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Restricted access

Correlations between bone mineral density, insulin-like growth factor I and auxological variables

Maria N Moreira-Andrés, Karen Papapietro, Francisco J Cañizo, Javier Rejas, Luisa Larrodera, and Federico G Hawkins

Moreira-Andrés MN, Papapietro K, Cañizo FJ, Rejas J, Larrodera L, Hawkins FG. Correlations between bone mineral density, insulin-like growth factor I and auxological variables. Eur J Endocrinol 1995; 132:573–9. ISSN 0804–4643

Recent studies have shown growth-related changes in spinal bone mineral density (BMD) in children; however, there is less information available on the relationship between BMD and insulin-like growth factor I (IGF-I). The aim of this study was to relate the BMD of the spine and radius with serum IGF-I levels and auxological variables in normally growing children. We used dual X-ray absorptiometry to measure the BMD in the lumbar spine (L1–L4) and distal radius of 121 children (69 boys, 52 girls) aged 3–18 years whose growth velocity was normal. Lumbar and radial BMD increased with age (p < 0.001) and puberty (p < 0.001) and was highly correlated to age, weight, height, body surface and bone age (r = 0.70–0.89 and p < 0.001 for all variables). Partial correlation, with age held constant, was weaker but still significant for most auxological variables. Serum IGF-I concentrations increased slowly during childhood and markedly during early stages of puberty, and correlated with lumbar and radial BMD (r = 0.55 and 0.45, respectively; p < 0.001) and with the auxological variables (p < 0.001). When age was held constant, IGF-I levels still correlated significantly with the auxological variables and with BMD, except in the case of radial BMD in boys. By multiple regression analysis IGF-I, unlike auxological variables, did not reach significance in the ability to predict BMD. Therefore, in healthy children, serum IGF-I levels show a weaker relationship to BMD than do auxological variables.

MN Moreira-Andrés, Servicio de Endocrinología, Hospital 12 de Octubre, Carretera de Andalucia km. 5,4, 28041 Madrid, Spain

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Decreased growth hormone response to growth hormone-releasing hormone in Turner's syndrome: Relation to body weight and adiposity

Jean-Claude Reiter, Margareta Craen, and Guy Van Vliet

Abstract.

A decreased growth hormone response to various secretagogues has been described in Turner's syndrome, but the mechanisms responsible for this decrease are unknown. Seventeen prepubertal girls with Turner's syndrome (age 6.4 to 15.7 years; height −0.2 to −5.4 sd, bone age −3.7 to −0.3 sd; weight 93 to 169% of ideal body weight) underwent a stimulation test with GHRH (0.5 μg/kg). Plasma GH and prolactin were measured by radioimmunoassay from −30 to +120 min and insulin-like growth factor-I at time 0. These values were compared with those observed in lean children with constitutional short stature. Peak plasma GH after GHRH was 17.0±3.6 μg/l (mean±sem), significantly lower (p<0.001) than in the short lean children (39.2±5.1 μg/l. In Turner's syndrome patients, the peak GH value was negatively correlated with the percentage of ideal body weight (r=−0.58, p<0.02) and of body fat (r=−0.59, p<0.02). Plasma prolactin levels in Turner's syndrome did not rise after GHRH and showed a normal circadian variation, from 8.0±1.0 μg/l at 08.30 h to 5.0±0.7 μg/l at 11.00 h (mean ±sem). Mean (±sem) baseline plasma insulin-like growth factor-I concentrations was 0.88±0.14 kU/l, higher than in the short lean children (0.49±0.08 kU/l, p<0.05). We conclude that the decreased GH response to GHRH of girls with Turner's syndrome is related, at least in part, to their excess body weight and fat and is associated with higher IGF-I levels than in short lean children.

Free access

Foetal testosterone and the child systemizing quotient

Bonnie Auyeung, Simon Baron-Cohen, Emma Chapman, Rebecca Knickmeyer, Kevin Taylor, and Gerald Hackett

This study examines foetal testosterone (fT) levels (measured in amniotic fluid) as a candidate biological factor, influencing sex differences in systemizing. Systemizing is a cognitive process, defined as the drive to analyze or construct systems. A recent model of psychological sex differences suggests that this is a major dimension in which the sexes differ, with males being more drawn to systemize than females. Participants included 204 children (93 female), age 6–9 years, taking part in a long-term study on the effects of fT. The systemizing quotient – children’s version was administered to these mothers to answer on behalf of their child. Males (mean = 27.79 ± 7.64) scored significantly higher than females (mean = 22.59 ± 7.53), confirming that boys systemize to a greater extent than girls. Stepwise regression analysis revealed that fT was the only significant predictor of systemizing preference when the sexes were examined together. Sex was not included in the final regression model, suggesting that fT levels play a greater role than the child’s sex in terms of differences in systemizing preference. This study suggests that the levels of fT are a biological factor influencing cognitive sex differences and lends support to the empathizing–systemizing theory of sex differences.

