Use Of Glucocorticoids Research Articles

Beneficial effect of sequential treatment with high-dose steroids and short-course oral glucocorticoids in patients with severe influenza virus-associated pneumonia

Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.

Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms

BackgroundSkeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms. MethodsZebrafish soaked in 0.01 % dexamethasone solution for 10 days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms. Results0.01 % dexamethasone reduced zebrafish skeletal muscle mass (p < 0.05), myofibre size and cross-sectional area (p < 0.001), and increased protein degradation (ubiquitination and autophagy) (p < 0.05). In addition, 0.01 % dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (p < 0.001), average velocity of movement (p < 0.001), oxygen consumption (p < 0.001), critical swimming speed (p < 0.01) and increased exhaustive swimming time (p < 0.001). Further, 0.01 % dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress. Conclusions0.01 % dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress.

Real-World Evaluation of the Effectiveness and Safety of Dupilumab in Bullous Pemphigoid: An Ambispective Multicenter Case Series.

Bullous pemphigoid affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable. Evaluate the effectiveness and safety of dupilumab in the treatment of bullous pemphigoid. A multicenter ambispective cohort study was conducted in 34 hospitals. Patients with bullous pemphigoid treated with Dupilumab were included. Most of patients (97.1%) received an initial 600 mg dose followed by 300 mg every two weeks. The primary outcome was the proportion of patients achieving complete remission within 4 weeks, defined as Investigator Global Assessment score of 0 or 1. Complete remission at weeks 16, 24, and 52, adverse events, reductions in peak pruritus numerical rating scale, and systemic glucocorticoid use were also assessed. The study included 103 patients with a median age of 77.3 years, 58.0% male. Complete remission was achieved by 53.4% within 4 weeks and 95.7% by week 52. Peak pruritus scale reduced by 70.0% by week 4 and was completely controlled by week 24. Thirteen patients presented adverse events, most of which were mild. Systemic glucocorticoid use reduced by 82.1% by week 52. Shorter disease duration and exclusive cutaneous involvement predicted better response at 16 weeks. No differences in response rates to dupilumab were observed between drug-associated bullous pemphigoid and idiopathic cases. No significant difference in response rates was observed between patients treated with dupilumab in monotherapy and those receiving dupilumab with concomitant treatments. Dupilumab is effective, rapid, and safe in managing bullous pemphigoid, reducing the need for corticosteroids and other treatments. Early initiation and exclusive skin involvement predict better outcomes.

Trajectories of disease evolution upon treatment initiation in systemic lupus erythematosus: results from four clinical trials of belimumab.

Upon commencement of therapy for active disease, patients with systemic lupus erythematosus (SLE) show varying evolution regarding disease activity measures and patient-reported outcomes (PROs). Our objective was to identify disease evolution trajectories to gain a deeper understanding of SLE progression, ultimately improving future trial design. Patients with ≥2 visits and available data on SLEDAI-2K, BILAG, PGA, FACIT-F, and glucocorticoid use were included in a post-hoc analysis of four randomised controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, EMBRACE). Growth mixture modelling identified latent classes. Among 2868 patients analysed, baseline median disease duration was 4.5 (IQR: 1.5-9.7) years and mean (± standard deviation) SDI 0.7 (±2.0), SLEDAI-2K 10.2 (±3.6), BILAG 17.0 (±7.8), PGA 1.5 (±0.5), FACIT-F 30.6 (±11.9), and prednisone dose 11.0 (±8.9) mg/day. In the initial model, glucocorticoid use and dose yielded high standard errors, indicating a weak link with the latent process. A refined model considered only clinical measures and FACIT-F, corrected for intervention and SDI; no other covariates improved the fit. Four classes best described disease evolution: highly active, responders; highly active, non-responders; moderately active, responders; moderately active, non-responders. LLDAS and DORIS remission attainment associated with latent classes. By linking disease activity measures with PROs, we identified four distinct trajectories describing SLE evolution following the initiation of therapy. This classification could be valuable for personalising treatment and guiding biological studies aimed at distinguishing patients with varying anticipated treatment responses, as no single clinical variable alone can predict disease progression.

Obesity Management in Youth with Duchenne Muscular Dystrophy: A Review of Metformin and Alternative Pharmacotherapies.

Background: Individuals with Duchenne muscular dystrophy (DMD) have increased risk of obesity from prolonged glucocorticoid use and progressive muscle weakness. Over 50% have obesity by the teenage years. Objectives: The current study examines literature on obesity management in DMD and describes how obesity pharmacotherapy can be used in this high-risk cohort. Methods: This review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A Pubmed Database search was conducted from January 2000 to May 2024. Included terms were DMD and topiramate, phentermine, metformin, glucagon-like peptide-1 receptor agonist, semaglutide, and liraglutide. Eligible studies were cataloged to examine obesity pharmacotherapy, side effect profiles, and clinical outcomes. Results: Twenty studies met inclusion criteria, 18 on metformin. Reviewed studies varied in duration from 4 to 24 weeks, ages 6.5-44 years old, with 112 participants total (range: 1-30 participants). Included studies were: eight animal studies, six clinical trials, four reviews, one cohort study, and one case report. Primary outcomes varied among studies: muscular degeneration and function (15 articles), cardiac function (2 articles), weight loss (2 articles), and general endocrine care (1 article). Conclusions: Adjunct obesity pharmacotherapy use in youth with DMD is promising but needs to be confirmed. Large gaps include appropriate agent selection, side effect monitoring, and dose escalation. The overall quality of pediatric-specific evidence for the use of obesity pharmacotherapy in youth with DMD is low. Future research is needed to investigate how to safely utilize these agents.

