Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥35 weeks.

AIM: Postnatal hypoglycaemia in newborn infants remains an important clinical problem where prolonged periods of hypoglycaemia are associated with poor neurodevelopmental outcome. The aim was to develop an evidence-based national guideline with the purpose to optimise prevention, diagnosis and treatment of hypoglycaemia in newborn infants with a gestational age ≥35 + 0 weeks. METHODS: A PubMed search-based literature review was used to find actual and applicable evidence for all incorporated recommendations. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used for grading the evidence of the recommendations. RESULTS: Recommendations for the prevention of neonatal hypoglycaemia were extended and updated, focusing on promotion of breastfeeding as one prevention strategy. Oral dextrose gel as a novel supplemental therapy was incorporated in the treatment protocol. A new threshold-based screening and treatment protocol presented as a flow chart was developed. CONCLUSION: An updated and evidence-based national guideline for screening and treatment of neonatal hypoglycaemia will support standardised regimes, which may prevent hypoglycaemia and the risk for hypoglycaemia-related long-term sequelae.

Anti-müllerian hormone compared with other ovarian markers after childhood cancer treatment.

BACKGROUND: Gonadal dysfunction is one of the major late complications after cancer diagnosis and treatment. The best markers of ovarian reserve in clinical practice are antral follicle count (AFC) and ovarian volume. We aimed to study the prevalence of premature ovarian insufficiency (POI) and evaluate anti-Müllerian hormone (AMH) and other serum markers for ovarian function in adult women who were childhood cancer survivors (CCS) in comparison with a control group. MATERIAL AND METHODS: Altogether, 167 female CCS were compared to 164 matched controls. Prevalence of POI was documented and serum levels of AMH, inhibin B, follicle stimulating hormone (FSH), and estradiol (E2) were compared with AFC and ovarian volume. RESULTS: POI was reported in 22 (13%) of the CCS and in none of the controls. Serum levels of AMH, inhibin B, and FSH, but not E2, correlated significantly with AFC and ovarian volume; AMH showed the highest correlation. There was no difference between CCS and controls regarding the different serum markers as measured by linear regression analysis. ROC curve AUC for primary POI showed the highest values for AMH (0.930) and AFC (0.944). For AFC <10, ROC curve AUC showed highest value for AMH for CCS (0.866) and controls (0.878). In a subgroup of female CCS <40 years (n = 120), the results were similar. CONCLUSION: We found POI in 13% among CCS, slightly more than in other studies. Serum levels of AMH, inhibin B, and FSH correlated significantly with AFC and ovarian volume, and no difference was noted between CCS and controls. AMH was the most reliable serum marker for ovarian function in terms of POI and low AFC.

Anti-Müllerian hormone and fertility in women after childhood cancer treatment: Association with current infertility risk classifications.

BACKGROUND: To identify childhood cancer survivors (CCSs) at risk of premature ovarian insufficiency (POI) and impaired fertility is important given its impact on quality of life. The aim of this study was to assess ovarian markers and fertility outcomes in adult female CCSs. We used the Swedish and the PanCareLIFE classifications for infertility risk grouping. METHODS: 167 CCSs, at median age 34.6 years (19.3-57.8) with a median follow-up time of 25.4 years (11.6-41.3), and 164 healthy matched controls were included in this cross-sectional study. We assessed anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), and fertility outcomes. Based on gonadotoxic treatments given, CCSs were categorized into infertility risk groups. RESULTS: The median levels of AMH, AFC and OV were lower in CCSs (1.9 vs. 2.1 ng/ml, 12.0 vs. 13.0, 6.8 vs. 8.0 cm3) compared with controls, although statistically significant only for OV (p = 0.021). AMH levels in CCSs <40 years were lower for those classified as high-risk (p = 0.034) and very high-risk (p<0.001) for infertility, based on the Swedish risk classification. Similarly, AFC was reduced in the high-risk (p<0.001) and the very high-risk groups (p = 0.003). CCSs of all ages showed a trend towards impaired fertility, especially in the very high-risk group. POI was diagnosed in 22/167 CCSs, of whom 14 were in the high- and very high-risk groups. The results according to the PanCareLIFE classification were similar. CONCLUSION: Both the Swedish and the PanCareLIFE infertility risk classifications are reliable tools for identifying those at risk of reduced ovarian markers and fertility, as well as POI. We recommend fertility preservation counselling for patients receiving highly gonadotoxic treatments (i.e., Cyclophosphamide Equivalent Dose ≥6 g/m2, radiotherapy exposure to ovaries or stem cell transplantation) with follow-up at a young reproductive age due to the risk of a shortened reproductive window.

