No abstract

To assess whether delaying puberty may improve final height in GH-deficient children with a poor height prediction at early puberty, we studied 24 girls with isolated GH deficiency until they reached their final height, in a controlled trial. Patients were taking recombinant human GH (r-hGH) substitutive therapy from 2.1 +/- 0.5 yr (0.1 IU/kg.day sc) before entering the study, without showing any improvement in height prediction (149.6 +/- 2.9 vs.150.3 +/- 2.2 cm) on entering puberty. Fourteen girls agreed to add a GnRH agonist (GnRHa) to r-hGH, whereas the remaining 10 decided against it and served as controls. At the start of the study, girls treated with or without GnRHa had similar auxological characteristics (bone age, 10.9 +/- 0.6 vs. 10.7 +/- 1.3 yr; height SD score for chronological age, -1.87 +/- 0.3 vs. -1.82 +/- 0.2), including pubertal development. The GnRHa (long-acting D-Trp-6-GnRH) was given at 60 microg/kg im every 28 days for 1.9 +/- 0.9 yr, then patients continued the r-hGH at the same dosage (3.1 +/- 0.7 yr). At the end of the study, bone age was 16.2 +/- 0.3 yr in GnRHa-treated girls and 16.6 +/- 0.9 yr in controls. Bone maturation was significantly slower during GnRHa (1.4 +/- 0.2 yr), and height SD score for bone age improved (-0.31 +/- 0.3) in comparison with controls (2.6 +/- 0.4 yr and -1.35 +/- 0.3 SD score; P < 0.001 and P < 0.0001, respectively). As a result, girls given the combined therapy reached a final height higher than that of controls (height SD score, -0.39 +/- 0.5 vs. -1.45 +/- 0.2; P < 0.0001) and also higher than their midparental height (-1.1 +/- 0.5; P < 0.0005). Controls reached their midparental height. In conclusion, our results demonstrate that slowing pubertal development with the administration of GnRHa for a limited time may improve final height in GH-deficient girls selected because of a poor height prediction at early puberty.

Although important advances in testicular physiology have been achieved, the aetiology of human cryptorchidism remains mostly unknown. Next to sex steroidal signaling pathways, morphogenetic genes are specifically involved in the testicular descent via gubernacular development. Mutations in the human genes encoding insulin-like factor 3 (INSL3) and its Leu-rich repeat-containing G protein-coupled receptor 8 (LGR8), homeobox A10 (HOXA10), zinc finger 214 (ZNF214) and 215 (ZNF215) have occasionally been identified but do not seem to be a frequent cause of cryptorchidism. On the other hand, common polymorphisms in these genes have recently been investigated as contributing risk factors for idiopathic isolated (nonsyndromic) cryptorchidism.

Five prepubertal girls (2.3-8.1 years old) were studied for isolated or recurrent vaginal bleeding in the absence of other signs of precocious puberty (premature menarche). Four of these girls with recurrent vaginal bleeding were studied for pulsatile gonadotropin secretory patterns. During sleep 3 girls showed luteinizing hormone (LH) pulses with low amplitude and a pubertal pattern of frequency whereas follicle-stimulating hormone (FSH) increased without demonstrable episodic secretion. Luteinizing hormone-releasing hormone (LHRH) tests demonstrated that FSH responses are greater than the LH responses, as in prepuberty. In 3 cases estradiol levels had augmented above normal prepubertal range. The menses spontaneously stopped during the follow-up. A reevaluation of the gonadotropin pattern, having the menses stopped for 6 months, in one of the girls with pulsatile LH secretion showed an apulsatile prepubertal LH pattern. Also estradiol levels returned to prepubertal range. A follow-up of 10-66 months of these patients did not show any growth and bone acceleration or signs of precocious puberty. Our data suggest that in premature menarche a partial and transient activation of hypothalamo-pituitary axis could be present. Premature menarche seems to be a benign and self-limiting condition and one of the girls had a normal onset of puberty during follow-up.

Spontaneous growth hormone (GH) secretion in 116 short children was studied by sampling blood for GH measurement every 20min over 24 h. We calculated 24-h mean GH concentration (MGHC), diurnal 12-h MGHC (dMGHC) and nocturnal 12-h MGHC (nMGHC). The children were subdivided into four groups: prepubertal children with ‘classical’ GH deficiency (group 1, n = 12, low responses to two provocative stimuli tests and MGHC < 3 ng/ml), prepubertal children with ‘nonclassical GH deficiency (group 2, n = 36, normal GH responses to two provocative tests and MGHC < 3 ng/ml), short normal children (normal GH responses to two provocative tests and MGHC > 3 ng/ml) at stage PI of puberty (group 3, n = 41) and at stage P2 of puberty (group 4, n = 27). The values of MGHC, dMGHC and nMGHC were significantly higher in groups 3 and 4 than in groups 1 and 2, and in group 4 than in group 3. The values of MGHC and nMGHC were significantly higher in group 2 than in group 1. MGHC correlated highly with nMGHC and dMGHC (r = 0.97 and 0.94, respectively; p < 0.001). On the basis of regression equations between MGHC and nMGHC or dMGHC, the study of the diagnostic accuracy showed values higher for nMGHC than for dMGHC: 94.1 vs. 89.6% for sensitivity, and 93.7 vs. 89.7% for specificity, respectively.