Extrafollicular CD19lowCXCR5−CD11c− double negative 3 (DN3) B cells are significantly associated with disease activity in females with systemic lupus erythematosus

ObjectiveB cells play a major role in the development and maintenance of systemic lupus erythematosus (SLE). Double negative (DN) B cells defined by the lack of surface expression of IgD and CD27 have attracted recent interest for their sensitivity to Toll-like receptor 7 (TLR7) ligands and their potential role in the production of autoantibodies. Here we aimed at investigating the possible association of DN B cells and their subsets with SLE disease activity specifically in female patients, in which TLR7 gene has been reported to escape X chromosome inactivation. MethodsPeripheral blood mononuclear cells were purified from woman participating to the clinically well-characterized Swiss SLE Cohort Study (SSCS). PBMC from age-matched healthy females were used as controls. PBMC were stained for cell surface markers, intracellular Tbet and analyzed by multicolor cytofluorimetry. Single nucleotide TLR7 polymorphisms were assessed by polymerase chain reaction. ResultsThe median SLE disease activity index of the 86 females was 2, IQR [0–6], all but 8 were under chronic SLE treatment. B cells co-expressing CD11c and Tbet were increased, the mean fluorescence intensity (MFI) of CD19 was considerably reduced and we observed a large increase in CD11c + CXCR5-and CD11c-CXCR5-concomitantly with a reduction of CD11c-CXCR5+ B cells in SLE compared to 40 healthy donors (HD). When focusing on the DN B cell subset, we found a reduction of DN1 (CD11c-CXCR5+) and an increase of DN2 (CD11c + CXCR5-) and most impressively of DN3 (CD11c-CXCR5-) cells. The DN subset, particularly DN3, showed the lowest level of CD19 expression. Both DN1 and DN3 percentages as well as the CD19 MFI of DN cells were associated with SLE disease activity. The use of glucocorticoids, immunosuppressants, and antimalarials impacted differentially on the frequencies of DN B cell subsets. CD19 MFI in B cells and the percentage of DN3 were the strongest biomarkers of disease activity. The TLR7 snp3858384 G allele was associated with increased percentages of B cells and CD19+CD11c-CXCR5+ and decreased CD19+CD11c-CXCR5-. ConclusionsDN3 B cells are strongly associated with SLE clinical activity pointing to their potential involvement in disease pathogenesis, and CD19 expression level performs accurately as disease activity biomarker.

8252 Central Adrenal Insufficiency Masquerading as Syndrome of Inappropriate Antidiuretic Hormone (SIADH): A Case Report

Abstract Disclosure: J.G. Sazon: None. J.L. Reyes: None. J.V. Chua: None. S.A. Kho: None. Hyponatremia, the most common electrolyte imbalance encountered in clinical practice, has various causes and presentation. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a frequent hospital-related cause, potentially leading to misdiagnosis with adrenal insufficiency due to shared clinical features which may cause potential deleterious effect. We present a case of a 41-year-old male hyponatremic patient with a two-month history of progressive generalized body weakness and lightheadedness, initially managed as SIADH. Upon admission, the patient persistently showed low serum sodium level (122mmol/L) (NV: 135-145mmol/L), exhibited signs of euvolemic hyponatremia despite fluid restriction, intravenous furosemide, and sodium chloride tablets. Further work-up revealed normocytic normochromic anemia (Hgb 107 g/L) (NV: 120-160g/L), elevated ESR of (31mm/hr) (NV: 0-15mm/hr), low Ft4 (2.97 pmol/L) (NV: 12-22 pmol/L) and normal TSH (2.2 uIU/mL) (NV: 0.27-4.20 uIU/mL). During hospital stay, he experienced an episode of hypotension at 80/50mmHg and hypoglycemia at 65 mg/dL. Investigation revealed adrenal insufficiency secondary to pituitary macroadenoma with apoplexy as showed in magnetic resonance imaging. Patient was started on Prednisone. Pre-operatively, hydrocortisone 100mg IV every 8 hours preoperatively. He underwent transsphenoidal surgery; excising a 2.5cm soft and grayish suprasellar mass. Post-operatively, he was given Prednisone and Levothyroxine resulting in symptom improvement and normal sodium levels.The occurrence of hyponatremia due to adrenal insufficiency is relatively uncommon, emphasizing the need for heightened suspicion when assessing patients with prolonged or recurring hyponatremia. This paper highlight the need to replace glucocorticoid prior supplementation of thyroid hormone in such cases, averting the occurrence of adrenal crisis. This case indicated a mechanism of persistent hyponatremia attributed to secondary adrenal insufficiency, with added therapeutic benefits observed through the use of glucocorticoids and transsphenoidal surgery. Presentation: 6/1/2024

