimmune pathogenesis of primary AI is unknown. Furthermore, while single cases have been reported, autoimmune-mediated primary adrenal insufficiency following COVID-19 illness has not been formally studied. Purpose: To determine the association and clinical presentation of primary autoimmune adrenal insufficiency in patients with COVID-19 disease. Methods: A retrospective chart review was performed on patients presenting to Massachusetts General Hospital (MGH) with primary AI in the setting of recent COVID-19 illness. Review of the literature was performed to identify additional cases. Clinical, biochemical and radiographic characteristics, and interval between the diagnosis of COVID-19 and primary AI diagnosis were evaluated. Criteria for inclusion were biochemical confirmation of AI, clinical signs and/or symptoms of adrenal insufficiency within 6 months of COVID-19 illness, and evidence of autoimmune etiology of AI. Results: Five novel cases of COVID-19 associated primary autoimmune-mediated adrenal insufficiency from our Center were identified. Review of the literature yielded five additional cases. This series combines our Center’s experience, and the cases reported to date, including a total of 10 patients, 6 men and 4 women. All men (6/6) and 2 women (2/4) were &lt; 30 years old. Patients demonstrated clinical evidence of adrenal insufficiency in a median time frame of 14 days (IQR 8.5-23.3) after SARS-CoV-2 infection. Vomiting, hypotension, and hyponatremia were present in all (N=10). Other common symptoms were nausea (90%), fatigue (70%), hyperpigmentation (70%) and hyperkalemia (50%). Nine (90%) had a positive past medical and/or family history of autoimmune disease. Nine (90%) had positive 21-hydroxylase antibodies. The median serum morning cortisol level was 1.1μg/dL with an IQR of 0.7-3.0 μg/dL. The mean ACTH level was 1235.2 pg/mL with a SD of 580.1 pg/mL. The mean ACTH was 19.3 x ULN with a SD of 10.0. Adrenal imaging did not show hemorrhage or necrosis but showed atrophy in 50%. Conclusions: This series reveals that autoimmune-mediated primary adrenal insufficiency may be diagnosed in the aftermath of COVID-19 illness. Age under 30, family history and/or past medical history of autoimmune disease may be associated. Future prospective studies are needed to determine causality.
Presentation: 6/1/2024
8567 Clinical Use of the Androgen Receptor Sensitivity CAG Repeat Polymorphism to Refine and Improve the Diagnosis of Male Hypogonadism
Authors: Mumdzic Enis , Rao Preethi , Jones Thomas Hugh 
Published: October 2024

Abstract
Disclosure: E. Mumdzic: None. P. Rao: None. T.H. Jones: Advisory Board Member; Self; Besins Healthcare. Grant Recipient; Self; Besins Healthcare, Grunenthal, UK. Speaker; Self; Besins Healthcare.
Male hypogonadism is a syndrome comprising symptoms and biochemical evidence of testosterone (T) deficiency. The prevalence of male hypogonadism differs due to different cut-offs in total T (TT) levels used by different guideline committees. TT is a combination of three T sub-fractions: Free T (FT), albumin-bound T, and SHBG-bound T . The FT and albumin-bound T are biologically active (BioT). The biological effects of androgenisation are not only dependent on circulating testosterone but also on the sensitivity of the androgen receptor (AR). The AR sensitivity correlates negatively with the number of CAG repeats in exon 1 of the AR gene (normal range 9 - 37 repeats). The objective of the study was to compare hypogonadal symptoms with the TT:CAG, BioT:CAG, and FT:CAG ratios compared to TT, BioT and FT alone as biochemical tests for the diagnosis of hypogonadism. All blood samples were taken fasting in the morning before 1100h. Subjects were divided, regardless of testosterone level, into Group 1 (G1) (N = 25), those with symptoms of hypogonadism; and Group 2 (G2) (N = 15), those without symptoms of hypogonadism. The Aging Male Symptom (AMS) score was used for symptom assessment. The Receiver Operating Characteristic (ROC) Curve Analysis was generated where testosterone levels (TT, BioT, FT) and TT:CAG and BioT:CAG, and FT:CAG ratios were used as variables. Results: Mean age (years) in G1 and G2 were 55.8 ± 2.0 (range 33 - 74) and 65.3 ± 2.7 (range 48 - 