Search

Introduction: Transient or persistent hypoparathyroidism is one of the most well-known complications of total thyroidectomy and may lead to symptomatic hypocalcaemia. In children, treatment of post-thyroidectomy hypocalcaemia usually consists of postoperative calcium and/or vitamin D supplementation. In 2013, we implemented prophylactic pre-thyroidectomy calcitriol supplementation for all children undergoing total thyroidectomy at the Amsterdam UMC. The objective of this study was to evaluate the efficacy of this prophylactic calcitriol supplementation in preventing post-thyroidectomy hypocalcaemia in children. Methods: In a retrospective case study, we included all children (age Results: A total of 51 patients were included; 26 with calcitriol prophylaxis and 25 controls. There was no significant difference in occurrence of hypocalcaemia (17/26 prophylaxis group; 18/25 control group). Median postoperative calcium concentrations in the first 72 h were significantly higher in the group with prophylaxis at 30–35 h (2.26 vs. 2.01 mmol/L) and 36–41 h (2.17 vs. 1.92 mmol/L). Occurrence of symptomatic hypocalcaemia, need for medical intervention, and length of hospitalization were not significantly different between the groups. Conclusion: Calcitriol prophylaxis resulted in somewhat higher postoperative calcium concentrations but did not reduce the occurrence of hypocalcaemia or affect clinical outcome measures such as occurrence of symptomatic hypocalcaemia and length of postoperative hospitalization.

ABCC8 and KCJN11 mutations cause the most severe diazoxide-resistant forms of congenital hyperinsulinism (CHI). Somatostatin analogues are considered as secondline treatment in diazoxide-unresponsive cases. Current treatment protocols include the first-generation somatostatin analogue octreotide, although pasireotide, a second-generation somatostatin analogue, might be more effective in reducing insulin secretion. Herein we report the first off-label use of pasireotide in a boy with a severe therapy-resistant form of CHI due to a homozygous ABCC8 mutation. After partial pancreatectomy, hyperinsulinism persisted; in an attempt to prevent further surgery, off-label treatment with pasireotide was initiated. Short-acting pasireotide treatment caused high blood glucose level shortly after injection. Long-acting pasireotide treatment resulted in more stable glycemic control. No side effects (e.g., central adrenal insufficiency) were noticed during a 2-month treatment period. Because of recurrent hypoglycemia despite a rather high carbohydrate intake, the boy underwent near-total pancreatectomy at the age of 11 months. In conclusion, pasireotide treatment slightly improved glycemic control without side effects in a boy with severe CHI. However, the effect of pasireotide was not sufficient to prevent near-total pancreatectomy in this case of severe CHI.

Objective Comparison of studies on remission rates in pediatric Graves’ disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves’ disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis. Methods PubMed and Embase were searched in August 2020 for studies on patients with Graves’ disease: (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least 1 year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis. Results Of 1890 articles, 29 articles consisting of 24 patient cohorts were included with a total of 3057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2880). Pooled remission rates based on treatment duration were 23.7, 31.0, 43.7, and 75% respectively after 1.5–2.5 years, 2.5–5 years, 5–6 years (two studies), and 9 years (single study) treatment duration. The occurrence of adverse events was 419 in 2377 patients (17.6%), with major side effects in 25 patients (1.1%). Conclusions Using a standardized calculation, the overall remission rate in methimazole-treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.

Background: Graves’ disease (GD) is the most common cause of hyperthyroidism. In children, the overall relapse frequency after treatment with antithyroid drugs is high. Therefore, many pediatric GD patients eventually require thyroidectomy as definitive treatment. However, the postoperative complications of thyroidectomy in pediatric GD patients are poorly reported. Objective: To identify the frequency of short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients. Methods: A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients according to the PRISMA guidelines. Results: Twenty-two mainly retrospective cohort studies were included in this review evaluating short- and long-term morbidities in 1,424 children and adolescents. The frequency of transient hypocalcemia was 22.2% (269/1,210), with a range of 5.0–50.0%. The frequency of permanent hypocalcemia was 2.5% (36/1,424), with a range of 0–20.0%. Two studies reported high frequencies of permanent hypocalcemia, 20.0 (6/30) and 17.4% (9/52), respectively. The 20% frequency could be explained by low-volume surgeons in poorly controlled GD patients. Only 21 cases of permanent hypocalcemia were reported in the 1,342 patients included in the other 20 studies (1.6%). Transient and permanent recurrent laryngeal nerve injury were reported less frequently, with frequencies between 0–20.0 and 0–7.1%, respectively. Infection, hemorrhage/hematoma, and keloid development were only rarely reported as postoperative complications. Conclusion: The results of this systematic review suggest that thyroidectomy is a safe treatment option for pediatric GD patients. The minority of patients will experience transient and benign morbidities, with hypocalcemia being the most common transient postoperative morbidity. Permanent postoperative morbidities are relatively rare.