Hypoaldosteronism due to a novel SEC61A1 variant successfully treated with fludrocortisone.

Background: Genetic variants in SEC61A1 are associated with autosomal dominant tubulointerstitial kidney disease. SEC61A1 is a translocon in the endoplasmic reticulum membrane and variants affect biosynthesis of renin and uromodulin. Methods: A patient is described that presented at 1 year of age with failure-to-thrive, kidney failure (glomerular filtration rate, GFR, 18 ml/min/1.73m2), hyperkalemia and acidosis. Genetic evaluation was performed by whole genome sequencing. Results: The patient has a novel de novo heterozygous SEC61A1 variant, Phe458Val. Plasma renin was low or normal, aldosterone was low or undetectable and uromodulin was low. Kidney biopsy at 2 years exhibited subtle changes suggestive of tubular dysgenesis without tubulocystic or glomerulocystic lesions and with renin staining of the juxtaglomerular cells. The patient experienced extreme fatigue due to severe hypotension attributed to hypoaldosteronism and at 8 years of age fludrocortisone treatment was initiated with marked improvement in her well-being. Blood pressure and potassium normalized. Biopsy at 9 years showed extensive glomerulosclerosis and mild tubulointerstitial fibrosis, as well as tubular mitochondrial abnormalities, without specific diagnostic changes. Her GFR improved to 54 ml/min/1.73m2. Conclusions: As the renin-angiotensin system promotes aldosterone release, and the patient had repeatedly undetectable aldosterone levels, the SEC61A1 variant presumably contributed to severe hypotension. Treatment with a mineralocorticoid had a beneficial effect and corrected the electrolyte and acid-base disorder. We suggest that the increased blood pressure hemodynamically improved the patient's kidney function.

Acute onset of ovarian dysfunction in young females after start of cancer treatment.

BACKGROUND: Female childhood cancer survivors are at risk of ovarian failure and premature ovarian insufficiency. We hereby present an interim analysis of a prospective observational study of ovarian function during cancer treatment of young females in relation to clinical factors. PROCEDURE: Thirty-four consecutive female cancer patients aged 0-18 year were included after informed consent. Serum/Plasma levels of anti-Müllerian hormone (AMH), inhibin B, FSH, LH, and oestradiol (E2) were measured at diagnosis and every 3-4 months during and after treatment. RESULTS: All patients had detectable AMH levels at diagnosis. Eleven patients had reached menarche (mean age 14½ years) and the remaining patients had a mean age of 6½ years. They all showed a rapid decline in AMH after 3 months of treatment, regardless of AMH at diagnosis, age, menarche, or treatment given. Those given radiotherapy below the diaphragm and/or stem cell transplantation (SCT) (n = 9) had no ovarian recovery during or 1½-year after treatment. However, recovery was observed in those given standard treatment for acute lymphatic leukemia (n = 7) already during maintenance chemotherapy. For the remaining patients, longer follow-up is required for analysis of ovarian recovery after treatment. CONCLUSIONS: Rapid ovarian dysfunction is observed in all females after initiation of cancer treatment as measured by AMH and inhibin B. Our data regarding those who require abdominal radiotherapy and/or SCT confirms the recommendations in the Nordic countries where these patients are eligible for cryopreservation of ovarian cortical tissue before start of cancer treatment.

Prevalence of refractoriness when testing growth hormone levels in children.

