Height benefit of GnRH agonists after age 8 in a Portuguese cohort of central precocious puberty.

OBJECTIVE: Idiopathic central precocious puberty (iCPP) is common in paediatric endocrinology. Gonadotropin-releasing hormone agonists (GnRHa) are safe, but the effect on final height and the ideal timing for treatment remains controversial. This study aims to assess the effectiveness of GnRHa on growth outcomes in girls with iCPP treated before and after the age of 8 years old. DESIGN AND PATIENTS: This retrospective longitudinal study evaluated data from Portuguese girls with iCPP who completed treatment between 2010 and 2021. MEASUREMENTS: Auxological and clinical characteristics were compared according to age at treatment onset. RESULTS: A cohort of 134 girls with iCPP, was divided into early treatment (ET) (<8 years, n = 48) and later treatment (LT) groups (≥8 years, n = 86). In both groups, most children presented with Tanner II and III. Tanner IV was more frequent in LT group (p = .003). At the end of treatment, predicted adult height increased in both groups (ET p = .032; LT p = .04) and bone age significantly slowed down in all participants (p = .008, p = .034). The height gain was greater in the ET group, but without significant differences (p = .065). CONCLUSIONS: Treatment with GnRHa improved final height in all girls with iCPP, even when initiated after 8 years. To achieve better outcomes, treatment should be provided promptly after diagnosis.

A Case Series Study on Growth Hormone Therapy in Children with Prader-Willi Syndrome in Portugal.

INTRODUCTION: Prader-Willi syndrome is a multisystemic genetic disorder associated with shorter adult height. Nowadays, all paediatric Prader-Willi syndrome patients are considered for growth hormone treatment. We present the experience of this treatment at a Portuguese paediatric endocrinology unit and intend to emphasise the importance of creating a follow-up national network of these patients. MATERIAL AND METHODS: Longitudinal, retrospective, analytical study of Prader-Willis syndrome patients using data between 1989 and 2021. Growth hormone therapy was offered to eligible patients. The analysis included all Prader-Willis syndrome patients, with a comparison between treated and untreated patients; a longitudinal analysis of patients receiving growth hormone therapy (baseline, 12 and 36 months of follow-up) was also carried out. The statistical analysis was carried out using STATA® v13.0. RESULTS: Out of 38 patients with Prader-William syndrome, 61% were male. The median age at diagnosis was four months and 61% received growth hormone therapy. The patients who reached adulthood, or 18 years old, had a median near-adult height, Z-score of -2.71, and their median body mass index indicated class 2 obesity, regardless of growth hormone therapy. Patients had a lower body mass index in the growth hormone group (35 vs 51 kg/m2, p < 0.042) near-adult height. CONCLUSION: This case series represents the first national study that included patients on growth hormone therapy after the National Health Service started supporting the treatment for Prader-Willi syndrome patients and supports its use, reinforcing the positive effects on growth and body mass index. Longer follow-up studies are needed to analyse the effect of growth hormone on patient metabolic profiling, body composition and cognitive level.

Introdução: A síndrome de Prader-Willi é uma doença genética multissistémica associada a baixa estatura. Atualmente, todos os doentes pediátricos com síndrome de Prader-Willi são candidatos a terapia com hormona do crescimento. Apresentamos a experiência desta terapêutica numa unidade de Endocrinologia Pediátrica portuguesa e realçamos a importância de criar uma base de dados nacional de seguimento destes doentes. Material e Métodos: Estudo longitudinal, retrospetivo e analítico de doentes com síndrome de Prader-Willi utilizando dados entre 1989 e 2021. A terapia com hormona de crescimento foi administrada aos doentes elegíveis. Foi realizada análise de todos os doentes com síndrome de Prader-Willi, com comparação doentes tratados/não tratados; foi também realizada uma análise longitudinal dos doentes sob hormona de crescimento (início/12/36 meses de seguimento). O tratamento estatístico foi realizado com recurso ao STATA® v13.0. Resultados: De um total de 38 doentes com síndrome de Prader-Willi, 61% eram do sexo masculino. Idade média de diagnóstico quatro meses e 61% sob hormona de crescimento. Os doentes que atingiram a idade adulta apresentaram um Z-score de mediana de estatura alvo de -2,71, e índice de massa corporal obesidade nível 2, independentemente da terapêutica com hormona de crescimento. Os doentes apresentaram um índice de massa corporal menor no grupo tratado com hormona de crescimento (35 vs 51 kg/m2, p < 0,042). Conclusão: Este estudo de série de casos de doentes com síndrome de Prader-Willi tratados com hormona de crescimento é pioneiro a nível nacional desde a comparticipação deste tratamento pelo Sistema Nacional de Saúde português e apoia esta terapêutica, reforçando os seus efeitos positivos no crescimento e índice de massa corporal. Serão necessários estudos com seguimento mais prolongado para analisar o seu efeito no perfil metabólico, composição corporal e cognição.