80), respectively. Mean values in ng/dl are included in square brackets after ranges. Mean TT (nmol/L), BioT (nmol/L) and FT (pmol/L) levels in G1 were 8.54 ± 0.48 (range 4.7 - 13.5)[246.3ng/dl], 2.83 ± 0.13 (range 1.86 - 4.28)[81.62ng/dl], and 189.2 ± 9.8 (range 95 - 300)[5.45ng/dl], respectively. Mean TT, BioT and FT levels in G2 were 15.41 ± 1.69 (range 6.4 - 29.5)[444.45ng/dl], 4.24 ± 0.34 (range 2.19 - 6.55)[122.9ng/dl], and 241.7 ± 18.5 (range 133 - 387)[6.97ng/dl], respectively. Mean AR CAG in G1 and G2 were 21.2 ± 0.7 (range 14 - 27) and 22.4 ± 0.6 (range 16 - 26), respectively. The ROC Curve showed that the area under the curve (AUC) for diagnosing male hypogonadism was the greatest for FT:CAG (.317), followed by FT (.289), BioT/CAG (.208), TT/CAG (.187), BioT (.173), and TT (.164). This exploratory study found that the TT:CAG, BioT:CAG and FT:CAG ratios compared to TT, BioT and FT alone may be better biochemical tests for diagnosis of Male Hypogonadism. The higher the value of the ratios the greater the biological androgen status is. Moreover, it could potentially provide a more accurate test to diagnose men with hypogonadism.
Presentation: 6/1/2024
6661 Critical Limb Ischemia - An Unusual Presentation Of A Pheochromocytoma
Authors: Hassan Sameen 
Published: October 2024

Abstract
Disclosure: S. Hassan: None.
Background: Pheochromocytomas can lead to vasoconstriction and its various clinical manifestations due to excess catecholamine release. Critical limb ischemia as a clinical manifestation of pheochromocytoma has been reported sparsely. Clinical Case: A 43 year old female with a past medical history of type 2 diabetes mellitus, Turner syndrome, and hypertension presented to the emergency department with acute on chronic left leg pain. She underwent workup with a CT angiography of the abdomen with runoff for evaluation of her vessels, which revealed an occlusion of her left superficial femoral artery with chronic stenosis of the right femoral system. Multiple unsuccessful attempts were made at revascularization of her left lower extremity, including femoropopliteal bypass, with eventual left above knee amputation, multiple fasciotomies, and angiogram and stenting of multiple vessels. The patient was on a combined OCP (norethindrone-ethinyl estradiol) for hormone replacement for Turner syndrome for the past 30 years, and did not have a personal or family history of clotting disorders. She underwent a hypercoagulable workup which was negative. Echocardiogram was negative for thrombi and was otherwise unremarkable. Incidentally discovered on her initial CT angiography was a heterogeneously enhancing right adrenal mass, which was further delineated on a dedicated CT of the adrenals, which showed a 3.7 cm right adrenal mass with pre-contrast Hounsfield units measuring 46. Biochemical workup revealed a normal plasma renin activity and aldosterone, plasma metanephrine elevated to 5.20 nmol/L (range 0.00 – 0.49 nmol/L), plasma normetanephrine elevated to 4.95 nmol/L (range 0.00 – 0.89 nmol/L), 24 hour urine metanephrine elevated to 3830 ug/d (range 36-229 ug/d), and 24 hour urine normetanephrine 1733 ug/d (range 95 – 650 ug/d). She reports a diagnosis of hypertension at age 36, with no secondary workup pursued; she had suboptimal control on three separate medications, lisinopril, metoprolol, and hydrochlorothiazide. Her blood pressure and heart rate were noted to be labile during her aforementioned surgery. Alpha blockade with doxazosin was started based on her significantly elevated plasma and urine metanephrines and normetanephrines, with improvement in her blood pressure control. She was not found to have a definitive cause of her critical limb ischemia; she was noted to have atherosclerosis in the vessels of her lower extremities, and her chronic oral contraceptive use may also have played a role. However, OCPs are often reported to cause venous rather than arterial thrombi. Therefore, it can be inferred that the catecholamine excess from her presumed pheochromocytoma caused vasoconstriction which may have played a role in the development of her critical limb ischemia. Conclusion: Catecholamine excess that is resultant from a pheochromocytoma may manifest as critical limb ischemia.