OBJECTIVE: Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during arginine-insulin-tolerance test (AITT) after a GH peak during a short spontaneous nocturnal profile (SSNP) in children with short stature or low growth velocity. DESIGN: Using SSNP and subsequent AITT, we examined 257 children 4-18 years old (138 (53.7%) males) recruited from three hospitals. Medical records were reviewed retrospectively. Refractory children were defined as a GH peak ≥7 µg/L during SSNP but no GH peak ≥7 µg/L during AITT. RESULTS: In total, 201/257 children had a GH peak ≥7 µg/L at SSNP and/or AITT. Of these, 21.9% were refractory. The proportion of males (p = 0.033) and body mass index (BMI) standard deviation score (SDS) (p = 0.037) were higher in the refractory group than in children with a GH peak ≥7 µg/L during AITT. The median period between last GH peak ≥7 µg/L during SSNP and GHmax at AITT was 210 (30-390) minutes. The GHmax at AITT occurred 30 min earlier for children without a peak ≥7 µg/L during the SSNP (p = 0.004). The number of refractoriness differed somewhat between the hospitals (p = 0.025). CONCLUSIONS: Many children with short stature were refractory at testing; among them we found few clinical characteristics. Refractoriness might be influenced by some differences in procedure, but needs to be considered when evaluating GH response in children.

Non-functioning pituitary microadenoma in children and adolescents: Is follow-up with diagnostic imaging necessary?

PURPOSE: No consensus exists regarding follow-up recommendations for suspected pituitary microadenoma in children. To address this knowledge gap, we investigated the growth potential of pituitary solid and cystic lesions <10 mm in children and evaluated the accuracy of magnetic resonance imaging (MRI) measurements. METHODS: The children included were <18 years at first pituitary MRI and radiologically diagnosed with a non-functioning microadenoma or cyst <10 mm. Lesion size at first and latest MRI as well as all individual MRI examinations were re-evaluated. RESULTS: In total, 74 children, median age 12 years (range 3-17), had a non-functioning microadenoma, probable microadenoma, or cyst. Of these, 55 underwent repeated MRI (median 3, range 2-7) with a median follow-up of 37 months (range 4-189). None of the pituitary lesions without hormonal disturbances increased significantly during follow-up. Two radiologists agreed that no lesion could be identified in 38/269 (14%) MRI examinations, and in 51/231 (22%) they disagreed about lesion location. In 34/460 (7%) MRI measurements size differed >2 mm, which had been considered significant progression. CONCLUSION: Non-functioning pituitary microadenoma in children has small size variations, often below the spatial resolution of the scanners. We suggest lesions <4 mm only for clinical follow-up, lesions 4-6 mm for MRI after 2 years and ≥7 mm MRI after 1 and 3 years, with clinical follow-up in between. If no progression, further MRI should only be performed after new clinical symptoms or hormonal disturbances.

Evaluation of self-assessment of pubertal maturation in boys and girls using drawings and orchidometer.

BACKGROUND: Self-assessment of puberty has been reported to correlate well with staging by a physician. No previous study has evaluated the use of an orchidometer to assess testicular size in boys. STUDY DESIGN: This study included 44 girls and 56 boys, 10-16 years old, with assessed Tanner staging. The boys also used an orchidometer. The correlation with a professional's staging was analyzed using percentage agreement (PA). RESULTS: For girls, the PA for breast development was 52%, and for pubic hair, 64%. There was no case of the difference being greater than one stage. For boys, the PA for pubic hair was 75%. For testicular volume, the PA was 36%; in 95%, the difference was only one size. CONCLUSIONS: We found pubertal self-assessment, including the use of an orchidometer for boys, to be a useful method. However, if the purpose is to determine exact pubertal onset, the assessment should be made by a trained professional.

Postoperative growth rate affects time to growth arrest after percutaneous physiodesis: A radiostereometric analysis.

