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Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy., Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL., Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%., Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To evaluate the influence of the type and treatment of CNS lesion causing central precocious puberty (CPP) on the presentation, hypothalamic-pituitary function and final height., Patients: One hundred patients with CPP caused by central nervous system (CNS) lesion., Results: The CPP was the presenting symptom of the lesion in 25 (10 boys) and occurred in 75 patients (23 boys) previously treated for lesions. These were optic glioma or astrocytoma (n = 45), hydrocephalus (n = 22), hypothalamic hamartoma (n = 15), suprasellar arachnoid cyst (n = 10) and others (n = 8). The percentages of patients with increased height, bone age advance, testicular volume, LH/FSH peaks ratio after gonadotrophin-releasing hormone (GnRH) test and plasma testosterone concentration in boys and oestradiol in girls varied from one aetiology to another. The boys with hamartoma were significantly taller and had greater bone age advance, LH peak and testosterone than boys with optic glioma. The girls with hamartoma and suprasellar arachnoid cyst were significantly younger and had greater LH peak than girls in the other groups. All patients treated for optic glioma had hypothalamic-pituitary deficiencies, including GH (100%), thyrotrophin (71.4%), corticotrophin (12.5%) and pubertal (34.3%) deficiencies. Sixty percent of those with suprasellar cysts lacked GH. Final height was below -2 SD in 15/59 (25%) patients, including 5/11 not treated with GnRH analogue, 3/5 not treated with GH despite GH deficiency, and 2 with hydrocephalus as a result of meningomyelocele., Conclusions: The type of CNS lesion influences the presentation of CPP. This is probably caused by differences in the mechanisms inducing puberty and to the hypothalamic-pituitary deficiencies associated with the CPP as a result of a lesion and/or its treatment.

Context: Defined as the loss of ovarian function within 5 yr of diagnosis, acute ovarian failure (AOF) is known to develop in a subset of survivors of pediatric and adolescent cancers. Its precise incidence is unknown, and data concerning its risk factors are limited., Objective: Our objective was to determine the incidence of and patient/treatment factors associated with AOF in a large cohort of pediatric cancer survivors., Design and Setting: We conducted a retrospective cohort, multicenter study., Patients: Female participants from the Childhood Cancer Survivor Study who were greater than 18 yr of age were considered for inclusion. We excluded survivors who received cranial irradiation at doses of more than 3000 cGy, those with hypothalamic/pituitary tumors, and survivors who underwent bilateral oophorectomy. Survivors who reported never menstruating or who had ceased having menses within 5 yr after their cancer diagnosis were considered to have AOF., Main Outcome: We assessed incidence and risk factors for AOF., Results: Of a total of 3390 eligible survivors, 215 cases (6.3%) developed AOF. Survivors with AOF were older at diagnosis and more likely to have been diagnosed with Hodgkin's lymphoma or to have received abdominal or pelvic radiotherapy than survivors without AOF. Among survivors with AOF, 116 (54%) had received at least 1000-cGy ovarian irradiation. In a multivariable logistic regression model, increasing doses of ovarian irradiation, exposure to procarbazine, and exposure to cyclophosphamide at ages 13-20 yr were independent risk factors for AOF., Conclusions: AOF develops in a small subset of survivors, especially those treated with at least 1000-cGy ovarian radiation. These results will facilitate patient counseling and selection of candidates for newer fertility preservation techniques.

Adrenal disorders causing hypertension can be related to the dysfunction of either the adrenal cortex or the adrenal medulla. These disorders, including congenital adrenal hyperplasia (CAH), owing to 11B-hydroxylase deficiency and to 17alpha-hydroxylase deficiency; apparent mineralocorticoid excess; familial hyperaldosteronism type I; primary aldosteronism; Cushing's syndrome; and familial glucocorticoid resistance, primarily affect the adrenal cortex and cause low-renin hypertension. The classic disorder of the adrenal medulla resulting in hypertension is pheochromocytoma, although hypertension in obesity might also be associated with catecholamine secretion. In this review, we discuss these etiologies and the most recent advances in our knowledge of their pathophysiology, diagnosis, and treatment.

