General Medicine
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21655
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Browsing General Medicine by Author "Hamilton, Luke"
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Item Are Patients with Adrenal Insufficiency and X-linked Adrenoleukodystrophy Substrate-Limited?(2018-03-14) Hamilton, Luke; Hamby, Tyler; Wilson, Don; Jack, BenjaminBACKGROUND X-linked adrenoleukodystrophy (X-ALD) results from inherited defects in the ATP-Binding Cassette Subfamily D Member 1 gene (ABCD1), which encodes adrenoleukodystrophy protein (ALDP), a peroxisomal protein involved in intracellular lipid transport. X-ALD phenotypes include various combinations of cerebral, neurological, and adrenal abnormalities, with up to 70% of affected males demonstrating primary adrenocortical insufficiency (AI). The pathogenesis of X-ALD is largely attributed to the accumulation of very long chain fatty acids (VLCFAs). It has been suggested that impaired intracellular transport of cholesterol may also play a role in the pathogenesis of AI in X-ALD. The objective of this case study is to review the mechanisms of cholesterol transport and availability in steroidogenic cells in patients with X-ALD who develop AI. CASE INFORMATION A 27-month-old male was referred for evaluation of adrenal function following a diagnosis of X-ALD. Serial laboratory results revealed progressive decline of both baseline and stimulated adrenal function. DISCUSSION In steroidogenic cells, cytosolic free cholesterol is incorporated into the outer mitochondrial membrane (OMM) by a complex of proteins, including mitochondrial transport protein TSPO. Steroidogenic acute regulatory protein transports cholesterol from the OMM to the inner mitochondrial membrane (IMM) where the initial steps of steroidogenesis occur. If cholesterol isn’t available at the IMM, no steroid hormones are produced. Because cholesterol is critical for steroid hormone synthesis, adrenal cortical cells have redundant mechanisms of cholesterol acquisition to ensure an adequate supply, including from circulating lipoproteins, intracellular stores, and de novo synthesis. Disorders affecting lipid and lipoprotein metabolism—as well as lipid lowering treatments, such as use of statins—could potentially alter adrenocortical function. However, there are few reports of AI in these disorders. CONCLUSION Because cortisol is essential for health and the body’s response to stress, redundant mechanisms of acquiring cholesterol allow steroidogenic cells to acquire cholesterol in spite of ALDP deficiency. The inability to process VLCFAs and accumulation of lipids in X-ALD, however, appears to overwhelm the adrenal cortical cells, resulting in cell death and primary AI.Item Would Guidelines for Maturity Onset Diabetes in Youth (MODY) Be Useful in Clinical Practice?(2018-03-14) Wilson, Don; Hamilton, Luke; Hamby, Tyler; Crenshaw, AubreyPurpose: Maturity Onset Diabetes in Youth (MODY) is a rare form of diabetes mellitus (DM) caused by a single gene mutation inherited in an autosomal dominant fashion. There are approximately 13 different gene mutations that can cause the MODY phenotype. MODY is typically diagnosed in Caucasian adolescents; the incidence is similar in males and females. Approximately 80-95% of MODY cases are misdiagnosed as T1D or T2D. Currently no algorithm is available to facilitate clinic decision making to assure proper diagnosis and treatment of affected youth. Methods: An online survey was conducted to better understand common approaches in the diagnosis of DM in youth and the need for a clinical algorithm to help guide testing for MODY. The survey was sent via email to PESTOLA providers (Pediatric Endocrinologists of Texas, Oklahoma, Louisiana, and Arkansas). Results: The survey was sent out to 188 providers; 32 responded (17% response rate). In establishing a diagnosis of MODY, a majority of providers agreed or strongly agreed that they needed more education (53%) and that they needed and algorithm (64%). Responses to the survey allowed us to construct a cost-effective diagnostic algorithm to assist in clinical decision-making in youth with diabetes. Conclusion: Confirming a diagnosis of MODY requires proper knowledge of the key features of the disease and its genetic mode of inheritance, a reliable family history, and predilection of race and phenotype. Because treatment options, outcomes, and genetic counseling differ in MODY compared to T1D and T2D, whenever appropriate clinicians should consider performing genetic testing. Using a diagnostic algorithm for children presenting with dysglycemia will provide physicians a cost-effective way to decide which patients may benefit from genetic testing and, hopefully, reduce the frequent misdiagnosis of MODY. Further studies are needed to determine the utility of the proposed model.