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Introduction: Exogenous insulin antibody syndrome (EIAS) rarely occurs in type 1 diabetes and should be considered in those with blood glucose levels outside the target range requiring greater than 2 units/kg/day of insulin without obesity. We describe the novel treatment of this condition using mycophenolate mofetil monotherapy in a pediatric patient in the outpatient setting., Case Presentation: A 17-year-old Caucasian male with type 1 diabetes experienced an abrupt increase in insulin requirements from 1.7 to 3.3 units/kg/day. Total insulin level was 7 µIU/mL with free insulin of 4.8 µIU/mL (68% of the total insulin), suggesting the presence of insulin antibodies. Switching from insulin aspart to glulisine was unsuccessful as insulin requirements increased to 4.4 units/kg/day. Treatment with oral mycophenolate mofetil decreased insulin requirements to 1.4 units/kg/day after 7 months. Total and free insulin levels improved to 5.2 and 4.6 µIU/mL, respectively (free insulin was 88% of total insulin). No adverse effects were encountered., Conclusion: Mycophenolate mofetil monotherapy is successful in safely treating EIAS in a pediatric patient., (© 2023 S. Karger AG, Basel.)

Background: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education., Methods: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers., Results: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results., Conclusion: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities., (© 2023. The Author(s).)

Context: Childhood papillary thyroid carcinoma (CPTC), despite bilateral thyroidectomy, nodal dissection and radioiodine remnant ablation (RRA), recurs within neck nodal metastases (NNM) in 33% within 20 postoperative years. These NNM are usually treated with reoperation or further radioiodine. Ethanol ablation (EA) may be considered when numbers of NNM are limited., Objective: We studied the long-term results of EA in 14 patients presenting with CPTC during 1978 to 2013 and having EA for NNM during 2000 to 2018., Methods: Cytologic diagnoses of 20 NNM (median diameter 9 mm; median volume 203 mm 3 ) were biopsy proven. EA was performed during 2 outpatient sessions under local anesthesia; total volume injected ranged from 0.1 to 2.8 cc (median 0.7). All were followed regularly by sonography and underwent volume recalculation and intranodal Doppler flow measurements. Successful ablation required reduction both in NNM volume and vascularity., Results: Post EA, patients were followed for 5 to 20 years (median 16). There were no complications, including postprocedure hoarseness. All 20 NNM shrank (mean by 87%) and Doppler flow eliminated in 19 of 20. After EA, 11 NNM (55%) disappeared on sonography; 8 of 11 before 20 months. Nine ablated foci were still identifiable after a median of 147 months; only one identifiable 5-mm NNM retained flow. Median serum Tg post EA was 0.6 ng/mL. Only one patient had an increase in Tg attributed to lung metastases., Conclusion: EA of NNM in CPTC is effective and safe. Our results suggest that for CPTC patients who do not wish further surgery and are uncomfortable with active surveillance of NNM, EA represents a minimally invasive outpatient management option., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objectives: There have been recent advances assessing copeptin levels in adults with suspected disorders of vasopressin release. Very limited data exits on copeptin levels in children and infants, especially in a critically-ill hospitalized population where hyper- and hypo-natremia are very common. Our objective is to describe the institutional experience assessing copeptin levels in hospitalized infants and children with hyper- or hypo-natremia., Methods: We performed a single-center retrospective case series of all infants, children, and adolescents who had an ultrasensitive plasma copeptin level obtained between 2019-2021., Results: A total of 29 critically ill patients (6 infants) were identified with 38 % of patients having copeptin levels after neurosurgical procedures for tumors or trauma. Approximately 13/17 children with hypernatremia had central diabetes insipidus (central diabetes insipidus) to diagnose CDI, A copeptin level ≤ 4.9 pmol/L resulted in an 88 % sensitivity (95 % CI 47-99 %), and 66 % specificity (95 % CI 30-93 %). Amongst those with hyponatremia levels were more variable, 8/12 children had syndrome of inappropriate antidiuresis (SIAD) with copeptin levels ranging 4.7-72.6 pmol/L., Conclusions: While difficult to conclude due to multiple limitations, this case series highlights that typical copeptin cutoffs used to diagnose DI in adults in an ambulatory setting may also translate to a critically-ill pediatric population. Large prospective studies are needed to confirm this observation. In addition, postoperative copeptin levels could potentially be utilized as an additional marker to predict permanent from transient DI, but much larger studies are needed. Further work is needed to establish normative copeptin levels in infants and patients with SIAD., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: Type 1 diabetes autoantibodies are directed against multiple antigens including: glutamic acid decarboxylase, protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence or titer of ZnT8 antibodies (Ab) was predictive for clinical presentation at diagnosis or for the subsequent disease course., Methods: Between January, 2003 and May, 2019, 105 patients aged ≤21 years with a clinical diagnosis of type 1 diabetes mellitus had at least 1 autoantibody measured. A retrospective chart review was completed. At diagnosis, we evaluated the body mass index z-score, hemoglobin (HbA1c), and the presence of diabetic ketoacidosis (DKA). Complications analyzed post-diagnosis included episodes of DKA, the diagnosis of autoimmune disease, and the presence of vascular complications. We evaluated cumulative lifetime excess glucose as HbA1c area under the curve (AUC) >6%., Results: Seventy-one patients were ZnT8-Ab(+) (68%), with 19 having low titer ZnT8-Ab and 52 with high titer ZnT8-Ab. Follow-up ranged from 10 days to 15.7 years (median 2.08 years). There were no differences in the characteristics at disease onset or in the subsequent follow-up between those with and those without ZnT8-Ab or those with high or low titers of ZnT8 Ab, except for a small but statistically significant difference in cumulative excess glucose (HbA1c AUC >6%) between those with low and high titers (p=0.0095)., Conclusion: Our study adds to the limited literature on the effect of the presence and titer of ZnT8-Ab in pediatric diabetes. The small effect of ZnT8-Ab titer on glucose excess as measured by HbA1c AUC warrants further study., (©Copyright 2023 by Turkish Society for Pediatric Endocrinology and Diabetes | The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