Purpose: The aim of this study was to determine the time at which physeal arrest is achieved after percutaneous physiodesis, and whether immediate postoperative growth rate affects the time to reach physeal arrest. Methods: Radiostereometric analysis, with implantation of tantalum balls as radiographic markers on each side of the physes, was used to measure residual longitudinal growth in 21 children (10 boys and 11 girls) after percutaneous physiodesis for leg length discrepancy or extreme tall stature. In total, 25 femoral and 20 tibial physes were operated on. Median age at surgery was 13.9 years (range = 11.4-16.1). Radiostereometric analysis was performed postoperatively and after 3, 6, 9, 12, 26, and 52 weeks. Longitudinal growth rate <50 µm per week was defined as physeal arrest. Descriptive statistics were used for evaluation. Results: Physeal arrest was obtained in 19 of the 21 children (40 physes) within 12 weeks postoperatively. One child was reoperated on in three out of four physes because of continued growth, and in one child, delayed physeal arrest was present at 26 weeks postoperatively. Time to physeal arrest was longer in physes with a higher immediate postoperative growth rate. Conclusion: Postoperative follow-up with radiostereometric analysis at 12 and 15 weeks can determine whether physeal arrest has been achieved. The immediate postoperative growth rate after physiodesis seems to affect the time to physeal arrest. This implies that the risk for complications is greater for children during an accelerated growth period, for example, in boys, younger children and in distal femoral physes. Level of evidence: level III.

Ectopic recurrence of a craniopharyngioma in a 15-year-old girl 9 years after surgery and conventional radiotherapy: case report.

This 15-year-old girl was operated due to an ectopic recurrence of a craniopharyngioma along the previous surgical route. She presented with a sellar craniopharyngioma at the age of 4 years and underwent a right subfrontal craniotomy. Two and a half years later she had a local recurrence in the sella that was resected along the same surgical route. Postoperative cranial radiotherapy was administered with 50 Gy divided into 28 fractions. Nine years later, magnetic resonance imaging (MRI) revealed a local recurrence within the sella together with a supraorbital cystic mass. Both tumors were surgically removed. Microscopic examination revealed recurrence of an adamantinous craniopharyngioma at both localisations. Histopathological preparations showed a higher MIB-1 index at the simultaneous recurrences in the sella and in the frontal lobe and also an elevated focal p53 expression, compared to previous operations, suggesting a transformation to a more aggressive tumor. This is the first case report of ectopic recurrence in a child that had received conventional radiotherapy of 50 Gy to the sella. Careful intra-operative procedure is probably crucial for preventing ectopic recurrences. The future will reveal if the transsphenoidal surgical route will put an end to ectopic tumor recurrence in patients with a craniopharyngioma.

Premature ovarian failure after childhood cancer and risk of metabolic syndrome: a cross-sectional analysis.

OBJECTIVE: Female childhood cancer survivors (CCS) are at risk of several late effects, such as metabolic syndrome (MetS) and premature ovarian insufficiency (POI). The objective is to study if POI is associated with risk of MetS and increased cardiovascular risk in CSS. DESIGN: A cross-sectional study with a median time since the cancer diagnosis of 25 (12-41) years. Patients and controls were recruited from the South Medical Region of Sweden. METHODS: The study included 167 female CCS, median age 34 (19-57) years, diagnosed with childhood cancer at median age 8.4 (0.1-17.9) years together with 164 controls, matched for age, sex, ethnicity, residence, and smoking habits. All subjects were examined with fasting glucose, insulin, HbA1c, and lipid profile. Fat mass was calculated with dual-energy X-ray absorptiometry (DXA), and questionnaires for medication were obtained. Detailed information of cancer treatment was available. RESULTS: POI was present in 13% (22/167) among CCS (hypothalamic/pituitary cause excluded) and in none among controls. MetS was present in 14% (24/167) among all CCS (P = 0.001), in 23% (5/22) of those with POI (P < 0.001), compared with 4% (6/164) among controls. OR for MetS in all CCS compared with controls was 4.4 (95% CI: 1.8, 11.1) (P = 0.002) and among CCS with POI the OR was 7.7 (CI: 2.1, 28.1) (P = 0.002). CONCLUSION: The prevalence of MetS was higher in females treated for childhood cancer compared with controls, and the presence of POI significantly increased the risk of developing MetS.

Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism.

