Pituitary dysfunction is now well recognised after traumatic brain injury (TBI) in adults; however, little except anecdotal evidence is known about this potential complication in childhood and adolescence. Histopathological evidence exists for both hypothalamic and pituitary damage, but few data specific to children have been published. We review the available paediatric data, which shows that after both mild and severe TBI, hypopituitarism may occur, with GH and gonadotrophin deficiencies appearing to be most common. Precocious puberty has also been documented. Road-traffic accidents, falls, sport and child abuse are the most common aetiological factors for paediatric TBI. There are no published data on the incidence or prevalence, neither within a population of children with TBI, of hypopituitarism, nor on its natural history or response to hormone replacement. We urge paediatric endocrinologists, in collaboration with adult endocrinologists, to perform formal prospective research studies in patients suffering from TBI to clarify these questions.
Carlo L Acerini, Robert C Tasker, Simonetta Bellone, Gianni Bona, Christopher J Thompson, and Martin O Savage
Helen L Storr and Martin O Savage
Cushing's disease (CD) is the commonest form of ACTH-dependent Cushing's syndrome and is a rare clinical diagnosis in paediatric and adolescent patients. CD is caused by an ACTH-secreting pituitary corticotroph adenoma and is associated with significant morbidity in children; therefore, early diagnosis and treatment are critical for optimal therapeutic outcome. This review highlights the key clinical and biochemical features of paediatric CD and appraises current practices in diagnosis and management. A close liaison with adult endocrinology colleagues, particularly, for interpretation of investigations and definition of therapeutic strategy is strongly advised.
P E Clayton, R C Cuneo, A Juul, J P Monson, S M Shalet, and M Tauber
The European Society for Paediatric Endocrinology held a consensus workshop in Manchester, UK in December 2003 to discuss issues relating to the care of GH-treated patients in the transition from paediatric to adult life. Clinicians experienced in the care of paediatric and adult patients on GH treatment, from a wide range of countries, as well as medical representatives from the pharmaceutical manufacturers of GH participated.
Valérie Bernard, Bruno Donadille, Tiphaine Le Poulennec, Mariana Nedelcu, Laetitia Martinerie, and Sophie Christin-Maitre
Turner syndrome (TS), affecting 1/2000 to 1/2500 live born girls, is a chromosomal aberration with a total or partial loss of one of the X chromosomes. The diagnosis can be established from the intra-uterine life to adulthood. TS is a chronic disease with particular morbidity and mortality. The loss to follow-up rate, during transition, between children and adult units, remains a crucial issue. This review focusses on the adolescent and young adult patients with TS. The different goals of TS transition are presented as well as some of the tools available in order to improve this transition. The involvement of the patient’s family, advocacy groups and therapeutic educational programs are discussed. A specificity concerning TS transition, as compared to other chronic diseases, relies on the fact that patients with TS may present a peculiar neurocognitive profile. They are in general more anxious than the general population. Therefore, psychological support should be offered to optimize transition. Data illustrating the beneficial impact of an organised transition of TS, from paediatric units to multidisciplinary adult care systems, within the same reference centre are presented. Further studies are required to evaluate the mid-to-long-term transition of paediatric patients with TS referred to adult units.
MO Savage, WM Drake, PV Carroll, and JP Monson
While the benefits of growth hormone (GH) therapy in adult hypopituitary patients with GH deficiency (GHD) are established, the role of continued GH therapy after final height in adolescent GH-deficient patients remains unclear. Preliminary data suggest that cessation of GH on completion of linear growth may be associated with impairment of somatic development and adverse changes in body composition. For the present time, the decision whether to continue GH treatment in adolescent patients with GHD is best made on an individual basis. For such patients, continuity of care is crucial. Children and adults with GHD are usually managed by physicians in separate departments, who may focus on different aspects of treatment and care. Close collaboration between paediatric and adult physicians is essential to ensure smooth transition and to minimize the drop-out rate from follow-up. Given the previous period of treatment during childhood, paediatric physicians should be best placed to discuss the potential benefits of continuing GH therapy and instigate retesting of GH secretion. Many children with isolated idiopathic GHD will produce normal GH responses if retested at adult height. Patients with multiple pituitary hormone deficits are more likely to have ongoing GHD, as are patients who have received CNS irradiation. Quality of life does not appear to be decreased in adolescents with GHD who stop treatment, so achievement of satisfactory bone mass is a major determinant of the decision whether to continue therapy.
H L Storr, K I Alexandraki, L Martin, A M Isidori, G A Kaltsas, J P Monson, G M Besser, M Matson, J Evanson, F Afshar, I Sabin, M O Savage, and A B Grossman
There are few published comparisons between paediatric and adult-onset Cushing's disease (CD). We compare the epidemiology, diagnostic features and cure rate by transsphenoidal surgery (TSS) in these groups.
Retrospective review of patient databases in a single university hospital centre.
