Steroid Use Research Articles

6469 Supplement Misadventures: A Case Of Acute Heart Failure, Cardiogenic Shock, And Hormonal Dysregulation Secondary To Surreptitious Use Of Multiple Hormonal Supplements

Abstract Disclosure: K.N. Grennan: None. S. Thota-Kammili: None. A.L. McKenna: None. C.G. Coyle: None. S.L. Samson: None. Introduction: Supplement misuse in the bodybuilding community is prevalent. With the availability of internet ordering and purchasing, patients have access to hormonal supplements without prescription or regulation. Here we present the case of a patient on self-administered hormonal supplements who presented in acute heart failure leading to cardiogenic shock in the setting of concurrent thyroid, adrenal, and gonadal axis dysfunction. Case Description: A 28-year-old male with no significant medical history was transferred to our hospital after presenting to an outside emergency room with dyspnea, cough, nausea, and a subjective fever. He developed acute hypoxic respiratory failure requiring intubation. Echocardiogram performed showed an ejection fraction (EF) of 10%. He was started on two vasopressors and methylprednisolone 1 g daily for two days, due to concern for myocarditis versus giant cell arteritis. Hormonal work-up showed TSH 0.02 mIU/L (normal range 0.3-4.2), free T4 0.4 ng/dL (0.9-1.7), total T3 48 ng/dL (80-200), FSH <0.3 IU/L (1.2-15.8), LH <0.2 IU/L (1.3-9.6), ACTH <5.0 pg/mL (7.2-63), cortisol 1.7 mcg/dL (2.5-12), estradiol 171 pg/mL (8.0-35), total testosterone 1730 ng/dL (240-950), and prolactin 47 ng/mL (4.0-15.2). He received 10 mg dexamethasone at the outside facility. A medication bag found by his family included online purchases of non-prescribed testosterone cypionate and enanthate, liothyronine, anastrozole, and clomiphene. None were medical grade. He was also taking the anabolic steroid clenbuterol for 3 days prior. Echocardiogram on day 3 of admission showed an improved EF of 36%. Cardiac magnetic resonance imaging (MRI) showed a papillary fibroelastoma and myocarditis. Patient was weaned off vasopressors and the ventilator. He was discharged on levothyroxine 50 mcg daily and hydrocortisone 10 mg twice daily for outpatient reassessment. Transesophageal echocardiogram confirmed diagnosis of papillary fibroelastoma. One month Endocrinology clinic follow-up showed no evidence of posterior pituitary, thyroid, or adrenal axis dysfunction or growth hormone excess, but he continued to have gonadal axis suppression with elevated prolactin and estradiol, the latter thought to be secondary to conversion from testosterone. Pituitary MRI showed no micro or macroadenoma. His EF recovered to 50%. He is pending surgical removal of the aortic valve fibroelastoma. Discussion: With hormonal supplements easily accessible online, it is important for physicians to counsel patients about the dangers of misuse. This case highlights a previously healthy 28-year-old man who presented in critical condition with cardiogenic shock and hypothalamic-pituitary axis dysfunction from supplements he purchased online. There should be targeted educational interventions regarding the harm of supplements aimed at the bodybuilding community to prevent similar cases. Presentation: 6/2/2024