Isolated aldosterone synthase deficiency is a rare autosomal recessive disorder caused by pathogenic variants in

Background: Graves’s disease (GD) is the most common cause of hyperthyroidism. Maximal 30% of pediatric GD patients achieve remission with antithyroid drugs. The majority of patients therefore require definitive treatment. Both thyroidectomy and radioactive iodine (RAI) are often used as definitive treatment for GD. However, data on efficacy and short- and long-term side effects of RAI treatment for pediatric GD are relatively scarce. Methods: A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting the efficacy or short- and long-term side effects of RAI treatment in pediatric GD. Results: Twenty-three studies evaluating 1,283 children and adolescents treated with RAI for GD were included. The treatment goal of RAI treatment changed over time, from trying to achieve euthyroidism in the past to aiming at complete thyroid destruction and subsequent hypothyroidism in the last 3 decades. The reported efficacy of a first RAI treatment when aiming at hypothyroidism ranged from 42.8 to 97.5%, depending on the activity administered. The efficacy seems to increase with higher RAI activities. When aiming at hypothyroidism, both short- and long-term side effects of treatment are very rare. Long-term side effects were mainly seen in patients in whom treatment aimed at achieving euthyroidism. Conclusion: RAI is a safe definitive treatment option for pediatric GD when aiming at complete thyroid destruction. When aiming at hypothyroidism, the efficacy of treatment seems to increase with a higher RAI activity. Prospective studies are needed to determine the optimal RAI dosing regimen in pediatric GD.

Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.

Context Hydrocortisone treatment of young patients with 21-hydroxylase deficiency (21OHD) is given thrice daily, but there is debate about the optimal timing of the highest hydrocortisone dose, either mimicking the physiological diurnal rhythm (morning), or optimally suppressing androgen activity (evening). Objective We aimed to compare 2 standard hydrocortisone timing strategies, either highest dosage in the morning or evening, with respect to hormonal status throughout the day, nocturnal blood pressure (BP), and sleep and activity scores. Methods This 6-week crossover study included 39 patients (aged 4-19 years) with 21OHD. Patients were treated for 3 weeks with the highest hydrocortisone dose in the morning, followed by 3 weeks with the highest dose in the evening (n = 21), or vice versa (n = 18). Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels were quantified in saliva collected at 5 am; 7 am; 3 pm; and 11 pm during the last 2 days of each treatment period. The main outcome measure was comparison of saliva 17OHP and A4 levels between the 2 treatment strategies. Results Administration of the highest dose in the evening resulted in significantly lower 17OHP levels at 5 am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. The 2 treatment dose regimens were comparable with respect to averaged daily hormone levels, nocturnal BP, and activity and sleep scores. Conclusion No clear benefit for either treatment schedule was established. Given the variation in individual responses, we recommend individually optimizing dose distribution and monitoring disease control at multiple time points.

Parathyroid hormone-like hormone (PTHLH) plays an important role in bone formation. Several skeletal dysplasias have been described that are associated with disruption of PTHLH functioning. Here we report on a new patient with a 898 Kb duplication on chromosome 12p11.22 including the PTHLH gene. The boy has multiple skeletal abnormalities including chondrodysplasia, lesions radiographically resembling enchondromas and posterior rib deformities leading to a severe chest deformity. Severe pulmonary symptoms were thought to be caused by limited mobility and secondary sputum evacuation problems due to the chest deformity. Imaging studies during follow-up revealed progression of the number of skeletal lesions over time. This case extends the phenotypic spectrum associated with copy number variation of PTHLH.

