Clinical characteristics and growth hormone treatment in patients with prader-willi syndrome

Objective: To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey. Methods: The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated. Results: The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged. Conclusion: The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start. Keywords: Prader-Willi syndrome, endocrine dysfunction, growth hormone treatment, body compositio

Çocuk ve adolesanlarda tiroid nodüllerinin değerlendirilmesi: Türkiye'de çok merkezli çalışma

Introduction: Ultrasonography and fine needle aspiration biopsy are reliable diagnostic methods used to predict malignancy in thyroid nodules. They are useful in identifying patients for therapy or preventing unnecessary surgery. Materials and Methods: The aim of this study was to compare clinical and ultrasonographic findings with fine needle aspiration biopsy and histopathological examination results in children with thyroid nodules. Retrospective study. This multicentre study included pediatric patients with thyroid nodules, followed up between July 2002 and November 2019 in nine Turkish Pediatric Endocrinology Units. Clinical, ultrasonographic, cytological and histopathological findings (malignant or benign) were analyzed retrospectively. Fine needle aspiration biopsy findings were classified according to American Thyroid Association criteria. Results: A total of 203 children were included, of whom 82.3% (n=167) were female. Mean±standard deviation age was 14.06±2.26 (range 3.7-19) years. Cytological diagnoses were: non–diagnostic or unsatisfactory 1.9%; benign 59.6%; atypia or follicular lesion of undetermined significance, suspicious for follicular neoplasm in 2.4%; suspicious for malignancy 12.8%; and malignant in 1.9%. Surgery was performed in 59 (29.1%) patients. In total 33 (16.3%) patients were diagnosed with malignancy. In patients with benign fine needle aspiration biopsy results, malignancy was detected in 17.6% when they underwent surgery. Malignancy was present in 44.4% of the patients with cytologically determined atypia or follicular lesion of undetermined significance. The diagnostic accuracy of fine needle aspiration biopsy was 79%. Conclusion: This study is first multicentre study investigating thyroid nodules in children and adolescents in Turkey. In this population fine needle aspiration biopsy has an important role in diagnosis, but ultrasonographic features of nodule should also be taken into consideration. Atypia or follicular lesion of undetermined significance may be of greater clinical significance than has previously been reported.Giriş: Ultrasonografi ve ince iğne aspirasyon biyopsisi, tiroid nodüllerinde maligniteyi öngörmede kullanılan güvenilir tanı yöntemleridir. Doğru hastayı bulmada ve gereksiz ameliyatları önlemede faydalıdırlar. Bu çalışmanın amacı tiroid nodülü bulunan çocuklarda ince iğne aspirasyon biyopsisi ile klinik, ultrasonografik bulgular ve histopatolojik inceleme sonuçlarını karşılaştırmaktır. Gereç ve Yöntem: Bu çok merkezli çalışmada, Türkiye’den 9 farklı Pediatrik Endokrinoloji Ünitesinde Temmuz 2002-Kasım 2019 tarihleri arasında takip edilen tiroid nodüllü hastaların verileri incelendi. Tiroid nodüllü çocuk hastaların klinik, ultrasonografik, sitolojik ve histopatolojik bulguları (malign veya benign) retrospektif olarak incelendi. İnce iğne aspirasyon biyopsisi ile takip edilen hastaların bulguları Amerikan Tiroid Birliği’ne göre sınıflandırıldı. Bulgular: Çalışmaya toplam 203 çocuk dahil edildi, hastaların %82,3’ü (n=167) kadındı. Hastaların ortalama yaşı 14,06±2,26 yıl (dağılım 3,7-19 yıl) idi. Hastaların sitolojik tanıları şu şekildeydi: %1,9’u tanı dışı veya yetersiz, %59,6’sı benign, önemi belirsiz atipi veya foliküler lezyon, %2,4’ü foliküler neoplazm şüpheli, %12,8’i malignite şüphesi, %1,9’u malign idi. 59 hastaya cerrahi uygulandı. Otuz üç hastaya malignite tanısı konuldu. Benign ince iğne aspirasyon biyopsisi sonucu olan hastaların %17,6’sında ameliyat olduklarında malignite saptandı. Önemi belirlenemeyen sitolojiye sahip atipi veya foliküler lezyonu olan hastaların %44,4’ünde malignite mevcuttu. İnce iğne aspirasyon biyopsisinin tanısal doğruluğu %79 idi. Sonuç: Bu çalışma, Türkiye’de çocuk ve ergenlerde tiroid nodüllerini araştıran ilk çok merkezli çalışmadır. Tiroid nodülü olan çocuklarda ince iğne aspirasyon biyopsisi tanıda önemli bir yere sahiptir ancak nodülün ultrasonografik özellikleri de dikkate alınmalıdır. Atipi veya önemi belirsiz foliküler lezyon bilinenden daha önemli olabilir

The association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness in children with obesity: a cross-sectional study