Do GnRH Agonists Really Increase Body Weight Gain? Evaluation of a Multicentric Portuguese Cohort of Patients With Central Precocious Puberty.

Introduction: There are several concerns associated with gonadotropin-releasing hormone agonist (GnRHa) treatment for central precocious puberty (CPP), such as obesity and changes in body mass index (BMI). We aimed to investigate whether any anthropometric differences exist and if they persist over time. Methods: We conducted an observational study of Portuguese children (both sexes) diagnosed with CPP between January 2000 and December 2017, using a digital platform, in order to analyze the influence of GnRHa treatment on BMI-SD score (BMI-SDS). Results: Of the 241 patients diagnosed with CPP, we assessed 92 patients (8% boys) in this study. At baseline, 39% of the patients were overweight. BMI-SDS increased with treatment for girls but then diminished 1 year after stopping GnRHa therapy (p = 0.018). BMI-SDS variation at the end of treatment was negatively correlated with BMI-SDS at baseline (p < 0.001). Boys grew taller and faster during treatment than did girls (p < 0.001), and therefore, their BMI-SDS trajectory might be different. Conclusions: This study showed an increase of body weight gain during GnRHa treatment only in girls, which reversed just 1 year after stopping treatment. The overall gain in BMI-SDS with treatment is associated with baseline BMI-SDS.

The multiple meanings of "wheezing": a questionnaire survey in Portuguese for parents and health professionals.

BACKGROUND: Most epidemiological studies on pediatric asthma rely on the report of "wheezing" in questionnaires. Our aim was to investigate the understanding of this term by parents and health professionals. METHODS: A cross-sectional survey was carried out in hospital and community settings within the south of Portugal. Parents or caregivers self-completed a written questionnaire with information on social characteristics and respiratory history. Multiple choice questions assessed their understanding of "wheezing". Health professionals (physicians, nurses and physiotherapists) were given an adapted version. We used bivariate analysis and multivariate models to study associations between definitions of "wheezing" and participants' characteristics. RESULTS: Questionnaires from 425 parents and 299 health professionals were included. The term "wheezing" was not recognized by 34% of parents, more frequently those who were younger (OR 0.4 per 10-year increment, 95% CI 0.3-0.7), had lower education (OR 3.3, 95% CI 1.5-7.4), and whose children had no history of respiratory disease (OR 4.6, 95% CI 2.5-8.7) (all ORs adjusted). 31% of parents familiar with "wheezing" either did not identify it as a sound, or did not locate it to the chest, while tactile (40%) and visual (34%) cues to identify "wheezing" were frequently used. Nurses reported using visual stimuli and overall assessments more often than physicians (p < 0.01). The geographical location was independently associated with how parents recognized and described "wheezing". CONCLUSIONS: Different meanings for "wheezing" are recognized in Portuguese language and may be influenced by education, respiratory history and regional terminology. These findings are likely applicable to other non-English languages, and suggest the need for more accurate questionnaires and additional objective measurement instruments to study the epidemiology of wheezing disorders.

Short Stature on a Boy: Mosaicism with an Isodicentric Y Chromosome.