8248 Glucocorticoid Induced Adrenal Crisis Masked By Metastatic Lung Carcinoma

Abstract Disclosure: N. Abrahimi: None. A. Abrahimi: None. Background: Chronic glucocorticoid use of three weeks or longer can cause hypothalamic-pituitary-adrenal axis inhibition by negative feedback, causing adrenal suppression. (1) Adrenal crisis is diagnosed by an acute clinical decompensation, persistent hypotension that resolves with high dose steroid administration. (2) Adrenal crisis is precipitated by several causes such as illness, dehydration, trauma, emotional distress and sometimes due to no identifiable cause. (2) Clinical Case: 64-year-old male past medical history of lung carcinoma metastatic to mediastinum who presented to the hospital with tachycardia. On presentation, patient was tachycardic, tachypneic, and hypotensive. Labs significant for WBC 22, Na+ 129, K+ 3.2, Cr 3.4. Patient received 2.5 L bolus of NS and was given one dose of azithromycin due to concern for sepsis. After fluid resuscitation, hypotension and tachycardia resolved. Presenting symptoms included ongoing nausea, decreased appetite and malaise for several weeks. Repeat labs post fluid resuscitation showed resolution of leukocytosis, improvement of AKI, and repletion of electrolytes. CT chest abdomen pelvis showed questionable pneumonia, however, consolidations were difficult to distinguish from known malignant masses. Clinical picture was not consistent with pneumonia and so additional antibiotics were held. Several hours later, blood pressure decreased, and patient began requiring vasopressors. Cefepime was started given concern for septic shock. Nearly 48 hours after initiation of broad-spectrum antibiotics hypotension persisted and patient remained on vasopressors. Given clinical decline, etiology of shock was reconsidered. Patient reported daily prednisone use over the last several months for COPD management. Given high clinical suspicion of adrenal crisis in setting of chronic steroid use and glucocorticoid withdrawal, patient was started on hydrocortisone 100 mg every 8 hours. Shortly after initiation of stress dosed steroids, the patient was successfully weaned off vasopressors with complete resolution of hypotension. Conclusion: Presentation and symptoms of adrenal insufficiency and crisis including nausea, anorexia, fatigue, malaise, hypotension and electrolyte abnormalities are nonspecific, can go unrecognized and be masked by other disease processes, such as metastatic cancer. (1) Adrenal crisis is life threatening and must be diagnosed and treated early to prevent mortality. (2) Therefore, adrenal crisis should always be on the differential in patients who present with shock.

6722 Increase in Femoral Neck BMD After Parathyroidectomy in Patients with Mild Primary Hyperparathyroidism

Abstract Disclosure: F. Abdul Kather: None. G.A. Clines: None. C. Janney: None. D.T. Hughes: None. N.H. Esfandiari: None. S. Saberi: None. Objective: This study aimed to assess changes in bone mineral density (BMD) following parathyroidectomy in patients with mild primary hyperparathyroidism, defined as serum calcium 10.4 mg/dl to 11.2 mg/dl, by comparing distinct patient variables. Hypothesis: Pre-op demographic factors, laboratory values, and BMD significantly influence post-parathyroidectomy BMD. Methods: This retrospective chart review included 93 subjects with primary hyperparathyroidism who underwent parathyroidectomy between 2000-2022 with BMD measurements performed at the same site pre- and post-parathyroidectomy. Exclusion criteria were age &amp;lt;50 years, GFR &amp;lt;30, recurrent primary hyperparathyroidism, chronic oral glucocorticoid use (&amp;gt;1 month), rheumatoid arthritis, suppressed serum TSH, hormone-deprivation therapy, cinacalcet use, and prescription osteoporosis medication therapy. Statistical analyses were performed using ANOVA and a p-value of &amp;lt;0.05 was considered statistically significant. Results: The mean age of the subjects was 63.65 ± 6.58 years, who were mostly female (84.9%) and white (88.2%). Pre-op laboratory values revealed mean uncorrected calcium 10.52 ±0.26 mg/dL, corrected calcium 10.25 ± 0.32 mg/dL, 25-OH vitamin D 35.82 ±15.31 ng/mL, and parathyroid hormone (PTH) 99.12 ±37.06 pg/mL. Pre-op mean bone densities for the lumbar spine, femoral neck, and total hip were 1.04 ± 0.16, 0.81 ± 0.11, and 0.87 ± 0.11 g/cm2, respectively, with corresponding T-scores of -1.13 ± 1.23, -1.60 ± 0.74, and -1.13 ± 0.89. Changes in BMD post-parathyroidectomy were determined by comparing pre-op and post-op DXA scans. No statistically significant differences in DXA were found between ages of 50-55 vs. &amp;gt;55, post-op timing of DXA 1-2 years post parathyroidectomy vs. &amp;gt;2 years post parathyroidectomy, number of parathyroid glands removed, the total weight of resected parathyroid glands, pre-op vitamin D level &amp;lt;30 ng/mL vs. ≥30 ng/mL, or pre-op urinary calcium levels &amp;lt;200 mg/day vs. ≥200 mg/day. Grouping subjects by pre-operative DXA T-scores revealed a statistically significant improvement in femoral neck bone density between osteoporotic and osteopenic subjects (p=0.018) and between osteoporotic and normal bone density subjects (p=0.019). No significant differences were identified in the spine and total hip bone density changes among these groups. Conclusion: In subjects with osteoporosis undergoing parathyroidectomy, a significant improvement in femoral neck bone density was observed, unaffected by pre-op variables of age, timing of DXA post parathyroidectomy, parathyroid gland characteristics, and pre-op vitamin D and urinary calcium levels. These findings underscore the potential for tailored interventions in managing bone health post-parathyroid surgery, emphasizing the need for personalized approaches to optimize outcomes in individuals with mild hyperparathyroidism. Presentation: 6/2/2024

12516 Bilateral Adrenalectomy And Bariatric Surgery For Hormonal And Metabolic Control Of Classic Congenital Adrenal Hyperplasia