9198 Dimeric [Cys25]PTH(1-34) Induces Differential Transcriptional Responses Versus Monomeric PTH(1-34)

Abstract Disclosure: M. Noh: None. H.J. Kim: None. J. Kim: None. M. Kang: None. S. Lee: None. H. Lee: None. S. Lee: None. Introduction: Patients with hypoparathyroidism caused by the homozygous mutation that changes arginine to cysteine at position 25 in parathyroid hormone (PTH) exhibit high bone densities, which suggests a potential influence of the mutant hormone on bone formation. We also have found that [Cys25]PTH forms homodimers, and that the dimeric peptide exhibits altered functionality versus monomeric PTH. Dimeric [Cys25]PTH(1-34) (Dimer) thus displays selective binding to the G protein-coupled PTH1R conformation (RG) in vitro and markedly diminished cAMP-inducing capability in vivo. Despite these alterations, Dimer induced bone anabolic effects in both calvarial injection assays and after injection in ovariectomized osteoporotic mice, closely mimicking the effects of PTH(1-34) (wtPTH). Our current objective is to explore the downstream signaling pathways activated by Dimer vs wtPTH to help elucidate the bone anabolic effects of the Dimeric analog and its therapeutic potential. Methods: A phospho-protein antibody array assay developed for G protein-coupled receptor (GPCR) downstream target proteins was employed in HEK293/hPTH1R (GP-2.3) cells following treatment with chemically synthesized wtPTH or Dimer. We further conducted RNA-seq analysis of transcriptome changes in primary cells collected from calvarial bones of mice treated with wtPTH or Dimer at 6, 12, and 24-hours post-injection. Finally, we used quantitative reverse transcription PCR (qRT-PCR) to analyze changes in specific marker genes in tibiae and kidney isolated from mice after treatment with Dimer vs. wtPTH. Results: The number of phosphorylated proteins significantly regulated by PTH1R upon exposure to Dimer was remarkably enhanced, relative to the number regulated upon exposure to wtPTH. RNA-seq analysis revealed that the early effects of wtPTH and Dimer on transcriptional regulation were similar, whereas marked differences in expression levels became apparent over time. qRT-PCR analyses of RNA expression levels in kidneys versus tibiae from mice treated with wtPTH or Dimer revealed in bone that the expression of genes associated with bone catabolism, particularly RANKL, was significantly lower in response to Dimer as compared to wtPTH treatment, while in kidney there was an overall reduced response to Dimer as compared to wtPTH. Conclusions: Our study supports the hypothesis that as compared to PTH(1-34), dimeric [Cys25]PTH (1-34) induces altered signaling responses in vivo and has a lower effect on bone catabolism. Dimeric [Cys25]PTH(1-34) thus holds interest as a potential bone anabolic agent that utilizes a distinct mechanism of action. Presentation: 6/3/2024

8279 Dimeric [Cys25]PTH(1-34) Induces Differential Transcriptional Responses Versus Monomeric PTH(1-34)

Abstract Disclosure: M. Noh: None. H.J. Kim: None. J. Kim: None. M. Kang: None. S. Lee: None. H. Lee: None. S. Lee: None. Introduction: Patients with hypoparathyroidism caused by the homozygous mutation that changes arginine to cysteine at position 25 in parathyroid hormone (PTH) exhibit high bone densities, which suggests a potential influence of the mutant hormone on bone formation. We also have found that [Cys25]PTH forms homodimers, and that the dimeric peptide exhibits altered functionality versus monomeric PTH. Dimeric [Cys25]PTH(1-34) (Dimer) thus displays selective binding to the G protein-coupled PTH1R conformation (RG) in vitro and markedly diminished cAMP-inducing capability in vivo. Despite these alterations, Dimer induced bone anabolic effects in both calvarial injection assays and after injection in ovariectomized osteoporotic mice, closely mimicking the effects of PTH(1-34) (wtPTH). Our current objective is to explore the downstream signaling pathways activated by Dimer vs wtPTH to help elucidate the bone anabolic effects of the Dimeric analog and its therapeutic potential. Methods: A phospho-protein antibody array assay developed for G protein-coupled receptor (GPCR) downstream target proteins was employed in HEK293/hPTH1R (GP-2.3) cells following treatment with chemically synthesized wtPTH or Dimer. We further conducted RNA-seq analysis of transcriptome changes in primary cells collected from calvarial bones of mice treated with wtPTH or Dimer at 6, 12, and 24-hours post-injection. Finally, we used quantitative reverse transcription PCR (qRT-PCR) to analyze changes in specific marker genes in tibiae and kidney isolated from mice after treatment with Dimer vs. wtPTH. Results: The number of phosphorylated proteins significantly regulated by PTH1R upon exposure to Dimer was remarkably enhanced, relative to the number regulated upon exposure to wtPTH. RNA-seq analysis revealed that the early effects of wtPTH and Dimer on transcriptional regulation were similar, whereas marked differences in expression levels became apparent over time. qRT-PCR analyses of RNA expression levels in kidneys versus tibiae from mice treated with wtPTH or Dimer revealed in bone that the expression of genes associated with bone catabolism, particularly RANKL, was significantly lower in response to Dimer as compared to wtPTH treatment, while in kidney there was an overall reduced response to Dimer as compared to wtPTH. Conclusions: Our study supports the hypothesis that as compared to PTH(1-34), dimeric [Cys25]PTH (1-34) induces altered signaling responses in vivo and has a lower effect on bone catabolism. Dimeric [Cys25]PTH(1-34) thus holds interest as a potential bone anabolic agent that utilizes a distinct mechanism of action. Presentation: 6/3/2024