Objectives: We aimed to evaluate the association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness (CIMT) among children with obesity in whom vitamin deficiencies are more frequent. Methods: Herein, 100 children with obesity (58 girls) were included (age, 5-18 years). Height, weight, body mass index (BMI), waist circumference (WC), puberty stage, blood pressure, and biochemical values were collected from medical records; standard deviations (SDS) and percentiles were calculated. Obesity was defined as BMI SDS of >+2SDS. Vitamin B12 and folate levels of <300 pg/mL and <4.8 ng/mL, respectively, were considered deficient. A radiologist quantified measurements from the carotid artery. Results: Mean patient age was 12.52 ± 3.63 years. The mean weight SDS, BMI SDS, and WC/height were +3.37 ± 0.93, +2.93 ± 0.55, and 0.65 ± 0.05, respectively. In pubertal cases, insulin (p<0.001), the homeostatic model assessment for insulin resistance (HOMA-IR) (p=0.001) and homocysteine (p=0.002) levels were higher; vitamin B12 (p<0.001) and folate (p<0.001) levels were lower than those in prepubertal ones. WC and HOMA-IR correlated with CIMT; however, homocysteine levels were not correlated with CIMT. Conclusions: In our study, pubertal cases had lower vitamin B12 and folate levels as well as higher homocysteine levels. Although no correlation was identified between homocysteine levels and CIMT, this condition may be related to our study group comprising children, who had a shorter duration of obesity than those in adults. As CIMT was higher in children/adolescents with increased WC, it is proposed that they need central obesity more frequently and carefully follow-up. © 2022 Walter de Gruyter GmbH, Berlin/Boston

Vitamin D Deficiency and Hashimoto’s Thyroiditis in Children and Adolescents: a Critical Vitamin D Level for This Association?

OBJECTIVE: Vitamin D has been suggested to be active as an immunomodulator in autoimmune diseases such as Hashimoto’s thyroiditis (HT). The goal of the present study was to investigate the vitamin D status in HT patients. METHODS: This prevalence case-control study was conducted on 90 patients with HT (of ages 12.32±2.87 years) and 79 age-matched healthy controls (11.85±2.28 years). Serum 25-hydroxyvitamin D3 [25(OH)D3] levels were measured in all 169 subjects. RESULTS: The prevalence of vitamin D deficiency in HT patients (64 of 90; 71.1%) was significantly higher than that in the control group (41 of 79; 51.9%) (p=0.025). Mean serum 25(OH)D3 level in the HT group was significantly lower compared to the control group (16.67±11.65 vs. 20.99±9.86 ng/mL, p=0.001). HT was observed 2.28 times more frequently in individuals with 25(OH)D3 levels <20 ng/mL (OR: 2.28, CI: 1.21-4.3). CONCLUSION: Vitamin D deficiency is associated with HT in children and adolescents. Levels lower than 20 ng/mL seem to be critical. The mechanism for this association is not clear

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population

Vitamin D-dependent rickets type 1A (VDDR-1A) (Online Mendelian Inheritance in Man #264700) is a rare, autosomal recessively inherited disorder due to inactivating mutations in CYP27B1. It is characterized by early onset of rickets with hypocalcemia. We aimed to describe the clinical and laboratory findings in a VDDR-1A case and to report a novel homozygote truncating mutation NM_000785.3 c.403C>T (p.Q135*) in CYP27B1 which to our knowledge is the first described mutation in the Uzbek population. The patient was admitted with tetany at the age of 12 months. He was a healthy Uzbek boy until 9 months of age when he had a seizure due to hypocalcemia. Vitamin D treatment was given orally in Turkmenistan (no data available for dose and duration). The patient was the product of a consanguineous marriage. His brother had died with hypocalcemia and pneumonia. At physical examination, anthropometric measurements were within normal limits; he had caput quadratum, enlarged wrists, and carpopedal spasm. Blood calcium, phosphorus, alkaline phosphatase, and parathormone (PTH) levels were 5.9 mg/dL, 3.5 mg/dL, 987 IU/L, and 182.8 pg/mL (12-72), respectively. Radiological findings included cupping and fraying of the radial and ulnar metaphyses. Renal ultrasound revealed nephrocalcinosis (grade 1). Despite high serum PTH and 25-hydroxyvitamin D3 levels, 1,25-dihydroxyvitamin D3 level was low, suggesting a diagnosis of VDDR-1A. The patient was treated with calcium carbonate and calcitriol. DNA sequencing revealed a novel homozygous mutation of NM_000785.3 c.403C>T (p.Q135*) in CYP27B1. VDDR-1A is a rare disorder which needs to be considered even in countries where nutritional vitamin D deficiency is still common

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome

Objective: To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey. Methods: The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated. Results: The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7 +/- 2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged. Conclusion: The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.WOS:0006880797000082-s2.0-85113322532PubMed: 3356575