The practice of maternal-fetal surgery (MFS) has expanded from lethal fetal conditions to conditions which are significantly disabling but not a lethal fetal abnormality. The inclusion of myelomeningocele within the scope of MFS in the 1990s sparked a renewed debate over the ethics of MFS. While demonstrating increasing efficacy and range of application, MFS continues to be ethically fraught due to the inherent tension between maternal and fetal interests. Ethical issues central to MFS include the patienthood of the fetus; the balance of risks and benefits between the woman and fetus; informed consent for experimental procedures; and determination of conditions that meet ethical qualifications for MFS intervention. These concerns are likely to persist and evolve as perinatal medicine continues to advance. Here we summarize the current state of MFS ethics, highlighting the major positions in the literature thus far as well as examine future directions. It is essential robust discussions of these important issues continue both to ensure ethical medical practice and to provide support to clinicians, pregnant women, and their families., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Study Objectives: To describe the structure of a pediatric fertility preservation (FP) program and to share safety and patient satisfaction data., Design: The FP program operates under prospective research protocols approved by the Mayo Clinic Institutional Review Board (IRB)., Setting: The FP program is a multidisciplinary effort between pediatric gynecology, reproductive endocrinology, pediatric urology, pediatric surgery, and laboratory medicine., Participants: The FP program enrolls patients between 0-17 years of age who have been diagnosed with a fertility-threatening condition and/or are scheduled to undergo gonadotoxic treatment., Interventions: FP is offered in the form of ovarian tissue cryopreservation (OTC) and testicular (TTC) tissue cryopreservation., Main Outcome Measures: The outcome measures are the safety of the procedure and results of patient surveys conducted by phone using a standard list of questions to assess attitudes towards FP., Results: To date, we have enrolled 38 OTC and 37 TTC patients. The median age (range) of OTC and TTC patients was 11 years (0.83-17 years) and 10 years (0.92-17 years) at the time of enrollment, respectively. Childhood cancers currently represent 88% of the fertility-threatening diagnoses. Meanwhile, patients with non-malignant conditions include those with gender dysphoria, aplastic anemia, and Turner's syndrome. To date, no serious adverse events (SAEs) have been reported following surgery. According to n = 34 one-year follow-ups, 100% of parents felt that FP was a good decision., Conclusion: Consistent with the literature, our data suggests FP is safe and improves the quality of care provided to pediatric patients for their fertility-threatening diagnoses and/or treatments., Trial Registration: NCT02872532, NCT02646384., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Recent evidence suggests prenatal fetoscopic tracheal occlusion (FETO) may improve the survival and long-term morbidity of neonates with congenital diaphragmatic hernia, yet little guidance exists in the medical literature as to the ethical permissibility of performing a maternal-fetal surgical intervention in a twin pregnancy discordant for a structural abnormality., Case: Here, we present a case of a twin pregnancy with an unaffected twin (Twin A) and a twin diagnosed with severe congenital diaphragmatic hernia (Twin B). A proposed fetoscopic tracheal occlusion (FETO) procedure may improve the likelihood of survival and postnatal outcome of Twin B; however, balloon placement may also initiate very preterm birth at 28 weeks of gestation. The Fetal Ethics Advisory Board was asked to provide guidance on the permissibility of FETO in this pregnancy., Discussion: A literature review identified one brief mention of FETO in a 34-week dichorionic twin pregnancy in the medical literature, which resulted in the rupture of fetal membranes in the sac of the nonsurgical twin. Only one paper specifically addressed the question of whether it would be ethically permissible to subject a healthy twin to the risks of maternal-fetal surgery for the benefit of a compromised twin, finding that any risk to the unaffected twin would be an ethical contraindication. We offer our own analysis of moral weight and risk/benefit considerations of this proposed intervention, and present our findings on the circumstances in which it may be ethically permissible to perform a maternal-fetal intervention in a twin pregnancy., Conclusion: While FETO was not ethically advisable in this pregnancy, we find that in limited circumstances, certain maternal-fetal surgical interventions may be ethically permissible in a twin pregnancy discordant for a structural abnormality if the risks to the unaffected twin are minimal and the procedure would improve the likelihood of survival and postnatal outcome of a critically compromised co-twin.

