Larger head circumference in Icelandic children 0-4 years of age compared to the World Health Organization and Swedish growth charts.

AIM: The World Health Organization (WHO) published universal growth standards for children below five year of age in 2006. Traditionally, Swedish growth references have been used to monitor growth of children in Iceland, but it is not yet known how they compare with these reference charts. METHODS: A total of 2128 longitudinal measurements of length or height, 2132 of weight and 2126 of head circumference between birth and four years of age were collected in 1996-2000 from 199 healthy children (53% boys) recruited at Landspitali University Hospital. Measurements were converted to z-scores using the WHO growth standards and Swedish growth references for further analysis with mixed-effects models. RESULTS: Length or height, weight and in particular head circumference largely exceeded the WHO standards, with average z-scores that fluctuated between 0.5 and 1.5. Likewise, the proportion of children with a z-score larger than 2 SD increased about 10-fold. Icelandic children were longer and heavier than their Swedish peers during the first six months of life, but differences were less pronounced thereafter. CONCLUSION: The growth of Icelandic children deviated significantly from the WHO growth standards. Although more comparable to the Swedish references, significant differences were found, suggesting that a national growth reference would be more appropriate.

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations.

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10-7, 4.3 × 10-9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.

Effect of sequence variants on variance in glucose levels predicts type 2 diabetes risk and accounts for heritability.

Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10-10), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7.5% per allele, P = 4.9 × 10-11 and 7.3% per allele, P = 7.5 × 10-18, respectively). Variants that increase mean and between-subject variance in fasting glucose levels tend to increase T2D risk, whereas those that increase the mean but reduce variance do not (r2 = 0.61). The variants that increase between-subject variance increase fasting glucose heritability estimates. Intuitively, our results show that increasing the mean and variance of glucose levels is more likely to cause pathologically high glucose levels than increase in the mean offset by a decrease in variance.

The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study.

OBJECTIVE: Pituitary adenomas (PA) are among the most common human neoplasms. To describe the epidemiology and assess the disease burden of clinically significant PAs, population-based studies are needed. Iceland has a small well-defined population. The aim of this study is to describe the epidemiology of PAs in Iceland over an expanded period of time. DESIGN: This is a retrospective observational study, including all PAs diagnosed in Iceland from 1955 to 2012. METHODS: Extensive clinical information was gathered in a database. Prevalence rates for all PA subtypes were calculated along with standardized incidence rates (SIR). Sex ratios and relationships with adenoma size, age, and symptoms were assessed. RESULTS: We identified 471 individuals: 190 men and 281 women. Total prevalence in 2012 was 115.57/100, 000, prolactinomas were most prevalent (54.37/100, 000) followed by non-functioning adenomas (NFPAs) (42.32/100 ,000). Throughout the period, NFPAs were most common (43.0%) followed by prolactinomas (39.9%) and 11.3% had acromegaly and 5.7% Cushing's disease. Women are diagnosed younger with smaller adenomas. Total SIR has increased significantly and is now 5.8/100 000 per year. CONCLUSION: In this nationwide study spanning six decades, we have confirmed PAs rising prevalence and incidence rates noted in recent studies. We demonstrated higher overall prevalence and incidence rates than ever previously recorded with an increasing predominance of NFPAs, which is not explained by incidental findings alone. There is a relationship with the introduction of imaging modalities, but the vast majority of patients are symptomatic at diagnosis. This underlines the importance of increased awareness, education, and appropriate allocation of resources for this growing group of patients.

Childhood diabetes in the Nordic countries: a comparison of quality registries.