7867 Treatment-Related Changes in Total Hip Bone Mineral Density and Fracture Risk Reduction for Drugs With Different Mechanisms of Action: The FNIH-ASBMR-SABRE Project

Abstract Disclosure: T. Vilaca: None. M.T. Schini: None. A.R. Thompson: None. E. Vittinghoff: None. L. Lui: None. S.K. Ewing: None. D.C. Bauer: None. D.M. Black: None. M. Bouxsein: None. R. Eastell: Consulting Fee; Self; Immunodiagnostic Systems, CL Bio, CureTeQ, Biocon, Takeda, UCB. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Osteolabs. Speaker; Self; Pharmacosmos, Alexion Pharmaceuticals, Inc., Amgen Inc, UCB. Introduction: To date, trials of new anti-osteoporosis therapies have used fractures as primary endpoints. In the FNIH-ASBMR-SABRE project, we posited that the treatment-related change in total hip BMD (THBMD) could be used as a surrogate endpoint for fractures in future clinical trials of new osteoporosis therapies. To demonstrate this, we compiled a large dataset of individual patient data (IPD) from randomized trials and showed a strong association between the change in THBMD at 24 months and reduction in fracture risk. To further explore the use of THBMD as a surrogate endpoint, here we examine whether the association is robust across drugs with different mechanisms of action. Methods: We used IDP (n>120,000 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications (17 anti-resorptive, 3 PTH analogs, 1 odanacatib, and 1 romosozumab). We calculated the treatment-related difference (active-placebo) in mean % change in THBMD at 12, 18, and 24 months for each trial. We determined the treatment-related fracture risk reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for all clinical fractures (a combination of non-vertebral and clinical vertebral fractures). We used meta-regression to estimate the study-level association (r2) between treatment-related differences in THBMD changes and fracture risk reduction, including only the 17 trials of anti-resorptive drugs and then using the entire set of 22 trials. Since there were only 3 trials of anabolic drugs, we did not perform separate analyses for the anabolic trials. Results: The r2 values were similar between all trials and antiresorptive trials only for both fracture outcomes at all time points. Specifically, for vertebral fractures, the r2 was 0.59 vs 0.70 at 12 mo, 0.69 vs 0.74 at 18 mo, and 0.73 vs 0.78 at 24 mo for all trials vs anti-resorptive trials only. For all clinical fractures, the r2 was 0.46 vs 0.51 at 12 mo, 0.64 vs 0.60 at 18 mo, and 0.71 vs 0.65 at 24 mo for all trials vs anti-resorptive trials only. Conclusion: These results demonstrate that the associations between treatment-related changes in THBMD and fracture risk reductions are robust across anti-osteoporosis therapies with varying mechanisms of action. We conclude that the treatment-related difference in THBMD change would predict fracture reduction equally well for drugs with different mechanisms of action. Presentation: 6/2/2024

Androgenic anabolic steroids and their effects on the cardiovascular system

Androgenic anabolic steroids and their effects on the cardiovascular system

Clinical Outcomes After Distal Bypass in Patients With Chronic Limb-Threatening Ischemia due to Connective Tissue Disease.

