Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries.

BACKGROUND: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. METHODS: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. RESULTS: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from 1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. CONCLUSIONS: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects.

Newborn screening in southeastern Europe.

The aim of our study was to assess the current state of newborn screening (NBS) in the region of southeastern Europe, as an example of a developing region, focusing also on future plans. Responses were obtained from 11 countries. Phenylketonuria screening was not introduced in four of 11 countries, while congenital hypothyroidism screening was not introduced in three of them; extended NBS programs were non-existent. The primary challenges were identified. Implementation of NBS to developing countries worldwide should be considered as a priority.

Graves' disease in Albanian children.

BACKGROUND: Graves' disease (GD) accounts for 10-15% of thyroid disorders in patients less than 18 years of age. It is the most common cause of thyrotoxicosis in children and accounts for at least 95% of cases in children. Pediatric Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial. OBJECTIVE: To review treatment outcome of pediatric Graves' disease in Albania. MATERIAL AND METHOD: Descriptive review of 15 children with Graves' disease, diagnosed from Jan.2007 to Dec. 2013, at the Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Centre "Mother Teresa", Albania was performed. RESULTS: All patients, mean age 10.56 ± 3.37 years, (range 2.02-16.09 years) were presented with goiter and increased serum FT4, mean 39.80 ± 16.02 ng/mL, (range 21.0-74.70 ng/mL), serum FT3, mean 12.98 ± 3.45 pg/mL, (range 6.90 -17.90 pg/mL) and suppressed TSH levels, mean 0.02 ± 0.01 mUI/L, (range 0.01-0.05 mUI/L). Anti TSH Receptor were positive in 100% of patients mean value 6.51 ± 3.61 UI/mL (range 1.63 - 14.10 UI/mL). Anti-thyroglobulin and Anti-TPO antibodies were positive in 60% and 46.6% respectively. Clinical course of 15 patients after treatment with anti-thyroid drugs mainly MMI for 3.19 ± 1.48 (range 0.60 - 6.20) years is as follows: seven (46.66%) underwent remission, five out of seven (71.41%) who underwent remission, relapsed. Three of them (20%) were treated with I(131), and two (13.3%) underwent to total thyroidectomy. CONCLUSION: MMI was the most common first line therapy in the presented patients with Graves' disease. Remission rate was 46.66% after an average 1.48 ± 0.71 years (range 0.60 - 2.70 years) of treatment with anti-thyroid drugs. Remission period was 2.70 ± 0.36 years (2.1 - 3.1 years) Relapse occurred in 71.41% of patient. I(131) and thyroidectomy were used as second line therapy in the present study.

Iodine treatment in children with subclinical hypothyroidism due to chronic iodine deficiency decreases thyrotropin and C-peptide concentrations and improves the lipid profile.

BACKGROUND: Chronic iodine deficiency (ID) increases thyrotropin (TSH) concentrations and produces a thyroid hormone pattern consistent with subclinical hypothyroidism (ScH). ScH may be associated with cardiovascular disease risk factors. Thus, the study aim was to determine if iodine treatment of children with elevated TSH concentrations due to ID would affect their lipid profile, insulin (C-peptide) levels, and/or subclinical inflammation. METHODS: In controlled intervention trials of oral iodized oil or iodized salt, 5-14-year-old children from Morocco, Albania, and South Africa with TSH concentrations > or = 2.5 mU/L (n = 262) received 400 mg iodine as oral iodized oil or household distribution of iodized salt containing 25 microg iodine/g salt. At baseline and after 5 or 6 months, urinary iodine (UI) and blood concentrations of total thyroxine, TSH, C-reactive protein (CRP), C-peptide, and lipids were measured. RESULTS: Median (range) UI at baseline was 46 (2-601) microg/L. Compared to the control group, iodine treatment significantly increased UI and total thyroxine and decreased TSH, C-peptide, and total and low-density lipoprotein cholesterol. The mean low-density lipoprotein/high-density lipoprotein cholesterol ratio fell from 3.3 to 2.4 after iodine treatment (p < 0.001). Iodine treatment had no significant effect on concentrations of high-density lipoprotein cholesterol, triglycerides, or C-reactive protein. CONCLUSIONS: Correction of ID-associated ScH improves the insulin and lipid profile and may thereby reduce risk for cardiovascular disease. This previously unrecognized benefit of iodine prophylaxis may be important because ID remains common in rapidly developing countries with increasing rates of obesity and cardiovascular disease.

Treatment of iodine deficiency in school-age children increases insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations and improves somatic growth.