Presentation: 6/1/2024
6453 Cushing Syndrome And Bilateral Adrenal Incidentalomas In A Patient With Mucopolysaccharidosis
Authors: John D , Kinaan M 
Published: October 2024

Abstract
Disclosure: D. John: None. M. Kinaan: None.
TITLE Cushing Syndrome & Bilateral Adrenal Incidentalomas in a patient with Mucopolysaccharidosis
Affiliation of Authors Dieula John M.D., M.B.A.,a,b Mustafa Kinaan M.D.,a,baEndocrinology, Diabetes, and Metabolism Fellowship, UCF HCA Healthcare GME, Orlando, FL. bDepartment of Internal Medicine, UCF College of Medicine, Orlando, FL. This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.
Introduction: Mucopolysaccharidoses (MPS) is a group of hereditary and incurable storage diseases characterized by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs) at the lysosomal level. MPS are usually inherited in autosomal recessive or x-linked pattern. MPS affects functioning of the cells, tissues and organs where the GAGs products typically accumulate. This can result in neurologic, developmental, and neoplastic issues. While endocrine disturbances in MPS have been reported, the literature on hypercortisolism and adrenal masses in MPS is limited. We present a case of a patient with MPS diagnosed with Cushing Syndrome (CS) as part of evaluation for adrenal incidentalomas. Case Description: A 50 year old male with a medical history of MPS, DVT, and developmental delay presented to our clinic accompanied by his mother for evaluation of adrenal incidentalomas. CT abdomen incidentally showed a left adrenal non-calcified, non-hemorrhagic mass measuring 3.9 x 3.6 cm with a pre-contrast attenuation of 45 Hounsfield units. Delayed washout was not obtained, and washout calculation couldn’t be performed. These radiologic features were suspicious for malignancy. Repeat CT with adrenal protocol showed left adrenal mass measuring 4.5 x 3.9 cm with central necrosis, unenhanced attenuation of 42 HU, and no drop-in attenuation on delayed phase indicating poor absolute and relative washout. There was also a right adrenal mass measuring up to 2.2 cm 54.5% absolute washout and 39.0% relative washout. Biochemical workup showed no pheochromocytoma, hyperaldosteronism, or adrenal hyperandrogenism. However, his dex suppression test was consistent with ACTH-independent CS. The patient was referred to an endocrine surgeon. We anticipate more information to be available based on the pathology of the excised tumor following his urgent surgery. Conclusion: MPS diseases are extremely rare and their effects on the endocrine system in general, and the adrenal gland specifically, is limited. Our case would serve as the first reported case of CS in MPS patient based on our literature search. In addition, we’ll discuss the pathology findings once the tumor is excised and highlight the connection between the adrenal mass and this lysosomal storage disease.
Presentation: 6/3/2024
6777 Exploring the comorbidity in males with 45,X/46,XY mosaicism unveils a pattern mirroring that of Turner syndrome
Authors: Stochholm K , Gravholt C H , Berglund A 
Published: October 2024

Abstract
Disclosure: K. Stochholm: None. C.H. Gravholt: None. A. Berglund: None.