Chronic limb-threatening ischemia (CLTI) is mostly caused by arteriosclerosis, but is sometimes due to connective tissue disease. However, there is a limited knowledge of clinical outcomes of patients with CLTI with connective tissue disease. The objective of the study was to assess outcomes after distal bypass in these patients using global vascular guidelines. Data from distal bypasses performed for CLTI at a single center from 2014 to 2023 were evaluated retrospectively. Clinical outcomes after distal bypass were compared for patients with CLTI with arteriosclerosis (AS group) and those with connective tissue disease (CD group). The primary endpoints were limb salvage and wound healing. Of the 282 distal bypasses performed for 222 patients with CLTI, 22 were conducted for 21 patients with connective tissue disease (CD group). The connective tissue disease was progressive systemic scleroderma (n = 11 patients), pemphigoid diseases (n = 2), polyarteritis nodosa (n = 2), rheumatoid arthritis (n = 2), and others (n = 4). Compared with the AS group, the CD group included more females (P = .007) and had greater oral steroid use (P < .001) and a higher Global Limb Anatomical Staging System (GLASS) inframalleolar (IM) modifier P2 (P < .001). The mean follow-up period of the whole cohort was 27 ± 22 months with no significant difference between the groups (P = .25), and 22 limbs required major amputation during this period. The 2-year limb salvage rate was significantly lower in the CD group compared to the AS group (75% vs 94%, P = .020). Wound healing was achieved in 220 (78%) limbs, and the 12-month wound healing rate was significantly lower in the CD group (52% vs 86%, P = .006). The low 2-year limb salvage and 12-month wound healing rates in patients with CLTI with connective tissue disease indicate that distal bypass may be challenging in these patients.

Dermoscopic Distinction of Tinea Incognito on the Face and Topical Steroid Damaged Face: A Cross-Sectional Study in Skin of Color

Abstract Background: Dermatophytosis is widespread in India due to recalcitrant and resistant infection. Tinea incognito (TI) is modified dermatophytosis due to the inadvertent use of topical steroids (TS). Similarly, topical steroid-damaged face (TSDF) is caused by prolonged use of TS. Distinction of TI and TSDF is difficult when the face is affected. Dermoscopy can assist in the differentiation of both by revealing characteristic features. We evaluated the dermoscopic features in TI affecting the face and TSDF. Aims and Objectives: To evaluate the clinical and dermoscopic features of TI affecting the face and TSDF. To observe the involvement of eyelids in TI as opposed to TSDF. Materials and Methods: The study was conducted in a tertiary hospital after obtaining ethical clearance and informed consent. Patients with signs of TI or TSDF were enrolled and demographic data were collected. Patients who had applied TS/combination creams were included. A handheld dermoscope with 10x magnification was used. A potassium hydroxide mount was used to confirm the diagnosis of TI. Results: Out of 80 patients, 27 males and 53 females were present. The mean duration of application was 8.25 ± 7 months. Clinical features were pruritus, erythema, scaling, and burning sensation. Eyelid involvement was noted in TI while it was spared in TSDF. On dermoscopy, morphological features were predominant in TI whereas vascular structures were found in TSDF in addition to white rosettes. Conclusion: Dermoscopy distinguishes TI from TSDF comprehensively by demonstrating definitive features. In addition, the involvement of the eyelid is an excellent clinical sign of TI.

Immune Checkpoint Inhibitors in the Management of Brain Metastases from Non-Small Cell Lung Cancer: A Comprehensive Review of Current Trials, Guidelines and Future Directions