In the original article, there was a mistake in the legend for Figure 6 as published. Three numbers were not in superscript which changed concentrations and there was an error in dosage. The correct legend appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Figure 6 | Our patient- and parent-friendly, multidisciplinary, centralized follow-up protocol. 1All follow-up appointments will be scheduled on the same day (Wednesday); 2Before 10:00 AM; 315 µg/kg/dose, max. 125 µg/dose; 410 µg/dL = 276 nmol/L, 18 µg/dL = 497 nmol/L; 510 mg/m2/day in three equal doses (3 times per day 33.3% of the total daily dose); when older than 6 months: 50% early in the morning, and 25% early in the afternoon and evening. Adrenal surveillance protocol adapted and modified from Regelmann et al. (2018). Abbreviations: ACTH, adrenocorticotropic hormone; K, potassium;Na, sodium; PRA, plasma renin activity; Q&A, questions & answers.

Introduction: Congenital hyperinsulinism (CHI), or nesidioblastosis, is the most common cause of severe persistent hypoglycemia in neonates. When left untreated, CHI may cause serious brain damage and could eventually even lead to death.1 In case of diffuse hyperinsulinism, when all beta cells are inappropriately over-secreting insulin, a near-total pancreatectomy may be indicated. With the goal of resecting 958 only a small residue of pancreatic tissue between the common bile duct (CBD) and the duodenal wall is left behind.2 To perform an adequate near-total pancreatectomy, the intrapancreatic segment of the CBD has to be safely dissected. Hereby, a feared complication is intraoperative CBD injury, associated with significant morbidity. Intraoperative injury has been reported to occur in up to 16,4 A laparoscopic near-total pancreatecomy is even more technically challenging, especially in the young. Therefore, to date, most near-total pancreatectomies in infants are done by traditional laparotomy. Fluorescence imaging with intravenous administration of indocyanine green (ICG) allows for clear intraoperative observation of the bile duct anatomy, which might ease the technical difficulties inherent to the near-total pancreatectomy, particularly with a laparoscopic approach.5 This video presents a 10-month-old boy, who presented with severe persistent hypoglycemia immediately after birth. Genetic testing was performed and confirmed the diagnosis of diffuse severe CHI based on a pathogenic homozygous ABCC8 mutation. Owing to the severely drug-resistant nature of his CHI, a laparoscopic spleen-preserving distal pancrearectomy was performed at the age of 8 weeks, later followed by a laparoscopic spleen-preserving central pancreatectomy at the age of 7 months. Although after these procedures only one third of the pancreas was left behind, the patient continued to have hypoglycemia despite maximal pharmaceutical treatment with different short- and long-acting somatostatin analogues and a high carbohydrate intake. Therefore, a third near-total pancreatic resection was indicated and was performed at the age of almost 11 months. Materials and Methods: Under general anesthesia, the patient was placed in supine position. A 5 mm trocar was introduced subumbilically with two trocars aside paraumbilically and one trocar positioned in the left flank, more laterally to allow access of the upper right abdomen. First, the stomach was lifted through an earlier placed percutane endoscopic gastrostomy, placed to supply an adequate intake of carbohydrates. After transecting the right gastroepiploic vein and artery, the proximal duodenum was retracted toward the upper right quadrant through a vessel loop exiting next to the most lateral port. Then, the gastroduodenal artery was transected, after placement of clips on the side of the hepatic artery, using the harmonic scalpel. Subsequently, the uncinate process of the pancreas was dissected after the superior mesenteric vein was identified. The pancreatic head was superficially split with harmonic scalpel in such a manner that the CBD with surrounding pancreatic tissue remained intact. Then, 1 mL ICG (0.5 mg/kg) was injected intravenously. After 15 minutes of waiting, the liver appeared as well as the duodenum by drainage through the ampulla of Vater. In between, the CBD was clearly observed. Thereafter, under direct vision of the CBD, the near-total pancreatectomy was continued by dissecting pancreatic tissue from the ventral and left border of the CBD. After the dissection of the pancreatic tissue was completed, the specimen was extracted using an endobag through the subumbilical incision. Results and Conclusions: Approximately 546 minutes and the measured blood loss was 10 mL. There were no perioperative complications and no iatrogenic injury to the CBD occurred. Any bile leakage from the CBD would immediately have been observed by fluorescence imaging, and in this case no leakage was seen during dissection of pancreatic tissue around the CBD. During the postoperative course, there were no surgical complications. The surgical drain was removed after 3 days, as amylase levels remained low. Postoperatively, carbohydrate intake could be reduced, medical treatment with somatostatin analogues was stopped, and the interval between feeding in portions could be extended up to 4 hours without resulting in hypoglycemic episodes. At discharge, just after his first birthday, there were no signs of exocrine pancreatic dysfunction, and glucose levels were acceptable on the current feeding schedule. We conclude that ICG fluorescence imaging may offer a benefit for laparoscopic near-total pancreatectomy in infants for drug-resistant diffuse CHI, as it clearly enhances the observation of the CBD intraoperatively, facilitating a safe and adequate pancreatic tissue dissection with maintenance of the integrity of the intrapancreatic segment of the CBD. No competing financial interests exist. Runtime of video: 4 mins 2 secs