Totally, 41 paediatric (mean age 12.3±3.5 years; range 5.7–17.8) and 183 adult (mean age 40±13 years; range 18.0–95.0) patients with CD were investigated.
Paediatric CD was characterised by male (63%) and adult CD by a female predominance (79%, P<0.0001). There were small but significant differences in clinical presentation. Biochemical features of CD were comparable except the serum cortisol increase during a CRH test: mean change (105%, n=39) in paediatric and (54%, n=123) in adult subjects (P<0.0001). Macroadenomas were more common in adult (15%, 28/183) than in paediatric (2%, 1/41, P=0.04) CD. Corticotroph microadenomas were more easily visualised by pituitary magnetic resonance imaging (MRI) in adult (76%, 50/66) compared with paediatric (55%, 21/38, P=0.045) CD with poorer concordance of imaging with surgical findings in children (P=0.058). The incidence of ACTH lateralisation by bilateral simultaneous inferior petrosal sinus sampling was comparable in paediatric (76%, 25/33) and adult (79%, 46/58; P=0.95) patients with good surgical concordance in both (82% paediatric and 79% adult). Cure rates by TSS were comparable, with a paediatric cure rate of 69%.
Several features of paediatric CD are distinct: increased frequency of prepubertal CD in males, the different clinical presentation, the decreased presence of macroadenomas and the frequent absence of radiological evidence of an adenoma on MRI.
Robin Michelet, Johanna Melin, Zinnia P. Parra-Guillen, Uta Neumann, J Martin Whitaker, Viktoria Stachanow, Wilhelm Huisinga, John Porter, Oliver Blankenstein, Richard J. Ross, and Charlotte Kloft
Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing’s syndrome and adrenal crisis.
To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens.
Design and methods:
Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate seven different hydrocortisone treatment regimens.
Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the seven treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC0- 24h within the 90% reference range for healthy children except in neonates where two regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 h were outside the 90% reference range for healthy individuals in 50%, 55–65% and 70–75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent.
Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC0- 24h, but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.
Aneta Gawlik and Ewa Malecka-Tendera
Transition in health care for young patients with Turner's syndrome (TS) should be perceived as a staged but uninterrupted process starting in adolescence and moving into adulthood. As a condition associated with high risk of short stature, cardiovascular diseases, ovarian failure, hearing loss and hypothyroidism, TS requires the attention of a multidisciplinary team. In this review paper, we systematically searched the relevant literature from the last decade to discuss the array of problems faced by TS patients and to outline their optimal management during the time of transfer to adult service. The literature search identified 233 potentially relevant articles of which 114 were analysed. The analysis confirmed that all medical problems present during childhood should also be followed in adult life. Additionally, screening for hypertension, diabetes mellitus, dyslipidaemia, and osteoporosis is needed. After discharge from the paediatric clinic, there is still a long way to go.
The term premature pubarche is given to conditions in which there is precocious growth of sexual hair (pubes and axillary hair) without any other symptoms of precocious puberty, i. e. without development of the genitals and, in girls, without growth of the breasts. Girls do not become virilized as in the case of the adrenogenital syndrome.
The series of cases comprises 17 patients, 12 girls and 5 boys. The symptoms in the former were observed before the age of 8, and in the latter before the age of 9 years. The patients were from the Dronning Louises Børnehospital (children's hospital, Copenhagen), the Paediatric Department of the University Hospital, Copenhagen, and 5 homes for the mentally defective: Andersvænge, Brejning, Ebberødgård, Ribe and Rødbygård.
Twelve of the patients had severe cerebral disorder, they were all mentally retarded, seven had epilepsy and seven spastic pareses. Four were blind, two had a coloboma of
E Martin Ritzén
The mode of treatment best for undescended testes is controversial, and local traditions often override knowledge gained from randomized controlled studies. In order to reach a consensus within the Nordic countries on the current state-of-the-art of treatment, a group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for 2 days. Before the meeting, reviews of the literature had been prepared by the participants. Judging from published meta-analyses, hormonal treatment has low efficacy. Although 15–20% of retained testes descend during hormonal treatment, one-fifth of these re-ascend later on. Also, treatment with human chorionic gonadotropin (hCG) may be harmful to future spermatogenesis through increased apoptosis of germ cells. Orchiopexy, on the contrary, results in about 95% anatomical success, with a low (about 1%) risk of complications. The optimal time for orchiopexy has also been debated. However, a recent randomized controlled study shows that surgery at 9 months of age is followed by a better post-operative growth of the testes than surgery at 3 years, which supports previous arguments for early surgery. The unanimous conclusion of the group was that surgery is generally the preferred mode of treatment, rather than hCG or GnRH treatments. Orchiopexy should be performed between 6 and 12 months of age, or soon after diagnosis, if that occurs later. If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery. Referral should be to paediatric rather than general surgeons/urologists if the boy is less than 1 year old, if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.