A multidisciplinary intervention programme has positive effects on quality of life in overweight and obese preschool children.

AIM: Up to 18.1% of Dutch children aged 3-5 are overweight and up to 3.3% are obese, with higher levels in girls. This study assessed the effect of a multidisciplinary intervention programme on health-related quality of life (HRQoL) in this patient group. METHODS: We randomised 75 children to a multidisciplinary intervention, comprising dietary advice, exercise sessions and psychological counselling for parents or the standard care programme, providing healthy lifestyle advice. The parents completed quality of life and child health questionnaires at baseline and after 16 weeks and 12 months. RESULTS: At 16 weeks, children in the intervention group experienced more bodily pain and less mental health than the standard care group, but at 12 months, this difference disappeared and they showed a more positive change in HRQoL than the standard care group, especially for the physical domain. When we combined both groups, a decreased BMIz-score over 12 months was associated with increased global health and reduced visceral fat correlated with increased general health. CONCLUSION: At 12 months, a multidisciplinary intervention programme for overweight and obese children aged 3-5 years had beneficial effects on HRQoL, especially for the physical domain. Reduced obesity parameters correlated with several increased HRQoL parameters.

Systemic effects of hypothermia due to hypothalamic dysfunction after resection of a craniopharyngioma: case report and review of literature.

OBJECTIVE: With this case report, we aim to improve recognition of the systemic effects of hypothermia due to hypothalamic dysfunctioning. We present a patient who developed temperature dysregulation after surgery for craniopharyngioma. He suffered from several episodes of hypothermia associated with a decreased level of consciousness, hypoventilation, bradycardia, pancreatitis, and pancytopenia. Rewarming resulted in complete recovery of all symptoms. DATA SOURCES: We discuss the literature on the pathophysiological consequences of hypothermia, referring to several medical databases (Cochrane, SUMSearch, Trip database, and PubMed). CONCLUSION: Hypothermia due to hypothalamic dysfunction can result in several systemic complications with complete recovery of all symptoms by rewarming.

New national recommendations for the treatment of pediatric differentiated thyroid carcinoma in the Netherlands.

BACKGROUND: Currently, there are no European recommendations for the management of pediatric thyroid cancer. Other current international guidelines are not completely concordant. In addition, medical regulations differ between, for instance, the US and Europe. We aimed to develop new, easily accessible national recommendations for differentiated thyroid carcinoma (DTC) patients <18 years of age in the Netherlands as a first step toward a harmonized European Recommendation. METHODS: A multidisciplinary working group was formed including pediatric and adult endocrinologists, a pediatric radiologist, a pathologist, endocrine surgeons, pediatric surgeons, pediatric oncologists, nuclear medicine physicians, a clinical geneticist and a patient representative. A systematic literature search was conducted for all existing guidelines and review articles for pediatric DTC from 2000 until February 2019. The Appraisal of Guidelines, Research and Evaluation (AGREE) instrument was used for assessing quality of the articles. All were compared to determine dis- and concordances. The American Thyroid Association (ATA) pediatric guideline 2015 was used as framework to develop specific Dutch recommendations. Discussion points based upon expert opinion and current treatment management of DTC in children in the Netherlands were identified and elaborated. RESULTS: Based on the most recent evidence combined with expert opinion, a 2020 Dutch recommendation for pediatric DTC was written and published as an online interactive decision tree (www.oncoguide.nl). CONCLUSION: Pediatric DTC requires a multidisciplinary approach. The 2020 Dutch Pediatric DTC Recommendation can be used as a starting point for the development of a collaborative European recommendation for treatment of pediatric DTC.

[Non-alcoholic fatty liver disease in children: a new complication of obesity]. / 'Non-alcoholic fatty liver disease' bij kinderen: een nieuwe complicatie van obesitas.

Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases from simple steatosis to steatohepatitis and cirrhosis with liver failure. In children, NAFLD is mainly associated with obesity and metabolic syndrome, the results of an unhealthy lifestyle. Insulin resistance and free fatty acids play a key role in the pathogenesis of NAFLD. NAFLD can therefore be seen as a metabolic complication of obesity. Since the prevalence of obesity in Dutch children is increasing, the prevalence of NAFLD in children is expected to increase as well. Prevention of obesity and identification of children with an increased risk of NAFLD are important steps in preventing irreversible liver damage. Lifestyle changes aimed at improving insulin sensitivity through healthy food and sufficient physical activity are essential in the treatment of NAFLD. Pharmacological treatment may have additional value.

Long-term effects of radioiodine treatment on salivary gland function in adult survivors of pediatric differentiated thyroid carcinoma.