In 2008 a Nordic collaboration was established between the quality registries in Denmark, Iceland, Norway, and Sweden to improve quality of care for children with diabetes. This study aimed to describe those registries and confirm that the registry variables are comparable. Selected variables were used to demonstrate outcome measurements. The organization of the registries and methodology are described. Cross-sectional data for patients between birth and 14.9 years with type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed. Variables were age, gender, and diabetic ketoacidosis at onset, together with age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in 2009. All 4 registries use a standardized registration at the onset of diabetes and at follow-up, conducted at the local pediatric diabetes centers. Methods for measuring HbA1c varied as did methods of registration for factors such as hypoglycemia. No differences were found between the outcomes of the clinical variables at onset. Significant variations were found at follow-up for mean HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%), (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers with severe hypoglycemia (range 5.6-8.3/100 patient years). In this large unselected population from 4 Nordic countries, a high proportion did not reach their treatment target, indicating a need to improve the quality of pediatric diabetes care. International collaboration is needed to develop and harmonize quality indicators and offers possibilities to study large geographic populations, identify problems, and share knowledge.

[A case report - Severe electrolyte disturbances in an eight week old boy]. / Sjúkratilfelli - lífshaettulegar truflanir á blódsöltum hjá átta vikna dreng.

Hyponatremia is the most common electrolyte abnormality in children and underlying causes are many. It is most often caused by excessive salt loss from the gut but is also associated with severe systemic disorders in which there is actual or apparent aldosterone deficiency, such as congenital adrenal hyperplasia (CAH), which is the most common inherited disorder of aldosterone synthesis, and pseudohypoaldosteronism (PHA). Abscent aldosterone activity also leads to hyperkalemia which is characteristic for PHA and can result in life threatening arrythmias. This is a case report about a boy presenting with life threatening electrolyte disturbances in conjunction with PHA resulting from pyelonephritis and vesicoureteral reflux.

[Childhood type 1 diabetes in Iceland; evaluation of quality of treatment]. / Insúlínhád sykursýki barna og unglinga á Islandi--mat á gaedum medferdar.

INTRODUCTION: The importance of adequate metabolic control in Type 1 DM has been repeatedly demonstrated in recent years. The care of diabetic children and adolescents in Iceland is centralized to one unit. The aim of the study was to analyze the quality of treatment and acute complications of Icelandic children with Type 1 diabetes. METHODOLOGY: The total number of diabetic children in paediatric care was 98. A cross-sectional survey was done for the period March 15th to July 14th, 2004. The results for the patient last visit to the diabetes clinic were recorded. HbA1c levels (DCA 2000) and number of severe hypoglycaemic episodes, were evaluated. RESULTS: The number of visits to the clinic during the 4 month interval were 83 (43 boys, 40 girls), mean age 13.3+/-3.78 years. Mean value of HbA1c in the cross-sectional survey was 8.16+/-1.31%. No difference in HbA1c was found between girls and boys. HbA1c increased with age in girls (p<0.01). Ten children experienced a total of 12 severe hypoglycaemic events during the period (43.4/100 patient years). CONCLUSION: Overall the metabolic control in children and adolescents with IDDM in Iceland is satisfactory compared to internationally published results. It is important to focus attention on children with inadequate metabolic control, especially adolescent girls, and children experiencing serious hypoglycaemic episodes.

Cryptorchidism: classification, prevalence and long-term consequences.

UNLABELLED: Undescended testis is a common finding in boys, and the majority of cases have no discernible aetiology. There are unexplained geographical differences and temporal trends in its prevalence. Cryptorchidism, especially bilateral, is associated with impaired spermatogenesis and endocrine function and increases the risk of testicular cancer. There is an urgent need to identify factors that adversely affect testicular development and optimize treatment. CONCLUSION: Cryptorchidism may reflect a primary testicular maldevelopment with long-term consequences.

Efficacy and safety of hormonal treatment of cryptorchidism: current state of the art.

UNLABELLED: Meta-analyses of randomised trials using hCG or GnRH for treatment on testicular descent show in most studies overall efficacy of about 20%, less if retractile testes were excluded. In recent years a number of potentially serious side effects have been reported. CONCLUSION: Considering the efficacy and the possible side effects of the hormonal treatment, the general use of hCG and GnRH in the treatment of cryptorchidism cannot be further recommended.