Free access

Circulating ghrelin levels in girls with central precocious puberty are reduced during treatment with LHRH analog

Claudio Maffeis, Roberto Franceschi, Paolo Moghetti, Marta Camilot, Silvana Lauriola, and Luciano Tatò

Decreased levels of ghrelin have been measured in growing children during puberty. No data are available for girls with central precocious puberty (CPP).

Aims: To explore ghrelin changes before, during, and after GnRH analog treatment in girls with CPP.

Subjects and methods: A sample of 20 Caucasian girls (8.08 ± 0.65 years of age) with CPP was recruited. Height and weight, bone age, LH, FSH, 17β estradiol (E2), and ghrelin were measured before starting treatment with GnRH analog, 18 months after therapy began and again 6 months after therapy discontinuation.

Results: LH and E2 serum levels decreased significantly during treatment (2.45 ± 2.03 vs 0.67 ± 0.49 UI/l, P < 0.01 and 28.17 ± 9.7 vs 15 pmol/l, P < 0.01 respectively), returning to baseline levels after the discontinuation of therapy (4.75 ± 1.66 UI/l and 29.23 ± 6.99 pmol/l respectively). LH peaked following LHRH stimulation significantly (P < 0.01) decreased during treatment (24.45 ± 14.17 vs 1.3 ± 0.18 UI/l) and then increased after therapy discontinuation (12.58 ± 6.09, P < 0.01). Ghrelin decreased significantly (P < 0.05) during treatment (1849 ± 322 vs 1207 ± 637 pg/ml), and increased, though not significantly (P = 0.09) after therapy withdrawal (1567 ± 629 pg/ml).

Conclusions: Contrary to what is expected in physiologic puberty, where ghrelin is progressively reduced, the prepubertal hormone milieau induced by GnRHa treatment in patients suffering from central precocious puberty (CPP) did not promote an increase in ghrelin circulating levels. Therefore, in CPP, ghrelin secretion seems to be independent from pubertal development per se. Concomitant estrogen suppression during treatment may play a potential role in the regulation of ghrelin secretion in these girls.

Open access

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline

A Nordenström, S F Ahmed, E van den Akker, J Blair, M Bonomi, C Brachet, L H A Broersen, H L Claahsen-van der Grinten, A B Dessens, A Gawlik, C H Gravholt, A Juul, C Krausz, T Raivio, A Smyth, P Touraine, D Vitali, and O M Dekkers

An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualised but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with sex development disorders or congenital pituitary deficiencies. The transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.

Restricted access

Spatiotemporal variation of childhood hyperthyroidism: a 10-year nationwide study

Joëlle Le Moal, Julie Chesneau, Sarah Goria, Priscilla Boizeau, Jérémie Haigneré, Florentia Kaguelidou, and Juliane Léger

Objective

Childhood hyperthyroidism is mostly caused by Graves’ disease, a rare autoimmune disease in children. Epidemiological data are scarce and the variability of within-region incidence is unknown. We aimed to provide the first description of temporal trends in pediatric hyperthyroidism in France and to explore spatial trends, with a view to identifying possible environmental triggers.

Design and methods

We performed an observational population-based study on data collected from the National Health Data System, covering the 2008–2017 period and the whole of France. We identified patients with an indicator reflecting incident cases of treated hyperthyroidism, in children aged 6 months–17.9 years, localized at the scale of the département (equivalent to a county) of residence. We performed descriptive analyses of incidence rate by sex, age, and year, and used a spatiotemporal model for estimation at département level.

Results

We identified 4734 incident cases: 3787 girls (80%) and 947 boys (20%). The crude incidence rate was 3.35 (95% CI: 3.26; 3.45) per 100 000 person-years over the study period. We estimated the increase in incidence between 2008 and 2017 at 30.1% (19.0%; 42.3%). Annual incidence rate increased linearly over the 10-year period in both girls and boys, rising similarly in all age groups and in all départements. The spatial model highlighted marked heterogeneity in the risk of childhood hyperthyroidism across France.

Conclusion

The trend toward increasing incidence observed may reflect changes in genetic and environmental interactions, and the marked spatial heterogeneity may reflect localized ethnic or environmental factors worthy of further investigation.

Open access

Prenatal exposure to glucocorticoids and the prevalence of overweight or obesity in childhood

Kristina Laugesen, Henrik Toft Sørensen, Jens Otto L Jorgensen, and Irene Petersen

Objective

Prenatal exposure to excess cortisol can affect postnatal metabolic health by epigenetic mechanisms. We aimed to investigate if prenatal exposure to pharmacological glucocorticoids increases the risk of overweight/obesity in childhood.

Design

A nationwide population registry-based cohort study.

Methods

We identified 383 877 children born in Denmark (2007–2012), who underwent routine anthropometric evaluation at 5–8 years of age. Prenatal exposure to glucocorticoids was divided into systemic and topical glucocorticoids, cumulative systemic dose, and use by trimester. The comparison cohort included children without exposure, born to maternal never-users. Negative control exposures were used to investigate confounding from an underlying disease or unmeasured characteristics. Such exposures included children without glucocorticoid exposure born to maternal users of non-steroidal anti-inflammatory drugs or immunotherapy during pregnancy, maternal former users of glucocorticoids, or paternal users of glucocorticoids during the pregnancy of their partner. We estimated sex-stratified adjusted prevalence ratios (aPR) of overweight/obesity at 5–8 years of age, as epigenetic modifications have shown to be sex-specific.

