Ana-Claudia Couto-Silva

Hypothalamic-Pituitary Lesions in Pediatric Patients: Endocrine Symptoms Often Precede Neuro-Ophthalmic Presenting Symptoms

OBJECTIVE To evaluate whether analyses of clinical and endocrine presenting symptoms could help to shorten the time to diagnosis of hypothalamic-pituitary lesions in children. STUDY DESIGN A retrospective, single-center, cohort study of 176 patients (93 boys), aged 6 years (range, 0.2-18 years), with hypothalamic-pituitary lesions was performed. RESULTS The lesions were craniopharyngioma (n = 56), optic pathway glioma (n = 54), suprasellar arachnoid cyst (n = 25), hamartoma (n = 22), germ cell tumor (n = 12), and hypothalamic-pituitary astrocytoma (n = 7). The most common presenting symptoms were neurologic (50%) and/or visual complaints (38%), followed by solitary endocrine symptoms (28%). Precocious puberty led to diagnosis in 19% of prepubertal patients (n = 131), occurring earlier in patients with hamartoma than in patients with optic-pathway glioma (P < .02). Isolated diabetes insipidus led to diagnosis for all germ-cell tumors. For 122 patients with neuro-ophthalmic presenting symptoms, the mean symptom interval was 0.5 year (95% CI, 0.4-0.6 year), although 66% of patients had abnormal body mass index or growth velocity, which preceded the presenting symptom interval onset by 1.9 years (95% CI, 1.5-2.4 years) (P < .0001) and 1.4 years (95% CI, 1-1.8 years) (P < .0001), respectively. Among them, 41 patients were obese before diagnosis (median 2.2 years [IQR, 1-3 years] prior to diagnosis) and 35 of them had normal growth velocity at the onset of obesity. The sensitivity of current guidelines for management of childhood obesity failed to identify 61%-85% of obese children with an underlying hypothalamic-pituitary lesion in our series. CONCLUSIONS Endocrine disorders occurred in two-thirds of patients prior to the onset of the neuro-ophthalmic presenting symptom but were missed. Identifying them may help to diagnose hypothalamic-pituitary lesions earlier.

Presentation and evolution of organic central precocious puberty according to the type of CNS lesion

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.

Idiopathic central precocious puberty in girls: presentation factors.

BackgroundIt is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP).Methods353 girls monitored 0.9 ± 0.7 year after the onset of CPP.ResultsThe age at CPP was < 3 years in 2%, 3–7 years in 38% and 7–8 years in 60% of cases. Pubic hair was present in 67%, growth rate greater than 2 SDS in 46% and bone age advance greater than 2 years in 33% of cases. Breast development was clinically isolated in 70 (20%) cases. However, only 31 of these (8.8% of the population) had a prepubertal length uterus and gonadotropin responses to gonadotropin releasing hormone and plasma estradiol. The clinical picture of CPP became complete during the year following the initial evaluation.25% of cases were obese. The increase in weight during the previous year (3.7 ± 1.4 kg) and body mass index were positively correlated with the statural growth and bone age advance (P < 0.0001).There was no relationship between the clinical-biological presentation and the age at puberty, the interval between the onset of puberty and evaluation, or the presence of familial CPP.ConclusionThe variation in presentation of girls with CPP does not depend on their age, interval between the onset and evaluation, or familial factors. This suggests that there are degrees of hypothalamic-pituitary-ovarian activation that are not explained by these factors.

Final height and gonad function after total body irradiation during childhood.

Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 μg/l. Final height was <−2s.d. in 29 (58%). The height loss between TBI and final height (2.4±1.1 s.d.) was greater in those who were younger when irradiated (P<0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4–8 years for the GH-treated and at 6–8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P=0.0008) and between plasma FSH and inhibin B (P=0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.