Background: Males with 45,X/46,XY mosaicism are rare with an apparent prevalence of 6 per 100,000 newborn males. Knowledge about associated health outcomes are limited. Females with 45,X/46,XY fall under the Turner syndrome diagnosis but males do not. Aim: To investigate the comorbidity pattern in a national cohort of males with 45,X/46,XY. Methods: Morbidity were investigated using Cox regression analysis on administratively longitudinally collected registry data regarding hospital diagnoses, prescribed medication, and surgery codes. Data were retrieved for all males diagnosed with 45,X/46,XY from 1960 to 2018 (n=135) and for 13,500 age-matched males from the general population, who served as comparator. Results: 45,X/46,XY was associated an increased overall risk of receiving a hospital diagnosis (HR: 1.6, CI: 1.3-1.9), being prescribed medication (HR: 1.2, CI: 1.03-1.5), and undergoing a surgical procedure (HR: 1.8, CI: 1.4-2.1). Dividing hospital diagnoses into 18 chapters according to the International Classification of Diseases (ICD-10), 45,X/46,XY had a significantly increased risk of diagnoses in all but three chapters. Among diagnoses with a significantly increased risk were gonadal dysfunction (HR=63.7, CI: 34.8-116.9), short stature (HR=24.7, CI: 10.0-60.6), pubertal disorders (HR=25.8, CI:7.2-92.6), type 1 (HR=4.1, CI: 1.8-9.4) and type 2 diabetes mellitus (HR=3.4, CI: 1.7-6.6), thyroid disorders (HR=3.8, CI: 1.4-10.4), obesity (HR=4.4, CI: 2.3-8.2), osteoporosis and osteopenia (HR=5.4, CI: 2.4-12.3), hearing loss (HR=2.2, CI: 1.3-3.8), otitis media (HR=1.6, CI: 1.3-1.9), ischemic heart disease (HR=2.4, CI: 1.3-4.4), hypertension (HR=2.3, CI: 1.4-3.9), inflammatory bowel disease (HR=2.5, CI: 1.2-5.4), cryptorchidism (HR=11.9, CI: 7.8-17.8), hypospadias (25.9, CI: 14.0-47.8), testis cancer (HR=6.4, CI: 2.0-20.6), infertility (HR=23.5, CI: 16.0-34.4), gynecomastia (HR=4.6, CI: 1.7-12.5), horse shoe kidney (HR=177,8, CI: 16.1-1968.8), coarctation of the aortae (HR=66.0, CI: 11.0-394.9), and bicuspid aortic valve (HR=53.4, CI: 12.7-223.7). Conclusion: Males with 45,X/46,XY mosaicism exhibit heightened morbidity, evidenced by a notable surge in hospital diagnoses, prescribed medications, and surgical interventions. This increased morbidity is linked to a broad spectrum of diseases, showcasing a comorbidity pattern reminiscent of Turner syndrome. This study emphasizes the need for systematic follow-up in individuals with 45,X/46,XY mosaicism, highlighting the imperative for proactive healthcare management in this population.
Presentation: 6/1/2024
12440 Exploring The Potential Protective Role Of The Bacterial-derived Metabolite Indole-3-propionic Acid Against Obesogenic Insults In Placenta Cell Lines
Authors: Ernst J , Conlon L , Gupta R , Kang L , Heard-Lipsmeyer M E 
Published: October 2024

Abstract
Disclosure: J. Ernst: None. L. Conlon: None. R. Gupta: None. L. Kang: None. M.E. Heard-Lipsmeyer: None.
