Thomas Moshang

Brain tumor recurrence in children treated with growth hormone: The National Cooperative Growth Study experience☆☆☆★★★

As of October 1993 the National Cooperative Growth Study included 1262 children with brain tumor who were treated with growth hormone. The type of brain tumor was specified in 947 (75%) of these children. The most common types were glioma, medulloblastoma, and craniopharyngioma, accounting for 91.3% of all those for which type was specified. Brain tumor recurred in 83 (6.6%) of the 1262 children over a total of 6115 patient-years at risk. The frequencies of tumor recurrence in children with low-grade glioma (18.1%), medulloblastoma (7.2%), and craniopharyngioma (6.4%) are lower than those in published reports of tumor recurrence in the general pediatric population with the same types of tumors. The analysis cannot conclusively show that no increased risk of tumor recurrence exists, however, because of the potential incompleteness of data reporting in the National Cooperative Growth Study. Nevertheless the findings are reassuring that children with the more common types of brain tumor who are treated with growth hormone do not seem to be at excessive risk for tumor recurrence.

Somatic growth failure after the Fontan operation.

Our study was designed to characterize the patterns of growth, in the medium term, of children with functionally univentricular hearts managed with a hemi-Fontan procedure in infancy, followed by a modified Fontan operation in early childhood. Failure of growth is common in patients with congenital cardiac malformations, and may be related to congestive heart failure and hypoxia. Repair of simple lesions appears to reverse the retardation in growth. Palliation of the functionally single ventricular physiology with a staged Fontan operation reduces the adverse effects of hypoxemia and prolonged ventricular volume overload. The impact of this approach on somatic growth is unknown. Retrospectively, we reviewed the parameters of growth of all children with functionally univentricular hearts followed primarily at our institution who had completed a staged construction of the Fontan circulation between January 1990 and December 1995. Measurements were available on all children prior to surgery, and annually for three years following the Fontan operation. Data was obtained on siblings and parents for comparative purposes. The criterions of eligibility for inclusion were satisfied by 65 patients. The mean Z score for weight was -1.5 +/- 1.2 at the time of the hemi-Fontan operation. Weight improved by the time of completion of the Fontan circulation (-0.91 +/- 0.99), and for the first two years following the Fontan operation, but never normalized. The mean Z scores for height at the hemi-Fontan and Fontan operations were -0.67 +/- 1.1 and -0.89 +/- 1.2 respectively. At most recent follow-up, with a mean age of 6.1 +/- 1.3 years, and a mean time from the Fontan operation of 4.4 +/- 1.4 years, the mean Z score for height was -1.15 +/- 1.2, and was significantly less than comparable Z scores for parents and siblings. In our experience, children with functionally univentricular hearts who have been palliated with a Fontan operation are significantly underweight and shorter than the general population and their siblings.

Endocrine outcome in long-term survivors of low-grade hypothalamic/chiasmatic glioma

We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy.

Late effects in survivors of tandem peripheral blood stem cell transplant for high-risk neuroblastoma.

Increasing numbers of children with advanced neuroblastoma are achieving cure. We describe the clinical late effects specific to survivors of stage IV neuroblastoma all similarly treated using tandem autologous peripheral blood stem cell rescue with TBI.

Serum IGF‐I and IGFBP‐3 concentrations do not accurately predict growth hormone deficiency in children with brain tumours

The growth hormone (GH)‐dependent growth factors insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein‐3 (IGFBP‐3) may be superior to provocative GH testing in diagnosing GH deficiency (GHD) in children. In adults with brain tumours (BT) and GHD, however, provocative GH testing more accurately reflects GHD than either IGF‐I or IGFBP‐3. We assessed growth factor levels in children with GHD due to BT with respect to brain tumour type, pubertal stage, growth velocity, bone age delay, and body mass index (BMI).

Constitutional delay of growth and development:Effects of treatment with androgens

Nineteen male children with “constitutional delay in growth and/or development”qualified for this retrospective study of the effects of androgens on final adult stature. Twenty-one patients served as untreated control subjects. The bone age was retarded in all patients. Those in the treatment groups received methyltestosterone (13 patients), fluoxymesterone (4 patients), or testosterone enanthate (2 patients). The average duration of treatment was 5.3 months, and low doses of all three androgens were used. Predictions of final height overestimated actual achieved final heights by an average of 1.3 inches in the control group. Androgen therapy as described did not affect ultimate height adversely and, in fact, treated patients achieved an average final height much closer to the average predicted height than the control group.