Purpose: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options., Methods: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively., Results: Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program., Conclusion: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

Trichorhinophalangeal syndrome type I (TRPSI) is a rare disorder that causes distinctive ectodermal, facial, and skeletal features affecting the hair (tricho-), nose (rhino-), and fingers and toes (phalangeal) and is inherited in an autosomal dominant pattern. TRPSI is caused by loss of function variants in TRPS1 , involved in the regulation of chondrocyte and perichondrium development. Pathogenic variants in TRPS1 include missense mutations and deletions with variable breakpoints, with only a single instance of an intragenic duplication reported to date. Here we report an affected individual presenting with a classic TRPSI phenotype who is heterozygous for a de novo intragenic ∼36.3-kbp duplication affecting exons 2-4 of TRPS1 Molecular analysis revealed the duplication to be in direct tandem orientation affecting the splicing of TRPS1 The aberrant transcripts are predicted to produce a truncated TRPS1 missing the nuclear localization signal and the GATA and IKAROS-like zinc-finger domains resulting in functional TRPS1 haploinsufficiency. Our study identifies a novel intragenic tandem duplication of TRPS1 and highlights the importance of molecular characterization of intragenic duplications., (© 2019 Zepeda-Mendoza et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: There is a lack of consensus on the cardiometabolic consequences of mild subclinical hypothyroidism (SCH) among children. The objective of the current study was to compare lipid profiles in children with mild SCH with those of euthyroid children., Study Design: Retrospective medical record review., Patients: Children (ages 2-18 years) who had undergone simultaneous measurement of TSH, free thyroxine (T4) and lipids. Lipids in children with mild SCH (TSH 5-<10 mIU/L and normal free T4, n = 228) were compared with those in euthyroid children (n = 1215)., Results: TSH level was positively associated with total cholesterol and nonhigh density lipoprotein (non-HDL) cholesterol [β 0.05(0.03-0.08), P < .0001 and β 0.05(0.03-0.08), P < .0001, respectively]. Total cholesterol was significantly higher in children and adolescents with mild SCH compared with euthyroid children (4.43 ± 1.14 mmol/L vs 4.2 ± 0.85 mmol/L, P = .0005). Similarly, non-HDL cholesterol level was also higher in children with mild SCH relative to euthyroid children (3.08 ± 1.14 mmol/L vs 2.91 ± 0.8 mmol/L, P = .001). The adjusted odds ratio of having elevated total cholesterol and elevated non-HDL cholesterol was greater in children with mild SCH compared with euthyroid children (OR 1.88, 95% CI; 1.28-2.73; P = .001 and 1.72, 95% CI 1.2-2.5; P = .003, respectively). The presence of thyroid autoimmunity was not associated with higher rates of dyslipidaemia., Conclusions: Mild SCH in children and adolescents was associated with higher rates of elevated total cholesterol and elevated non-HDL cholesterol. Randomized placebo controlled studies are warranted to determine if treatment of mild SCH in children leads to improvement in lipid profile., (© 2018 John Wiley & Sons Ltd.)