Abstract Disclosure: G. Palú: None. A.M. Rodrigues: None. Background: Hyperandrogenism is sometimes difficult to control in female patients with classic congenital adrenal hyperplasia (CAH), requiring supra-physiologic glucocorticoid dose with its metabolic consequences. Clinical Case: A 25-year woman with salt-losing CAH has been followed since she was born, requiring high glucocorticoid dose (hydrocortisone dose equivalent 50-75 mg), in addition to fludrocortisone (0.1-0.15 mg/day), without control of hyperandrogenism (testosterone and androstenedione levels more than 3 times ULN). She progressively gained weight, reaching 116 kg (256 pounds) and BMI of 46 kg/m2 when she was 17 years old. Bilateral adrenalectomy was performed in 2016 for disease control and to lower glucocorticoid dose. Androgen levels were supressed, glucocorticoid dose was reduced to 5mg prednisone (hydrocortisone dose equivalent 20mg) and she lost 10 kg of weight, but she remained in class III Obesity (BMI 42.5 kg/m2). Serious adrenal crises were not reported after bilateral adrenalectomy. Pharmacologic obesity treatment was done (sibutramine plus topiramate) and she lost 16 kg of weight, reaching 90 kg and a BMI of 36 from April 2017 to February 2020. She stopped treatment during the COVID- 19 pandemic and regained weight, reaching 106 kg again. She was lost to follow-up and returned in November 2023. In May 2022, she was submitted to a gastric bypass in a country town. She achieved 71 kg with a BMI of 28. She was feeling very well, taking post-bariatric vitamins and minerals, combined oral contraceptive, prednisone 5 mg/day (hydrocortisone dose equivalent 20 mg/day) and fludrocortisone 0.1 mg/day. Until now, she did not have any adrenal crises requiring parenteral glucocorticoid use. Conclusion: Even though treatment was aggressive with two surgeries that could lead to increased risk of adrenal crises, the patient had a benign course. New medicines that block CRH or ACTH action in CAH patients could prevent excessive glucocorticoid doses and weight gain and would be a better alternative to bilateral adrenalectomy in cases such as this one. Presentation: 6/1/2024

8239 Recurrent Superior Laryngeal Nerve Glucocorticoid Injections: A Likely Cause Of Secondary Adrenal Insufficiency In An Otherwise Healthy Man

Abstract Disclosure: A. Lorin: None. M.C. Pranger: None. J. Park: None. C.A. Clutter: None. Background: Secondary adrenal insufficiency is well described in the literature with various offending agents implicated. Superior laryngeal nerve (SLN) glucocorticoid injections, however, have rarely been recorded as causal agents of secondary adrenal insufficiency. We present a case of a generally healthy man with secondary adrenal insufficiency after chronic administration ofsuperior laryngeal nerve glucocorticoid injections without other identifiable etiologies. Clinical Case: A 68-year-old man with no significant medical history presented to endocrinology clinic due to persistent nausea and severe fatigue. His initial labs were notable for morning cortisol of 1.66 mcg/dL (5-25) and an undetectable ACTH (&amp;lt;3.2 pg/mL, 10-60) suggestive of adrenal insufficiency. FSH/LH, testosterone, FT4, and IGF-1 were otherwise normal. On initial review of his medication history, the only glucocorticoid exposure appeared to be intranasal beclomethasone, with remote courses of oral prednisone. Further history revealed that the patient was receiving superior laryngeal nerve glucocorticoid injections for chronic cough every three weeks for over a year. The injection consisted of 1:1 mixture of 1 mL of triamcinolone acetonide 200 mg/5 mL and local anesthetic, which is equivalent to triamcinolone 40 mg or hydrocortisone 200 mg. Given the volume and chronicity of the glucocorticoid injections, the patient developed secondary adrenal insufficiency as above. Since the diagnosis, the patient discontinued SLN glucocorticoid injections and was placed on physiologic hydrocortisone replacement, with gradual recovery of his HPA axis. Conclusions: Sequelae of percutaneous glucocorticoid injection into the superior laryngeal nerve for treatment of chronic cough are not well documented in terms of their effects on the HPA axis. While an effective and increasingly common treatment for chronic cough, SLN glucocorticoid injection has the potential to cause suppression of the HPA axis and cause secondary adrenal insufficiency. Excess glucocorticoid appeared to solely inhibit ACTH production, as the other anterior pituitary hormones were not affected. Understanding consequences of glucocorticoid use in any formulation is important when considering such therapies, as these may alter normal HPA function with recurrent dosing. Recovery from a disrupted HPA axis may be achieved with the use of physiologic doses of hydrocortisone replacement in the case of secondary adrenal insufficiency. Presentation: 6/3/2024

