13 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
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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
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Neonatal diabetes mellitus due to a novel variant in the INS gene
Neonatal diabetes mellitus (NDM) is a rare condition that presents with diabetes in the first few months of life. The treatment of NDM may differ depending on the genetic etiology, with numerous studies showing the benefit of sulfonylurea therapy in cases caused by mutations in KCNJ11 or ABCC8 Mutations in the insulin gene (INS) have also been identified as causes of NDM; these cases are generally best treated with insulin alone. We report a case of a female infant born small for gestational age (SGA) at late preterm diagnosed with NDM at 7 wk of life who was found by rapid whole-genome sequencing to harbor a novel de novo c.26C>G (p.Pro9Arg) variant in the INS gene. She presented with diabetic ketoacidosis, which responded to insulin therapy. She did not respond to empiric trial of sulfonylurea therapy early in her hospital course, and it was discontinued once a genetic diagnosis was made. Early genetic evaluation in patients presenting with NDM is essential to optimize therapeutic decision-making