Browsing by Author "Schneider Aguirre, Rebecca"

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    Central precocious puberty: From genetics to treatment
    (Elsevier, 2018) Schneider Aguirre, Rebecca; Eugster, Erica A.; Medicine, School of Medicine
    Central precocious puberty (CPP) results from early activation of the hypothalamic - pituitary -gonadal (HPG) axis and follows the same sequence as normal puberty. While many factors involved in pubertal initiation remain poorly understood, the kisspeptin system is known to play a key role. Currently, mutations in the kisspeptin system, MKRN3, and DLK1 have been identified in sporadic and familial cases of CPP. The diagnosis is based on physical exam findings indicating advancing puberty and on laboratory tests confirming central HPG axis activation. GnRH analogs are the mainstay of treatment and are used with the goal of height preservation. Newer extended release formulations continue to be developed. Currently there is no evidence of long-term complications associated with treatment. However, many areas remain to be explored such as targeted therapies and aspects of clinical management. Further investigation into psychological effects and additional data regarding long-term outcomes, particularly in males, is needed.
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    The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function
    (Bioscientifica, 2022-06-14) Davidson, Rebecca K.; Weaver, Staci A.; Casey, Nolan; Kanojia, Sukrati; Hogarth, Elise; Schneider Aguirre, Rebecca; Sims, Emily K.; Evans-Molina, Carmella; Spaeth, Jason M.; Biochemistry and Molecular Biology, School of Medicine
    Type 2 diabetes (T2D) is associated with loss of transcription factors (TFs) from a subset of failing β-cells. Among these TFs is Pdx1, which controls the expression of numerous genes involved in maintaining β-cell function and identity. Pdx1 activity is modulated by transcriptional coregulators and has recently been shown, through an unbiased screen, to interact with the Chd4 ATPase subunit of the nucleosome remodeling and deacetylase complex. Chd4 contributes to the maintenance of cellular identity and functional status of numerous different cell types. Here, we demonstrated that Pdx1 dynamically interacts with Chd4 under physiological and stimulatory conditions within islet β-cells and established a fundamental role for Chd4 in regulating insulin secretion and modulating numerous Pdx1-bound genes in vitro, including the MafA TF, where we discovered Chd4 is bound to the MafA region 3 enhancer. Furthermore, we found that Pdx1:Chd4 interactions are significantly compromised in islet β-cells under metabolically induced stress in vivo and in human donor tissues with T2D. Our findings establish a fundamental role for Chd4 in regulating insulin secretion and modulating Pdx1-bound genes in vitro, and disruption of Pdx1:Chd4 interactions coincides with β-cell dysfunction associated with T2D.
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    Hypocalcemia in a 15 Year Old With New Onset Type 2 Diabetes Mellitus
    (Oxford University Press, 2021) Becerril Romero, Carlos C.; Schneider Aguirre, Rebecca; Imel, Erik Allen; DiMeglio, Linda A.; Gohil, Anisha; Pediatrics, School of Medicine
    Background: Diabetic ketoacidosis and significant hyperglycemia are associated with known electrolyte derangements in sodium, potassium, and phosphorus. Hypocalcemia and hypoparathyroidism occurring in uncontrolled diabetes are rare. We present a case of new-onset diabetes with severe hypocalcemia. Case: A 15-year-old obese Caucasian male with ADHD and autism presented to the Emergency room due to hyperglycemia found on laboratory evaluation for hypertension. Serum glucose was 563 mg/dL, serum bicarbonate 24 meq/L (21 - 31 meq/L), and HgbA1C 11.4% (4.0 - 5.6%). He was admitted to initiate insulin and for diabetes education. On admission, hypocalcemia was noted: serum calcium 6.6 mg/dL (8.5 - 10.5 mg/dL), alkaline phosphatase 352 units/L (48 - 277 units/L), and albumin 4.6 g/dL (3.5 - 5.0 g/dL). Repeat testing revealed serum calcium 5.1 mg/dL, phosphorus 4.3 mg/dL (2.5 - 4.5 mg/dL), and magnesium 1.7 mg/dL (1.6 - 2.9 mg/dL). He endorsed a 2 month history of tetany, paresthesia, and muscle weakness. Due to food aversions, his dietary intake of calcium and vitamin D was minimal. He had limited sun exposure. Subsequent PTH was 40 pg/mL (10 - 65 pg/mL) with concurrent serum calcium of 6.5 mg/dL. QTc was prolonged [529 msec (<440 msec)], prompting transfer to the intensive care unit for telemetry, intravenous calcium gluconate, and regular calcium monitoring. Treatment was commenced with cholecalciferol 2000 international units daily and oral calcium carbonate (50 mg elemental calcium/kg/day) in divided doses for presumed Vitamin D deficiency. After several intravenous calcium gluconate doses over 24 hours, the patient’s QTc and ionized calcium normalized. At discharge, calcium was 8.5 mg/dL. He was discharged on the above regimen of calcium and cholecalciferol, and basal and bolus insulin. After discharge, laboratory results returned indicating negative diabetes autoantibodies (GAD 65, Insulin, IA-2) and 25-OH Vitamin D <10 ng/mL (30 - 100ng/mL). Two days after discharge, calcium was 7.3 mg/dL. Two weeks later, labs were: 25-OH Vitamin D 11.3 ng/mL, PTH 10.4 pg/mL, and calcium 9.6 mg/dL. Conclusion: This teen presented with new-onset type 2 diabetes and symptomatic hypocalcemia, an atypical feature of new-onset diabetes. This patient’s hypocalcemia was likely due to both vitamin D deficiency and hypoparathyroidism. He had a low vitamin D level and poor calcium intake with elevated alkaline phosphatase; however, his high normal serum phosphorus and inappropriately normal PTH (instead of elevated in the setting of severe hypocalcemia) indicated a component of hypoparathyroidism. Calcium normalized with detectable 25-OH Vitamin D levels but PTH remained low. Our case highlights the importance of recognizing both that electrolyte abnormalities at diabetes onset may not be directly attributable to diabetes/hyperglycemia and that vitamin D deficiency and hypoparathyroidism may co-exist.