9182 Metastatic Extra-Gastrointestinal Stromal Tumor Presenting As Hypoglycemia

Abstract Disclosure: O. faour: None. D. John: None. S.K. Suryanarayanan: None. A.A. Rizvi: None. Introduction: Non islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome seen in association with solid abdominal tumors of mesenchymal and epithelial origin. We report a case of metastatic extra-gastrointestinal stromal tumor (E-GIST) presenting with severe hypoglycemia as its initial manifestation. CASE DESCRIPTION: A 46-year-old patient was found to have a blood glucose of &amp;lt;45 mg/dl during a routine clinic visit with her primary care physician. Although she was asymptomatic, she was sent to the emergency room (ER) for further evaluation. She had a history of prediabetes managed by lifestyle modification. She has been experiencing multiple episodes of hypoglycemia previously which fulfilled the Whipple’s triad in the preceding months. These hypoglycemic episodes included loss of unconsciousness, falls in the shower with head injury, and several hospital visits. Serum glucose in the ER was 14 mg/dl and hypoglycemia persisted despite continuous dextrose solution. Physical examination was notable for a distended, non-tender abdomen and cervical lymphadenopathy. CT scan showed a 15 cm mass in the liver, multiple large masses in the mesentery, and a 11 cm lesion in the left pelvis. There were enlarged lymph nodes in the abdomen, chest, and neck. Serum chemistries drawn when the patient was hypoglycemic revealed potassium level of 2.7 mg/dl (3.5-5.5) an insulin level of &amp;lt;1.0 mIU/L (5-25), C-peptide &amp;lt;0.1 ng/mL (0.5-2), cortisol 13.8 mcg/dL (5-25), and insulin-like growth factor-2 (IGF-2) was 270 ng/mL (38-267). The IGF-2/IGF-1 molar ratio was 3.4 (normal &amp;lt;3:1). The sulfonylurea drug screen came back negative. Upper and lower endoscopies were unrevealing. Biopsy of the liver lesion showed cytology and immunohistochemical findings consistent with a epithelioid metastatic extra-gastrointestinal stromal tumor. A provisional diagnosis of NICTH was made. The patient responded well to intravenous glucose, oral carbohydrate intake and high-dose corticosteroids. She was subsequently started on therapy with the tyrosine kinase inhibitor (TKI) imatinib. Discussion: Paraneoplastic hypoglycemia is often seen in association with metastatic epithelial and mesenchymal tumors. IGF-2 and incompletely processed pro-IGF-2 activates autocrine, paracrine, and endocrine pathways that lead to tumor growth, fasting hypoglycemia, rarely of acromegalic features. Treatment with octreotide, diazoxide, and glucagon is generally ineffective, while glucocorticoid use and surgical intervention are helpful in ameliorating the hypoglycemia. Tumor-directed therapy with TKIs, primarily imatinib, appears promising in achieving remission. Our case is a clinical reminder that hypoglycemia secondary to NICTH can be the predominant presenting feature in patients with underlying E-GIST. Presentation: 6/3/2024

7627 Prevalence Of True Endocrinopathies In Patients Presenting To An Endocrine Clinic With Fatigue

Abstract Disclosure: C. Dimech: None. K. Barnett: None. F. Hasan: None. Introduction: Fatigue is a common chief complaint, resulting in approximately 7 million physician office visits per year in the US. Fatigue is a non-specific symptom which can be associated with many acute or chronic conditions. In our clinical experience fatigue is a frequent reason for referral to the endocrine clinic, and often assessment does not reveal an endocrine pathology. However, the prevalence of endocrinopathies discovered following endocrinology assessment has not been well studied. Methods: In this retrospective study, we completed chart review of electronic medical records of patients who were evaluated for a chief complaint of fatigue at outpatient endocrinology centers belonging to an integrated health network in the Pittsburgh Metro area. We included patients aged 18-40 years old from 01/01/2019- 12/31/2022. We hypothesized that there is not a significant incidence of endocrinopathies found on evaluation. Results: Extensive clinical and laboratory data were gathered for 226 patients during the study period. 39.9% of patients were self-referred. 60.1% of patients seen were through physician referrals, however 17.9% of these patients had no prior investigations completed. The majority of patients evaluated for fatigue were female (76.5% vs 23.5%). 55.3% of patients were 30-39 years of age. 27% of patients were overweight and 23% were obese with BMI 30 or greater. Nearly half of all patients had a diagnosis of anxiety or depression (51.7% and 48.2% respectively). Of those patients with anxiety, 57.3% were prescribed an SSRI or SNRI. Similarly, 58.7% of patients with depression were prescribed an SSRI/SNRI. Patients most commonly reported other non-specific symptoms such as weight gain, poor sleep and poor mood (51.3%, 38.9%, 25.2% respectively). 54.9% of female patients presenting with fatigue were concerned for thyroid dysfunction whereas 45.3% of male patients were concerned for hypogonadism. 12.3% of patients evaluated never completed the recommended testing. Vitamin D deficiency was notably prevalent in 42.4% of patients tested. One patient was found to have secondary adrenal insufficiency in the setting of chronic exogenous glucocorticoid use for back pain. Of 163 patients tested for thyroid dysfunction, no new diagnoses of thyroid abnormalities were revealed. Conclusion: In this study, laboratory testing from an endocrinology consultation was not useful in detecting newly discovered endocrinopathies as a cause of fatigue. Presentation: 6/2/2024

