[New indications of protontherapy for adults intracranial tumours]. / Nouvelles indications de protonthérapie et essais cliniques en cours : tumeurs intracrâniennes.

Considering intracranial tumours, only few indications of protontherapy, such as chordoma, chondrosarcoma or uveal melanoma, are uniformly approved in the world. Other indications, excluding paediatric pathologies, are still debated. The aim of this article is to describe the rationale for the use of protonbeam irradiation for meningioma, pituitary adenoma, craniopharyngioma, paraganglioma, glioma, and schwannoma, and to inform the radiation oncologists if prospective studies or randomized studies are opened for inclusions. This article deals only with indications for adults.

[Digital applicator by 3D printing in contact brachytherapy]. / Applicateur numérique par impression tridimensionnelle en curiethérapie de contact.

Brachytherapy of skin tumours uses custom applicators that are manufactured manually. The integration of 3D printing customization of applicators during hidh dose rate brachytherapy planning could allow a better skin conformation and a better reproducibility of the positioning and treatment. We present the technical implementation of this method for our first two patients. A provisional planning scanner was carried out to create a digital applicator. The creation of the digital applicator used successively several software programs. The first, commercial, was RhinocerosR 3D used via Grasshopper, an integrated open source plug-in. The 3D applicator was then exported to the commercial software Simplify3DR. A g-code format file was generated for the printer. A second scanner was made with a 3D applicator in place to plan the final treatment. The treatment was planned by reverse optimization. The applicator could be designed within 15 days. For patient A, it was noted that 95 % of the clinical target volume received at least 35.4Gy (63Gy EQD2). For patient B, 95 % of the clinical target volume received at least 36Gy (64.8Gy EQD2). The forecast and actual planimetry met the coverage criteria of D95. Contact brachytherapy with 3D bioimpression is feasible, after software training, for complex treatment lesions. This technique could be extended to other indications.

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation.

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c., during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GH deficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 +/- 2.0 to 10.1 +/- 1.7 cm/y; p < 0.001) and with the first year of observation in Group 2 (p < 0.001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3 y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 +/- 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3 y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.

Turner's syndrome with X-isochromosome and Hashimoto's thyroiditis.

OBJECTIVE: The higher frequency of Hashimoto's thyroiditis in Turner's syndrome compared with the general population is well known. We have attempted to establish clearly the more frequent association of thyroiditis with the X-isochromosome, since previous reports of this aspect have included only small numbers of patients. DESIGN: Retrospective study of patients with Turner's syndrome investigated within the past 12 years. PATIENTS: Sixty-seven cases of Turner's syndrome were reviewed. MEASUREMENTS: Peripheral blood leucocyte karyotype and screening for thyroid disturbances on the basis of clinical examination and laboratory evaluation (anti-thyroglobulin and anti-microsomal antibodies, basal TSH levels and TSH levels after TRH stimulation) were made for each patient. RESULTS: A diagnosis of thyroiditis, based on the association of positive antibody titres, elevated TSH and an abnormal thyroid gland on clinical examination, was established in 20.9% (14/67) of cases. A significantly higher frequency of thyroiditis was found among the patients presenting with an X-isochromosome (57.3%, 9/16), compared to patients with other karyotypes (9.8%, 5/51) (P = 0.0001). CONCLUSIONS: Our results, obtained by investigation of a larger number of patients with an X-isochromosome karyotype than in previous reports, confirm conclusively that patients with X-isochromosome Turner's syndrome have an increased risk of developing thyroiditis.

[Growth retardation of psychosocial origin. Clinical and biological aspects in four cases]. / Retard de croissance d'origine psychosociale. Aspects cliniques et biologiques de quatre observations.