Mosaicism brings great variability into the clinical expression of numerical and structural chromosomal abnormalities. The phenotypic variability of 45,X/46,XY mosaicism extends from Turner syndrome to apparently physically normal males. We present a case of a 14-year-old adolescent with short stature and delayed puberty, who was admitted in a Paediatric Endocrinology outpatient clinic. After a careful investigation, he was found to have a 45,X/46,X,idic(Y)(p11.32) mosaicism. This case report emphasizes the wide range of etiologies that can be involved in short stature and that chromosomal study is an important tool when firstly approaching males with short stature, avoiding unnecessary tests. There is an important clinical need for gonadal follow-up in this situation and for support in the decision about sex of rearing and sex orientation, when justifiable.

Familial Turner syndrome: the importance of information.

Turner syndrome is a common genetic disorder with an incidence of 1 in 2500 live births. Spontaneous fertility is rare in such patients and is most likely in women with mosaicism or very distal Xp deletions. The authors report an unusual case of familial Turner syndrome in a woman with mosaicism 45,X/46,Xdel(Xp) karyotype with three documented spontaneous pregnancies, which resulted in two daughters with 46,Xdel(X)(p11.4)mat karyotype and a healthy son. The mother was first diagnosed by the age of 11 and did not receive contraceptive medication, due to information that she would be infertile. Both daughters were referred to an endocrinology unit and are now under growth hormone treatment, and have been growing in the 3rd percentile. This family illustrates the complexity and difficulties in counseling, follow-up and treatment in Turner syndrome, namely referring to a tertiary center, fertility and treatment such as growth hormone and hormonal replacement, due to the heterogeneity of the clinical spectrum.

Adrenal Hypoplasia Congenita: A Rare Cause of Primary Adrenal Insufficiency and Hypogonadotropic Hypogonadism.

Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal insufficiency. During follow-up, adrenal hypoplasia congenita (AHC) was suspected given his persistently raised adrenocorticotropic hormone levels, with markedly low 17-OH progesterone and androstenedione levels. DNA sequence analysis revealed a mutation in NR0B1 gene (c.1292delG), confirming the diagnosis. Delayed puberty and persistent low levels of gonadotropins led to testosterone replacement therapy. X-linked AHC is a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism, related to mutations in NR0B1 gene. Despite its rarity, AHC should be considered in patients who present with primary adrenal failure, low levels of 17-OH progesterone and hypogonadotropic hypogonadism.

[Growth and puberty in type 1 diabetes mellitus - experience from a pediatric endocrinology unit]. / Crescimento e puberdade na diabetes mellitus tipo 1 - experiência de uma unidade de endocrinologia pediátrica.

BACKGROUND: Type 1 Diabetes Mellitus (T1DM) is the most common endocrine-metabolic disease in children. It is associated with vascular and neuropathic complications, and may also affect growth and development. OBJECTIVE: To correlate the metabolic control and disease duration with growth and puberty in patients with T1DM followed in a Pediatric Endocrinology Outpatient Clinic. SUBJECTS AND METHODS: Retrospective analysis. Sample obtained from patients with T1DM followed in Hospital Santa Maria Pediatric Endocrinology Outpatient Clinic (Lisbon - Portugal) since 1994 until March 2011. INCLUSION CRITERIA: patients diagnosed before the onset of puberty and who had attained their final height during the follow-up. VARIABLES: sex, age, weight and height at diagnosis and final, parents' height, growth velocity, pubertal height gain, age at menarche and metabolic control during puberty. RESULTS: 39 patients, 51% female, 82% diagnosed less than five years before puberty. Fifty-four percent presented an average HbA1c between 8-10%, what we considered reasonable. There seems to be a trend towards an inverse association between HbA1c and the maximum speed of growth and pubertal height gain, although not statistically significant. These patients were taller than average at diagnosis (z-score: male 0.9; female: 0.5) and lost height during puberty, yet attained final heights within normal range and matching their target heights. CONCLUSIONS: Although HbA1c seems to negatively influence maximum growth rate and pubertal height gain, there was no compromise in final height in this group of patients.