17 research outputs found
Successful use of long acting octreotide in two cases with Beckwith-Wiedemann syndrome and severe hypoglycemia
INTRODUCTION: Hyperinsulinism associated with Beckwith-Wiedemann syndrome (BWS) can occur in about 50% of cases, causing hypoglycemia of variable severity. Parenteral use of octreotide may be indicated if unresponsive to diazoxide. There is limited data on use of octreotide in BWS. OBJECTIVE: Chart review describing 2 cases with BWS and hypoglycemia treated with long acting Octreotide as a monthly injection. CASES: We describe two unrelated females born large for gestational age found to have clinical features consistent with BWS, who developed severe hypoglycemia. Genetic diagnosis of BWS was confirmed. The first patient was born at 37 weeks and developed hypoglycemia shortly after birth. She was initially started on diazoxide but developed pulmonary congestion and was therefore switched to depot octreotide (LAR). She maintained euglycemia with LAR. In the second patient (born at 26-4/7 weeks), onset of hypoglycemia was delayed till 11 weeks of age due to hydrocortisone (indicated hemodynamically) and continuous feeding, and was partially responsive to diazoxide. She was switched to octreotide 4 times daily, treated till at age 18 months. Despite frequent feeds, she required treatment again between ages 4–6.5 years, initially with diazoxide but due to severe hypertrichosis she was switched to LAR with an excellent response. Both patients treated with LAR for over two years achieved euglycemia above 70 mg/dl and had normal height gain, without side effects. CONCLUSION: Successful treatment of hypoglycemia can be achieved and maintained with LAR in infants and children with BWS who are either resistant or cannot tolerate diazoxide
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Undescended retropharyngeal parathyroid adenoma with adjacent thymic tissue in a 13-year-old boy with primary hyperparathyroidism.
We describe a rare presentation of a symptomatic parathyroid adenoma located in an ectopic retropharyngeal position in a 13-year-old boy. Preoperative CT scan and MRI demonstrated the ectopic location of the parathyroid adenoma. The patient underwent successful parathyroidectomy with cure of his hyperparathyroidism. On pathologic exam, the specimen was made up of a parathyroid adenoma and adjacent thymic tissue, indicating that it was likely an undescended lower parathyroid gland arising from the third pharyngeal pouch. Ectopic retropharyngeal parathyroid adenomas are very rare and to our knowledge, none have been previously described in adolescents
Mutational Analysis in Pediatric Thyroid Cancer and Correlations with Age, Ethnicity, and Clinical Presentation.
BackgroundWell-differentiated thyroid cancer (WDTC) incidence in pediatrics is rising, most being papillary thyroid carcinoma (PTC). The objective of the study was to assess the prevalence of different mutations in pediatric WDTC and correlate the genotype with the clinical phenotype.MethodsThis is a single-center retrospective study. Thyroid tissue blocks from 42 consecutive pediatric WDTC patients who underwent thyroidectomy between 2001 and 2013 were analyzed at Quest Diagnostics for BRAF(V600E), RAS mutations (N,K,H), and RET/PTC and PAX8/PPARγ rearrangements, using validated molecular methods. Thyroid carcinomas included PTC, follicular thyroid carcinoma (FTC), and follicular variant of PTC (FVPTC).ResultsThirty-nine samples (29 females) were genotyped. The mean age at diagnosis was 14.7 years (range 7.9-18.4 years), and most were Hispanic (56.4%) or Caucasian (35.9%). The mean follow-up period was 2.9 years. Mutations were noted in 21/39 (53.8%), with both BRAF(V600E) (n = 9), and RET/PTC (n = 6) detected only in PTC. Mutations were detected in 2/5 FTC (PAX8/PPARγ and NRAS) and 3/6 FVPTC cases (PAX8/PPARγ). Of 28 PTC patients, 57.1% had mutations: 32.1% with BRAF(V600E), 21.4% with RET/PTC, and 3.6% with NRAS. Of patients with BRAF(V600E), 77.8% were Hispanic and 88.9% were >15 years, while all RET/PTC-positive patients were ≤15 years (p = 0.003). Tumor size, lymph node involvement, and distant metastasis at diagnosis (or soon after (131)I ablation) did not vary significantly based on the mutation.ConclusionsBRAF(V600E) was the most common mutation, especially in older and Hispanic adolescents. A larger, ethnically diverse pediatric cohort followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed
Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies
Context: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction.
Objective: Assess tildacerfont safety and efficacy.
Design and setting: Two Phase 2 open-label studies.
Patients: Adults with 21OHD.
Intervention: Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2).
Main outcome measure: Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 ≤ 2× upper limit of normal (ULN) or A4 > 2× ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments.
Results: In Study 1, evaluable participants with baseline A4 > 2× ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (-59.4% to -28.4%), 17-OHP (-38.3% to 0.3%), and A4 (-24.2% to -18.1%), with no clear dose response. In Study 2, participants with baseline A4 > 2× ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤ 2× ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%).