Four cases of psychosocial dwarfism are reported. The growth follow-up of these four children does not fit to the classical description of rapid improvement once separated from their defective or careless family. This illustrates the difficulties for some children to adapt themselves to a foster family and the need to refer them to an institutional center in order to solve their different somatic, nutritional and psychological problems, together with those of their family. In such cases the important growth retardation and hormonal changes may hide severe psychopathological troubles such as hyperkinetic syndrome, anxiety and, possibly, depression.

[Prolactin-secreting macroadenoma in an adolescent girl: response to the medical treatment and follow-up method]. / Macroadénome à prolactine chez une adolescente: réponse au traitement médical et méthode de surveillance.

The authors report the case of a 14 year-old-girl presenting with a prolactin-secreting pituitary macroadenoma and followed over one year of bromocriptine therapy. They focus on the specific clinical features, on the medical management as initial therapy at this age, and on the interest of magnetic resonance imaging and spontaneous hormonal secretion studies for the diagnosis and follow-up.

[Thyroiditis and Turner's syndrome]. / Thyroïdite et syndrome de Turner.

Two patients with Turner's syndrome and Hashimoto's thyroiditis are described. The incidence of the karyotype 46 XX (iq), 45 X is high in this association reported in the literature; thus, 17 patients among 25 with Turner's syndrome and thyroiditis had a structural abnormality of the X chromosome. Routine thyroid antibodies determination should be carried out in patients with gonadal dysgenesis between 10 and 20 years of age, and early replacement therapy should be undertaken in Turner's syndrome with Hashimoto's thyroiditis, since clinical signs of hypothyroidism are usually delayed.

[Growth of children treated for leukemia or malignant lymphoma. Influence of cranial radiotherapy]. / Croissance des enfants traités pour leucémie ou lymphome malin. Influence de la radiothérapie crânienne.

We studied the height growth of 96 children presenting with acute leukemia or non Hodgkin lymphoma, together with an investigation of GH and TSH in 41 of them. There were 2 groups: group I consisting of 19 patients without brain irradiation and group II consisting of 77 patients with prophylactic brain irradiation. Initial average height was identical in both groups. Growth rate was significantly decreased in group II but not in group I (p less than 0.01). There is a correlation between the decrease of growth rate and the decrease of GH to arginine stimulation test (p less than 0.03). A lack of response to GRF-44 was noted in 4 of 11 investigated patients. TSH and prolactin secretions were unchanged.

1-year treatment with recombinant somatropin in prepubertal and pubertal growth hormone deficient patients: results from a French multicentre trial.

In this French study with recombinant somatropin, the stimulation of growth in 32 prepubertal (age 10.0 +/- 3.5 years; mean +/- SD) and 19 pubertal (age 14 +/- 1.5 years) GH deficient children was compared; the stimulation of growth was similarly good in the two groups. The height velocity SD scores increased from -2.5 +/- 1.7 and -0.9 +/- 1.5 to 2.2 +/- 1.9 and 1.6 +/- 1.6 in prepubertal and pubertal children, respectively. Expressed as cm/year, these correspond to increases from 3.2 +/- 1.3 cm/year and 4.1 +/- 1.2 cm/year to 8.1 +/- 1.5 cm/year and 8.6 +/- 1.9 cm/year in the prepubertal and pubertal patients, respectively. Safety and tolerance were good and the immunogenicity of Genotonorm was low.

[Turner's syndrome and the urocytogram]. / Syndrome de Turner et urocytogrammes.

The cellular material studied in the urinary sediment mainly obtained from exfoliated cells of the bladder trigone was submitted to hormonal stimulation. These cell changes constitute the basis of a cytological method called urocytogram. The urinary sediment was examined in twenty seven girls with Turner's syndrome. The authors consider the interest of repeat examinations in the follow-up and treatment of these patients.

Trisomy 11p15 and Beckwith-Wiedemann syndrome. Report of two new cases.