7522 Effects of Trikafta On Bone Mineral Density And Body Composition In Patients With Cystic Fibrosis

Abstract Disclosure: N. Mon: None. S.S. Krishnasamy: None. G. Bakeerathan: None. L. Healy: None. E. Favier: None. S. Foushee: None. Background: Cystic fibrosis related bone disease (CFBD) is a common complication of adult Cystic fibrosis (CF) patients due to calcium, vitamin D and K malabsorption from exocrine pancreatic insufficiency, increased inflammatory cytokines, glucocorticoid therapy, delayed puberty, physical inactivity, and hypogonadism. Newer CF transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (Trikafta) has proven benefit in pulmonary and nutritional outcomes. There is limited data on effects of Trikafta on bone health and body composition. The aim is to examine the effects of Trikafta on bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), and body composition in terms of fat free mass index (FFMI) and fat mass index (FMI) in our CF patients. Method: We conducted a cross sectional and retrospective review of 38 adults with CF (Ages 20-59, 28 males and 10 females) in our CF clinic. Body Mass Index (BMI), Body composition measured by bioelectric impedance analysis, BMD of LS and FN by Dual-energy X-ray absorptiometry, Vitamin D level, and forced expiratory volume in one second (FEV1 % predicted) in patients taking Trikafta were analyzed and compared with control CF group who were not on Trikafta. Results: 38 subjects on Trikafta, aged 33.29 ± 10.36 years with FEV1 % predicted 65.11± 28.14% were studied. Serum 25-hydroxyvitamin D level was 35.92 ± 18.52 ng/dL. Of the 38 study patients, 23 (60.53%) had a diagnosis of CF related diabetes (CFRD). Among the Trikafta cohort, 18 (50%) had low BMD with Z-scores ≤ -2.0 and 7 (19.44%) of them had Z score ≤ -1.0 and &amp;gt; -2.0. Compared with the control group, LS BMD 0.93 ± 0.16 g/cm2 and FN BMD 0.73± 0.13g/cm2 (p &amp;gt;0.05) were not improved significantly. BMI of study population 23.09 ± 4.21 kg/m2 (p &amp;lt;0.05) and FMI 6.11 ± 4.25 kg/m2 (p &amp;lt;0.05) increased significantly; however, there was a decrease in FFMI 9.60 ± 1.44 kg/m2 (p &amp;lt;0.05). Conclusion: Treatment with Trikafta in CF patients was associated with increases in BMI and fat mass index but decrease in fat free mass index. There was no statistically significant difference in BMD at LS and FN in our study cohort. This study has limitations in terms of gender differences within the study cohort, duration of Trikafta use in relation to bone mass, and also extent of glucocorticoid use among the study subjects. Larger prospective clinical trials are needed to study efficacy of Trikafta on CFBD. Presentation: 6/3/2024

8693 Dexamethasone Increases Bone Mass In Mice

Abstract Disclosure: F. Sultana: None. M.L. Temple: None. S. Kim: None. V. Ryu: None. F. Korkmaz: None. A. Gumerova: None. P. Georgii: None. U. Cheliadinova: None. D. Vasilyeva: None. V. Laurencin: None. R. Witztum: None. O. Barak: None. L. Cullen: None. A.R. Pallapati: None. S. Rojekar: None. J. Gimenez Roig: None. D. Lizneva: None. W. Zhou: None. T. Yuen: None. M. Zaidi: None. Severe osteoporosis and bone fractures are strongly associated with long-term or recurring glucocorticoid use in people. Steroids have traditionally been used as an anti-inflammatory and immunosuppressive agent, and while their use has been widely implicated in causing bone loss by suppressing osteoblastic bone formation, recent data have consistently shown mixed results in mice. It is also important to stress that dexamethasone (DEX) in particular has been used for over three decades in cell cultures to stimulate osteoblast formation. We therefore posit that mechanisms other than direct steroid effects on osteoblasts contribute to bone loss, and that, at least physiologically, steroids stimulate (rather than inhibit) bone formation. Here, we have aimed to clarify the effects of DEX on bone metabolism. We first studied the effects of low and high doses of DEX (1 mg/kg and 10 mg/kg), given daily as intraperitoneal injections to 8-week-old C57BL/6 mice. Micro-CT showed that DEX markedly increased bone microarchitecture, including the bone volume fraction, connectivity density, and trabecular number, while decreasing trabecular spacing in femoral epiphyses compared with vehicle-injected controls. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone did not change following DEX. These findings suggest that both low and high DEX doses are anabolic to the skeleton. Reaffirming these data, we found that adrenalectomy (with salt replacement) caused a significant decline in bone mineral density. Likewise, Tpit-/- mice, in which ACTH and corticosterone are both reduced, display reduced bone microarchitectural parameters, together with low mineralizing surface and bone formation rates on dynamic histomorphometry, impaired osteoblast formation in Cfu-f cultures, and lowered expression of the osteoblastogenesis genes Bmp2, Ibsp, Runx2 and Sp7. Finally, deleting the glucocorticoid receptor (Gr) specifically in osteoclasts in Acp5-Cre;Grfl/fl mice had no effect on microarchitectural parameters at the spine or proximal tibial metaphysis. However, and importantly, absent GR in the osteoclast, DEX increased bone mass significantly, suggesting that its notable anabolic action was mediated by the osteoblast. Our findings challenge the longstanding premise that steroids directly impact the osteoblast to cause bone loss, and that other mechanisms, such as reduced ACTH levels and/or central effects of DEX, may play a key role. Presentation: 6/1/2024