Pediatric differentiated thyroid cancer (DTC) is a rare disease. Initial treatment of DTC consists of a (near) total thyroidectomy and radioactive iodine (131I) therapy. Previous studies in adults showed that 131I treatment may result in a reduced salivary gland function. Studies regarding salivary gland function in children treated for DTC are sparse. Our aim was to assess long-term effects of 131I treatment on salivary gland function in survivors of pediatric DTC. Methods: In a nationwide cross-sectional study, salivary gland function of patients treated for pediatric DTC between 1970 and 2013 (>5 years after diagnosis, ≥18 years old at time of evaluation) was studied. Salivary gland function was assessed by sialometry, sialochemistry and a xerostomia inventory. Salivary gland dysfunction was defined as unstimulated whole saliva flow ≤0.2mL/min and/or a stimulated whole saliva flow ≤0.7 mL/min. Results: Sixty-five patients (median age at evaluation 33 [IQR, 25-40] years, 86.2% female, median follow-up period 11 [IQR, 6-22] years) underwent 131I treatment. Median cumulative 131I activity was 5.88 [IQR, 2.92-12.95] GBq, 47.7% underwent multiple 131I administrations. Salivary gland dysfunction was present in 30 (47.6%) patients. Levels of amylase and total protein in saliva were reduced. Moderate to severe xerostomia was present in 22 (35.5%) patients. Stimulated salivary secretion was lower and severity of xerostomia complaints higher in patients treated with higher cumulative 131I activity. Conclusion: In survivors of pediatric DTC, clinically significant salivary gland dysfunction was found in 35.5% and was related to the cumulative 131I activity of the treatment.

[Chance finding of foetal and neonatal ovarian cysts on echography]. / Foetale en neonatale ovariumcysten als toevalsbevinding bij echografie.

Cystic abnormalities of the adnex were found by chance in 2 baby girls, one aged 2.5 months and the other aged 2 months. Both had been born dysmaturely and the abnormalities were found on echographic investigation carried out for suspected urinary-tract infection. On monitoring investigation one month later, the abnormalities had become smaller and some time later had disappeared altogether. With the increasing use of ultrasound, ovarian cysts are being detected more often in the foetus and neonate. The majority of these cysts are benign functional follicular cysts and resolve spontaneously. The decision to perform surgery depends on the clinical symptoms and appearance on ultrasound. Large uncomplicated cysts can be managed by antenatal or postnatal aspiration in order to prevent torsion and the subsequent loss of the adnex.

[Cushing's syndrome in children]. / Het syndroom van Cushing bij kinderen.

In two girls, aged 13 and 16 years, Cushing's syndrome was diagnosed. In addition, the first showed a decrease in linear growth and weight gain; a pituitary adenoma was found, which was surgically excised. The second girl was examined because of a male body-hair pattern and weight increase. She had an adrenal adenoma, visible on MRI, which was excised during laparoscopy. Cushing's syndrome is a rare disease in childhood. A decrease in linear growth and a gain in weight are early recognisable features. Arriving at an aetiological diagnosis may be difficult and is based on the performance and interpretation of endocrinologic function and laboratory tests such as determination of the cortisol level in blood, saliva and urine, a dexamethasone-suppression test, and a corticotropin assay in blood drawn from the cerebral cavernous sinuses.

[A girl with Cushing's syndrome due to primary pigmented nodular adrenocortical disease]. / Een meisje met het syndroom van Cushing door primaire gepigmenteerde nodulaire adrenocorticale ziekte.

A 12.5-year-old girl with diabetes mellitus type 1 presented with stunted growth and an increase in body weight. Also, her blood-sugar levels were difficult to manage. An adrenocorticotropin-(ACTH)-independent form of Cushing's syndrome was diagnosed. During the dexamethasone-suppression test, a paradoxical increase in urinary-free cortisol excretion was observed, which is a clear indication of primary pigmented nodular adrenocortical disease (PPNAD). The treatment for patients with PPNAD is bilateral adrenalectomy and hormone substitution. PPNAD may be part of the Carney complex, an autosomal dominant multiple neoplasia syndrome. Screening of family members is mandatory. Further investigation for mutations in the gene encoding the regulatory subunit 1A of the protein kinase A (PRKAR1A) may be helpful.

Gonadotropin releasing hormone analogue therapy in children with isolated growth hormone deficiency: final height benefit from postponing puberty?

Although growth hormone (GH) treatment has improved final height prognosis in children with GH deficiency (GHD), adult heights are still disappointing. Final height could be improved by increasing the duration of puberty and in this way increasing total pubertal height gain. Many studies have been published on the effect of gonadal suppression, mostly by gonadotropin releasing hormone (GnRH) analogues, on final height in children with GHD. Because of the different methodologies used in these studies, results are difficult to compare. Both positive and marginal effects on final height have been reported; however, patient numbers are limited. Children with GHD who start puberty at a relatively young age and who have a poor predicted adult height, can benefit from the addition of GnRH analogues. From previous studies, we might conclude that when there is a positive effect, height benefit is marginal. However, additional prospective, randomized controlled trials are needed to further elucidate whether delaying puberty is indicated in children with GHD to improve final height.

Bone mineral density in children and adolescents with Prader-Willi syndrome: a longitudinal study during puberty and 9 years of growth hormone treatment.