Background: Brain metastases (BM) are a common, severe complication in patients with non-small cell lung cancer (NSCLC) and are difficult to treat due to their complex tumor biology and the intricate microenvironment of the brain. Objectives: This review examines the current role of immune checkpoint inhibitors (ICIs) in treating NSCLC with BM, focusing on the latest clinical trials, emerging strategies, current guidelines, and future directions. We highlight the efficacy of ICIs as monotherapy and in combination with other treatments such as radiotherapy, stereotactic radiosurgery, chemotherapy, and anti-VEGF agents. Results: While no single treatment sequence is universally accepted, combining ICIs with traditional therapies forms the core of the current treatment protocols. ICIs targeting the PD-1/PD-L1 pathway have significantly advanced NSCLC treatment, demonstrated by improved overall and progression-free survival in various settings. However, optimizing these benefits requires careful consideration of potential side effects, including cognitive decline and radiation necrosis, and the impact of steroid use on ICI efficacy. Conclusion: The review underscores the necessity for a personalized, integrated multidisciplinary treatment approach. Future research should focus on refining combination therapies and understanding the optimal sequence and timing of treatment.

Abuse of Anabolic-Androgenic Steroids as a Social Phenomenon and Medical Problem—Its Potential Negative Impact on Reproductive Health Based on 50 Years of Case Report Analysis

Background/Objectives: Illegal anabolic-androgenic steroids are a significant lifestyle factor in infertility. The aim of our study was to analyze clinical cases resulting from their use for their frequency, geographical location, dynamics, substances used, the age and gender of the users, and the types of clinical complications. Methods: Publications were obtained by searching PubMed for the following terms: ‘anabolic-androgenic steroids’ and ‘clinical case’. Publications from 1973 to 2022 were qualified for the analysis. Results: An increasing trend in the number of clinical cases resulting from the use of steroids, as well as the number of substances used simultaneously, was observed. The substances changed over the decades, but in the last 20 years, testosterone, nandrolone, stanozolol, methandienone, trenbolone, and methenolone have predominated. Cardiological side effects predominated in each period, with a continuous increase in their occurrence. The most common among these were myocardial infarctions and hypertrophic cardiomyopathy. The next most numerous adverse events involved psychiatric, endocrinological, hepatic, and oncological problems. We demonstrated a possible relationship between the use of individual steroids and medical issues; the strongest associations were between testosterone and endocrine complications, and methylstenbolone and hepatic complications. Conclusions: There has been an increasing trend in case reports describing serious health problems associated with the use of anabolic-androgenic steroids, a tendency to use several substances simultaneously, and a preferential use of substances with a high potential of causing serious side effects. These phenomena mainly concern men, with an average age of 30, and the health problems that dominate in clinical case reports—including serious cardiological, psychiatric, endocrinological, hepatic, and oncological diseases—may potentially affect reproductive health and pose a challenge for reproductive medicine.

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.

Effect of anabolic steroid nandrolone on prostate of prepubertal albino rats (Histological and Immunohistochemical study)

Effect of anabolic steroid nandrolone on prostate of prepubertal albino rats (Histological and Immunohistochemical study)

Physician-dentist dual referral model concept for coordinated bone anabolic therapy

BackgroundBone anabolic drugs used for the pharmacologic treatment of osteoporosis have the potential to enhance alveolar bone regeneration to improve implant success. There are no US Food and Drug Administration–approved drugs indicated to improve oral bone density around teeth or implants. MethodsThe authors summarized expert opinions on a novel coordinated treatment approach leveraging the effects of systemic bone anabolic drugs to enhance dental implant therapy in patients with osteoporosis and a dual referral model for physicians and dentists to address the clinical needs of patients with osteoporosis from a comprehensive perspective of oral-systemic health. Interviews of key opinion leaders were conducted with a bone health specialist group consisting of specialists in orthopedic surgery, internal medicine, geriatrics, endocrinology, and clinical densitometry and a surgical dental specialist group consisting of periodontists and oral surgeons. ResultsOverall, both groups shared positive feedback on the idea of strategically timing administration of anabolic osteoporosis drugs with dental treatment. Both groups expressed interest in the dual referral model. ConclusionsThe feedback of key opinion leaders supported the coordinated bone anabolic therapy concept and identified a need for improved interdisciplinary collaboration, education, and communication to realize the synergies of physician-dentist clinical cooperation. Practical ImplicationsStrategic timing of osteoporosis therapy could improve skeletal bone health and reduce fracture risk while offering adjunctive dental benefits.

