Sejal Shah

All Publications

• Adrenoleukodystrophy: Guidance for Adrenal Surveillance in Males Identified by Newborn Screen. The Journal of clinical endocrinology and metabolism Regelmann, M. O., Kamboj, M., Miller, B. S., Nakamoto, J. M., Sarafoglou, K., Shah, S., Stanley, T. L., Marino, R., Pediatric Endocrine Society Drug and Therapeutics & Rare Disorders Committee 2018

  Abstract

  Context: Adrenoleukodystrophy (ALD) is a peroxisomal disorder associated with neurologic decompensation and adrenal insufficiency. Newborn screening for ALD has recently been implemented in five states with plans to expand to all 50 states in the US. Adrenal insufficiency ultimately develops in most males with ALD but the earliest age of onset is not well established.Objective: These clinical recommendations are intended to address screening for adrenal insufficiency in boys identified to have ALD by newborn screen.Participants: Seven members of the Pediatric Endocrine Society Drug and Therapeutics & Rare Diseases Committee, with clinical experience treating children with ALD and adrenal insufficiency, and a pediatric endocrinologist and laboratory director were selected to be on the working committee.Consensus Process: The authors comprised the working group and performed systematic reviews of the published literature regarding adrenal insufficiency and ALD. The recommendations were reviewed and approved by the larger Pediatric Endocrine Society Drug and Therapeutics & Rare Diseases Committee and then by the Pediatric Endocrine Society Board of Directors.Conclusions: There is limited literature evidence regarding monitoring of evolving adrenal insufficiency in male infants and children with ALD. The recommendations suggest initiating assessment of adrenal function at diagnosis with ALD and regular monitoring, in order to identify boys with adrenal insufficiency in a timely manner and prevent life-threatening adrenal crisis. These recommendations are intended to serve as an initial guide, with the understanding that additional experience will inform future guidelines.

  View details for PubMedID 30289543

• Large Doses of Vitamin D Fail to Increase 25-Hydroxyvitamin D Levels or to Alter Cardiovascular Risk Factors in Obese Adolescents: A Pilot Study. journal of adolescent health Shah, S., Wilson, D. M., Bachrach, L. K. 2015; 57 (1): 19-23

  Abstract

  Vitamin D deficiency and cardiometabolic risk factors are common in obese adolescents. Observational studies demonstrate an inverse relationship among serum 25-hydroxyvitamin D (25OHD) and obesity, insulin resistance, and inflammatory cytokines. This pilot study explores if vitamin D supplementation could reduce serum concentrations of inflammatory cytokines (interleukin [IL] 6, IL-10, tumor necrosis factor α), adiponectin, lipids, hemoglobin A1C, and high-sensitivity C-reactive protein (hs-CRP). A secondary aim was to determine the associations between baseline serum 25OHD concentrations and body mass index (BMI), hs-CRP, inflammatory cytokines, and lipids.Overweight and obese adolescents enrolled in this 24-week, randomized, double-blind study were given 150,000 IU ergocalciferol or placebo at baseline and 12 weeks. Outcome measurements included serum 25OHD, inflammatory cytokines, adiponectin, hs-CRP, lipids, hemoglobin A1C, and BMI at baseline, 12, and 24 weeks.Of 40 participants, 31 (78%) completed the study. Mean ± standard error 25OHD levels were similar in vitamin D and placebo groups at baseline (19.6 ± 5.3 vs. 25.8 ± 10.8 ng/mL) and 24 weeks (20.1 ± 3.4 vs. 24.6 ± 8.4 ng/mL). Inflammatory and cardiovascular markers were not significantly different between groups at 24 weeks. Serum 25OHD at baseline was associated with BMI (r = -.44 [95% confidence interval, -.66 to -.15]) but not with other outcome measures.Supplementation with vitamin D at 150,000 IU every 3 months failed to increase serum 25OHD or alter inflammatory markers and lipids in overweight and obese youth. Further studies are needed to establish the dose of vitamin D required to increase 25OHD and determine potential effects on metabolic risk factors in obese teens.

  View details for DOI 10.1016/j.jadohealth.2015.02.006

  View details for PubMedID 25873553

• A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism. International journal of pediatric endocrinology Shah, S., Forghani, N., Durham, E., Neely, E. K. 2014; 2014 (1): 12-?

  Abstract

  Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure.20 prepubertal adolescent females with ovarian failure, ages 12-18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test.Mean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone.Treatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls, but larger prospective randomized trials are required.NCT01023178.