In this case series, we describe four children and adolescents with tall stature or growth acceleration to illustrate the diagnostic evaluation of tall stature according to the new Paediatric Association of the Netherlands (NVK) Guideline on growth disorders. A 14-year-old girl with tall stature and a relatively late onset of puberty was diagnosed with idiopathic familial tall stature, and the patient decided not to opt for epiphysiodesis. A 14-year-old boy with prepubertal growth acceleration and a history of behavioural problems was diagnosed with Klinefelter syndrome. A 7-year-old boy with tall stature, arachnodactyly, pectus excavatum and lumbar scoliosis was diagnosed with Marfan syndrome. Finally, a 16-year-old girl with isolated progressive tall stature was diagnosed with growth hormone excess caused by a pituitary somatotroph adenoma. The most clinically relevant conditions associated with tall stature are Klinefelter and Marfan syndrome, and secondary growth disorders such as precocious puberty and growth hormone excess.

An epidermal/(epi)dermoid cyst of the thyroid is a rare cause of an intrathyroidal mass. At radiological evaluation, it may initially be misinterpreted as a thyroid adenoma or carcinoma. We present a case report of a 15-year-old boy, who was evaluated because of a neck mass which caused globus pharyngeus and pain at swallowing. Ultrasound examination revealed a hypoechoic nodule-like structure in the left thyroid lobe. Aspiration of the nodule yielded white fluid. Cytological evaluation confirmed the diagnosis of an epidermal inclusion cyst of the thyroid.

BACKGROUND Hyperandrogenism and exogenous glucocorticoid excess may cause unfavourable changes in the cardiovascular risk profile of patients with congenital adrenal hyperplasia (CAH). OBJECTIVE To evaluate the cardiac function in paediatric patients with CAH. PATIENTS AND METHODS Twenty-seven paediatric patients with CAH, aged 8-16 years, were evaluated by physical examination, electrocardiogram (ECG), conventional echocardiography, tissue Doppler imaging and two-dimensional (2D) myocardial strain (rate) imaging. Results were compared to 27 age- and gender- matched healthy controls. RESULTS No signs of left ventricular hypertrophy or dilatation were detected on echocardiography. ECG revealed a high prevalence (25.9%) of incomplete right bundle branch block. Left ventricular posterior wall thickness in diastole (LVPWd) was significantly lower in patients with CAH compared to controls (5.55 vs 6.53 mm; P = .009). The LVPWd Z-score was significantly lower in patients with CAH yet within the normal range (-1.12 vs -0.35; P = .002). Isovolumetric relaxation time was significantly lower in patients with CAH (49 vs 62 ms; P = .003). Global longitudinal, radial and circumferential strain was not significantly different compared to controls. Global radial strain rate was significantly higher compared to healthy controls (2.58 vs 2.06 1/s; P = .046). Global longitudinal strain was negatively correlated with 24-hour blood pressure parameters. CONCLUSION Cardiac evaluation of paediatric patients with CAH showed no signs of left ventricular hypertrophy or ventricular dilatation. LVPWd was lower in patients with CAH than in controls but within the normal range. A shorter isovolumetric relaxation time in patients with CAH may be a sign of mild left ventricular diastolic dysfunction.

Item does not contain fulltext We report the case of a 16-year-old female patient with hypothyroidism, goiter, and pancytopenia. Biopsy of the thyroid showed leukemic infiltration. After confirmation of the diagnosis of B-lymphoblastic leukemia, treatment was started. Histologic follow-up at day 33 and 79 showed no residual signs of leukemic infiltration. Hypothyroidism persisted despite successful antileukemic treatment. Leukemic infiltration of the thyroid should be considered as a differential diagnosis in patients with hypothyroidism, goiter, and pancytopenia. We suggest that follow-up of thyroid function and histology should be incorporated in the follow-up of rare patients with acute lymphoblastic leukemia with thyroid infiltration.

