Search

Purpose: This study aimed to evaluate the time interval to menarche after gonadotropin-releasing hormone agonist (GnRHa) treatment in females with central precocious puberty (CPP) and to identify factors contributing to timing of menarche.Methods: We retrospectively reviewed medical records of 39 females with CPP who reached menarche after GnRHa treatment (leuprolide or histrelin). CPP diagnostic criteria were breast development at

Background Diabetes is a risk factor for poor COVID‐19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies. Methods T1D Exchange coordinated a US type 1 diabetes COVID‐19 registry. Forty‐six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID‐19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization. Results Data from 266 patients with previously established type 1 diabetes aged, Highlights Outcomes for children with type 1 diabetes who experience COVID‐19 are currently unknown. We report 266 cases from US diabetes clinics of children with type 1 diabetes who had COVID‐19. Diabetic ketoacidosis was the major adverse outcome, and it was associated with higher A1c.

Background Antifungals act on fungal sterols structurally similar to human cholesterol. Ketoconazole reversibly suppresses steroidogenesis by inhibiting cytochrome P450 enzymes and interferes with dihydrotestosterone (DHT) activity by binding to the androgen receptor. Hypospadias was reported in infants exposed to nystatin in utero. Case presentation A male infant exposed to antepartum nystatin presented with severe under-undervirilization and transient adrenal corticosteroid abnormalities. He was born in USA at 31 weeks gestation to a mother treated with vaginal Polygynax capsules (nystatin-100,000 international units, neomycin sulphate-35,000 international units and polymyxin B-35,000 international units) for vaginal discharge in the Ivory Coast. She used approximately 60 capsules between the first trimester until delivery. The infant was born with micropenis, chordee, perineo-scrotal hypospadias and bifid scrotum with bilaterally palpable gonads. The karyotype was 46,XY. No Mullerian structures were seen on ultrasound. Serum 17-hydroxyprogesterone (17 OHP) on newborn screening was high (304 ng/ml, normal Conclusions We report severe undervirilization in a 46,XY infant born to a mother treated with prolonged and high dose nystatin during pregnancy. This presentation suggests that prolonged antepartum use of high dose nystatin could lead to severe but transient defects in androgen synthesis and/or action possibly by acting as an endocrine disruptor. Further studies are warranted to confirm this finding. Thus, endocrine disruptors should be considered in male newborns with atypical genitalia not explained by common pathologies.

Cortisol and growth hormone (GH) deficiencies are causes of neonatal hypoglycemia. When they coexist, a pituitary disorder is suspected. We present an infant with hypoglycemia in whom an ACTH receptor defect was associated with transient GH deficiency. A full-term boy with consanguineous parents presented with hypoglycemia (serum glucose 18 mg/dL) at 4 hours of life with undetectable serum cortisol (

Introduction: Deterioration in glycemic control often occurs during adolescence in children with type 1 diabetes (T1D). Shared appointments have been shown to improve quality of life scores and treatment adherence in children with chronic illnesses. Objective: To examine the impact of combined individual visits and shared education appointments in adolescents with T1D on diabetes control, self-management, and diabetes related distress. Methods: Adolescents ages 11-19y with T1D for over 1y and poor control/adherence defined by HbA1C > 9%, 2 or more DKA episodes in the past year or 2 missed appointments were enrolled in a 6 month DKA prevention program consisting of monthly individual visits followed by an hour long shared education visit. HbA1C levels were obtained every 3 mo. Participants completed a diabetes distress score (DDS) and diabetes self-management questionnaire (DMSQ) prior to participation and at the 6th visit. Participants were followed for an additional 6 months after completion of the program. Those who attended 2 or more session were included in the analysis. Results: Ten adolescents (8 female, average age 13.9 y, diabetes duration from 1-11 y, average A1C 10.6% SD 2.0) were enrolled. None of the 10 participants had DKA during the program. There was no statistically significant change in A1C. No changes were noted in the DDS; however there was improvement in dietary control on DMSQ from 4.0 to 5.7 (p value 0.058). Six attended 5 or more of the sessions. Those 6 participants had a decrease in average A1C by 0.3% over 6 mo with no DKA episodes within 6 mo of completion. The 4 participants who attended 2-4 sessions had an increase in average A1C of 0.85% over the same period and 3 had DKA episodes within 6 mo after completion. Conclusions: Shared education visits may be a valuable approach to the care of adolescents with diabetes. No episodes of DKA and no significant changes in glycemic control were noted in 6 mo; however larger long-term studies are needed to explore whether continued shared visits can improve glycemic control. Disclosure M. Wilkes: None. T. Murphy: None. A. Aluf: None. D. Sperber: None. A. Sherry: None. S. Sethuram: None. L. Choleva: None. R. Rapaport: None.

Background: Beta thalassemia is characterized by the abnormal synthesis of β hemoglobin chains resulting in hemolytic anemia. Treatment involves frequent blood transfusions, which leads to the deposition of iron in many organs, including endocrine tissue such as the thyroid gland. Iron overload has been associated with various malignancies, most notably liver and hematological. To date, 7 cases of papillary thyroid cancer in patients with beta thalassemia have been reported in the adult literature, but none in pediatrics. Clinical Case: The patient is a 15 year 4 month old female with beta thalassemia requiring chronic red blood cell transfusions since the age of 5 months. She initially presented to us for evaluation of secondary amenorrhea. She underwent a splenectomy at the age of 10 years and received chelating therapy with deferasirox and deferiprone. Her ferritin levels had been stable around 1500ng/mL for the year prior to presentation; however, MRI revealed iron deposition in her pancreas, liver, kidneys, bone marrow and pituitary gland. On exam, her thyroid gland was asymmetric with the right lobe measuring 1cm larger than the left. The gland was firm in consistency with palpable lymph nodes along the right anterior cervical chain. A thyroid ultrasound was completed which revealed an enlarged right lobe containing 3 focal hypoechoic masses with calcific foci. Biopsy obtained via fine needle aspiration was consistent with papillary thyroid carcinoma. She underwent total thyroidectomy and histological examination confirmed the diagnosis. Her postoperative course was uncomplicated and she was started on replacement therapy with levothyroxine. Conclusion: To our knowledge this is the first case of papillary thyroid carcinoma in a pediatric patient with beta thalassemia. The incidence of thyroid cancer in patients with beta thalassemia is currently unknown, however there may be utility in routine surveillance of this patient population.