CONTEXT: Iodine deficiency in utero impairs fetal growth, but the relationship between iodine deficiency and postnatal growth is less clear. OBJECTIVE: The objective of the study was to determine whether iodine repletion improves somatic growth in iodine-deficient children and investigate the role of IGF-I and IGF binding protein (IGFBP)-3 in this effect. DESIGN, PARTICIPANTS, AND INTERVENTIONS: Three prospective, double-blind intervention studies were done: 1) in a 10-month study, severely iodine-deficient, 7- to 10-yr-old Moroccan children (n = 71) were provided iodized salt and compared with children not using iodized salt; 2) in a 6-month study, moderately iodine-deficient, 10- to 12-yr-old Albanian children (n = 310) were given 400 mg iodine as oral iodized oil or placebo; 3) in a 6-month study, mildly iodine-deficient 5- to 14-yr-old South African children (n = 188) were given two doses of 200 mg iodine as oral iodized oil or placebo. At baseline and follow-up, height, weight, urinary iodine (UI), total T4 (TT4), TSH, and IGF-I were measured; in Albania and South Africa, IGFBP-3 was also measured. RESULTS: In all three studies, iodine treatment increased median UI to more than 100 microg/liter, whereas median UI in the controls remained unchanged. In South Africa, iodine repletion modestly increased IGF-I but did not have a significant effect on IGFBP-3, TT4, or growth. In Albania and Morocco, iodine repletion significantly increased TT4, IGF-I, IGFBP-3, weight-for-age z scores, and height-for-age z scores. CONCLUSION: This is the first controlled study to clearly demonstrate that iodine repletion in school-age children increases IGF-I and IGFBP-3 concentrations and improves somatic growth.

Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study.

BACKGROUND: Iodine is required for the production of thyroid hormones, which are necessary for normal brain development and cognition. Although several randomized trials examined the effect of iodine supplementation on cognitive performance in schoolchildren, the results were equivocal. OBJECTIVE: We aimed to ascertain whether providing iodized oil to iodine-deficient children would affect their cognitive and motor performance. DESIGN: In a double-blind intervention trial, 10-12-y-old children (n = 310) in primary schools in rural southeastern Albania were randomly assigned to receive 400 mg I (as oral iodized oil) or placebo. We measured urinary iodine (UI), thyroid-stimulating hormone (TSH), and total thyroxine (TT4) concentrations and thyroid gland volume (by ultrasound). The children were given a battery of 7 cognitive and motor tests, which included measures of information processing, working memory, visual problem solving, visual search, and fine motor skills. Thyroid ultrasound and the biochemical and psychological tests were repeated after 24 wk. RESULTS: At baseline, the children's median UI concentration was 43 microg/L; 87% were goitrous, and nearly one-third had low concentrations of circulating TT4. Treatment with iodine markedly improved iodine and thyroid status: at 24 wk, median UI in the treated group was 172 microg/L, mean TT4 was approximately 40% higher, and the prevalence of hypothyroxinemia was < 1%. In the placebo group after the intervention, these variables did not differ significantly from baseline. Compared with placebo, iodine treatment significantly improved performance on 4 of 7 tests: rapid target marking, symbol search, rapid object naming, and Raven's Coloured Progressive Matrices (P < 0.0001). CONCLUSION: Information processing, fine motor skills, and visual problem solving are improved by iodine repletion in moderately iodine-deficient schoolchildren.

Severe iodine deficiency in southern Albania.

Albania does not yet have a national program for control of iodine deficiency and there are no recent data on the severity of the iodine deficiency disorders (IDD) in the country. The aim of the present study was to assess current IDD status in southern Albania. In primary school children in urban and rural areas urinary iodine concentration (UI) and iodine concentration in salt at retail and household levels was measured. Goiter was graded by palpation and thyroid volume determined by ultrasound. Children aged 5-14 yr (n = 826) were sampled at 2 urban and 5 rural primary schools. In the 2 urban schools, the median UI was 45 micrograms/L, the goiter prevalence was 32%, and salt iodine levels were inadequate (< 15 micrograms/g) in 78% of household salt samples. In the rural schools, the median UI was 17 micrograms/L, the goiter prevalence was 95%, and no household salt samples were adequately iodized. Among children in the rural schools, 73% had grade 2 goiter and 20% had nodular changes detected by thyroid ultrasound. In southern Albania, school children in urban areas are moderately iodine deficient and those in rural villages are severely iodine deficient. These findings suggest that regional distribution of oral iodized oil capsules is indicated to control IDD in vulnerable groups until salt iodization is implemented.