Item does not contain fulltext

A defect in adrenal steroidogenesis may cause a disorder of sex development (DSD). Importantly, DSD of adrenal origin is not restricted to a genital phenotype but is in most cases accompanied by mild to severe impairment in glucocorticoid and/or mineralocorticoid synthesis. If a patient is suspected of DSD of adrenal origin evaluation of glucocorticoid and mineralocorticoid metabolism is therefore essential to provide adequate medical care in the case of a severe and potentially life-threatening insufficiency. The adrenal steroidogenic defects causing DSD, their clinical features and diagnostic work-up are discussed. In this review we provide an overview of defects in the adrenal steroidogenesis and its impact on gonadal function and sex development.

Item does not contain fulltext After the introduction of replacement therapy with glucocorticoids and mineralocorticoids in the 1950s, congenital adrenal hyperplasia (CAH) is no longer a life-limiting condition. However, due to the successful introduction of medical steroid hormone replacement, CAH has become a chronic condition, with associated comorbidities and long-term health implications. The aim of treatment is the replacement of mineralocorticoids and glucocorticoids and the normalisation of elevated androgen concentrations. Long-term consequences of the condition and current treatment regimens include unfavourable changes in the cardiovascular risk profile, impaired growth, testicular adrenal rest tumours (TART) in male and subfertility in both male and female patients with CAH. Optimising replacement therapy in patients with CAH remains challenging. On one hand, treatment with supraphysiological doses of glucocorticoids might be required to normalise androgen concentrations and decrease size or presence of TARTs. On the other hand, treatment with supraphysiological doses of glucocorticoids is associated with an increased prevalence of unfavourable cardiovascular and metabolic risk profiles as well as impaired longitudinal growth and gonadal function. Therefore, treatment of children and adults with CAH requires an individualised approach. Careful monitoring for early signs of complications is already warranted during paediatric healthcare provision to prevent and reduce the impact of comorbidities in later life.

Background:The aim of the study was to evaluate the cardiovascular and metabolic risk profile in pediatric patients with congenital adrenal hyperplasia (CAH).Methods:A cross-sectional study was performed in 27 CAH patients (8–16 years). Blood samples were taken to evaluate circulating cardiovascular risk (CVR) markers. Insulin resistance (IR) was evaluated by homeostatic model assessment (HOMA)-IR. Blood pressure (BP) was evaluated by office BP measurements and 24-h ambulatory BP measurements (24-h ABPM). Dual energy X-ray absorptiometry (DXA) scans were performed in patients >12 years.Results:Body mass index (BMI) standard deviation score (SDS) was elevated (0.67), with seven patients being overweight and four obese. DXA scans showed percentage body fat SDS of 1.59. Office BP levels were higher than reference values. Twenty-four hour ABPM showed systolic hypertension (n=5), while 11 patients had a non-dipping BP profile. HOMA-IR was >75th percentile in 12 patients.Conclusions:CAH patients develop an unfavorable CVR profile already in childhood with increased BMI, increased fat mass, elevated BP levels, a non-dipping BP profile and IR compared to population reference values.

Contains fulltext : 169249.pdf (Publisher’s version ) (Open Access) BACKGROUND: Henoch-Schonlein vasculitis is the most common systemic vasculitis in children. Arthritis or arthralgia occurs in 80 % of patients. We believe this to be the first case report to describe the finding of polyarthritis in a fludeoxyglucose positron emission tomography-computed tomography scan in a patient with Henoch-Schonlein vasculitis without clinical signs of arthritis. CASE PRESENTATION: A 4.5-year-old Caucasian boy presented with fever of 4 days' duration followed by debilitating migratory arthralgia and inflammation. He underwent a fludeoxyglucose positron emission tomography-computed tomography scan to exclude a possible malignant cause or to detect any infectious or autoimmune focus of his symptoms. Fludeoxyglucose uptake was observed in multiple large joints and in multiple tendons. These findings suggested active polyarthritis and polytendinitis. However, physical and ultrasound evaluations did not show any signs of arthritis in our patient, despite his evident arthralgia. CONCLUSIONS: Fludeoxyglucose positron emission tomography-computed tomography might be able to detect inflammatory activity in painful joints that cannot yet be detected clinically or with ultrasound evaluation in a patient with Henoch-Schonlein vasculitis. Therefore, fludeoxyglucose positron emission tomography-computed tomography can be of additional value in the diagnostic workup of patients with an unresolved diagnosis of suspected autoimmune disease, especially in patients with unresolved arthralgia and fever of unknown cause.