Background: A thyroid storm (TS) is a rare, but life-threatening condition in hyperthyroid patients. Mortality in adult TS patients may be as high as 10%. Typically, a trigger precipitates the storm in hyperthyroid patients., Case Presentation: We report the case of an adolescent girl with untreated hyperthyroidism who developed fulminant TS after a significant choking episode. Initially, she was found to have neck swelling and tachycardia leading providers to suspect infection. She deteriorated after a CAT Scan (CT) was performed with iodine contrast, potentially worsening storm symptoms. Here, we describe the case, the treatment strategy and propose a treatment modification for pediatric patients., Conclusions: While many children are found to have minor abnormalities in thyroid studies, this case highlights the critical importance of prompt medical attention for any child with significantly elevated free thyroxine (FT4) levels as morbidity can occur when left untreated.

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Fertility preservation therapies can conserve future reproductive potential for persons facing serious medical diagnoses. With cure rates for childhood cancer reaching almost 80%, quality-of-life concerns for long-term survivors, including future parenting, are becoming more pertinent. Late effects of childhood cancer can be divided into physical, social, psychological, and spiritual domains. Potential loss of fertility threatens the well-being of these children in all these domains. Providers often hesitate to discuss fertility preservation with the patients. However, parental attitudes toward discussion of fertility preservation have been found to be open to such conversations for both prepubertal and postpubertal children who have a cancer diagnosis. Multiple national and international organizations recommend discussion with all persons having gonadotoxic therapy, including children, regarding the effect of planned treatment on future fertility and their options for fertility preservation. Renal or rheumatologic disease treated with high-dose cyclophosphamide and chromosomal anomalies such as Turner or Klinefelter syndrome may be amenable to fertility preservation. This essay reviews fertility preservation options available to children, as well as the expanding list of indications for fertility preservation., (Copyright© of YS Medical Media ltd.)

Klinefelter syndrome is the most frequent chromosomal aneuploidy in males occurring in about 1 in 660 males. Epidemiological studies have demonstrated increased risk of type 1 diabetes and type 2 diabetes in adults with Klinefelter syndrome. There is only one previous report of neonatal diabetes in a patient with Klinefelter syndrome. We report transient neonatal diabetes due to a pathogenic heterozygous variant in KCNJ11 in a male infant with Klinefelter syndrome. A 78-day old male infant was noted to have sustained hyperglycemia with serum glucose ranging between 148 mg/dL (8.2 mmol/L) and 381 mg/dL (21.2 mmol/L) three days after undergoing a complete repair of an atrioventricular defect. Hemoglobin A1c was 6.6%. The patient was born at term with a birth weight of 2.16 kg following a pregnancy complicated by gestational diabetes that was controlled with diet. The patient was initially started on a continuous intravenous insulin drip and subsequently placed on subcutaneous insulin (glargine, human isophane and regular insulin). Insulin was gradually decreased and eventually discontinued at seven months of age. Chromosomal microarray at 11 weeks of age showed XXY and a panel-based, molecular test for neonatal diabetes revealed a pathogenic heterozygous variant c.685G>A (p.Glu229Lys) in KCNJ11. The patient is now 34 months old and continues to have normal fasting and post-prandial glucose and HbA1C levels. The patient will need prospective follow up for assessment of his glycemic status. To our knowledge this is the second reported case of neonatal diabetes in an infant with Klinefelter syndrome and the first due to a mutation in the KCNJ11 in a patient with Klinefelter syndrome.