CONTEXT: Longitudinal data on bone mineral density (BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. OBJECTIVE: This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMADLS) in children with PWS. DESIGN AND SETTING: This was a prospective longitudinal study of a Dutch PWS cohort. PARTICIPANTS: Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. INTERVENTION: The children received GH treatment, 1 mg/m(2)/day (≅ 0.035 mg/kg/d). MAIN OUTCOME MEASURES: BMDTB, BMDLS, and BMADLS was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. RESULTS: In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMADLSSDS remained stable. During adolescence, BMDTBSDS and BMADLSSDS decreased significantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lower BMADLSSDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful predictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. CONCLUSIONS: This long-term GH study demonstrates that BMDTB, BMDLS, and BMADLS remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty.

Peripheral blood lymphocyte appearance in a case of I cell disease.

In general, peripheral blood smears are performed to obtain information with regard to various morphological features as an aid in the diagnosis of infection or malignancy. This report presents a patient with I cell disease (inclusion cell disease), a fatal lysosomal storage disorder caused by a defect in an enzyme responsible for the transfer of mannose-6-phosphate ligands to precursor lysosomal enzymes. As a consequence, most lysosomal enzymes are transported outside the cell instead of being correctly targeted into the lysosomes, resulting in the storage of macromolecules in lysosomes. I cell disease, with its heterogeneous clinical presentation, can be diagnosed by the presence of intracellular vacuole-like inclusions in lymphocytes and fibroblasts, high serum lysosomal enzyme activities, and a defect of N-acetylglucosamine-1-phosphotransferase. This report describes the morphological aspects of peripheral lymphocytes in a blood smear of a patient, the first clue to the final diagnosis of I cell disease. The observed vacuole-like inclusions in lymphocytes of this patient were negative for periodic acid Schiff (PAS) and Sudan black B staining, in contrast to earlier reports.

Growth hormone treatment in cartilage-hair hypoplasia: effects on growth and the immune system.

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder characterized by metaphyseal chondrodysplasia with severe growth retardation and impaired immunity. We studied the effects of growth hormone treatment on growth parameters and the immune system in four children with CHH. The effects of growth hormone on growth parameters are the most prominent in patients with the mildest growth retardation. However, the effects are temporary and last only for 1 year. There is no gain in final height. Serum immunoglobulins did not change during growth hormone treatment. We conclude that growth hormone treatment is not beneficial in children with CHH.

Eight years of growth hormone treatment in children with Prader-Willi syndrome: maintaining the positive effects.

BACKGROUND: The most important reason for treating children with Prader-Willi syndrome (PWS) with GH is to optimize their body composition. OBJECTIVES: The aim of this ongoing study was to determine whether long-term GH treatment can counteract the clinical course of increasing obesity in PWS by maintaining the improved body composition brought during early treatment. SETTING: This was a multicenter prospective cohort study. METHODS: We have been following 60 prepubertal children for 8 years of continuous GH treatment (1 mg/m(2)/d ≈ 0.035 mg/kg/d) and used the same dual-energy x-ray absorptiometry machine for annual measurements of lean body mass and percent fat. RESULTS: After a significant increase during the first year of GH treatment (P < .0001), lean body mass remained stable for 7 years at a level above baseline (P < .0001). After a significant decrease in the first year, percent fat SD score (SDS) and body mass index SDS remained stable at a level not significantly higher than at baseline (P = .06, P = .14, resp.). However, body mass index SDSPWS was significantly lower after 8 years of GH treatment than at baseline (P < .0001). After 8 years of treatment, height SDS and head circumference SDS had completely normalized. IGF-1 SDS increased to +2.36 SDS during the first year of treatment (P < .0001) and remained stable since then. GH treatment did not adversely affect glucose homeostasis, serum lipids, blood pressure, and bone maturation. CONCLUSION: This 8-year study demonstrates that GH treatment is a potent force for counteracting the clinical course of obesity in children with PWS.

Defective proximal tubular function in a patient with I-cell disease.

A girl with a proven diagnosis of I-cell disease is presented. Proximal tubular dysfunction was characterized by increased excretion of low molecular proteins, aminoaciduria, hyperphosphaturia, and high/slightly increased urinary calcium. The concentration of 1,25-dihydroxycalciferol in serum was increased. Rickets were present on X-rays. As the proximal tubular dysfunction resembles the dysfunction in Dent disease, one can speculate about a common pathogenesis. Impairment of acidification in lysosomes due to loss of function of the chloride-5 channel impairs intralysosomal protease activity in Dent disease, while in I-cell disease the intralysomal protease activity is lacking.

Optic neuropathy in McCune-Albright syndrome: an indication for aggressive treatment.

McCune-Albright syndrome consists of the triad polyostotic fibrous dysplasia, café-au-lait spots and autonomous hyperfunction of one or more endocrine systems. The most frequent neurological complication of craniofacial fibrous dysplasia is visual loss. We describe a 17-y-old boy with McCune-Albright syndrome and acute loss of vision in the left eye caused by encroachment of the left optic nerve by fibrous dysplastic lesions. Neurosurgical intervention improved left eye vision. Aggressive intervention is indicated in cases of acute visual loss in patients with craniofacial fibrous dysplasia. This is supported by a review of other reported cases.