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.

The effect of subclinical hypothyroidism on body composition parameters in children.

BACKGROUND: It's known that overt hypothyroidism increases body fat content and weight. There's limited research about the effect of subclinical hypothyroidism (SH) on body composition in children and the effect of LT4 treatment. We aimed to evaluate body composition parameters in healthy subjects and in children with mild SH (MSH) and determine the effect of LT4 treatment. METHODS: Sixty-four healthy children and 32 children with MSH were included. Anthropometric measurements and hormonal parameters were evaluated. Body composition was evaluated using bioelectric impedance analysis (BIA). Patients were put on LT4 treatment. BIA was performed again after 12 months of therapy. RESULTS: There was no significant difference between the anthropometric parameters and basal metabolic rate of the healthy children and the MSH group. The percentage of trunk muscle mass (TMM) in the MSH group was lower than in the control group (P < .05). After 12 months of LT4 treatment, the percentage of total fat-free mass (FFM), TMM and trunk fat-free mass (TFFM) were increased and percentage of total body fat mass and trunk fat mass were decreased (P < .05). The difference between the percentage of TMM in the MSH group and control group was insignificant after LT4 treatment (P > .05). CONCLUSIONS: The percentage of TMM in children with MSH was found lower than healthy control group. After LT4 treatment, the percentage of the FFM, TMM and TFFM were increased and the difference between percentage of TMM in children with MSH and healthy controls was insignificant. Our data indicated that MSH might be associated with early changes in body composition parameters.

Novel Mutations in Obesity-related Genes in Turkish Children with Non-syndromic Early Onset Severe Obesity: A Multicentre Study

Objective: Non syndromic monogenic obesity is a rare cause of early onset severe obesity in the childhood period. This form may not be distinguishable from other forms of severe obesity without genetic analysis, particularly if patients do not exibit any physical abnormalities or developmental delay. The aim of this study was to screen 41 different obesity-related genes in children with non-syndromic early onset severe obesity. Methods: Children with severe (body mass index-standard deviation score >3) and early onset (<7 years) obesity were screened by next-generation sequencing based, targeted DNA custom panel for 41 known-obesity-related genes and the results were confirmed by Sanger technique. Results: Six novel variants were identified in five candidate genes in seven out of 105 children with severe obesity; two in SIM1 (p.W306C and p.Q36X), one in POMC (p.Y160H), one in PCSK1 (p.W130G fs Ter8), two in MC4R (p.D126E) and one in LEPR (p.Q4H). Additionally, two previously known variations in MC4R were identified in four patients (p.R165W in three, and p.V166I in one). Conclusion: We identified six novel and four previously described variants in six obesity-related genes in 11 out of 105 childrens with early onset severe obesity. The prevalence of monogenic obesity was 10.4% in our cohort.

Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey

Objective: We aimed to report the characteristics at admission, diagnosis, treatment, and follow-up of cases of pediatric hyperprolactinemia in a large multicenter study. Methods: We reviewed the records of 233 hyperprolactinemic patients, under 18 years of age, who were followed by different centers. The patients were divided as having microadenomas, macroadenomas, drug-induced hyperprolactinemia and idiopathic hyperprolactinemia. Complaints of the patients, their mode of treatment (medication and/or surgery) and outcomes were evaluated in detail. Results: The mean age of the patients with hyperprolactinemia was 14.5 years, and 88.4% were females. In terms of etiology, microadenomas were observed in 32.6%, macroadenomas in 27%, idiopathic hyperprolactinemia in 22.7% and drug-induced hyperprolactinemia in 6.4%. Other causes of hyperprolactinemia were defined in 11.3%. Common complaints in females (n=206) were sorted into menstrual irregularities, headaches, galactorrhea, primary or secondary amenorrhea and weight gain, whereas headache, gynecomastia, short stature and blurred vision were common in males (n=27). Median prolactin levels were 93.15 ng/mL, 241.8 ng/mL, 74.5 ng/mL, 93.2 ng/mL, and 69 ng/mL for microadenomas, macroadenomas, idiopathic hyperprolactinemia, drug-induced hyperprolactinemia, and other causes of hyperprolactinemia, respectively. Of 172 patients with hyperprolactinemia, 77.3% were treated with cabergoline and 13.4% with bromocriptine. 20.1% of the patients with pituitary adenomas underwent pituitary surgery. Conclusion: We present the largest cohort of children and adolescents with hyperprolactinemia in the literature to date. Hyperprolactinemia is more common in females and cabergoline is highly effective and practical to use in adolescents, due to its biweekly dosing. Indications for surgery in pediatric cases need to be revised.

