X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative demyelinating disorder with variable presentations. We report a case of a 32-year-old African American male with adult-onset X-ALD presenting with primary adrenal insufficiency (PAI) and marfanoid musculoskeletal features. He was initially diagnosed with PAI of unclear etiology and taking only hydrocortisone monotherapy. Further workup revealed negative 21-alpha-hydroxylase antibodies and elevated plasma very long chain fatty acids. Genetic testing confirmed the diagnosis of X-ALD resulting from novel ATP-binding cassette transports sub-family D member 1 gene (ABCD1) pathogenic variant. Evaluations for comorbidities by ophthalmology, neurology, and neuropsychiatry were insignificant. Magnetic resonance imaging of the brain and entire spine was unremarkable. There were no cardiac or eye findings to suggest Marfan syndrome and no genetic testing for Marfan syndrome was pursued. This case highlights X-ALD as a potential diagnosis of PAI and the importance of screening plasma very long chain fatty acid levels after ruling out common etiologies.

Disclosure: A. Jin: None. A. Bryant: None. A. Bhatnagar: None. K. Soe: None. X-linked adrenoleukodystrophy (X-ALD) is a rare congenital neurodegenerative demyelinating disorder and primary adrenal insufficiency with variable presentations. The diagnosis can be delayed and easily missed especially among adults. We report a case of a 32-year-old African American male with adult-onset X-ALD presenting with primary adrenal insufficiency only and Marfanoid features. He was diagnosed with primary adrenal insufficiency of unknown etiology at the age of 22 when he was hospitalized with generalized weakness, dehydration and acute renal failure. He was able to maintain normal blood pressure and functionality by taking hydrocortisone only without fludrocortisone replacement. The patient was also noted to have marfanoid habitus. Further workup for primary adrenal insufficiency revealed negative 21-alpha-hydroxylase antibodies and elevated Very Long Chain Fatty Acids (VLCFA). Genetic testing showed the novel mutation of ABCD1 gene, p.His97Arg, confirming the diagnosis of X-ALD. Evaluation by ophthalmology, neurology and neuropsychiatry was insignificant, and he was found to have normal cognition and neurological function. MRI of the brain and the entire spine was unremarkable. No genetic testing for Marfanoid features was done, as there were no cardiac and eye findings to support the diagnosis of Marfan syndrome. The patient has no known family members with significant endocrine disorder and X-ALD genetic screening for his family is in progress. This case highlights the importance of considering X-ALD as a potential diagnosis and screening by checking VLCFA in the plasma in male patients with primary adrenal insufficiency without adrenal antibodies. This case is unique in the novel genetic mutation found on testing and association with marfanoid features. Even though X-ALD is rare, it should be considered as a possible etiology for primary adrenal insufficiency because of associated endocrinopathies, neurological deficits, and significant variations in clinical presentation. It is important to raise awareness among providers that diagnosis with measurement of VLCFA is commercially available. It is crucial to counsel patients that diagnosis can be difficult due to limitations in currently available genetic testing methodology, lack of genotype to phenotype correlation, and the possibility of unknown genetic variants with unpredictable prognosis and clinical course. It is imperative that this rare but consequential diagnosis be kept on the differential so that patients are offered appropriate testing and referrals for life or family planning. Though there is no definitive treatment apart from steroid supplementation in adrenal insufficiency and monitoring, patients should be counseled on sick day rules for steroids, medical alert bracelets for adrenal insufficiency, and hydrocortisone administration in emergencies, which may be life-saving. Presentation: Monday, July 14, 2025

The Dallas VA is one of the 50 VA sites participating in a national quality improvement initiative called VALOR-QI: VA Lipid Optimization Reimagined Quality Improvement Project. VALOR-QI is a collaborative project between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting veterans’ cardiovascular (CV) health. As part of the program, VA sites work with an AHA QI Consultant to develop and deploy a local quality improvement plan to help overcome site specific barriers preventing veterans from achieving optimal cholesterol levels. We hypothesize that the QI strategies implemented will positively impact lipid levels and ultimately CV outcomes among high-risk patients. We aim to assess potential barriers to achieving LDL-C <70 mg/dL and develop efficient ways to maintain LDL-C goal. Our approach to the VALOR-QI program at Dallas VA is by enrolling patients with established ASCVD and LDL-C > 70 mg/dL from cardiology, vascular, diabetes, lipid, and independent PharmD clinics. These patients are followed by a health coach every 2- 6 months. Medical adherence is enforced by the health coach ensuring timely refills and reminders. Lifestyle modifications are encouraged via educational materials, referral to dieticians, recreation classes, and tobacco cessation. Patients are also encouraged to sign up for patient portal (my HealtheVet) to access electronic medical records and expedite communication with their healthcare team. The health coach provides individualized counseling regarding lipid lowering treatment and acts as liaison between patients and their providers. VALOR-QI was launched at Dallas VA in Jan 2023. As of May 17 th , 2024, an interim analysis showed that out of 132 veterans engaged, 49 (37.1%) achieved target LDL-C, 66 (50%) received educational material, 4 (3.03%) were referred to dieticians, 10 (7.58%) were referred to recreation programs, and 4 (17.4% of active smokers) were interested in quitting. In conclusion, our VALOR-QI strategy at Dallas VA showed encouraging results, but it is premature to make final conclusions. The support of a health coach showed improved medication adherence, health literacy, and lifestyle modification, thus achieving LDL-C target. Major barriers to achieving target LDL-C were health literacy about high cholesterol, challenges in navigating the health care system, and treatment inertia among patients and providers.