Concentrations of Plasma Luteinizing Hormone in Infants, Children, and Adolescents with Normal and Abnormal Gonadal Function

Extract: This communication reports the edevelopment of a sensitive, reproducible, and specific radioimmunoassay for luteinizing hormone (LH) in plasma and the application of this method to a cross-sectional survey of plasma LH concentrations in 243 infants, children, and adolescents with normal and abnormal growth and sexual development. One nanogram of Hartree purified human pituitary LH standard was immunologically equivalent to 13.7 mIU of the Second International Reference Preparation of Human Menopausal Gonadotropin. The lower limit of sensitivity of the assay varied between 0.025 and 0.05 ng/ml. Specimens of plasma containing <0.25 ng/ml (<3.7 mIU/ml) have been considered indistinguishable from ‘zero’.Plasma LH concentrations increased after 9 years of age in normal boys and after 6 years of age in normal girls. In males with constitutional delay in growth and development, LH levels were generally lower than in normal boys of comparable ages (figs. 3 and 4). The plasma LH concentration also increased with advancing sexual maturation (fig. 5).Levels of LH were <0.25 ng/ml in 15 of 18 males (6-20 years old) and in 10 of 11 females (6-19 years old) with hypopituitarism and documented lack of human growth hormone response to hypoglycemia. In three such patients, plasma LH concentrations correlated with their degrees of sexual maturation, but in a 16-year-old clinically prepubertal male, patient SA, with hypopituitarism secondary to a craniopharyngioma, LH levels higher than normal male values were noted.Plasma LH concentrations were 1.2 and 1.45 ng/ml in 2 of 3 girls less than 4 years old, with gonadal dysgenesis, and ranged between 0.33 and 3.6 ng/ml in 10 of 15 older patients with this diagnosis (table III). The plasma LH concentration was 1.7 ng/ml in a 3-month-old male pseudohermaphrodite. Plasma LH concentrations ranged between 0.38 and 0.88 ng/ml in five of seven children with true sexual precocity. In 13 of 15 girls with precocious thelarche, and in all of 10 patients with premature pubarche, LH levels were <0.25 ng/ml. The intravenous infusion of conjugated equine estrogens was followed by a prompt decline in polasma LH values in patient SA (fig. 6A,B,C). Administration of clomiphene citrate and cisclomiphene citrate increased plasma LH concentrations in normal males, but failed to do so in patients with hypopituitarism, including patient SA (fig. 7A,B). The intramuscular administration of medroxyprogesterone acetate was associated with suppression of plasma LH levels in two patients with true sexual precocity (fig. 8).Speculation: The hypothalamic-pituitary-gonadal axis is active in the prepubertal human subject, and is responsive to abnormal function in one segment of the system.

Growth hormone releasing hormone plus arginine stimulation testing in young adults treated in childhood with cranio-spinal radiation therapy.

Objective  Growth hormone deficiency (GHD) secondary to cranio‐spinal radiation therapy (CSRT) is a complication seen in medulloblastoma survivors. The standard for diagnosis of adult GHD is a peak GH < 3 µg/l by the insulin tolerance test (ITT). However, insulin tolerance testing exposes patients to the risks of hypoglycaemia. Recent studies suggest that the GH releasing hormone + arginine (GHRH + ARG) test can identify GHD in cranially irradiated patients at longer time intervals after radiation. We evaluated the GHRH + ARG stimulation test compared to the ITT in young adults diagnosed with medulloblastoma during childhood.

Diagnostic Dilemmas: Results of Screening Tests for Congenital Hypothyroidism

The natural history of congenital hypothyroidism has changed drastically since the institution of newborn screening in North America, Europe, and Japan. Before screening was available, diagnosis of this condition was often delayed. The IQ of 65% of all patients with congenital hypothyroidism was below 85, and 19% were profoundly retarded (IQ less than 15). In two large screening programs in which long-term IQ data are available, no child has tested below the IQ of 74. Furthermore, a comparison of affected children treated within the first month of life with matched controls demonstrated no significant difference in IQ scores between the two groups. Widespread screening has lead to the evaluation of over 7 million infants annually. This represents over 1200 fewer children with subnormal intelligence, and approximately 360 children annually who are saved from the effects of profound mental retardation. There is little doubt that newborn screening is one of the greatest advances in diagnosis and treatment of endocrine disease in the newborn period to occur in the past 20 years. However, even experienced screening programs are not perfect, so the practitioner must remain alert to the possibility of undiagnosed hypothyroidism presenting in infancy.

Noonan syndrome with intestinal lymphangiectasis: A metabolic and anatomic study

A child with Noonan syndrome presented with failure to thrive, edema of the extremities, and a seemingly mild cardiac lesion at age four months. The edema progressed with the development of anasarca at six years, accompanied by severe hypoproteinemia. Investigation revealed a protein-losing enteropathy (intestinal lymphangiectasis) which responded to medium-chain triglycerides and a low-fat diet. The improvement was transient, and a compartmental shift of fluids further stressed an already compromised myocardium. The pulmonary valvular stenosis was relieved surgically, but the patient died postoperatively. It is suggested that this intestinal abnormality may be another manifestation of a generalized defect in cardiovascular-lymphatic organogenesis in this syndrome. Perhaps the cardiovascular lesion should be corrected before attempting to relieve the malabsorption.