Presentation of 493 Consecutive Girls with Idiopathic Central Precocious Puberty: A Single-Center Study

Background Despite the number of reported data concerning idiopathic central precocious puberty (CPP) in girls, major questions remain including its diagnosis, factors, and indications of gonadotropin releasing hormone (GnRH) analog treatment. Methods A retrospective, single-center study was carried out on 493 girls with CPP. Results Eleven girls (2.2%) were aged less than 3 years. Breast development was either isolated (Group 0, n = 99), or associated with one sign, pubic hair development, growth rate greater than 2 standard deviation score (SDS) or bone age (BA) >2 years above chronological age, (Group 1, n = 187), two signs (Group 2, n = 142) or three signs (Group 3, n = 65). The interval between onset of puberty and evaluation, body mass index (BMI) SDS, plasma luteinising hormone (LH) concentrations (basal and peak) and LH/ follicle-stimulating hormone (FSH) peak ratio after GnRH test, plasma estradiol and uterus length were significantly greater in Groups 2 and 3 than in Groups 0 and 1 respectively. 211 (42.8%) patients were obese and/or had excessive weight gain during the year before puberty. Obese girls more often had BA advance of >2 years (p = 0.0004) and pubic hair development (p = 0.003) than the others. BMI did not correlate with LH or with LH/FSH peak ratio. Girls with familial history of early puberty (41.4%) had greater frequencies of pubertal LH/FSH peak ratios (p = 0.02) than the others. During the 31 years of the study, there was no increase in the frequency of CPP or variation in its characteristics. Conclusion Obesity is associated with a higher BA advance and higher frequency of pubic or axillary hair development but not with LH secretion, suggesting that obesity accelerates adrenarche but not the maturation of the hypothalamic-pituitary-ovarian axis. The LH/FSH peak ratio was more frequently pubertal in girls with a familial history of early puberty, suggesting that this maturation depends on genetic factors.

Predicting the adult height of girls with central precocious puberty

Summary Background There are no absolute criteria for identifying those girls with idiopathic central precocious puberty (CPP) who will benefit from gonadotropin-releasing hormone analog (GnRHa) treatment. Our objective was to predict at initial evaluation the differences between adult height (AH) and target height (TH) and (for untreated girls) the time between puberty onset and first menstruation. Material/Methods The 122 girls with CPP who reached their AH included 70 who were given GnRHa because their predicted AH was <155 cm (n=24), their luteinising hormone (LH)/follicle-stimulating hormone peaks (FSH) ratio was >0.66 (n=41) and/or their estradiol was >15 pg/ml (n=40). The other 52 were untreated because their predicted AH was >155 cm. Multiple linear regressions were performed on several subsets of variables. Results Treated: the difference between AH and TH (−0.6±5.4 cm) was predicted by (using SDS) =3.68 (height at initial evaluation – TH) − 1.94 (height at initial evaluation-predicted AH) − 4.23; R2=0.73. Untreated: the difference between AH and TH (1.7±4.3 cm) was predicted by =2.76 (height at initial evaluation – TH) − 3.68 LH/FSH peaks ratio − 3.49; R2=0.77. Time between puberty onset and first menstruation (years) was predicted by =12.2 – 1.06 age CPP − 0.4 (height at initial evaluation – TH); R2=0.75. Conclusions A greater difference between height at initial evaluation and TH (SDS) is associated with a greater AH in treated and untreated girls, as are smaller differences between height at initial evaluation and predicted AH in treated and lower LH/FSH peaks ratios in untreated girls.

Bone markers after total body irradiation in childhood

Total body irradiation (TBI) can cause short stature because of decreased growth hormone (GH) and skeletal abnormalities. To evaluate the plasma concentrations of markers of bone formation (osteocalcin and procollagen type 1 amino-terminal propeptide, P1NP) and resorption (carboxy-terminal telopeptide, CTX), in patients (n=65) who had been given TBI at 6.6±0.4 years were evaluated at 9.8±0.4 years. Patients given single 10 Gy or fractionated 12 Gy TBI had similar characteristics, except that plasma insulin-like growth factor (IGF-1) was lower in those given a single 10 Gy. Seven had lower osteocalcin and two had higher CTX than controls. Bone markers (as zs) were positively correlated (osteocalcin with P1NP, ρ=0.42, P=0.0007; osteocalcin with CTX, ρ=0.3, P<0.02), but not P1NP with CTX. Plasma osteocalcin and CTX were also positively correlated with plasma IGF-1, but not with growth rate during the first year on GH (n=28). Adult height was −2.5±0.2 s.d.s. (n=49). Those irradiated when young (P=0.0002) or given single TBI lost more height between TBI and adult height. Most TBI patients had normal bone formation and resorption markers. Thus, impaired bone turnover is probably not the cause of their short stature and poor response to GH.

Factors predicting the adult height and age at first menstruation in 138 girls with idiopathic central precocious puberty

Multiple linear regression models are built to predict either the adult height or the age at first menstruation, for girls with an idiopathic central precocious puberty.