Background: Contemporary guidelines for managing PTC advise an approach wherein primary tumor and regional metastases (RM) are completely resected at first surgery and radioiodine remnant ablation (RRA) is restricted to high-risk patients, policies our group has long endorsed. To assess our therapeutic efficacy, we studied 190 children and 4242 adults consecutively treated during 1936-2015., Subjects and Methods: Mean follow-up durations for children and adults were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed in 86% of children and 88% of adults, followed by RRA in 30% of children and 29% of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor recurrence (TR) and cause-specific mortality (CSM) details were taken from a computerized database., Results: Children, when compared to adults, had larger primary tumors which more often were grossly invasive and incompletely resected. At presentation, children, as compared to adults, had more RM and distant metastases (DM). Thirty-year TR rates were no different in children than adults at any site. Thirty-year CSM rates were lower in children than adults (1.1 vs. 4.9%; p = 0.01). Comparing 1936-1975 (THEN) with 1976-2015 (NOW), 30-year CSM rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08). However, MACIS <6 children and adults in 1976-2015 had significantly higher recurrence at local and regional, but not at distant, sites. MACIS 6+ adults, NOW, compared to THEN, had lower 30-year CSM rates (30 vs. 47%; p < 0.001), unassociated with decreased TR at any site., Conclusions: Children, despite presenting with more extensive PTC when compared to adults, have postoperative recurrences at similar frequency, typically coexist with DM and die of PTC less often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30-year CSM rate of 30%.

Background: Pediatric thyroid nodules are more likely to be malignant compared to those in adults and may have different concerning ultrasound (US) features. Recent adult guidelines stratify malignancy risk by US features. Our aim is to (1) describe and confirm US features that predict pediatric malignancy, and (2) apply the Adult American Thyroid Association (ATA) Risk Stratification Guidelines to a large pediatric cohort., Methods: We identified 112 children with 145 thyroid nodules from 1996 to 2015. Two blinded pediatric radiologists independently read all US images, described multiple features, and reported their overall impression: benign, indeterminate, or malignant. Each nodule was assigned an ATA risk stratification category. Radiologists' impressions and ATA risk stratification were compared to histology and cytology results., Results: Multiple US features including a solid composition, presence of microcalcifications, irregular margins, increased blood flow, and hypoechogenicity were associated with increased odds of malignancy. ATA risk stratification correlated with the radiologists' overall impression (p < 0.001). The sensitivity for detecting malignancy was comparable between both ATA stratification (91%) and the radiologists' overall impression (90%). The specificity of the radiologists' malignant overall impression (80%) was better compared to the ATA high risk stratification (54%)., Conclusions: At our institution, pediatric radiologists' overall impressions had similar sensitivity but better specificity for detecting malignancy than the ATA risk stratification tool by our convention. However, neither US-based methods perfectly discriminated benign from malignant nodules, supporting the continued need for fine needle aspiration for suspicious nodules. Further work is needed to develop an US-based scoring system specific to pediatric patients., (© 2018 S. Karger AG, Basel.)