Mosaic genome-wide paternal uniparental disomy (GW-pUPD) is a rarely recognised disorder. The phenotypic manifestations of multilocus imprinting defects (MLIDs) remain unclear. We report of an apparently non-syndromic infant with severe congenital hyperinsulinism (CHI) and diffuse pancreatic labelling by 18F*-DOPA-PET/CT leading to near-total pancreatectomy. The histology was atypical with pronounced proliferation of endocrine cells comprising >70% of the pancreatic tissue and a small pancreatoblastoma. Routine genetic analysis for CHI was normal in the blood and resected pancreatic tissue. At two years' age, Beckwith-Wiedemann Syndrome (BWS) stigmata emerged, and at five years a liver tumour with focal nodular hyperplasia and an adrenal tumour were resected. pUPD was detected in 11p15 and next in the entire chromosome 11 with microsatellite markers. Quantitative fluorescent PCR with amplification of chromosome-specific DNA sequences for chromosomes 13, 18, 21 and X indicated GW-pUPD. A next generation sequencing panel with 303 SNPs on 21 chromosomes showed pUPD in both blood and pancreatic tissue. The mosaic distribution of GW-pUPD ranged from 31 to 35% in blood and buccal swap to 74% in the resected pancreas, 80% in a non-tumour liver biopsy, and 100% in the liver focal nodular hyperplasia and adrenal tumour. MLID features included transient conjugated hyperbilirubinaemia and lack of macrosomia from BWS (pUPD6); and behavioural and psychomotor manifestations of Angelman Syndrome (pUPD15) on follow-up. In conclusion, atypical pancreatic histology in apparently non-syndromic severe CHI patients may be the first clue to BWS and multi-syndromal CHI from GW-pUPD. Variations in the degree of mosaicism between tissues explained the phenotype.

Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome.

The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.

Number of islet autoantibodies present in newly diagnosed type 1 diabetes children born to non-diabetic mothers is affected by islet autoantibodies present at birth.

OBJECTIVE: Cord blood islet autoantibodies in children born to mothers with type 1 diabetes may be associated with a reduced risk of islet autoimmunity and diabetes. The aim of this study was to investigate in children with type 1 diabetes but born to non-diabetic mothers whether islet autoantibodies at birth affected their presence at diagnosis. PATIENTS AND METHODS: Serum samples at birth and at diagnosis were available from 141 children who developed type 1 diabetes between 1 and 19 yr of age (median 9.0 yr; male/female ratio 83/58). The samples were tested for autoantibodies against glutamic acid decarboxylase, insulinoma-associated antigen 2, and insulin as well as for islet cell antibodies. The human leukocyte antigen genotype was also determined. RESULTS: The frequency of islet autoantibodies in the umbilical cord blood was 11% compared with 91% at diagnosis. Children with fewer islet autoantibodies at diagnosis were more likely to have had autoantibodies at birth (p = 0.02). Autoantibodies present in cord blood at birth were observed in 25% (3/12) of children with no islet autoantibodies at diagnosis, in 17% (7/42) of children with one or two antibodies at diagnosis, and in only 5% (4/86) of children with more than two antibodies, demonstrating an inverse relationship between autoantibodies at birth and at diagnosis (test for trend, p < 0.001). CONCLUSIONS: Our preliminary data suggest that exposure to cord blood islet autoantibodies may influence the presence of islet autoantibodies at the time of diagnosis of type 1 diabetes and explain why some type 1 diabetes children are islet autoantibody negative at clinical diagnosis.

Clinical and Immunological Characteristics of Autoimmune Addison Disease: A Nationwide Swedish Multicenter Study.

Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality. Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors. Design, Setting, and Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008-2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls. Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined. Results: The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046). Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.

Vaginal Bleeding in Prepubertal Girls: Etiology and Clinical Management.