ContextPatients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity.ObjectivesTo assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles.DesignRandomized placebo controlled crossover trial.ParticipantsTwelve CAH patients and 12 body mass and age-matched control subjects.InterventionSixteen-week treatment with pioglitazone (45 mg/day) or placebo.Main outcome measureInsulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles.ResultsCAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5±11.6 to 38.9±11.0 μmol/kg per min, P=0.000, GIR in controls 46.2±23.4 μmol/kg per min, PPPConclusionsCAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.

Purpose To determine the inter- and intraobserver reproducibility of cardiac magnetic resonance (CMR)-derived measurements of right ventricular (RV) mass, volume, and function in patients with normal and dilated ventricles. Materials and methods CMR studies of 60 patients in three groups were studied: a normal RV group (N = 20) and two groups with RV dilation-atrial septal defect (ASD) (N = 20) and repaired tetralogy of Fallot (TOF) (N = 20). Two independent observers analyzed each study on two separate occasions. Inter- and intraobserver reproducibility of biventricular mass, volume, ejection fraction (EF), and stroke volume (SV) measurements were calculated. Results High intraclass correlation coefficients (ICC) were found for interobserver (ICC = 0.94-0.99) and intraobserver (ICC = 0.96-0.99) comparisons of RV and left ventricular (LV) mass, volume, and SV measurements. RV and LV EF measurements were less reproducible (ICC = 0.79-0.87). RV mass measurements were significantly less correlated than the respective LV measurements. Small but statistically significant differences in correlation were noted in RV measurements across groups. Conclusion Except for RV mass, inter- and intraobserver reproducibility of RV size and function measurements is high and generally comparable to that in the LV in patients with both normal and dilated RV.

A neonate was born with a sacrococcygeal mass. Initially, spina bifida was suspected. However, neurological examination was unremarkable. An MRI of the neuraxis showed a large cystic presacral lesion without signs of spina bifida. Surgical resection of the lesion was performed. Pathologic evaluation confirmed the diagnosis of a sacrococcygeal teratoma.

WOS: 000363267400006, PubMed: 26053152, ObjectiveSteroid 11-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11OHD appears to be a rare condition. Our study assessed the residual CYP11B1 function of detected mutations, adding to the spectrum of mild 11OHD, and illustrates the variability of the clinical presentation of 11OHD. Patients and methodsFive patients presented with mild to moderate 11OHD. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,XX female patient was diagnosed with virilization of the external genitalia 2years after birth. Direct DNA sequencing was carried out to perform CYP11B1 mutation analysis. The CYP11B1 mutations were functionally characterized using an invitro expression system. ResultsCYP11B1-inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual CYP11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of CYP11B1 enzymatic activity. ConclusionMutations causing partial impairment of 11-hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11OHD, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11OHD can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11OHD and consequently initiation of personalized treatment is essential to prevent co-morbidities caused by androgen excess and hypertension., ZonMW AGIKO Grant; European CommissionEuropean Commission Joint Research Centre [IEF-GA-2009-255424]; Medical Research CouncilMedical Research Council UK (MRC) [G0900567], This work was supported by the ZonMW AGIKO Grant (to C.F.M.), the European Commission (Marie Curie Intra-European Fellowship IEF-GA-2009-255424 to S.P.).