Comparison of Treatment Regimens in Management of Severe Hypercalcemia Due to Vitamin D Intoxication in Children

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (rs=0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

Intracranial Lesions in Children and Adolescents with Morbid Obesity.

BACKGROUND: Intracranial lesions may affect the hypothalamo-hypophyseal axis and lead to some neuro-endocrinological dysfunctions (hyperphagia, sleep disorders and hormonal dysfunctions). There is a very limited number of studies about childhood obesity and intracranial lesions. AIMS: To evaluate the incidence of intracranial lesions and its role in clinical symptoms and aetiology in cases with morbid obesity who have been admitted to the paediatric endocrinology department with this complaint. STUDY DESIGN: Cross-sectional study. METHODS: A total of 120 cases admitted to the paediatric endocrinology department with the complaint of morbid obesity between 2002 and 2015 were included in this study. A detailed history was taken and a physical examination was performed; biochemical, hormonal parameters were evaluated. Contrast dynamic magnetic resonance imaging was performed in order to visualize cranial pathologies. RESULTS: An intracranial lesions was detected in 16.6% of the patients and 55% of these lesions were adenoma of the hypophysis. Prolactin levels were increased in six patients but front hypophyseal hormone levels were within normal range in the rest of the patients. Growth velocity of the patients was not affected. CONCLUSION: In our study, the incidence of intracranial lesions in children and adolescents with morbid obesity was much higher than in the normal population. According to this data, we are of the opinion that contrast dynamic magnetic resonance imaging is helpful in children with morbid obesity for the early detection of the mass before it causes any clinical or neurological symptoms and in the prevention of future complications.

Psychopathology and its effect on treatment compliance in pediatric obesity patients.

Obesity is a common health problem in children and adolescents and has life-threatening physical complications as well as psychological consequences, including negative self-image, low self-esteem and social difficulties. Psychiatric disorders, especially depression and anxiety disorders, are present at higher rates in obese patients. The aim of this study was to investigate the presence and type of psychopathology in a group of obese children and to determine the effect of comorbid psychiatric disorders on treatment compliance. Fifty-four obese patients were evaluated by clinical interviews as well as Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version (KIDI-SADS-PL) for psychiatric diagnosis. Fifty percent of the sample was found to have psychopathology and treatment compliance was found to be poor in the group with comorbid psychiatric disorders. This shows that child and adolescent psychiatrists should be included as team members while treating pediatric obese patients.

Spondyloepiphyseal dysplasia tarda with progressive arthropathy.

Spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) is a rare autosomal recessive skeletal dysplasia affecting primarily the articular cartilage. Here we present a nine-year-old girl from Middle Anatolia (Sivas) with SEDT-PA. Her complaints were pain and progressive deformity of the joints. She had a short stature with increased thoracic kyphosis and lumbar lordosis. The range of motion was limited in the spine and the peripheral joints and she had deformities. Radiologic examination revealed generalized platyspondyly and irregularity of the vertebral endplates. There was minimal joint space narrowing at proximal interphalangeal joints, but there were no bone erosions. Metaphyses were widened and epiphyses were squared in other joints with generalized osteopenia and severe osteoarthritic changes prominent in hips. Laboratory examination revealed a mild increase in acute phase reactants. Genetic disorders like SEDT-PA may also have rheumatological involvement, so they should be kept in mind in differential diagnosis of inflammatory joint diseases.