An association between trisomy 11p15 and Beckwith-Wiedemann syndrome is described in two brothers. The first presented at birth with gigantism and macroglossia, umbilical hernia and abdominal distention, hypoglycemia and atresia of the pulmonary artery, leading to the diagnosis of Beckwith-Wiedemann syndrome. Facial dysmorphism also included: a hypoplastic midface, hypertelorism, and a short nose with a flattened bridge. The karyotype showed a trisomy 11p15 with a monosomy 18p11, due to a t(11;18)(p154;p111)pat. His brother, born a year later, showed the same signs. The association between trisomy 11p15 and Beckwith-Wiedemann syndrome is in certain cases well established.

Familial male pseudohermaphroditism due to 17-20-desmolase deficiency. I. In vivo endocrine studies.

In two siblings with male pseudohermaphroditism (ambiguous external genitalia, XY karyotype) and apparently normal glucocorticoid function, plasma concentrations of 10 progestagens or androgens measured by specific RIAs were found to be abnormal under either basal or dynamic conditions. Basal levels of delta 4-androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were subnormal and failed to rise after ACTH stimulation both before and after castration. Meanwhile, levels of pregnenolone, pregnenolone sulfate, 17 alpha-hydroxyprogesterone, and 17 alpha-hydroxypregnenolone were extremely high under basal conditions and rose further after ACTH. All of the progestagens and cortisol were suppressed by dexamethasone. After hCG stimulation, either before treatment or during dexamethasone therapy, the rise in testosterone was less than 100 ng/dl, while the progestagens showed an abnormally high rise. The latter were markedly reduced after castration. These findings are consistent with steroid 17--20-desmolase deficiency in both the testes and adrenal glands. In the third brother, who had only slight abnormalities of his genitalia, a mild form of the same defect was suspected. Low androgens, high 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone levels were found in the amniotic fluid and umbilical cord and peripheral blood at birth. The parents, who were not consanguine, had normal baseline levels of all hormones. The familial occurrence of the disease is suggestive of autosomal recessive inheritance.

Low serum somatomedin activity in celiac disease. A misleading aspect in growth failure from asymptomatic celiac disease.

In 4 children with celiac disease, aged 7 months to 11 years, serum somatomedin activities (SMA) were consistently low: less than 0.40 U/ml (N greater than 0.50 U/ml). Basal plasma growth hormone (GH) levels were not elevated and increased normally under arginine-insulin stimulation in 3 patients. Human GH administration at a dosage which usually determines an increase of serum SMA in children with GH deficiency (4 mg/day/2 days) did not modify significantly the low serum SMA. However, in 1 child a clear-cut increase of serum SMA (0.22-0.82 U/ml) was noted under a higher dosage of human GH (8 mg/day/2 days). In 3 patients serum SMA was studied 3 weeks to 4 months after starting the gluten-free diet and was found to be normal. A limitation of the somatomedin generation unrelated to a deficit in GH secretion and probably resistant to GH appears therefore to be present in celiac disease. The rapid normalization of serum SMA under gluten-free diet suggests that the low serum SMA is induced through some unknown hormonal or metabolic signal by the protein malabsorption and/or the nutritional deficiency present in celiac disease.

[Urocytogram and precocious puberty]. / Urocytogramme et puberté précoce

After a review of the technique of urocytogram the authors report the results obtained in 39 children between the ages of 3 and 12 years. Before the appearance of the first signs of puberty, urocytograms are similar in both girls and boys. Differences were seen in seven cases of male or female precocious puberty. Urocytograms are also different in patients with incomplete precocious puberty but less marked than in those with true precocious puberty. The authors consider the possibility of repeat urocytograms during the supervision or treatment of incomplete and complete precocious puberty.

[Cerebral gigantism in twins]. / Gigantisme cérébral chez des jumeaux

Two probably monozygotic twins with cerebral gigantism are reported. They showed three typical features: pneumo-encephalography demonstrated a fifth anterior ventricular dilatation; in both patients dermatoglyphic findings showed a thenar exit of the Aline and a vertical palmar alignement; Growth hormone and sulfatation factor blood concentration were low but within normal limits.