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to accumulation of steroid precursors and adrenal androgens. These steroids may have a biological effect on the steroid receptor with clinical consequences on diagnostics and treatment in CAH patients. Therefore, we analysed the effect of accumulated steroids [17-hydroxyprogesterone (17OHP), progesterone, androstenedione and testosterone] on aldosterone-mediated transactivation of the human mineralocorticoid receptor (hMR). Methods: A transactivation assay using transiently transfected COS7 cells was employed. Cells were co-transfected with hMR-cDNA, MMTV-luciferase and renilla-luciferase expression vectors. Transfected cells were incubated with six different steroid concentrations in addition to aldosterone (10-10M). Luciferase and renilla activities were measured to quantify hMR transactivation. Results: Linear regression analysis showed statistically significant linear inhibition of transactivation of the hMR by 10-10M aldosterone in the presence of increasing 17OHP [F(1,5) = 11.34, p = 0.019] and progesterone [F(1,5) = 11.08, p = 0.021] concentrations. In contrast, neither androstenedione nor testosterone affected hMR transactivation by aldosterone at a concentration of 10-10M. Conclusion: Our study shows for the first time that neither androstenedione nor testosterone has a biological effect on aldosterone-mediated transactivation of the hMR. 17OHP and progesterone have an anti-mineralocorticoid effect in vitro that may clinically lead to an increased requirement of mineralocorticoids in poorly controlled CAH patients.

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) facilitates the first and rate-limiting step of steroidogenesis. Only nine patients with CYP11A1 deficiency have been described. All patients presented with adrenal insufficiency (AI) and disorder of sex development in 46,XY individuals.Our objective was to define the pathogenic consequences of a novel CYP11A1 mutation (p.R451W) found in two brothers with isolated adrenal insufficiency.The two brothers (46,XY) presented with AI and normal male genital development. The older boy first presented with signs and symptoms suggestive of AI at the age of 2.8 yr but was only diagnosed at the age of 4.1 yr during an adrenal crisis. The younger brother was diagnosed with AI at the age of 2.5 yr while being clinically asymptomatic. Both boys had entirely normal appearance of their external genitalia.The novel p.R451W mutation and five published missense CYP11A1 mutations were characterized employing two in vitro approaches using the natural substrate cholesterol and the intermediate 22R-hydroxycholesterol, respectively. Pregnenolone generation was measured by highly specific liquid chromatography tandem mass spectrometry. p.R451W had 30% of wild-type activity consistent with the clinical phenotype in our patients. Two previously published mutations (p.L222P and p.A359V) had 2- to 3-fold higher in vitro activities than originally reported, correlating better with the associated phenotypes.We provide the first evidence that partial CYP11A1 deficiency has to be considered as a differential diagnosis in clinically isolated adrenal insufficiency. Our assays demonstrate a tighter genotype-phenotype correlation in CYP11A1 deficiency than previous in vitro studies.

Contains fulltext : 96615.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Treatment with glucocorticoids and mineralocorticoids has changed congenital adrenal hyperplasia (CAH) from a fatal to a chronic lifelong disease. Long-term treatment, in particular the chronic (over-)treatment with glucocorticoids, may have an adverse effect on the cardiovascular risk profile in adult CAH patients. The objective of this study was to evaluate the cardiovascular risk profile of adult CAH patients. DESIGN: Case-control study. PATIENTS AND MEASUREMENTS: In this case-control study the cardiovascular risk profile of 27 adult CAH patients and 27 controls, matched for age, sex and body mass index was evaluated by measuring ambulatory 24-hour blood pressure, insulin sensitivity (HOMA-IR), lipid profiles, albuminuria and circulating cardiovascular risk markers (PAI-1, tPA, uPA, tPA/PAI-1 complex, hsCRP, adiponectin, IL-6, IL-18 and leptin). RESULTS: 24-Hour systolic (126.3 mmHg+/-15.5 vs 124.8 mmHg+/-15.1 in controls, P = 0.019) and diastolic (76.4 mmHg+/-12.7 vs 73.5 mmHg+/-12.4 in controls, P

Background: Congenital chylothorax (CC) is a severe congenital disorder characterized by the collection of chyle in the pleural space. Recent case reports suggest that the use of octreotide in the treatment of CC may be useful. Objective: To evaluate the effect of octreotide on pleural effusions in CC. Methods: Hospital records of 7 patients with a CC, who were admitted to the Neonatal Intensive Care Unit of the Radboud University Nijmegen Medical Centre between 2006 and 2010 and were treated with octreotide, were retrospectively evaluated. Results: There was no clear and consistent effect of octreotide treatment on pleural effusions. Pleural effusions eventually decreased in all patients after reaching a dose of 5–6 µg/kg/min, but this could also reflect the natural history of CC. Out of 7 patients, 4 were diagnosed with persistent pulmonary hypertension of the newborn. No other known side effects of octreotide were found. There was a mortality rate of 30%. Conclusions: No clear and consistent effect of octreotide was identified. Pulmonary hypertension was a common problem in this patient group. It is not clear whether or not this was caused or maintained by octreotide treatment. A randomized controlled trial is needed to investigate the safety and usefulness of octreotide. Until then, clinicians should be careful in using octreotide, especially when persistent pulmonary hypertension is present.