Postnatal Steroids Use for Bronchopulmonary Dysplasia in a Quaternary Care NICU.

Intercenter variation and trends in postnatal steroids (PNS) use among preterm infants for prevention or treatment of bronchopulmonary dysplasia (BPD) is known. Understanding intracenter PNS use patterns facilitate implementation of center-specific change interventions to optimize outcomes.This study aimed to (i) quantify the proportion of infants who received PNS, and describe the timing, type, trends over time, regimen used, and deviations, and (2) describe the clinical characteristics and unadjusted outcomes of infants who received PNS. This was a cohort study in a quaternary neonatal intensive care unit including infants born at less than 33 weeks, and who received PNS for prevention or treatment of BPD between 2011 and 2021. Following data were included: proportion of babies who received PNS; type of PNS; age at initiation and duration; trends over time; deviation from published regimen; morbidity, mortality, and cointerventions. One hundred and eighty four infants (8% of <33 week' infants) received PNS. The median (interquartile range [IQR]) gestational age and birth weight were 25 (24-26) weeks and 720 (625-841) grams, respectively. The median (IQR) day of initiation and duration of PNS use were 29 (19-38) and 10 (10-22) days, respectively. One hundred and fifty-seven (85%) infants received dexamethasone (DX) and 22 (12%) received hydrocortisone as the first PNS course, and 71 (39%) infants received multiple courses. The proportion of infants receiving PNS remained unchanged, but the cumulative median dose received for BPD per patient increased by 56%. Nearly one-third of cumulative PNS dose came from PNS used for non-BPD indications. Forty-six percent infants had a deviation from published regimen (±20% deviation in duration or ±10% deviation in dose). Survival, survival without major morbidity, moderate-to-severe BPD, and technology dependence at discharge were 87, 2, 91, and 67%, respectively. Increased variation in PNS use, deviation from published regimen, and concurrent PNS exposure from non-BPD indication offer insights into implementing interventions to improve processes. · In this quaternary NICU, 8% of infants born before 33 weeks were administered postnatal steroids (PNS).. · The percentage of infants given PNS remained stable; however, the cumulative dose per patient for BPD rose.. · The study identified targeted interventions to minimize clinical practice variations at the center..

Persistent physiological benefits from doping? Ethical implications for sports integrity.

The effects of some widely abused doping substances such as anabolic androgenic steroids (AAS) on performance are well documented, particularly in the short term, and the use of these substances is banned by various sporting authorities, with athletes sanctioned from competing for up to 4 years. However, controversy exists on whether residual physiological effects of some doping practices could persist even years after discontinuation, granting unfair advantages to athletes long after sanctions have been served. Particularly, in support of the so-called muscle memory theory, growing evidence in both animals and humans suggests that AAS administration could exert long-term effects at the muscle level, notably a higher number of myonuclei. This effect could enhance retraining/muscle remodeling capacity long after AAS cessation, thus supposing an advantage for doped athletes even +4 years after doping practices have been discontinued. If confirmed, the persistence of physiological improvements resulting from past doping practices raises serious ethical concerns in the sports field and opens the door to lifelong sanctions.

Nandrolone decanoate-induced hypogonadism in male rats: Dose- and time-dependent effects on pituitary and testicular hormonal functions.

Anabolic-androgenic steroids (AASs) impairment of reproduction has been reported. We investigated dose- and time-dependent effects of Nandrolone decanoate (ND) on reproductive system in comparison with Testosterone enanthate (TE). Male Wistar rats were administrated with 1, 3, and 9 mg/kg/weeks ND or 1 and 3 mg/kg/weeks TE for 8 weeks, and testicular phenotype and reproductive hormones were assessed at 4 and 8 weeks post-treatments. AASs × treatment period interaction was significant for gonadosomatic index (GSI), testosterone (T), 17β-estradiol (E2), and luteinizing hormone (LH). At 4 weeks post-treatment, GSI was decreased in rats treated with 3 mg/kg/weeks ND and T was decreased in all ND-treated groups, while no significant changes in LH levels were observed. At 8 weeks post-treatment, GSI was decreased in rats treated with 1 and 3 mg/kg/weeks ND and with 3 mg/kg/weeks TE, T was decreased in all groups, and E2 and LH were increased and decreased, respectively, in rats treated with 9 mg/kg/weeks ND and with 3 mg/kg/weeks TE. The testes showed histopathological defects in both ND- and TE-treated rats suggesting a delay in seminiferous cycle. This study shows AASs-induced hypogonadism at low-dose that coincided with inhibition of T biosynthesis and disruption of T feedback on pituitary.