12434 History Of Surgical Menopause Is Associated With An Accelerated “Adrenal Aging” In Menopausal Women

Abstract Disclosure: J. Saini: None. R. Nathani: None. J. Larson: None. V. Fell: None. I. Bancos: None. Background: Surgical menopause due to bilateral salpingo-oophorectomy (BSO) at a younger age is associated with an increased risk of cardiovascular disease, cognitive decline, and increased mortality. Aging is associated with abnormalities in steroid metabolome, most notably an increased glucocorticoid to androgen ratio (“adrenal aging”). We hypothesized that in postmenopausal women of the same age, the duration of menopause is associated with adrenal aging. Objective: To determine the differences in the adrenal steroid metabolome of women with a history of BSO as compared to age-matched women following natural menopause. Methods: We conducted a single-center cross-sectional study in postmenopausal women with or without a history of BSO, between December 2020 to December 2022 Each participant collected 24-hour urine, which was analyzed for steroid profiling by liquid chromatography-tandem mass spectrometry (25 steroids). Exclusion criteria were inability to collect a 24h urine sample, exogenous glucocorticoid use, advanced malignancy, and chronic opioid use. Primary endpoints were glucocorticoid/androgen ratio, 11β-hydroxysteroid dehydrogenase type 2 activity (cortisol/cortisone, Tetrahydrocortisol (THF) + 5 α-tetrahydrocortisol (5 α-THF)/ Tetrahydrocortisone, THE) and 5 α-reductase type activity (Tetrahydrocortisol (THF)/5 α-tetrahydrocortisol (5 α-THF) and Etiocholanolone/Androsterone, Et/An). Results: A total of 245 women were enrolled: 124 women (median age of 66 years, IQR 63-72) with a history of BSO and 121 women (median age of 68 years, IQR 64-71) who underwent natural menopause (P=0.214). Median age at menopause was 44 years (IQR 41-46) in the BSO group, and 50 years (IQR 48-53) in the natural menopause group. History of hormone replacement therapy with estrogen was reported in 161 (66%) women, more frequently (92% vs 39%, P&amp;lt;0.001) and for a longer duration (median 12 years (IQR 6-16) vs 6 years (IQR 3-9), P&amp;lt;0.001) in in the BSO group, as compared to the natural menopause group. Although both groups had similar levels of urinary androgens (median 1387 vs 1686 mcg/24h, P=0.063) and total glucocorticoids (median 10877 vs 10277 mcg/24h, P=0.354), women with a history of BSO demonstrated a higher glucocorticoid/androgen ratio (median 7.9 (IQR 5.0-11.1) vs 6.7 (4.3-9.9), P=0.014), and a lower Et/An ratio (median 1.4 vs 1.6, P=0.045), but not THF/5aTHF ratio (median 1.7 vs 1.8, P=0.380) in comparison to women with natural menopause. No differences were found in other ratios. Conclusion: Women with a history of BSO demonstrated a higher glucocorticoid/androgen ratio in comparison to women undergoing natural menopause, suggestive of BSO-induced accelerated “adrenal aging”. Future studies need to examine associations between the abnormal steroid metabolome and increased cardiovascular morbidity, frailty, and mortality reported following BSO. Presentation: 6/3/2024

6422 Identifying Predictive Symptoms Of Adrenal Insufficiency

Abstract Disclosure: A.J. Han: None. S.J. Achenbach: None. B.J. Atkinson: None. I. Bancos: None. Background: Diagnosis of adrenal insufficiency (AI) is often delayed due to its vague and non-specific symptomatology. As classic symptoms of AI such as fatigue and nausea are prevalent in the general population, identifying clinical features that are more specific to AI may help clinicians determine which patients require additional testing. Methods: A single-center retrospective study was performed of patients who underwent outpatient Cosyntropin stimulation testing (CST) between 2005-2018. Patients with oral glucocorticoid or estrogen use within 2 months of CST, and patients without available Current Visit Information (CVI) form at the time of CST were excluded. Presence of symptoms was obtained from CVI, and laboratory findings were electronically extracted. Adrenal insufficiency was defined as post-CST peak cortisol &amp;lt;18 mcg/dL. Morbidity was assessed using the Elixhauser index. Variables for multivariable analysis were defined a priori and included fatigue, dizziness, muscle pain, joint pain, weight loss &amp;gt;10 pounds, abdominal pain, nausea/vomiting, and hyponatremia. Results: Among 5347 patients who underwent CST, 376 (7.0%) of patients were found to have AI. There were no sex differences between patients with and without AI, however patients with AI were slightly older (median age 48.9 vs 47.1 years, p=0.026), and had a higher median BMI (26.5 vs 25.6 kg/m2, p=0.002). Prevalence of comorbidities was similar between the two groups, with a median Elixhauser index of 1 (IQR 1-3), however, patients with AI were more likely to report difficulties with activities of daily living (69% vs 57%, p&amp;lt;0.001). Hyponatremia was diagnosed in 4% of patients with AI and 3% of those without AI, p=0.208. Although patients in our cohort reported a high prevalence of fatigue (79%), dizziness (50%), joint pain (50%), muscle pain (48%), nausea (40%), abdominal pain (39%), and weight loss in the past 6 months (29%), there were no statistically significant differences in reported symptoms between patients with and without AI with the exception of joint pain (59% vs 49%, p&amp;lt;0.001) and muscle pain (54% vs 47%, p=0.009). Based on multivariable analysis, only joint pain (OR 1.51, 95% CI 1.14-1.99) and weight loss &amp;gt;10 pounds in the past 6 months (OR 1.31, 95% CI 1.02-1.68) were associated with higher odds of AI diagnosis. Interestingly, patients who reported fatigue had lower odds of AI diagnosis on CST (OR 0.66, 95% CI 0.49-0.88). Conclusions: Commonly associated symptoms of AI such as fatigue, dizziness, nausea, and abdominal pain were poor predictors of AI diagnosis based on CST. Consequently, the presence of these symptoms alone may not warrant additional testing. Notably, clinical features such as myalgia, arthralgia, and weight loss &amp;gt;10 pounds in the past 6 months were found to be more predictive of AI. Presentation: 6/1/2024

