S.M.P.F. de Muinck Keizer-Schrama

Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure

Abstract Stunted growth is a serious problem for children with chronic renal failure (CRF) despite normal endogenous growth hormone secretion and normal or elevated plasma concentrations of insulin-like growth factors (IGF) I and II. Biosynthetic growth hormone (GH) was given to 20 prepubertal children (eleven boys, nine girls; mean age 9·5 years, range 4-16) with CRF and severe growth retardation in a placebo-controlled, double-blind, cross-over trial. 6 months of subcutaneous injection of GH (4 IU/m 2 per day) was either preceded or followed by 6 months of placebo injection. The patients had a full examination every 3 months. Sixteen children completed the study. Height velocity improved significantly with GH therapy (p

Auxological and Biochemical Evaluation of Pubertal Suppression with the GnRH Agonist Leuprolide Acetate in Early and Precocious Puberty

We studied the auxological effects of treatment with the GnRH agonist leuprolide acetate (Lucrin®) at 3.75 mg/ 28 days in 38 children with early or precocious puberty. We present our newly developed scoring system, the Puberty Suppression Score (PSS), in which clinical and biochemical parameters determine whether suppression was effective. Leuprolide acetate suppressed pubertal development in the majority of cases. During treatment there was a significant correlation between the number of times that PSS was >0 and gain in predicted adult height (PAH) compared to initial prediction at the start of treatment. After 6 months of treatment, ineffective suppression measured by PSS was associated with the magnitude of gain in PAH. We conclude that a leuprolide acetate dosage of 3.75 mg every 28 days effectively suppresses puberty. PSS is helpful in monitoring the suppressive capacity of a GnRH agonist. We recommend to start with leuprolide acetate at 3.75 mg/28 days and to increase the injection frequency or dose in case PSS is >0 after 6 months of treatment.

Long-term endocrine side effects of childhood Hodgkin's lymphoma treatment: a review

BACKGROUND Since childhood cancer survival has increased, long-term effects of treatment have gained interest. Childhood Hodgkins lymphoma has been treated successfully for decades now. We provide an overview of the literature on long-term endocrine side effects, such as gonadal dysfunction and growth retardation, as a result of childhood Hodgkins lymphoma treatment. METHODS A comprehensive search of the Pubmed database was performed. RESULTS We identified 16 studies (10 studies: 298 male survivors and 6 studies: 230 female survivors) about gonadal dysfunction. In survivors treated with alkylating agents or pelvic radiotherapy, severe gonadal damage is described. Recovery was rarely described. Seven studies (481 survivors) about bone mineral density (BMD) and growth were identified. The effects on BMD appear to be small. Data on growth are scarce, but show that radiotherapy in a dose of >30 Gy including the spine, especially in pre-pubertal children, results in reduced height. We included 10 studies (4012 survivors) about thyroid complications. Hypothyroidism is the most common thyroid disorder after radiotherapy. There is also a significant incidence in thyroid carcinoma after low-dose radiation. In survivors treated with chemotherapy only, hypothyroidism and thyroid cancer have not been reported. CONCLUSIONS The severity of endocrine toxicity after childhood Hodgkins lymphoma depends on the type of treatment. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy. The knowledge obtained in specific follow-up programmes for paediatric cancer survivors will help to find the optimal balance between curability and long-term side effects.

Growth hormone treatment in Turner syndrome accelerates growth and skeletal maturation

Sixteen girls with Turner syndrome (TS) were treated for 4 years with biosynthetic growth hormone (GH). The dosage was 4IU/m2 body surface s.c. per day over the first 3 years. In the 4th year the dosage was increased to 61 U/m2 per day in the 6 girls with a poor height increment and in 1 girl oxandrolone was added. Ethinyl oestradiol was added after the age of 13. Mean (SD) growth velocities were 3.4 (0.9), 7.2 (1.7), 5.3 (1.3), 4.3 (2.0) and 3.6 (1.5) cm/year before and in the 1st, 2nd, 3rd and 4th year of treatment. Skeletal maturation advanced faster than usual in Turner patients especially in the youger children. Although the mean height prediction increased by 5.6 cm and 11 of the 16 girls have now exceeded their predicted height, the height of the 4 girls who stopped GH treatment exceeded the predicted adult height by only 0 to 3.4 cm.