Introduction: Thyroid ultrasound (US) is a widely used tool for evaluating thyroid nodules. Various US features have been suggested as predictors of thyroid cancer in children., Objective: To conduct a systematic review and meta-analysis to assess the diagnostic accuracy of different thyroid US features in detecting thyroid cancer in children., Methods: We searched multiple online databases for cohort studies that enrolled paediatric patients with thyroid nodules (age <21 years) and evaluated the accuracy of 12 relevant ultrasound features. Diagnostic measures were pooled across studies using a random effects model., Results: The search strategy yielded 1199 citations, of which 12 studies met the predefined inclusion criteria (750 nodules). The prevalence of thyroid cancer was 27·2% (40·8% in patients with a history of radiation exposure and 23·2% in patients without a history of exposure to radiation). The most common cancer was papillary thyroid cancer (86·7%). The presence of internal calcifications and enlarged cervical lymph nodes were the US features with the highest likelihood ratio [4·46 (95% CI: 1·87-10·64) and 4·96 (95% CI: 2·01-12·24), respectively] for thyroid cancer. A cystic nodule was the feature with highest likelihood ratio for benign nodules [1·96 (95% CI: 0·87-4·43)]., Conclusion: Thyroid US features are not highly accurate predictors of benign or malignant aetiology of thyroid nodules in children. Internal calcification may predict malignancy, and cystic appearance may suggest benign aetiology., (© 2015 John Wiley & Sons Ltd.)

Context: Surgically managed endocrinopathies are rare in children. Most surgeons have limited experience in this field. Herein we report our operative experience with pediatric patients, performed over two decades by high-volume endocrine surgeons., Setting: The study was conducted at the Mayo Clinic (a tertiary referral center)., Patients: Patients were <19 years old and underwent an endocrine operation (1993-2012)., Main Outcome Measures: Demographics, surgical procedure, diagnoses, morbidity, and mortality were retrospectively reviewed., Results: A total of 241 primary cases included 177 thyroid procedures, 13 neck dissections, 24 parathyroidectomies, 14 adrenalectomies, 7 paragangliomas, and 6 pancreatic procedures. Average age of patients was 14.2 years. There were 133 total thyroidectomies and 40 hemithyroidectomies. Fifty-three cases underwent a central or lateral neck dissection. Six-month follow-up was available for 98 total thyroidectomy patients. There were four cases of permanent hypoparathyroidism (4%) and no permanent recurrent laryngeal nerve (RLN) paralyses. Sequelae of neck dissections included temporary RLN neurapraxia and Horner's syndrome. Parathyroidectomy was performed on 24 patients: 20 with primary hyperparathyroidism (HPT), three with tertiary HPT, and one with familial hypocalciuric hypocalcemia. Three patients (16%) had recurrent HPT, all with multiglandular disease. One patient had temporary RLN neurapraxia. We performed seven bilateral and seven unilateral adrenalectomies; eight were laparoscopic. Indications included pheochromocytoma, Cushing's syndrome, adrenocortical carcinoma, congenital adrenal hyperplasia, and ganglioneuroma. One death was due to adrenocortical carcinoma. Five paraganglioma patients had succinate dehydrogenase subunit B mutations, and one recurred. Six patients with insulinoma underwent enucleation (n = 5) or distal pancreatectomy (n = 1). A single postoperative abscess was managed nonoperatively., Conclusion: Pediatric endocrine procedures are uncommon but can be safely performed with complication rates comparable to those of the adult population. It is imperative that these operations be performed by high-volume surgeons.

Heme oxygenase-1 (HO-1) is induced in the vasculature in the DOCA-salt model of hypertension in rats. Whereas the HO system and its products may exert vasodilator effects, recent studies have suggested that the HO system may predispose to hypertension. The present study examined the effects of selected components of the HO system, specifically, the HO-1 isozyme and the product bilirubin in the DOCA-salt model of systemic hypertension; the experimental approach employed mutant rodent models, namely, the HO-1(-/-) mouse and the hyperbilirubinemic Gunn rat. DOCA-salt induced HO-1 protein in the aorta in HO-1(+/+) mice and provoked a significant rise in systolic arterial pressure in HO-1(-/-) mice but not in HO-1(+/+) mice; this effect could not be ascribed to impaired urinary sodium excretion or impaired glomerular filtration rate in the DOCA-salt-treated HO-1(-/-) mice. The administration of DOCA salt to uninephrectomized rats significantly increased systolic arterial pressure in wild-type rats, an effect that was attenuated in the mutant Gunn rat; this reduction in systemic hypertension in the DOCA-salt-treated Gunn rat was not due to a greater induction of HO-1 in the vasculature or to a more avid urinary sodium excretion. DOCA-salt impaired endothelium-dependent and endothelium-independent vasorelaxation in wild-type rats but not in Gunn rats; prior exposure to bilirubin repaired the defect in endothelium-dependent vasorelaxation in aortic rings in DOCA-salt-treated rats. DOCA salt stimulated vascular production of superoxide anion in wild-type but not in Gunn rats. We suggest that HO-1 and the product bilirubin may exert a countervailing effect in the DOCA-salt model of systemic hypertension.