  View details for DOI 10.1186/1687-9856-2014-12

  View details for PubMedID 24982681

• Adrenal Suppression from Topical and Subconjunctival Steroids after Pediatric Cataract Surgery. Ophthalmology Lambert, S. R., Shah, S. 2018; 125 (10): 1644–45

  View details for DOI 10.1016/j.ophtha.2018.06.012

  View details for PubMedID 30243335

• Effectiveness of Early Intensive Therapy on beta-Cell Preservation in Type 1 Diabetes DIABETES CARE Buckingham, B., Beck, R. W., Ruedy, K. J., Cheng, P., Kollman, C., Weinzimer, S. A., Dimeglio, L. A., Bremer, A. A., Slover, R., Tamborlane, W. V. 2013; 36 (12): 4030-4035

  Abstract

  To assess effectiveness of inpatient hybrid closed-loop control (HCLC) followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7 days of diagnosis of type 1 diabetes on the preservation of β-cell function at 1 year.Sixty-eight individuals (mean age 13.3 ± 5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP therapy (intensive group; N = 48) or to the usual-care group treated with multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C-peptide concentrations during mixed-meal tolerance tests at 12 months.Intensive-group participants initiated HCLC a median of 6 days after diagnosis for a median duration of 71.3 h, during which median participant mean glucose concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at 12 months, only 33% of intensive participants averaged sensor use ≥6 days/week. In the usual-care group, insulin pump and CGM use were initiated prior to 12 months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in both groups throughout the study. At 12 months, the geometric mean (95% CI) of C-peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide concentration ≥0.2 pmol/mL (P = 0.30).In new-onset type 1 diabetes, HCLC followed by SAP therapy did not provide benefit in preserving β-cell function compared with current standards of care.

  View details for DOI 10.2337/dc13-1074

  View details for Web of Science ID 000327211500053

  View details for PubMedID 24130350

• Newborn with prenatally diagnosed choroidal fissure cyst and panhypopituitarism and review of the literature. AJP reports Chitkara, R., Rajani, A., Bernstein, J., Shah, S., Hahn, J. S., Barnes, P., Hintz, S. R. 2011; 1 (2): 111-114

  Abstract

  Little has been reported on fetal diagnosis of choroidal fissure cysts and prediction of the clinical complications that can result. We describe the case of a near-term male infant with prenatally diagnosed choroidal fissure cyst and bilateral clubfeet. His prolonged course in the neonatal intensive care nursery was marked by severe panhypopituitarism, late-onset diabetes insipidus, placement of a cystoperitoneal shunt, and episodes of sepsis. Postnatal genetic evaluation also revealed an interstitial deletion involving most of band 10q26.12 and the proximal half of band 10q26.13. The patient had multiple readmissions for medical and surgical indications and died at 6 months of age. This case represents the severe end of the spectrum of medical complications for children with choroidal fissure cysts. It highlights not only the importance of comprehensive evaluation and multidisciplinary management and counseling in such cases, but also the need for heightened vigilance in these patients.

  View details for DOI 10.1055/s-0031-1293512

  View details for PubMedID 23705098

• Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation JOURNAL OF BIOLOGICAL CHEMISTRY Misra, P., Qi, C., Yu, S. T., Shah, S. H., Cao, W. Q., Rao, M. S., Thimmapaya, B., Zhu, Y. J., Reddy, J. K. 2002; 277 (22): 20011-20019

  Abstract

  PIMT (PRIP-interacting protein with methyltransferase domain), an RNA-binding protein with a methyltransferase domain capable of binding S-adenosylmethionine, has been shown previously to interact with nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR)-interacting protein) and enhance its coactivator function. We now report that PIMT strongly interacts with transcriptional coactivators, CBP, p300, and PBP but not with SRC-1 and PGC-1alpha under in vitro and in vivo conditions. The PIMT binding sites on CBP and p300 are located in the cysteine-histidine-rich C/H1 and C/H3 domains, and the PIMT binding site on PBP is in the region encompassing amino acids 1101-1560. The N-terminal of PIMT (residues 1-369) containing the RNA binding domain interacts with both C/H1 and C/H3 domains of CBP and p300 and with the C-terminal portion of PBP that encompasses amino acids 1371-1560. The C-terminal of PIMT (residues 611-852), which binds S-adenosyl-l-methionine, interacts respectively with the C/H3 domain of CBP/p300 and with a region encompassing amino acids 1101-1370 of PBP. Immunoprecipitation data showed that PIMT forms a complex in vivo with CBP, p300, PBP, and PRIP. PIMT appeared to be co-localized in the nucleus with CBP, p300, and PBP. PIMT enhanced PBP-mediated transcriptional activity of the PPARgamma, as it did for PRIP, indicating synergism between PIMT and PBP. In contrast, PIMT functioned as a repressor of CBP/p300-mediated transactivation of PPARgamma. Based on these observations, we suggest that PIMT bridges the CBP/p300-anchored coactivator complex with the PBP-anchored coactivator complex but differentially modulates coactivator function such that inhibition of the CBP/p300 effect may be designed to enhance the activity of PBP and PRIP.

  View details for DOI 10.1074/jbc.M201739200

  View details for Web of Science ID 000175894800101

  View details for PubMedID 11912212