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    Mental Health Disorders and Hyperthyroidism in the Pediatric Population
    (American Academy of Pediatrics, 2019-11) Schneider Aguirre, Rebecca; Fuqua, John S.; Medicine, School of Medicine
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    Methimazole Desensitization in a 4-Year-Old With Refractory Graves Disease
    (Elsevier, 2021-02-20) Schneider Aguirre, Rebecca; Khalid, Ariba; Ismail, Heba M.; Nabhan, Zeina; Pediatrics, School of Medicine
    Objective: To describe a 4-year-old girl with Graves disease and methimazole allergy who underwent desensitization, allowing continued methimazole use when other treatments were contraindicated. Methods: We formulated a desensitization plan utilizing cetirizine and prednisone for a patient with previously diagnosed Graves disease who developed urticaria and arthralgias from methimazole. She was admitted for monitoring of rash, urticaria, angioedema, and anaphylaxis. Her methimazole dose was increased as tolerated and then titrated as an outpatient. Results: A 4-year-old girl presented with a heart rate of 195 beats/minute, blood pressure of 145/108, and subsequent labs of undetectable thyroid stimulating hormone (TSH), free T4 5.8 ng/dL, thyroid peroxidase antibody 11.5 IU/ml, and TSH receptor antibody 39.03 IU/L, consistent with Graves disease. She developed urticaria and arthralgias after 2.5 weeks on methimazole, which resolved with drug cessation. Because of her age, the risks of radioactive iodine ablation and surgery were concerning; therefore, methimazole desensitization was attempted. Prednisone (1 mg/kg/day) and cetirizine (5 mg/day) were started prior to low-dose methimazole reintroduction and continued for 7 days. Methimazole was then gradually increased to a final dose of 15 mg daily (0.8 mg/kg/day). Free T4 normalized within a month (1.12 ng/dL), and her TSH normalized within 10 months (4.61 mcU/mL). Except for 2 possible breakthrough allergic responses that resolved with pulse steroids, she continues to tolerate methimazole. Conclusion: We describe a case of methimazole desensitization. In this patient, pretreatment with prednisone, coupled with daily cetirizine, successfully induced methimazole tolerance when other treatment modalities were contraindicated.
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    Predictors of glycemic worsening in the next year in adults with screen-detected type 2 diabetes
    (medRxiv, 2024-04-27) Schneider Aguirre, Rebecca; Hannon, Tamara S.; Considine, Robert V.; Patel, Yash; Kirkman, M. Sue; Mather, Kieren J.; Pediatrics, School of Medicine
    Background and aims: Identifying simple markers of risk for worsening glucose can allow care providers to target therapeutic interventions according to risk of worsening glycemic control. We aimed to determine which routine clinical measures herald near-term glycemic worsening in early type 2 diabetes(T2D). Methods: The Early Diabetes Intervention Program (EDIP) was a clinical trial in individuals with screendetected T2D [HbA1C 6.3+0.63%(45+5mmol/mol)]. During the trial some participants experienced worsening fasting blood glucose (FBG). We investigated the time course of FBG, HbA1c, weight, and other clinical factors to determine which might herald glycemic worsening over the next year. Results: Progressors (62/219, 28.5%) had higher FBG than non-progressors at baseline [118 vs 130mg/dL (6.6 vs 7.2 mmol/L), p=<0.001]. FBG was stable except in the year of progression, when progressors exhibited a large 1-year rise [mean change 14.2mg/dL(0.79 mmol/L)]. Current FBG and antecedent year change in FBG were associated with progression(p<0.01), although the magnitude of change was too small to be of clinical utility (0.19 mg/dL; 0.01 mmol/L). Current or antecedent year change in HbA1c, weight, TG or HDL were not associated with progression. In the year of glycemic worsening, rising glucose was strongly associated with a concurrent increase in weight (p<0.001). Conclusions: Elevated FBG but not HbA1c identified individuals at risk for imminent glycemic worsening; the subsequent large rise in glucose was associated with a short-term increase in weight. Glucose and weight surveillance provide actionable information for those caring for patients with early diabetes.