Integrating diabetes care into an oncology practice: A patient-centric model of care delivery at a safety-net health system.

2 Background: Oncologic treatments can disrupt glycemic control in people with diabetes and induce dysglycemia in individuals without diabetes through the use of steroids and/or targeted therapies. Severe hyperglycemia can result in delay/interruption of oncologic care and emergency department (ED) utilization. Here we report on an integrated model of diabetes care at a safety-net system, where patients commonly use the ED for their care. Methods: Parkland Health is an academic-affiliated safety-net system, primarily providing care for the un-/under-insured patients in Dallas County. An advanced nurse practitioner specializing in diabetes care (DM-ANP), supervised by an endocrinologist, was embedded in oncology clinics. Patients were referred to the DM-ANP by their oncology provider, or through an automated process if they had a recent hemoglobin A1c &gt;8.0% or a random blood sugar &gt; 250mg/dL. Patient education was provided by a trained nurse educator. Nutrition consult was available through an oncology dietitian. An acute hyperglycemia management protocol was developed to manage patients in the infusion center and prevent unnecessary ED visits. Results: Between March 2021 and March of 2024, the DM-ANP provided 4,276 visits to 797 distinct patients (average, 1425 visits per year). Breast cancer was the most common malignancy among patients seen in the integrated clinic. DM-ANP visits were coupled with oncology visits (clinic or infusion) or via telehealth, thereby increasing access and decreasing number of days patients had to come to clinic to receive care. Telehealth visit rate was highest in 2021 (27.5%) reflecting the impact of the pandemic, and subsequently dropped to 10.1% in 2023. Patients who were seen by the DM-ANP had an overall lower number of ED visits. Comparing prior vs post establishing care with the DM-ANP, the total number of ED visits by patients with diabetes significantly reduced in 2021-2022 (2021: 970 vs. 241, p &lt;0.01; 2022: 796 vs. 501, p&lt;0.01) before equilibrating in 2023-2024; (2023: 426 vs. 468, p=0.24). On average, patients had 1.2 less ED visits after receiving care from the DM-ANP. Since in-person visits were coupled with other oncology visits, the no-show rate for DM-ANP mirrored the rates for oncology clinics/infusion visits. Conclusions: Integrating diabetes/glycemic management into our oncology practice provided a patient-centric model of care delivery, improved visit adherence compared to an off-site model, reduced the time-toxicity by having fewer clinic visit days. Future directions include comparing oncologic outcomes in patients who had DM-ANP management to those who were managed by primary care.

Steroids in severe community-acquired pneumonia.

There is conflicting evidence regarding the use of steroids in severe community-acquired pneumonia (CAP), with previous randomised controlled trials limited by small sample sizes. ESCAPe and CAPE COD are two recently published large trials on steroids in severe CAP. ESCAPe assessed the initiation of methylprednisolone within 72-96 h of hospital admission, while CAPE COD studied the use of hydrocortisone within 24 h of the development of severe CAP. ESCAPe did not show any differences in all-cause 60-day mortality or any of its secondary outcomes. CAPE COD showed that hydrocortisone improved all-cause 28-day mortality and reduced the risk of intubation or vasopressor-dependent shock. Important differences between the trials included the steroid regimens used, timing of steroid administration and baseline characteristics, with more diabetic patients included in ESCAPe. The results of CAPE COD support the initiation of hydrocortisone within 24 h of developing severe CAP, but more research is needed to evaluate long-term outcomes and optimum dosing regimens for steroids in severe CAP.