STUDY OBJECTIVE: We aimed to investigate the etiology and clinical management of vaginal bleeding in girls aged 0-9 years and to compare our results with previous publications. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: The records of all girls younger than 10 years of age who were seen between 2001 and 2011 at Skåne University Hospital Lund for vaginal bleeding were retrospectively collected. RESULTS: We identified 86 girls with vaginal bleeding. Of those, 47 (54.7%) were diagnosed with a local lesion, the etiology was hormonal in 16 (18.6%), and in 23 (26.7%) the etiology was unclear. Trauma was the most frequent cause of local lesions and hormonal withdrawal of the newborn was the most common hormonal etiology. Two girls were diagnosed with a tumor, 1 with relapse of a vaginal rhabdomyosarcoma, and the other with recurrence of an ovarian granulosa cell tumor. There were large disparities in the clinical management of vaginal bleeding. A genital examination was conducted in 70 of 86 (81.4%), and colposcopy in only 8 of 86 of the patients (9.3%). CONCLUSION: This study confirmed vaginal bleeding as a rare finding in girls younger than 10 years of age. It is usually a benign symptom, but because there might be a serious underlying condition, proper investigation and follow-up are needed. Clinical management varied in our patient cohort. This might be because of insufficient knowledge and might indicate the need for general guidelines.

Severe gonadotoxic insult manifests early in young girls treated for Ewing sarcoma.

We prospectively investigated anti-Müllerian hormone (AMH) as a measure of ovarian insult in young females during and after treatment for Wilms tumor (WT), osteosarcoma (OS), and Ewing sarcoma (ES).Twenty-one female childhood cancer patients, with a mean age of 7.9 years (range 0.6-17), entered the study. Levels of AMH, follicle-stimulating hormone (FSH), and luteinizing hormone were monitored at diagnosis and every 3 to 4 months during, and regularly for a mean of 2.6 years after treatment.A profound decline in AMH was seen in the majority of the 21 study patients 3 to 4 months after the beginning of treatment, the exception being patients with WT, of whom 60% showed no such decline. During the remaining treatment, all patients except those with WT not treated with whole abdominal radiotherapy or stem cell transplantation (SCT) had AMH below detection limit.After completion of treatment, patients with OS and WT (without whole abdominal radiotherapy and SCT) recovered in AMH and had FSH in the normal range. In contrast, ES patients showed no AMH recovery and highly fluctuating FSH in the first years of follow-up, except for the 2 youngest patients, who had a late, slow AMH recovery.In conclusion, young female ES patients already showed signs of severe ovarian dysfunction during the first years after cancer treatment similar to patients treated with SCT and abdominal radiotherapy, in contrast to females with WT and OS. Fertility counseling and information concerning fertility preservation procedures should be considered before starting to treat young females with ES.

Hypothalamic involvement predicts cognitive performance and psychosocial health in long-term survivors of childhood craniopharyngioma.

CONTEXT: Hypothalamic damage caused by craniopharyngioma (CP) is associated with poor functional outcome. OBJECTIVE: To assess cognitive function and quality of life in childhood-onset CP on hormonal replacement, including GH treatment. DESIGN: A cross-sectional study with a median follow-up time of 20 years (1-40). SETTING: Patients were recruited from the South Medical Region of Sweden. PARTICIPANTS: The study included 42 patients (20 women) surgically treated for a childhood-onset CP between 1958 and 2000. Patients were aged ≥17 years. Equally many controls, matched for age, sex, residence, and smoking habits, were included. Tumor growth into the third ventricle was found in 25 patients. MAIN OUTCOME MEASURES: All subjects were examined with a battery of cognitive tests and the following questionnaires: Symptom Checklist-90, the Interview Schedule for Social Interaction, and the Social Network concept. RESULTS: The CP patients had lower cognitive performance, reaching statistical significance in 12 of 20 test variables, including executive function and memory. Comparison of patients with tumor growth into the third ventricle to controls revealed a significant lower mean total score (P = .006). A significant negative correlation was recorded between mean z-score of cognitive performance and years since operation (r = -0.407; P = .014). No statistically significant group differences were observed across any of the 9 Symptom Checklist-90 subscales. CONCLUSIONS: Adults with childhood-onset CP, on hormone replacement, including GH treatment, have memory defects, disturbed attention, and impaired processing speed. Patients with hypothalamic involvement are more affected. Patients rated their quality of life as good as their matched controls.

A nested case-control study of intrauterine exposure to persistent organochlorine pollutants in relation to risk of type 1 diabetes.

BACKGROUND: The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes. METHODOLOGY/ PRINCIPAL FINDINGS: The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p'-DDE (OR 0.56, 95% CI 0.29, 1.08). CONCLUSIONS: The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes.