Search Results

You are looking at 31 - 40 of 1,596 items for

  • Abstract: adolescen* x
  • Abstract: boy* x
  • Abstract: child* x
  • Abstract: girl* x
  • Abstract: neonat* x
  • Abstract: paediatric x
  • Refine by Access: All content x
Clear All Modify Search
Free access

Emilia Sbardella, Carlotta Pozza, Andrea M Isidori, and Ashley B Grossman

Introduction

The transition age is the period between childhood to adulthood; it refers to a broad set of physical, cognitive and sociocultural modifications, arbitrarily defined as starting in late puberty and ending with full adult maturation. Pituitary disorders in adolescence represent a challenge that requires careful management during the transition to adult care.

Methods

Given the complexity of care of pituitary disorders in the transition age, we have reviewed the relevant medical literature focusing on aetiology, clinical manifestations, treatment strategies of GH deficiency (GHD), hypogonadotrophic hypogonadism (HH) in male and female adolescents, central hypothyroidism (CH), central adrenal insufficiency (CAI) and cranial diabetes insipidus (CDI) at this time. The objective of the present review is to provide an up-to-date evaluation of the transition period to evaluate the specific needs of adolescents with chronic pituitary disease in order to optimise their management.

Results

We provide an overview of current clinical management of GHD, HH, CH, CAI and CDI in the transition age.

Conclusions

Specific changes occur in pituitary function during the transition period. A holistic approach including discussion of patients’ concerns and emotional support should constitute a key component of managing pituitary disorders in adolescence. Special transition clinics where paediatric and adult endocrinologists work together, should be increasingly created and strengthened to bridge care, to promote continuity and adherence to treatment and to limit potential negative development, metabolic, skeletal and cardiovascular sequelae of discontinuity of care among adolescents with pituitary disorders.

Free access

Romina P Grinspon, Carolina Habib, Patricia Bedecarrás, Silvia Gottlieb, and Rodolfo A Rey

Objective

Compensatory hypertrophy has been classically described in patients with monorchidism. However, it remains unclear whether there is a functional compensatory activity of the different cell populations. Our aim was to assess the functional capacity of the solitary testis in monorchid males from infancy through puberty in order to determine whether the remaining gonad is capable of compensating the functional activity of Sertoli and Leydig cells of the absent gonad.

Design

In a retrospective, cross-sectional, analytical study performed at a tertiary paediatric public hospital, we included 89 boys with monorchidism and 358 healthy controls, aged 6 months–18 years. Testicular volume and circulating levels of reproductive hormones were compared between patients with monorchidism and normal boys. Serum anti-Müllerian hormone (AMH) and FSH were used as biomarkers of the functional mass of prepubertal Sertoli cells, whereas serum testosterone and LH were used as biomarkers of Leydig cells.

Results

In the vast majority of the cases, the testicular volume of monorchid boys was smaller than the sum of the volume of both testes of healthy controls. Serum AMH was lower and FSH was higher in patients with monorchidism than in controls aged <3 and >13 years. Serum testosterone and LH did not differ significantly between patients and controls.

Conclusion

In boys and adolescents with monorchidism, there is a dissociated capacity of the remaining testis to compensate for the absence of the other gonad: while Leydig cell function is largely compensated, Sertoli cell proliferation and function was lower than in controls.

Free access

M Rix, P Laurberg, A S Hoejberg, and B Brock-Jacobsen

Objective: The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour.

Design: To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism.

Methods: Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age.

Results: A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being.

Conclusions: We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

Free access

Leo Dunkel

The Food and Drug Administration (FDA) approved the use of biosynthetic GH for the treatment of children with idiopathic short stature (ISS) in the US in 2003. Primarily, the decision was based on two studies: a randomized placebo-controlled study and a dose–response study, both demonstrating an increase in adult height over the predicted height at baseline and over placebo-treated controls by an average of 4–7 cm. Despite these data and FDA approval of GH treatment for ISS, there is still a significant controversy among paediatric endocrinologists about how, and to what extent, GH should be used in this indication. GH is clearly efficacious in several growth disorders and has the potential to alleviate debilitating short stature. However, it has been questioned whether ISS should be considered a condition warranting pharmacological treatment, whether the degree of morbidity of untreated ISS is clinically significant, and whether improved psychosocial status or well-being is achieved through GH treatment and height gain. The benefits must outweigh treatment costs and risks to justify GH treatment in ISS. The safety of GH treatment in ISS has been the main subject in two recent articles from pharmaceutical companies that conducted the pioneering studies mentioned earlier. No new safety concerns were observed in the ISS populations, but there were some limitations in study designs that prevent clinicians, their patients and families from ‘resting assured’. Studies addressing these controversial issues are needed before the widespread use of GH treatment in ISS is warranted.

Restricted access

H. Gerdes and W. Teller

ABSTRACT

The results are reported of routine determinations of free C21-steroids in plasma and urine by a method which involved thin layer and gas liquid chromatography. The following steroids were simultaneously determined: Cortisol, cortisone, 6β-hydroxycortisol and -cortisone, 20-hydroxycortisol and -cortisone, tetrahydrocortisol and -cortisone, and 11-deoxycortisol (Reichstein S). The specificity, reproducibility and accuracy are discussed in detail. The overall recoveries of the procedure were examined by the addition of 1,2-3H-cortisol and 1,2-3H-cortisone prior to extraction. They ranged between 50 and 60 per cent.

The method was clinically applied to various tests of adrenal cortical function and its pituitary regulation (e. g. ACTH test, dexamethasone suppression, metopirone test). The simultaneous determination in plasma and urine of a number of C21-steroid-hormones including their metabolites proved to yield valuable information about adrenal cortical function and C21-steroid metabolism. In the paediatric age group the metopirone test measuring 11-deoxycortisol in plasma rather than its tetrahydro derivative in urine was particularly useful since it avoided unpleasant 24 h-urine collections in young children.

Open access

Tansit Saengkaew, Heena R Patel, Kausik Banerjee, Gary Butler, Mehul T Dattani, Michael McGuigan, Helen L Storr, Ruben H Willemsen, Leo Dunkel, and Sasha R Howard

Context

Pubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents.

Objective

To assess whether gene panel testing can assist with clinical differential diagnosis and to allow accurate and timely management of delayed puberty patients.

Design

Retrospective study.

Methods

Patients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rarely predicted deleterious variants. Deleterious variants were verified by in silico prediction tools. The correlation between clinical and genotype diagnosis was analysed.

Results

Forty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only three patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP.

Conclusion

This study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately.

Restricted access

Idoia Martínez de LaPiscina, Nancy Portillo Najera, Itxaso Rica, Sonia Gaztambide, Susan M Webb, Alicia Santos, Maria Dolores Moure, Miguel Paja Fano, Maria Isabel Hernandez, Maria Jesús Chueca-Guindelain, Laura Cristina Hernández-Ramírez, Alfonso Soto, Nuria Valdés, and Luis Castaño

Objective

Pituitary adenomas (PA) are rare in young patients, and additional studies are needed to fully understand their pathogenesis in this population. We describe the clinical and genetic characteristics of apparently sporadic PA in a cohort of young patients.

Design

Clinical and molecular analysis of 235 patients (age ≤ 30 years) with PA. Clinicians from several Spanish and Chilean hospitals provided data.

Methods

Genetic screening was performed via next-generation sequencing and comparative genomic hybridization array. Clinical variables were compared among paediatric, adolescent (<19 years) and young adults’ (≥19–30 years) cohorts and types of adenomas. Phenotype–genotype associations were examined.

Results

Among the total cohort, mean age was 17.3 years. Local mass effect symptoms were present in 22.0%, and prolactinomas were the most frequent (44.7%). Disease-causing germline variants were identified in 22 individuals (9.3%), more exactly in 13.1 and 4.7% of the populations aged between 0–19 and 19–30 years, respectively; genetically positive patients were younger at diagnosis and had larger tumour size. Healthy family carriers were also identified.

Conclusions

Variants in genes associated with syndromic forms of PAs were detected in a large cohort of apparently sporadic pituitary tumours. We have identified novel variants in well-known genes and set the possibility of incomplete disease penetrance in carriers of MEN1 alterations or a limited clinical expression of the syndrome. Despite the low penetrance observed, screening of AIP and MEN1 variants in young patients and relatives is of clinical value.

Open access

Oliver Blankenstein, Marta Snajderova, Jo Blair, Effie Pournara, Birgitte Tønnes Pedersen, and Isabelle Oliver Petit

Objective

To describe real-life dosing patterns in children with growth hormone deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) receiving growth hormone (GH) and enrolled in the NordiNet International Outcome Study (IOS; Nbib960128) between 2006 and 2016.

Design

This non-interventional, multicentre study included paediatric patients diagnosed with GHD (isolated (IGHD) or multiple pituitary hormone deficiency (MPHD)), born SGA or with TS and treated according to everyday clinical practice from the Czech Republic (IGHD/MPHD/SGA/TS: n = 425/61/316/119), France (n = 1404/188/970/206), Germany (n = 2603/351/1387/411) and the UK (n = 259/60/87/35).

Methods

GH dosing was compared descriptively across countries and indications. Proportions of patients by GH dose group (low/medium/high) or GH dose change (decrease/increase/no change) during years 1 and 2 were also evaluated across countries and indications.

Results

In the Czech Republic, GH dosing was generally within recommended levels. In France, average GH doses were higher for patients with IGHD, MPHD and SGA than in other countries. GH doses in TS tended to be at the lower end of the recommended label range, especially in Germany and the UK; the majority of patients were in the low-dose group. A significant inverse association between baseline height standard deviation score and GH dose was shown (P < 0.05); shorter patients received higher doses. Changes in GH dose, particularly increases, were more common in the second (40%) than in the first year (25%).

Conclusions

GH dosing varies considerably across countries and indications. In particular, almost half of girls with TS received GH doses below practice guidelines and label recommendations.

Free access

Leo Dunkel and Richard Quinton

Puberty is the period during which we attain adult secondary sexual characteristics and reproductive capability. Its onset depends upon reactivation of pulsative GNRH, secretion from its relative quiescence during childhood, on the background of intact potential for pituitary–gonadal function. This review is intended: to highlight those current practices in diagnosis and management that are evidence based and those that are not; to help clinicians deal with areas of uncertainty with reference to physiologic first principles; by sign-posting relevant data arising from other patient groups with shared issues; to illustrate how recent scientific advances are (or should be) altering clinician perceptions of pubertal delay; and finally, to emphasise that the management of men and women presenting in advanced adult life with absent puberty cannot simply be extrapolated from paediatric practice. There is a broad spectrum of pubertal timing that varies among different populations, separated in time and space. Delayed puberty usually represents an extreme of the normal, a developmental pattern referred to as constitutional delay of growth and puberty (CDGP), but organic defects of the hypothalamo–pituitary–gonadal axis predisposing to hypogonadism may not always be initially distinguishable from it. CDGP and organic, or congenital hypogonadotrophic hypogonadism are both significantly more common in boys than girls. Moreover, around 1/3 of adults with organic hypogonadotrophic hypogonadism had evidence of partial puberty at presentation and, confusingly, some 5–10% of these subsequently may exhibit recovery of endogenous gonadotrophin secretion, including men with Kallmann syndrome. However, the distinction is crucial as expectative (‘watch-and-wait’) management is inappropriate in the context of hypogonadism. The probability of pubertal delay being caused by organic hypogonadism rises exponentially both with increasing age at presentation and the presence of associated ‘red flag’ clinical features. These ‘red flags’ comprise findings indicating lack of prior ‘mini-puberty’ (such as cryptorchidism or micropenis), or the presence of non-reproductive congenital defects known to be associated with specific hypogonadal syndromes, e.g. anosmia, deafness, mirror movements, renal agenesis, dental/digital anomalies, clefting or coloboma would be compatible with Kallmann (or perhaps CHARGE) syndrome. In children, interventions (whether in the form or treatment or simple reassurance) have been historically directed at maximising height potential and minimising psychosocial morbidity, though issues of future fertility and bone density potential are now increasingly ‘in the mix’. Apubertal adults almost invariably harbour organic hypogonadism, requiring sensitive acknowledgement of underlying personal issues and the timely introduction of sex hormone replacement therapy at more physiological doses.

Free access

HL Fideleff, HR Boquete, MG Suarez, GF Ruibal, PG Sobrado, M Azaretsky, AB Pujol, AM Sequera, J Giuseppucci, and R Ponzio

OBJECTIVE: To study hormonal and histological parameters of paediatric-adolescent varicocele in order to know certain aspects of its natural history, in an attempt to find prognostic markers of testicular damage. DESIGN AND METHODS: In a prospective cross-sectional study, we evaluated 93 children and adolescents with left unilateral varicocele and 29 healthy males as control group. All of them were classified according to Tanner stage. Scrotal Doppler in both testes and GnRH and human chorionic gonadotrophin (hCG) tests were performed in all subjects. Surgery was performed in 28 patients and homolateral testicular biopsy in 18. RESULTS: Hormonal measurements of patients with varicocele were compared with a control group for each Tanner stage. Testicular biopsy specimens were analysed by light and electron microscopy. We only observed statistical differences in Tanner III patients in basal FSH (median and range) controls=1.70 (1.10-3.70) IU/l vs varicocele=4.20 (1.00-7.50) IU/l, P<0.05 and in Tanner IV patients in LH post-GnRH: controls=11.0 (7.50-15.0) IU/l vs varicocele=18.0 (5.10-29.0) IU/l, P<0.05 and in testosterone post-hCG: controls=9.50 (7.7-10.0) ng/ml vs varicocele=12.0 (6.2-23.0) ng/ml, P<0.01. No correlation was found between the various clinical grades of varicocele and hormonal measurements for each Tanner stage. No statistically significant differences were found between pre- and post-operative hormonal findings, either in basal levels or in maximal responses. On the other hand, no morphological abnormalities were observed by electron microscopy in germ cells, tubular wall and interstice. CONCLUSIONS: There appears to be no reliable biochemical marker in children and adolescents that may predict impaired testicular function. A significant size discrepancy between both testes, testicular pain and a hyperresponse to GnRH stimulation should continue to be, for the time being, the indications for surgery.