Female hyperandrogenism

Hyperandrogenism in women is a clinical syndrome resulting from an excess of circulating androgens in the blood. They can be produced either in the ovary or the adrenal gland. The clinical manifestations are highly variable. Patients present characteristic physical signs (alopecia, hirsutism, acne) as well as menstrual cycle irregularities. The most common cause of hyperandrogenism in women of childbearing age is polycystic ovary syndrome. There are specific criteria to establish a clear diagnosis of this syndrome. Nevertheless, in the presence of hyperandrogenism, a differential diagnosis must be made among other possible causes, such as congenital adrenal hyperplasia, use of drugs (anabolic agents), or the presence of androgen-secreting tumors. The specific treatment of this disease is usually chronic and aimed at controlling secondary symptoms of the disease, attempting to improve patients’ quality of life.

Comprehensive evaluation of bone health among kidney transplant recipients – A prospective, single center, observational cohort study from India

Background: There is a paucity of studies describing trabecular bone score (TBS) and bone mineral density (BMD) in kidney transplant (KT) recipients from developing countries. Study setting: This prospective observational study, from a tertiary teaching hospital in India assessed clinical, biochemical parameters including bone turnover markers and dual-energy X-ray absorptiometry (DXA) for BMD/TBS, hip structural analysis (HSA) and vertebral fracture assessment (VFA) at pre-KT, 3 months and 12 months post-KT. Results: A total of 53 KT recipients (90.6% living related) were recruited from August 2019 to March 2020 and followed till 1-year post-KT. The mean age was 33.9±10.4 years, 71.7% were males, and 11.5% had a history of pre-KT steroid use. Baseline fractures pre-KT as assessed by VFA were seen in 4 patients (7.5%). Mean BMD at spine and femoral neck and HSA variables at narrow neck and femoral shaft continued to decline till 3 months, but stabilised and reached pre-KT values 12 months post-KT. However, TBS and bone turn over markers continued to decline till 12 months post-KT (p value <0.001). New onset vertebral fractures were seen in 2(3.7%) and 1 patient (2.3%) at 3- and 12-months post-KT respectively. Pre-KT BMD significantly influenced bone health at 12 months post-KT, with patients in each quartile maintaining a similar trajectory over the follow up period (p < 0.001). Conclusion: Despite significant improvement in kidney function following transplant, TBS and BMD of the spine significantly decreased mainly in the early post-KT period suggesting the effect of immunosuppressants on the bone. Strategies to improve bone health in KT patients are warranted.

Possible sex and racial disparities in myasthenia gravis care.

Given the importance of early diagnosis and treatment of myasthenia gravis (MG), it is critical to understand disparities in MG care. We aimed to determine if there are any differences in testing, treatment, and/or access to neurologists for patients of varying sex and race/ethnicity with MG. We used a nationally representative healthcare claims database of privately insured individuals (2001-2018) to identify incident cases of MG using a validated definition. Diagnostic testing, steroid-sparing agents, intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and thymectomy were defined using drug names or CPT codes. Steroid use was defined using AHFS class codes. We also determined whether an individual had a visit to a neurologist and the time between primary care and neurologist visits. Logistic regression determined associations between sex and race/ethnicity and testing, treatments, and access to neurologists. Female patients were less likely to get a computed tomography (CT) chest (odds ratio (OR) 0.73, 95% confidence interval (CI): 0.64-0.83), receive steroids (OR: 0.85, 95% CI: 0.75-0.97), steroid-sparing agents (OR: 0.84, 95% CI: 0.72-0.97), and IVIG or PLEX (OR: 0.80, 95% CI: 0.67-0.95). Black patients were less likely to receive steroids (OR: 0.78, 95% CI: 0.63-0.96). No significant disparities were seen in access to neurologists. We found healthcare disparities in MG treatment with female and Black patients receiving less treatment than men and those of other races/ethnicities. Further research and detailed assessments accounting for individual patient factors are needed to confirm these apparent disparities.