Results

In the study, 21 246 (11%) boys and 27 851 (15%) girls were overweight/obese at 5–8 years of age. Overall, neither systemic nor topical glucocorticoids were associated with overweight/obesity. In boys, high-dose systemic glucocorticoids was associated with higher prevalence of overweight/obesity vs the comparison cohort (aPR: 1.41 (95% CI: 1.07–1.86), prevalence: 16% vs 11%). Negative control exposures indicated robustness to confounding.

Conclusion

Overweight/obesity might be an adverse effect of prenatal exposure to high-dose systemic glucocorticoids in boys. We found no association for neither prenatal exposure to lower doses of systemic nor topical glucocorticoids. These results merit clinical attention.

Free access

High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles

Dinane Samara-Boustani, Ana Colmenares, Caroline Elie, Myriam Dabbas, Jacques Beltrand, Virgile Caron, Claude Ricour, Paul Jacquin, Nadia Tubiana-Rufi, Claire Levy-Marchal, Christine Delcroix, Delphine Martin, Lila Benadjaoud, Evelyne Jacqz Aigrain, Christine Trivin, Kathleen Laborde, Elisabeth Thibaud, Jean-Jacques Robert, and Michel Polak

Objectives

To compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM).

Methods

Data were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years.

Results

High prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls.

Conclusions

Hirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.

Free access

Type 2 diabetes from pediatric to geriatric age: analysis of gender and obesity among 120 183 patients from the German/Austrian DPV database

Wendy L Awa, E Fach, D Krakow, R Welp, J Kunder, A Voll, A Zeyfang, C Wagner, M Schütt, B Boehm, M de Souza, and R W Holl

Aim

To characterize the clinical phenotype of type 2 diabetes mellitus (T2DM) with respect to age, gender, and BMI.

Method

Anonymized data of 120 183 people with T2DM from the German/Austrian multicenter Diabetes Patienten Verlaufsdokumentation database were analyzed based on chronological age or age at diagnosis (0–19, 20–39, 40–59, 60–79, and ≥80 years). Age, gender, and BMI comparisons with clinical phenotype were made using χ 2 and Kruskal–Wallis tests (SAS V9.2).

Results

Of all the patients, 51.3% were male, average age was 67.1±12.7 years, and average disease duration was 9.9±9.1 years. More girls than boys were diagnosed during adolescence and more men than women during adulthood (20–60 years). No gender differences existed when age at diagnosis was ≥60 years. Patients were obese on average (BMI: 30.5±6.1 kg/m2) and had significantly higher BMI values than German population peers. The BMI gap was widest in the younger age categories and closed with increasing age. Adult women were significantly more obese than men. Obese patients more often had elevated HbA1c (≥7.5%), hypertension or dyslipidemia (irrespective of age), microalbuminuria (adults), or retinopathy (elderly) than nonobese patients. More men than women (20–60 years) had hypertension, dyslipidemia, or microalbuminuria while more women than men (≥60 years) had hypertension or dyslipidemia.

Conclusion

During puberty, more girls than boys were diagnosed with T2DM while during adulthood males predominated. T2DM manifested at comparatively lower BMI in males, and younger patients were more obese at diagnosis. Age, gender, and BMI were also associated with poor metabolic control and cardiovascular disease comorbidities/complications.

Free access

Cognitive outcome of offspring from dexamethasone-treated pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Heino F L Meyer-Bahlburg, Curtis Dolezal, Rita Haggerty, Michael Silverman, and Maria I New

Objectives

To test whether dexamethasone (DEX) treatment in pregnancies at risk for congenital adrenal hyperplasia (CAH) impairs cognitive functioning in the offspring.

Design

Observational follow-up of prenatally DEX-exposed offspring and controls.

Methods

Study 1 included 140 children aged 5–12 years: 67 DEX-exposed (long-term: eight CAH girls) and 73 unexposed (with 15 CAH girls). Study 2 included 20 participants aged 11–24 years: seven DEX-exposed (long-term: one CAH woman) and 13 unexposed (with four CAH women). Neuropsychological testing was done in hospital settings or at patients' homes. Data analysis aimed at maximizing detection of the effects of DEX exposure.

Results

The vast majority of group comparisons were not marginally or conventionally significant. The few significant findings on short-term prenatal DEX exposure suggested more positive than adverse outcomes. By contrast, few significant findings in females with CAH and long-term DEX exposure indicated slower mental processing than in controls on several neuropsychological variables, although partial correlations of DEX exposure duration with cognitive outcome did not corroborate this association.

Conclusions

Although our studies do not replicate a previously reported adverse effect of short-term prenatal DEX exposure on working memory, our findings on cognitive function in CAH girls with long-term DEX exposure contribute to concerns about potentially adverse cognitive after effects of such exposure. Yet, our studies are not definitive, and replications in larger samples are required.