8723 Glucose Metabolism Disturbances in Non-Classic Adrenal Hyperplasia (NCAH)

Abstract Disclosure: B. Domagała: None. A. Gamrat: None. A. Skalniak: None. E. Przybylik-Mazurek(†): None. M. Trofimiuk-Muldner: None. A. Hubalewska-Dydejczyk: None. Introduction: There is data reporting an increased risk of cardiovascular and metabolic complications in patients with NCAH. This is frequently attributed to glucocorticoid (over)use or misdosing. It seems that long-term exposure to increased androgens concentrations may also itself lead to diminished insulin sensitivity and increased risk of prediabetes and diabetes. Aim: The study aimed to assess the link between NCAH diagnosis and glucose metabolism disturbances. Material and methods: The study included 327 subjects (315 females and twelve males, median age 25 years) referred for a cosyntropin stimulation test due to the suspected NCAH. Serum 17-OH-progesterone (17-OHP) was assessed with an ELISA assay. The diagnosis of NCAH was confirmed if the initial or stimulated 17-OHP concentration exceeded 10.0 ng/mL. None of the tested subjects was treated with glucocorticoids. A history of preexisting prediabetes or diabetes was recorded. Anthropometric measurements were obtained to calculate body mass index (BMI). Fasting glucose was measured in each subject. Mann-Whitney U and Yates’ χ2 tests were used in statistical analyses, with p&amp;lt;0.05 as the cut-off value of statistical significance. Results: 62 patients (60 females, two males; median age 26 years) were diagnosed with NCAH; the rest of the tested subjects were considered the control group. Preexisting type 2 diabetes was recorded in ten subjects in the entire study group (6 of them were diagnosed with NCAH). There was no significant difference in the fasting glucose levels (p=0.08) and BMI (p=0.32) between subjects with and without NCAH diagnosis (median fasting glucose: 4.96 mmol/L and 4.86 mmol/L, respectively; median BMI: 23.82 kg/m2 and 23.26 kg/m2, respectively). Diabetes was significantly more frequent in patients with NCAH diagnosis (p = 0.004; power: 0.74). The median 17-OHP was higher in patients with diabetes compared to those without it at both 30 (12.25 ng/mL vs 3.25 ng/mL; p=0.003) and 60 minutes (14.93 ng/mL vs 3.95 ng/mL; p=0.046) after stimulation. Conclusions: NCAH seems to be linked to increased diabetes risk, even in glucocorticoid-naïve patients. It seems advisable to screen NCAH patients for glucose metabolism disorders. Presentation: 6/1/2024

Osteoporosis in older men

Osteoporosis, characterized by reduced bone mass and compromised skeletal microarchitecture, significantly increases the risk of fractures and is the most prevalent metabolic bone disease. While it is commonly associated with post-menopausal women, osteoporosis and subsequent fractures are also substantial concerns in men. Men experience sustained bone loss after the sixth decade, with estimates indicating that 20% of Americans with osteopenia or osteoporosis are men. Approximately one in eight men over 50 will suffer an osteoporotic fracture, with hip fractures in men leading to a two- to threefold increase in mortality compared to women. The prevalence of osteoporosis in men has risen, doubling in prevalence since the early 1990s. Men generally have higher peak bone mass and greater bone size, offering some protection against osteoporosis; however, aging leads to increased bone resorption and decreased bone formation, exacerbated by lower androgen and estrogen levels. Secondary causes, such as hypogonadism and chronic glucocorticoid use, are prevalent in men. Diagnosis primarily involves bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA), with fracture risk assessment tools like FRAX and MORES aiding in clinical decisions. Treatment includes calcium and vitamin D supplementation, bisphosphonates, denosumab, and anabolic agents like teriparatide and abaloparatide. Special considerations are necessary for men undergoing androgen deprivation therapy for prostate cancer due to accelerated bone loss. Effective management requires early diagnosis, lifestyle modifications, and appropriate pharmacological interventions to reduce fracture risk and improve patient outcomes.

Prompt response to rituximab in a patient with resistant polymyositis with complications of dysphagia and dysphonia: a case report

Introduction and importance: Polymyositis is an inflammatory process, primarily affecting proximal muscles, characterized by elevated muscle enzymes and distinctive electromyography patterns. Case presentation: The authors present a case of a 33-year-old male patient experiencing complications of polymyositis, including pharyngeal and laryngeal involvement leading to dysphagia and dysphonia. Steroids and intravenous immunoglobulin (IVIG) therapy proved ineffective. Subsequently, rituximab was administered, resulting in significant improvement in dysphagia, dysphonia, and proximal muscles within 3 days of the initial rituximab dose. Additionally, there was a remarkable decrease in creatine phosphokinase (CPK) levels. Clinical discussion: Immune-mediated myopathies (IMM) are rare diseases characterized by muscle inflammation and weakness. This case of probable polymyositis, diagnosed through clinical features and elevated CPK, was complicated by the patient’s lack of response to glucocorticoids and IVIG therapy. Remarkably, rituximab treatment led to rapid improvement in muscle strength and symptoms, highlighting its potential effectiveness in refractory cases of polymyositis. Conclusions: Primary treatment for cases of polymyositis typically involves the use of glucocorticoids. However, approximately half of the patients do not respond adequately to corticosteroids alone. Alternatives, in such cases, encompass IVIG therapy and rituximab.