Background: Up-regulation of heme oxygenase-1 (HO-1) occurs in, and often confers protection to, the injured kidney. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) promotes not only acute and chronic nephritides but also acute ischemic and nephrotoxic injury. The present study was stimulated by the hypothesis that expression of MCP-1 is suppressed by HO-1, and analyzed the effect of HO-1 on the expression of MCP-1 in stressed and unstressed conditions., Methods: Expression of MCP-1 and pathophysiologic correlates were examined in HO-1 knockout (HO-1-/-) and wild-type (HO-1+/+) mice in the unstressed state in young and aged mice, and following nephrotoxic and ischemic insults., Results: In unstressed HO-1-/- mice, plasma levels of MCP-1 protein were elevated, and MCP-1 mRNA expression was increased in circulating leukocytes and in the kidney. Such early and heightened up-regulation of MCP-1 was eventually accompanied by phenotypic changes in the aged kidney consistent with MCP-1, namely, proliferative changes in glomeruli, tubulointerstitial disease, and up-regulation of transforming growth factor-beta1 (TGF-beta1) and collagens I, III, and IV. In response to a nephrotoxic insult such as hemoglobin, MCP-1 mRNA was up-regulated in a markedly sustained manner in HO-1-/- mice. In response to a duration of ischemia that exerted little effect in HO-1+/+ mice, HO-1-/- mice exhibited higher expression of MCP-1 mRNA, enhanced activation of nuclear factor-kappaB (NF-kappaB) (the transcription factor that regulates MCP-1), markedly greater functional and structural renal injury, increased caspase-3 expression, and increased mortality., Conclusion: In the absence of HO-1, expression of MCP-1 is significantly and consistently enhanced in unstressed and stressed conditions. We speculate that the protective effects of HO-1 in injured tissue may involve, at least in part, the capacity of HO-1 to restrain up-regulation of MCP-1.

Mayer-Rokitansky-Küster-Hauser (MRKHA) is a malformation complex comprising absent vagina and absent or rudimentary uterus. The aim of our study was to describe the type and frequency of anomalies associated with the MRKHA. Between 1975 and 2002, 25 patients with a diagnosis of MRKHA were identified at the Mayo Clinic. These charts were reviewed retrospectively. Two of the 25 patients were found to have absence of one ovary and two patients had unilateral oophorectomies performed for benign cysts. Four patients had minor anomalies and two had digital anomalies. The frequency of scoliosis (20%), unilateral renal agenesis (28%), non-vertebral skeletal anomalies (16%) and of the MURCS association (Mullerian agenesis, renal agenesis/ectopia and cervical somite dysgenesis), 16%, was similar compared to that of other published studies. Vertebral abnormalities were found more frequently in our patients (44%). Four patients had cardiac defects, an anomaly not previously described, including truncus arteriosus, patent ductus arteriosus and patent foramen ovale, mitral valve prolapse, and mild mitral regurgitation. We document cardiac anomalies in 16% of our patients with MRKHA suggesting that a search for associated anomalies including cardiac defects is indicated in all such patients.

Barriers to early identification of children with developmental delays include time constraints during well-child visits and lack of easily administered, quantitative measures that can be used by pediatricians. This study assesses the ease of administration of the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) during well-child visits from 2 to 36 months of age. During a single visit 177 children were assessed by either a developmental pediatrician (n = 121) or a third-year pediatric resident (n = 56). The mean time required to complete the CAT/CLAMS for all subjects was 6 minutes and 10 seconds (SD 2 minutes 44 seconds); less than 10 minutes was required in 92% of children assessed. There were no significant differences in the time required by the 2 examiners at any age level. Its ease of administration and psychometric properties make the CAT/CLAMS an excellent choice for the assessment of early development by primary care pediatricians.