Introduction: SARS-Cov-2 (severe acute respiratory distress syndrome- coronavirus 2) viral infection has a predilection for pancreatic beta cells causing insulin deficiency. Studies from the SARS-CoV outbreak in 2003 highlighted the relationship between SARS-CoV and ACE-2 (angiotensin-converting enzyme 2) receptors in pancreatic islet cells. We describe a pediatric patient who developed Diabetes Mellitus after exposure to the Sars-CoV-2 virus. Case Report: A previously healthy 13-year-old female of Mexican descent was found to be hyperglycemic at her annual visit. The patient endorsed polyuria and polydipsia for 3 weeks, and weight loss for 3months. 3 months prior to presentation, her mother became ill and tested positive for SARS-CoV-2 by PCR analysis. The patient had no SARS-CoV-2 associated symptoms. Her exam was notable for a BMI was in the 78%ile for age with no acanthosis nigricans. She had no family history of diabetes or autoimmune disease. Initial blood glucose was 729 mg/dL, with bicarbonate of 20.6 mEq/L, pH 7.45, and anion gap of 14 mEq/L. Large ketones were present in the urine. Her concomitant C-peptide level of 1.0 ng/ml was low in the setting of hyperglycemia. Her HbA1c was 14.3%. Diabetes-related autoantibodies, celiac, and thyroid antibodies were negative. Her Sars-CoV-2 antibody titer was positive with a negative PCR. The patient was treated with a basal-bolus regimen of subcutaneous insulin at a maximal total daily dose of 0.7 u/kg/day. 5 weeks later, her insulin requirement and HbA1C were both lower; at 0.5 u/kg/day and 9.3% respectively. Discussion: This patient’s symptoms of hyperglycemia started shortly after her exposure to the SARS-CoV-2 virus. She had no features consistent with Type 2 DM. She similarly had no serological evidence of DM related autoimmunity, thus being different from reports of new-onset Type 1 DM with confirmed autoimmunity presenting during the Sars-CoV-2 pandemic. Although Type 1B DM without evidence of humoral islet autoimmunity and monogenic DM could not be fully excluded, we postulate that the patient developed SARS-CoV-2 associated DM given her time course and documented exposure to SARS –CoV-2 with the presence of SARS-CoV antibodies. One similar case has previously been reported By Holstein et al. 1 While we share the lack of direct evidence of causation, we postulate that more patients with similar presentations will be reported during the current pandemic. Reference: 1.Hollstein, T et al. Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report [published online ahead of print, 2020 Sep 2]. Nat Metab. 2020;10.1038/s42255-020-00281-8. doi:10.1038/s42255-020-00281-8

The N-terminal SH4 domain of Src family kinases is responsible for promoting membrane binding and plasma membrane targeting. Most Src family kinases contain an N-terminal Met-Gly-Cys consensus sequence that undergoes dual acylation with myristate and palmitate after removal of methionine. Previous studies of Src family kinase fatty acylation have relied on radiolabeling of cells with radioactive fatty acids. Although this method is useful for verifying that a given fatty acid is attached to a protein, it does not reveal whether other fatty acids or other modifying groups are attached to the protein. Here we use matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify fatty acylated species of the Src family kinase Fyn. Our results reveal that Fyn is efficiently myristoylated and that some of the myristoylated proteins are also heterogeneously S-acylated with palmitate, palmitoleate, stearate, or oleate. Furthermore, we show for the first time that Fyn is trimethylated at lysine residues 7 and/or 9 within its N-terminal region. Both myristoylation and palmitoylation were required for methylation of Fyn. However, a general methylation inhibitor had no inhibitory effect on myristoylation and palmitoylation of Fyn, suggesting that methylation occurs after myristoylation and palmitoylation. Lysine mutants of Fyn that could not be methylated failed to promote cell adhesion and spreading, suggesting that methylation is important for Fyn function.

The N-terminal SH4 domain of Src family kinases is responsible for promoting membrane binding and plasma membrane targeting. Most Src family kinases contain an N-terminal Met-Gly-Cys consensus sequence that undergoes dual acylation with myristate and palmitate after removal of methionine. Previous studies of Src family kinase fatty acylation have relied on radiolabeling of cells with radioactive fatty acids. Although this method is useful for verifying that a given fatty acid is attached to a protein, it does not reveal whether other fatty acids or other modifying groups are attached to the protein. Here we use matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify fatty acylated species of the Src family kinase Fyn. Our results reveal that Fyn is efficiently myristoylated and that some of the myristoylated proteins are also heterogeneously S-acylated with palmitate, palmitoleate, stearate, or oleate. Furthermore, we show for the first time that Fyn is trimethylated at lysine residues 7 and/or 9 within its N-terminal region. Both myristoylation and palmitoylation were required for methylation of Fyn. However, a general methylation inhibitor had no inhibitory effect on myristoylation and palmitoylation of Fyn, suggesting that methylation occurs after myristoylation and palmitoylation. Lysine mutants of Fyn that could not be methylated failed to promote cell adhesion and spreading, suggesting that methylation is important for Fyn function.