Objectives: To optimize the indications for treating girls with idiopathic central precocious puberty with GnRH analogues, since outcomes may vary., Design: Comparison of adult heights with the data at initial evaluation and the target heights., Patients: Group 1 patients (n = 43) were treated with GnRH analogue from 7.9 +/- 0.2 years to 10.8 +/- 0.1 years (bone age: 10.3 +/- 0.2 years to 12.2 +/- 0.1 years) and group 2 patients (n = 29) were monitored without treatment because their predicted adult heights were > 155 cm. The criteria for treatment were a predicted height < 155 cm and/or a LH/FSH peaks ratio of > 0.6., Results: At initial evaluation, group 1 patients had greater breast development (P = 0.001) and bone age advances (2.0 +/- 0.2 years) than those of group 2 (1.3 +/- 0.2 years, P < 0.3), and higher plasma oestradiol concentrations (139 +/- 11 pmol/l vs. 62 +/- 7 pmol/l, P = 0.0001), LH peak (12.2 +/- 1.8 IU/l vs. 5.8 +/- 2.2 IU/l, P = 0.0001) and LH/FSH peaks ratio (1.3 +/- 0.2 vs. 0.5 +/- 0.1, P = 0.0001). The predicted height for group 1 at the onset of treatment (156 +/- 1.2 cm) was lower than the adult height (159.5 +/- 0.8 cm, P = 0.002), but the two were similar (164.1 +/- 1.2 cm vs. 162.7 +/- 0.9 cm) for group 2. In group 1, the difference between these heights (mean 3.4 cm) was positively correlated with the bone age advance (r = 0.51, P = 0.001), but not with chronological or bone ages, oestradiol, LH peak, LH/FSH peaks ratio before treatment or its duration. It was 5.3 +/- 1.2 cm in the 28 patients with a bone age advance of > 2 years and 0 +/- 1.3 cm in the other 15 (P < 0.02). It was 6.1 +/- 1.3 cm in the 24 patients with predicted height < 155 cm, and -0.1 +/- 1.1 cm in the other 18 (P = 0.002). The 72 patients included nine who attained an adult height over 5 cm shorter than the target height (seven treated and two untreated). The seven treated subjects included two who had retarded intrauterine growth., Conclusions: Treatment of girls with idiopathic central precocious puberty with GnRH analogues produced a mean height increase of 3.4 cm between the predicted and adult heights. The increase was greater for girls with a bone age advance of > 2 years and a predicted height < 155 cm. Adult height is spontaneously preserved in the slowly progressing form. The classical and slowly progressing forms can be distinguished by the degrees of breast development and bone age advance.

Objective: To identify predictors of central precocious puberty (CPP) that reveal central nervous system (CNS) abnormalities in girls with CPP., Methods: A retrospective cohort study was conducted of all girls younger than 8 years with breast development related to CPP, seen between 1982 and 2000, in a university pediatric hospital in Paris, France. For a pilot population (186 idiopathic, 11 revealing CNS abnormalities), the accuracy of the Lawson Wilkins Pediatric Endocrine Society recommendations were evaluated. Potential clinical, radiological, and biological predictors of CNS abnormalities were assessed by univariate and multivariate analyses. A diagnosis tree aiming for 100% sensitivity for the detection of CNS abnormalities was constructed and was tested on a validation population (39 idiopathic, 3 revealing CNS abnormalities)., Results: Applying the Lawson Wilkins Pediatric Endocrine Society recommendations, 2 of 11 girls with CPP that revealed CNS abnormalities would not have been considered to require brain imaging. Independent predictors of CNS abnormalities were age at onset of puberty <6 years (adjusted odds ratio [AOR]: 6.7; 95% confidence interval [CI]: 1.5-29), lack of pubic hair at diagnosis (AOR: 7.7; 95% CI: 1.8-33), and estradiol >110 pmol/L (AOR: 4.1, 95% CI: 1.0-17). The diagnosis tree that was constructed on the basis of these predictors had 100% sensitivity and 56% specificity for the validation population., Conclusion: The identification of girls who have CPP and require cerebral imaging seems possible on the basis of validated, simple, and reproducible predictors: age and estradiol. However, this process needs to be tested on other populations.