Conclusions: For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal
Lipoprotein Particle Concentrations in Children and Adults following Kawasaki Disease
OBJECTIVE: To test the hypothesis that children and adults with history of Kawasaki disease (KD) are more likely to have abnormal lipoprotein particle profiles that could place them at increased risk of atherosclerosis later in life. STUDY DESIGN: Fasting serum samples were obtained from 192 children and 63 adults with history of KD and 90 age-similar healthy controls. Lipoprotein particle (P) concentrations and sizes were measured by Nuclear Magnetic Resonance (NMR) spectroscopy (Liposcience Inc., Raleigh, NC) and serum was assayed for total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL)-C. Low-density lipoprotein cholesterol (LDL)-C was estimated using the Friedewald formula. Data were analyzed in a least-square means model adjusting for age and sex and using Holm correction for multiple comparisons. RESULTS: Compared with respective control groups, both adult and pediatric subjects with KD had significantly lower mean very-low-density lipoprotein-chylomicron particle concentrations (VLDLC-P), intermediate-density lipoproteins (IDL), TG, and TC concentrations. Pediatric subjects with KD had significantly lower LDL-P and LDL-C concentrations and lower mean TC/HDL-C ratio (p<0.001). In contrast, the adult subjects with KD had significantly lower HDL-P, small HDL-P, and HDL-C concentrations (p<0.001), but HDL-C was within normal range. CONCLUSIONS: NMR lipoprotein particle analysis suggests that pediatric and adult subjects with KD regardless of their aneurysm status are no more likely than age-similar, healthy controls to have lipid patterns associated with increased risk of atherosclerosis
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Extended Use of Histrelin Implant in Pediatric Patients
PurposeHistrelin implant (HI) is a gonadotropin-releasing hormone agonist (GnRHa) used in pediatrics to treat central precocious puberty (CPP) and for pubertal suppression in transgender/non-binary (TG/NB) youth with gender dysphoria. HI is designed for annual removal/replacement; however, effectiveness has been reported beyond 1 year. No previous study has assessed prolonged HI use in TG/NB youth. We hypothesize that HI is effective >12 months in TG/NB youth as described in children with CPP.MethodsThis retrospective, two-center study included 49 subjects with 50 HI retained ≥17 months, in TG/NB (42) and CPP (7). Pubertal suppression was assessed biochemically and/or clinically (testicular/breast exams). Escape from pubertal suppression and HI removal is also characterized.ResultsMost implants (42/50) maintained clinical/biochemical suppression for the duration of the study. The average use of a single HI was 37.5±13.6 months. Pubertal suppression escape occurred in eight subjects at average 30.4 months from placement: five had only biochemical; two clinical; and one both clinical and biochemical escape. After an average of 32.9 months, only 3/23 HI removed had adverse effects (HI broken, difficult removal).ConclusionExtended use of HI in our TG/NB and CPP subjects was efficacious, resulting in sustained biochemical and clinical pubertal suppression in most. Suppression escape occurred at 15-65 months. Complications at HI removal were infrequent. Keeping HI for extended time would improve cost and morbidity, while maintaining efficacy and safety for most patients
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Diagnostic utility of fine needle aspiration cytology in pediatric thyroid nodules based on Bethesda Classification
ObjectivesThe Bethesda system for reporting cytopathology (TBSRTC) has been widely adopted in the management of thyroid nodules. Based on the limited pediatric data available, the implied malignancy risk for each of the categories may be significantly different in pediatrics vs. adults, especially in the indeterminate categories (Bethesda Class III or IV). We report the diagnostic utility of fine needle aspiration (FNA) biopsy at our institution based on the Bethesda system and the risk of malignancy in each category.MethodsWe retrospectively reviewed all patients who underwent a thyroid FNA at our tertiary pediatric hospital from 12/1/2002 to 11/30/2018. FNA results were classified according to TBSRTC. Patient demographics, cytology, histopathology, radiological and clinical follow-ups were examined.ResultsA total of 171 patients were included with 203 cytological samples. Average age at initial FNA was 14.7 years (range 6.9-18.6 years). The numbers of nodules reported for Bethesda categories I-VI were 29, 106, 22, 14, 6 and 26, respectively, and the rate of malignancy was: 13.8, 4.7, 22.7, 35.7, 83.3 and 100%, respectively. Use of ultrasound guidance reduced the non-diagnostic rate from 38.1 to 11.5%. Introduction of on-site adequacy testing further reduced the non-diagnostic rate to 6.5% since 2014.ConclusionsThe risk of malignancy for thyroid nodules in this pediatric cohort is higher than reported in adults. However, rates described here are much closer to adult ranges than previously published pediatric cohorts. The addition of adequacy testing improved the non-diagnostic rate of FNA procedures performed with ultrasound guidance