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Free access

Feyza Darendeliler, Sukran Poyrazoglu, Firdevs Bas, Ozlem Sancakli, and Gulbin Gokcay

Background

Ghrelin is the natural ligand of GH secretagogue receptor. It has several metabolic functions including regulation of food intake, energy homeostasis, and body weight. An inverse relationship between fasting plasma ghrelin and insulin concentrations has been shown. Being born large for gestational age (LGA) has an increased risk of developing insulin resistance.

Objective

The aim of this study was to evaluate ghrelin levels in LGA born children who have no obesity at prepubertal ages and the effect of intrauterine and postnatal growth on ghrelin levels.

Patients and methods

Thirty-two (17F, 15M) LGA born non-obese children (mean (±s.e.m.) age 4.4±0.3 years) were evaluated with respect to glucose, insulin, and ghrelin levels. Their data were compared with that of non-obese 45 (19F, 26M) appropriate for gestational age (AGA) children (mean (±s.e.m.) age 4.0±0.1 years).

Results

LGA children, who had similar age and body mass index (BMI) standard deviation score (SDS) as AGA children, had significantly higher insulin (P=0.044) and at a borderline significance higher homeostasis model assessment-insulin resistance levels (P=0.054) than AGA children. Ghrelin level was significantly lower in LGA born than AGA born children (P=0.001) even after controlling for age, sex, and BMI (P=0.006). There were no differences between genders in insulin and ghrelin levels. Multivariate analysis revealed that birth weight was the only significant parameter influencing ghrelin levels (R 2=0.13, B=−0.007, P=0.002).

Conclusions

LGA born non-obese prepubertal children have lower ghrelin levels when compared with age and BMI matched AGA children. Birth weight seems to have the only significant effect on the reduced ghrelin levels.

Free access

Feyza Darendeliler, Firdevs Bas, Ruveyde Bundak, Asuman Coban, Rian Disci, Ozlem Sancakli, Gulbin Gokcay, Zeynep Ince, and Gulay Can

Background

Ghrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effect. Ghrelin levels are negatively associated with insulin secretion, increased in anorexia, and reduced in obesity. Increased ghrelin levels may be associated with early postnatal growth in preterm born children.

Objective

Aim of this study was to evaluate ghrelin and insulin levels at prepubertal ages in preterm born children born appropriate for gestational age (AGA) or small for gestational age (SGA) and relationships with catch-up growth (CUG) in a prospective cross-sectional study.

Methods

Eighty-four preterm born children grouped as preterm SGA (n=28) and preterm AGA (n=56) were evaluated at age 4.7±0.2 and 4.7±0.1 years with respect to their ghrelin and insulin levels. Their data were compared with that of body mass index matched term SGA (n=35) and term AGA (n=44) children of age 4.6±0.2 and 3.8±0.1 years. All children had height appropriate for their target height. CUG was defined as the difference between birth size and recent size and expressed as Δ height and Δ weight SDS.

Results

Preterm SGA and preterm AGA children had similar ghrelin levels (1717.0±166.9 and 1656.5±103.8 pg/ml), although Δ height and Δ weight SDS in preterm SGA were significantly higher than in preterm AGA children (P<0.001). Ghrelin levels in both preterm groups were higher than term SGA (469.2±132.5 pg/ml) and term AGA children (659.6±143.3 pg/ml; P<0.001 for all). Δ Height and Δ weight SDS of the term SGA children were similar to that of preterm SGA children. Ghrelin did not have correlation with CUG but had inverse correlation with recent anthropometric indices. Insulin was significantly higher in term SGA children than other groups (P<0.001).

Conclusions

Preterm children have higher ghrelin levels at prepubertal ages regardless of the magnitude of their CUG. Term SGA children, on the other hand, behave differently and have lower ghrelin levels than preterm children at prepubertal ages, which may be related to elevated insulin levels in this group.

Open access

Irina Bacila, Nicole Freeman, Eleni Daniel, Marija Sandrk, Jillian Bryce, Salma Rashid Ali, Zehra Yavas Abali, Navoda Atapattu, Tania A Bachega, Antonio Balsamo, Niels Birkebæk, Oliver Blankenstein, Walter Bonfig, Martine Cools, Eduardo Correa Costa, Feyza Darendeliler, Silvia Einaudi, Heba Hassan Elsedfy, Martijn Finken, Evelien Gevers, Hedi L Claahsen-van der Grinten, Tulay Guran, Ayla Güven, Sabine E Hannema, Claire E Higham, Violeta Iotova, Hetty J van der Kamp, Marta Korbonits, Ruth E Krone, Corina Lichiardopol, Andrea Luczay, Berenice Bilharinho Mendonca, Tatjana Milenkovic, Mirela C Miranda, Klaus Mohnike, Uta Neumann, Rita Ortolano, Sukran Poyrazoglu, Ajay Thankamony, Jeremy W Tomlinson, Ana Vieites, Liat de Vries, S Faisal Ahmed, Richard J Ross, and Nils P Krone

Objective

Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH.

Design

This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry.

Methods

Data were collected from 461 patients aged 0–18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were analyzed from 4174 patient visits.

Results

The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0–14.5) mg/m2/day at age 1–8 years and the highest dose of 14.0 (11.6–17.4) mg/m2/day at age 12–18 years. Glucocorticoid doses decreased after 2010 in patients 0–8 years (P < 0.001) and remained unchanged in patients aged 8–18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement.

Conclusions

Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.

Open access

Angela K Lucas-Herald, Jillian Bryce, Andreas Kyriakou, Marie Lindhardt Ljubicic, Wiebke Arlt, Laura Audi, Antonio Balsamo, Federico Baronio, Silvano Bertelloni, Markus Bettendorf, Antonia Brooke, Hedi L Claahsen van der Grinten, Justin H Davies, Gloria Hermann, Liat de Vries, Ieuan A Hughes, Rieko Tadokoro-Cuccaro, Feyza Darendeliler, Sukran Poyrazoglu, Mona Ellaithi, Olcay Evliyaoglu, Simone Fica, Lavinia Nedelea, Aneta Gawlik, Evgenia Globa, Nataliya Zelinska, Tulay Guran, Ayla Güven, Sabine E Hannema, Olaf Hiort, Paul-Martin Holterhus, Violeta Iotova, Vilhelm Mladenov, Vandana Jain, Rajni Sharma, Farida Jennane, Colin Johnston, Gil Guerra Junior, Daniel Konrad, Odile Gaisl, Nils Krone, Ruth Krone, Katherine Lachlan, Dejun Li, Corina Lichiardopol, Lidka Lisa, Renata Markosyan, Inas Mazen, Klaus Mohnike, Marek Niedziela, Anna Nordenstrom, Rodolfo Rey, Mars Skaeil, Lloyd J W Tack, Jeremy Tomlinson, Naomi Weintrob, Martine Cools, and S Faisal Ahmed

Objectives

To determine trends in clinical practice for individuals with DSD requiring gonadectomy.

Design

Retrospective cohort study.

Methods

Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019.

Results

Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries.

Conclusions

The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.