Abstract Disclosure: N. Mulpuri: None. A. Bryant: None. D. Shahin: None. K. Soe: None. Background: Hemoglobin Wayne (Hb Wayne) is a rare, silent alpha chain variant caused by a frameshift mutation in the HbA2 gene. Although clinically silent, this mutation falsely elevates HbA1c values. Clinical cases: We are presenting three cases of Hb Wayne patients referred to our diabetes clinic within the last 5 years. All three cases were Caucasian-American males diagnosed with uncontrolled diabetes based on high HbA1c values of ranging from 10.1-10.6 %. One of the patients was initially started on metformin while the other patients’ treatment plan included dietary and lifestyle modifications. Review of the labs showed that renal function, complete blood count and fasting plasma glucose were within the normal range. High HbA1c value was noted by routine screening lab without having any symptoms related to DM or features of insulin resistance. The discrepancy between high HbA1c values and other glycemic index parameters (serum glucose and FSBG values) was noted. Subsequently, further work up was done (repeat HbA1c with different assay and fructosamine) to verify the diagnosis of uncontrolled DM. Fructosamine levels and repeat HbA1c with a different assay (enzymatic assay at Quest lab) were normal. Hemoglobin electrophoresis confirmed presence of an abnormal alpha variant consistent with Hb Wayne. The patients were reassured and educated about this Hb variant, and no further treatment for DM was pursued. Conclusion: Rare hemolgobinopathies may be more common than previously expected as they can be clinically silent and easily overlooked. While HbA1c has been an important clinical tool for diagnosis and management of diabetes, clinicians should look for underlying reasons which can affect HbA1c assay if there is any discrepancy between HbA1c, FSBG and plasma glucose values. The laboratory at our institution uses cation- exchange High Performance Liquid Chromatography method (Bio-Rad D-100 instrument) resulting in falsely high HbA1c values. Some hemoglobinopathies can affect the widely used HbA1c testing method such as CE-HPLC. The impact on HbA1c values will differ depending on hemoglobin variant and specific method and assay used. Given the limitations of HbA1c testing, clinicians should avoid relying heavily on HbA1c values in management and diagnosis of diabetes. It is vital that clinicians use their clinical judgment to correlate HbA1c with other clinical parameters such as continuous glucose monitoring data, glycated albumin,1,5 anhydroglucitrol (1,5 –AG), fingerstick blood glucose, plasma glucose and fructosamine values. Presentation: Thursday, June 15, 2023

Abstract Background Circulating sex hormones exert unique effects on metabolism, leading to sexual dimorphism in white adipose tissue distribution and function. The gender affirming hormone therapy (GAHT) or cross-sex hormone therapy (CSHT) for transgender patients lower the endogenous sex hormones while raising the opposite sex hormones. Sex hormones are known to have a significant impact on white adipose tissue and metabolism. However, long-term metabolic changes with GAHT in transgender individuals have not been studied, nor are the underlying mechanisms properly elucidated. Hypothesis We test the hypothesis that GAHT will result in sexual dimorphic changes in morphology and function of white adipose tissue according to the type of sex hormones used and the native sex of the patients. Aim 1 To study the effect of cross-sex hormones on clinical parameters such as blood pressure, weight, waist-hip circumference ratio, serum lipids, insulin sensitivity Aim 2 To study the changes in human subcutaneous white adipose tissue (SWAT) distribution and expansion with GAHT Aim 3 To study changes in circulating metabolites and adipokines, and pro-inflammatory and pro-fibrotic gene expression in SWAT with GAHT. Methodology 31 hormone-naive patients (19 Male-to-Female; MtF and 12 Female-to-Male; FtM) were enrolled in the longitudinal study and followed up for 3 years. Clinical parameters and blood samples were gathered at baseline and at 6 month intervals. DXA scans and fat biopsies (peri-umbilical SWAT) were performed at baseline and at 1 year intervals. Results The results presented here compare baseline and at 1 year of GAHT. There was an increase in total cholesterol in the MtF group. HOMA-IR, total fat mass and visceral fat mass increased in MtF group, while they decreased in the FtM group. In MtF group, lean mass and bone mineral content (BMC) decreased at 1 year, but no change was observed in the FtM group. On histological assessment, fat cell size increased in MtF group, while it decreased in the FtM group. Conclusion In MtF transgender patients, androgen deprivation and estrogen treatment resulted in reduced insulin sensitivity together with a rise in total cholesterol possibly via a decrease in lean mass and adipose tissue expansion through significant adipocyte hypertrophy. In FtM transgender patients, testosterone treatment caused improved insulin sensitivity possibly via a decrease in total and visceral fat mass. The greatest strengths of our project include its longitudinal nature over 3 years to capture long-term effects in the same patients as well as deeper mechanistic insights into the underlying metabolite, adipokine and gene expression changes. The limitations of our study include the small sample size with heterogeneity of study population in terms of demographics and lifestyles. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.