Hormonal treatment of cryptorchidism.

Hormonal treatment of cryptorchidism with a gonadotropic substance from pregnancy urine or with an anterior-pituitary-like substance dates from the early 1930s. Success rates varied from 25 to 100%. Subsequently, human chorionic gonadotropin (hCG) administered intramuscularly came into use. The success rates of several large studies have varied from 25 to 55%. Widely divergent results have, likewise, been reported following the intranasal administration of luteinizing-hormone-releasing hormone (LHRH), the efficacy of which has been investigated in many studies, including placebo-controlled trials. Combined LHRH and hCG treatment schedules have been recently assessed, with equally divergent success rates. The most important factor influencing the rate of success is the testicular position before treatment: the lower the position of the testis before treatment the better the result. The experience with LHRH nasal spray treatment for cryptorchidism in 252 prepubertal boys is presented in this study, including several years follow-up, and the results compared with data reported in the literature.

Long-term effects of oxandrolone treatment in childhood on neurocognition, quality of life and social-emotional functioning in young adults with Turner syndrome

Turner syndrome (TS) is the result of (partial) absence of one X-chromosome. Besides short stature, gonadal dysgenesis and other physical aspects, TS women have typical psychological features. Since psychological effects of androgen exposure in childhood probably are long-lasting, we explored long-term psychological functioning after oxandrolone (Ox) therapy during childhood in adults with TS in terms of neurocognition, quality of life and social-emotional functioning. During the initial study, girls were treated with growth hormone (GH) combined with placebo (Pl), Ox 0.03 mg/kg/day, or Ox 0.06 mg/kg/day from the age of eight, and estrogen from the age of twelve. Sixty-eight women participated in the current double-blinded follow-up study (mean age 24.0 years, mean time since stopping GH/Ox 8.7 years). We found no effects on neurocognition. Concerning quality of life women treated with Ox had higher anxiety levels (STAI 37.4 ± 8.4 vs 31.8 ± 5.0, p=0.002) and higher scores on the depression subscale of the SCL-90-R (25.7 ± 10.7 vs 20.5 ± 4.7, p=0.01). Regarding social-emotional functioning, emotion perception for fearful faces was lower in the Ox-treated patients, without effect on interpersonal behavior. Our exploratory study is the first to suggest that androgen treatment in adolescence possibly has long-term effects on adult quality of life and social-emotional functioning. However, differences are small and clinical implications of our results seem limited. Therefore we would not recommend against the use of Ox in light of psychological consequences.

Calcinosis cutis, osteoma cutis, poikiloderma and skeletal abnormalities (COPS syndrome) — a new entity?

A 4-year-old boy with subcutaneous tumours is described. These tumours were calcified and had secondary osteoma formation. In addition the patient showed poikiloderma on the face and less prominently on arms and legs. X-ray films of the distal metaphyses of the radius, ulna and tibia revealed irregular mineralisation. Repeated laboratory tests revealed no abnormalities of fat, bone and mineral metabolism. This patient showed a unique combination of symptoms. We propose to call this syndrome: COPS-syndrome (Calcinosis cutis,Os-teoma cutis.Poikiloderma andSkeletal abnormalities).

Growth hormone deficiency: Etiology, pathology, science and diagnosis

Although the diagnosis GHD is easy in children with the severe form of GHD caused by gene deletion, it is much more complicated to distinguish the less severe cases of GHD from the short child without GHD with regard to growth velocity and GH secretory status. The results of GH stimulation test should be viewed with caution and supplemented with IGF-I measurements and spontaneous 24 hours GH profiles when neurosecretory dysfunction is suspected. Statural growth should be followed very carefully. Pediatric endocrinologists are more and more convinced that a low growth velocity is a more important indication for GH treatment than the results of biochemical measurements and tests.ConclusionAlthough the diagnosis GHD is easy in children with the severe form of GHD caused by gene deletion, it is much more complicated to distinguish the less severe cases of GHD from the short child without GHD with regard to growth velocity and GH secretory status. The results of GH stimulation test should be viewed with caution and supplemented with IGF-I measurements and spontaneous 24 hours GH profiles when neurosecretory dysfunction is suspected. Statural growth should be followed very carefully. Pediatric endocrinologists are more and more convinced that a low growth velocity is a more important indication for GH treatment than the results of biochemical measurements and tests.