A 2-year-old boy presented with a 1.5-year history of recurrent cough, wheeze and feeding problems. An x-ray of the thorax and an oesophagogram showed constriction of the trachea and proximal portion of the oesophagus. On endoscopy a foreign body was found, embedded in extensive granulation tissue. This could only be removed surgically via oesophagotomy, and turned out to be a plastic toy coin.

Contains fulltext : 87566.pdf (Publisher’s version ) (Open Access) CONTEXT: As a result of the introduction of treatment with glucocorticoids and mineralocorticoids, now 60 years ago, congenital adrenal hyperplasia has become a lifelong chronic disease. Whether long-term treatment of the disease leads to long-term side effects remains unknown. In this respect, especially cardiovascular risk seems to be important. EVIDENCE SYNTHESIS: We reviewed the reported prevalence of conventional cardiovascular risk factors, i.e. obesity, insulin resistance, high blood pressure and dyslipidaemia in patients with congenital adrenal hyperplasia. Overall, the studies suggest a tendency towards an increased body mass index and fat mass, the presence of insulin resistance and hypertension, although data are relatively scarce and obtained in heterogeneous populations. CONCLUSIONS: Our findings suggest that adult CAH patients tend to have a cluster of metabolic risk factors, which are consistent with the metabolic syndrome. This notion may have consequences for the care for this group of patients. 01 augustus 2010

Aims: Evaluation of blood pressure in the first year of life in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Methods: Twenty-four children were included. Retrospective blood pressure values, fludrocortisone dosages, and serum renin, 17-hydroxyprogesterone (17-OHP) and androstenedione levels in the first year of life were evaluated. Blood pressure values were compared to reference values. Correlations between blood pressures and serum renin levels, and the dosage of fludrocortisone were calculated. Results: Mean peak systolic blood pressure values were generally not elevated, most values were around the 50th percentile, except incidentally higher mean peak systolic blood pressure values most below the 95th percentile. No significant correlations between blood pressure and serum renin, androstenedione and 17-OHP levels and fludrocortisone dosage were found. Conclusion: In this pilot studyin CAH patients, blood pressure values do not seem to be elevated in the first year of life. Further investigations are necessary to evaluate blood pressure in the first year of life in CAH patients in more detail.

Contains fulltext : 70671.pdf (Publisher’s version ) (Closed access) BACKGROUND: Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which plays a role in vasodilatation and in the regulation of cell growth and apoptosis. eNOS-deficient mice have impaired cardiac development resulting in congenital heart defects (CHDs). In humans, a single nucleotide polymorphism in the gene coding for eNOS (894G>T) is associated with birth defects. METHODS: We investigated the eNOS 894G>T polymorphism in relation to CHDs using a case-control study and a case-parent study. Possible interaction with maternal cigarette smoking during pregnancy and periconceptional folic acid supplementation was also investigated in a case-only approach. RESULTS: The eNOS 894G>T polymorphism was genotyped in 170 CHD-affected children, in 161 of their mothers, 215 control children and 240 control women. For the case-parent study, 135 complete triads were available. The sum of eNOS 894 GT and TT vs. GG genotypes in children was associated with increased CHD risk [odds ratio, OR 1.5 (95% CI 1.03-2.31)]. There was no preferential transmission of the 894T allele [OR 1.2 (95% CI 0.81-1.69)]. Overall, the maternal eNOS 894 GT or TT vs. GG genotypes were not associated with increased CHD risk. The maternal 894TT genotype in combination with maternal smoking was associated with an increased risk, particularly for a subgroup of other than conotruncal heart defects [OR 3.3 (95% CI 1.00-11.1)]. No interaction with periconceptional folic acid supplementation was observed. CONCLUSIONS: Our data indicate that the eNOS 894G>T polymorphism is associated with increased CHD risk. The study also provides evidence of a possible gene-environment interaction effect on CHD risk between the maternal eNOS 894G>T variant and maternal cigarette smoking during pregnancy. This observation should be interpreted with caution because of the relatively small subgroups. Further study in a larger group of CHD subjects is required.