Obesity during pregnancy is associated with detrimental changes in placental function that lead to the development of complications such as gestational diabetes and preeclampsia as well as altered metabolism in the offspring. With the incidence of obesity reaching epidemic levels world-wide, it is imperative to find mechanisms to mitigate these risks during pregnancy. The gut-microbiome is a diverse system that regulates numerous body functions through the secretion of specific metabolites. Gut dysbiosis has recently emerged as one mechanism that contributes to placental dysfunction and clear associations between obesity and gut dysbiosis are evident. Indole-3-propionic acid (IPA) is a gut microbiome-derived metabolite that has anti-inflammatory, anti-oxidative stress and glucose regulatory functions, all of which are dysregulated in obesity. Previous studies have found diminished levels of IPA in serum of women with overweight/obesity. However, it remains unknown what the physiological functions of IPA are in the placenta and if it could have potential protective effects against perturbations caused by obesity. The objective of this study is to determine what physiological role IPA plays in the placenta and if IPA can protect against obesogenic insults that contribute to placental pathology. For this study, we developed an in vitro model of obesity where two human placental cell lines, BeWo (choriocarcinoma) and HTR8 (normal immortalized trophoblasts) were cultured in media conditioned by mature human adipocytes (ACM). RNA sequencing (RNAseq) analysis was used to determine acute effects of IPA treatment after 24 hours in the presence and absence of ACM. We further examined the influence of IPA on insulin signaling with physiological and hyperinsulinemia levels of insulin at 24 and 72 hours utilizing QPCR and western blot analyses. RNAseq analysis revealed treatment with physiological levels of IPA induced changes in genes associated with normal placental function, autophagy and inflammatory mediated processes and other pathways. Our RNAseq analysis offers initial insight into the molecular mechanisms of IPA in placental cells. Future analyses will investigate the potential role of insulin signaling, glucose homeostasis and oxidative stress. Collectively, this study highlights the importance of a healthy gut microbiome and potentially serves as a window of opportunity to mitigate the onset or severity of pregnancy-related disorders such as gestational diabetes by enhancing the gut microbiome prior to pregnancy.
Presentation: 6/1/2024
6693 Hypopituitarism in Pregnancy
Authors: Mcheik Nora A , Howarth Hannah , Banka Ajaz 
Published: October 2024

Abstract
Disclosure: N.A. Mcheik: None. H. Howarth: None.
Background: Hypopituitarism in pregnancy requires careful management to ensure both maternal and fetal well-being. Disruptions of the pituitary gland in pregnancy can be due to adenomas, pituitary infarction, autoimmune disease, trauma, etc. Complications of hypopituitarism in pregnancy stem from inadequate production of thyroid stimulating hormone, growth hormone, gonadotropins and cortisol. Hormone replacement therapy will be necessary in such cases. For instance, patients in late pregnancy may require an increased dose of hydrocortisone due to the rise of corticosteroid-binding globulin. Patients may need increased doses of glucocorticoid therapy during labor given the major surgical stress. Antenatal care should include close follow up with endocrinologists and obstetricians and regular assessment of maternal hormone levels and fetal growth. Case: We present a case of a 37-year-old female G3P0020 at 24 weeks who presented with complaint of constant headache for 6 days. Associated with photophobia, intermittent blurry vision, nausea, and vomiting. She was admitted and given 1 g Magnesium bolus as well as Robaxin and Tylenol for headache without relief. Given persistence of symptoms and non-focal neurologic exam, MRI brain was completed that showed an enlarged pituitary gland with blood products. MRI pituitary showed an approximately 1.3 x 1.2 x 1.8 cm hemorrhagic lesion on the right side of pituitary gland with fluid level, most in keeping with hemorrhagic pituitary apoplexy. Thyroid function studies were consistent with central hypothyroidism with a low TSH 0.05, low Ft4 0.5, and normal Ft3 2.4. Luteinizing hormone was 0.1 mIU/mL (&lt;1.5 normal in pregnancy), follicle stimulating hormone was &lt;0.5 mIU/mL (&lt;0.1 normal in pregnancy), estradiol &gt;5000 pg/mL (1278-7192 normal in pregnancy), and prolactin 254 ng/mL (80-400 normal in pregnancy). IGF-1 was normal at 148 ng/ml. Morning cortisol was low at 1.8 ug/dL and ACTH was 9 pg/mL (low normal). Cortrosyn stimulation test at 60 minutes was normal at 17.7 ug/dL, however, given clinical improvement on steroids, the clinical picture is consistent with central hypoadrenalism. For treatment, she was started on IV hydrocortisone 50 mg every 8 hours and oral levothyroxine 100 mcg daily. The patient was discharged home on oral hydrocortisone 20 mg daily in the morning and 10 mg daily in the afternoon with close follow up. Conclusion: Ultimately, the management of hypopituitarism in pregnancy requires a personalized approach to hormone replacement and obstetric care and this is done through multidisciplinary care involving endocrinologists and obstetricians to optimize outcomes for both the mother and the baby.
Presentation: 6/1/2024