G Massa

Linear Growth in Patients With Turner Syndrome - Influence of Spontaneous Puberty and Parental Height

Growth data on 100 patients with Turner syndrome are reported. Seventeen had spontaneous puberty. Between the ages 11 and 13 years, height and height velocity were higher in these girls than in those with induced puberty. Final adult height, however, was not different. Patients disomic for Xp chromosome were taller than the monosomic ones, and the majority of them had spontaneous puberty. Significant positive correlations were found between height of Turner syndrome patients and corrected mid parental height, mothers height and fathers height from the age of 6 years. It is concluded that in patients with Turner syndrome spontaneous puberty and parental height should be accounted for in the evaluation of linear growth.

Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism

CONTEXTnGonadectomy is avoided whenever possible in boys with 45,X/46,XY. However, no clinical markers are currently available to guide clinicians in predicting gonadal tumor risk or hormone production.nnnOBJECTIVEnThe objective of the study was to test the hypothesis that gonadal histology and risk for development of a malignant germ cell tumor are reflected by the clinical presentation of a 45,X/46,XY individual.nnnDESIGNnThe design of the study was the correlation of clinical data [external masculinization score (EMS), pubertal outcome] with pathology data (gonadal phenotype, tumor risk).nnnSETTINGnThis was a multicenter study involving two multidisciplinary disorder of sex development teams.nnnPATIENTSnPatients included genetically proven 45,X/46,XY (and variants) cases, of whom at least one gonadal biopsy or gonadectomy specimen was available, together with clinical details.nnnINTERVENTIONSnPatients (n = 48) were divided into three groups, based on the EMS. Gonadal histology and tumor risk were assessed on paraffin-embedded samples (n = 87) by morphology and immunohistochemistry on the basis of established criteria.nnnMAIN OUTCOME MEASURESnGonadal differentiation and tumor risk in the three clinical groups were measured. Clinical outcome in patients with at least one preserved gonad was also measured.nnnRESULTSnTumor risk in the three groups was significantly related to the gonadal differentiation pattern (P < 0.001). In boys, hormone production was sufficient and was not predicted by the EMS.nnnCONCLUSIONSnThe EMS reflects gonadal differentiation and tumor risk in patients with 45,X/46,XY. In boys, testosterone production is often sufficient, but strict follow-up is warranted because of malignancy risk, which appears inversely related to EMS. In girls, tumor risk is limited but gonads are not functional, making gonadectomy the most reasonable option.

Five‐year follow‐up of growth hormone antibodies in growth hormone deficient children treated with recombinant human growth hormone

OBJECTIVE The aim was to investigate the long‐term evolution of circulating growth hormone antibodies (GH‐AB) during and after treatment with methionyl‐recombinant human growth hormone (met‐rhGH).

Serum levels of growth hormone-binding protein and insulin-like growth factor I in children and adolescents with Type 1 (insulin-dependent) diabetes mellitus

SummarySerum levels of insulin-like growth factor I are reduced in patients with Type 1 (insulin-dependent) diabetes mellitus. To evaluate the role of the hepatic growth hormone receptor in the decreased serum concentrations of insulin-like growth factor I, serum levels of the high affinity growth hormone-binding protein, which is qualitatively and quantitatively related to the hepatic growth hormone receptor, and of insulin-like growth factor I were measured in 70 children and adolescents with Type 1 diabetes and 105 healthy control children. Analysis of variance revealed a significant negative effect of Type 1 diabetes on serum levels of the growth hormone-binding protein and of insulin-like growth factor I. In the diabetic patients, serum levels of the growth hormone-binding protein were positively related to body mass index and to insulin dose per kg body weight, and were not influenced by pubertal stage, gender, or plasma levels of haemoglobin A1c. Serum levels of insulin-like growth factor I increased during early puberty reaching peak levels at midpuberty and decreasing thereafter. No relationship was found between serum levels of growth hormone-binding protein and of insulin-like growth factor I. Our data suggest that decreased liver somatogenic receptor levels, as reflected by the concentrations of circulating growth hormone-binding protein, play a minor role in the suppressed concentrations of circulating insulin-like growth factor I. Post-growth hormone receptor defects or changes in the insulin-like growth factor binding proteins probably contribute more to the lower serum levels of insulin-like growth factor I.

Serum Levels of Immunoreactive Inhibin, FSH, and LH in Human Infants at Preterm and Term Birth

Serum levels of immunoreactive inhibin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined in 112 fetal cord blood samples obtained at birth between 26 and 40 weeks of gestation. High levels of inhibin immunoreactivity were detected in all samples. Between the gestational age of 26 and 28 weeks, the levels (mean +/- SE) were higher (p less than 0.05) in male (21.6 +/- 1.0 U/ml; n = 12) than in female (12.8 +/- 0.2 U/ml; n = 12) fetuses. With ongoing gestation, the serum inhibin immunoreactivity decreased and was found to be similar in male (12.1 +/- 0.3 U/ml; n = 13) and female (9.1 +/- 0.7 U/ml; n = 8) fetuses at term. Serum FSH and LH levels were elevated at the beginning of the 3rd trimester of pregnancy and decreased with ongoing gestation to undetectable values at term birth. Between 26 and 32 weeks of gestation, the FSH levels were higher in females (p less than 0.02), whereas the LH levels were higher in males (p less than 0.01). These observations suggest that in the human fetus the pituitary-gonadal axis is active and presents sexual dimorphism; both characteristics are pronounced early during the 3rd trimester of gestation and decrease towards term.

Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations

Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in PTPN11, KRAS, SOS1, and RAF1. We performed SOS1, RAF1, BRAF, MEK1, and MEK2 mutation analysis in a cohort of 102 PTPN11‐ and KRAS‐negative NS patients and found pathogenic SOS1 mutations in 10, RAF1 mutations in 4, and BRAF mutations in 2 patients. Three novel SOS1 mutations were found. One was classified as a rare benign variant and the other remains unclassified. We confirm a high prevalence of pulmonic stenosis and ectodermal abnormalities in SOS1‐positive patients. Three patients with SOS1 mutations presented with tumors (embryonal rhabdomyosarcoma, Sertoli cell testis tumor, and granular cell tumors of the skin). One patient with a RAF1 mutation had a lesion suggestive for a giant cell tumor. This is the first report describing different tumor types in NS patients with germ line SOS1 mutations.

SERUM GROWTH HORMONE-BINDING PROTEINS IN THE HUMAN FETUS AND INFANT

ABSTRACT: Growth hormone-binding protein (GH-BP) levels were studied in cord serum of 69 human infants born after 24 to 41 wk of gestation and in serum of 14 infants aged 1 to 3 mo. GH-BP levels were measured by HPLC-gel filtration of serum incubated overnight with 125I-hGH. The radioactive elution profile revealed two small 125I-hGH peaks of high molecular weight and a large peak, corresponding to monomeric 125I-hGH. The first peak of high molecular weight was variable, showed some of the characteristics (high molecular weight, displaceability by a large excess of unlabeled hGH) of the described low affinity, high capacity GH-BP, and did not correlate with gestational age or birth weight (peak I-BP). The second peak was identified as 125I-hGH bound to the high affinity, low capacity GH-BP (peak II-BP). Mean ± SD specific binding of 125I-hGH to this peak was significantly (p < 0.0001) different between preterm infants (3.1 ± 1.1%; n = 51), term infants at birth (4.2 ± 1.1%; n = 18), and 1-to 3-mo-old infants (8.5 ± 1.6%; n = 14). To evaluate the effect of intrauterine nutritional state, the ponderal index (weight/length3) was calculated. Peak II-BP levels were lower (p < 0.05) in infants with the ponderal index < 2.35 (2.8 ± 1.0%; n = 20) than in those with the ponderal index between 2.35 and 2.65 (3.4 ± 1.2%; n = 29) or > 2.65 (3.8 ± 1.2%; n = 20). We conclude that GH-BP are present in human cord serum throughout the 3rd trimester of gestation. The levels of peak II-BP are influenced by fetal age and intrauterine growth and increase quickly after birth.

Growth Hormone (GH) Secretion in Patients with Childhood-Onset GH Deficiency: Retesting after One Year of Therapy and at Final Height

Background: Recent studies have shown that many patients treated with growth hormone (GH) during childhood because of idiopathic GH deficiency (GHD) are no longer GH deficient when retested after cessation of GH therapy when final height is achieved. These patients are labelled as transient GHD. We hypothesized that normalization of GH secretion in transient GHD could occur earlier during the course of GH treatment, which could allow earlier cessation of GH treatment. Methods: In a retrospective study, GH secretion was re-evaluated after cessation of GH treatment at final height in 43 patients diagnosed during childhood as idiopathic GHD (10 with multiple pituitary hormonal deficiencies (MPHD) and 33 with isolated GHD (IsGHD)). In a prospective study, GH secretion was re-assessed after interruption of GH treatment given for 1 year in 18 children with idiopathic GHD (2 MPHD, 16 IsGHD). GH secretion was evaluated by glucagon or insulin stimulation tests. Results: In the retrospective study, all the 10 patients with MPHD and 64% of the 33 patients with IsGHD were still deficient at re-evaluation using the paediatric criteria to define GHD (GH peak <10 ng/ml at provocative test). The proportion of persisting deficiency was greater in patients with complete IsGHD (86%, 12/14 patients) than in patients with partial IsGHD (47%, 9/19 patients). With the criteria proposed in adulthood (GH peak <3 ng/ml), all the 10 patients with MPHD were still considered to be deficient. In contrast, only 15% (5/33 patients) with IsGHD had a maximal GH value <3 ng/ml (36% of the 14 patients with complete IsGHD and none of the 19 patients with partial IsGHD). In the prospective study, after interruption of GH therapy given for 1 year, the 2 patients with MPHD were still GHD at re-evaluation and they resumed GH treatment. Among the 16 patients with IsGHD, 13 (81%) were still deficient (peak response <10 ng/ml) after 1 year. Two of the 3 patients in whom GHD was not confirmed at retesting after 1 year GH showed again a deficient response at second retesting. Conclusions: Although many patients diagnosed with IsGHD during childhood have a normalized GH secretory capacity when retested during adulthood, early retesting after interruption of GH treatment given for 1 year during childhood does not enable to determine if GH therapy has to be discontinued before cessation of growth.

Effect of oestrogen status on serum levels of growth hormone-binding protein and insulin-like growth factor-I in non-pregnant and pregnant women

OBJECTIVE Since there appears to be a relationship between circulating oestrogens and growth hormone, we have investigated the effect of the oestrogen status of adult women on serum levels of GHBP and IGF‐I.

Deletion of the short arm of the X chromosome: A hereditary form of Turner syndrome

In the mothers of two girls with Turner syndrome due to a deletion of the short arm of an X chromosome, the same chromosomal anomaly was detected. Both mothers and daughters had short stature but normal pubertal development. Short parents and normal pubertal development do not exclude Turner syndrome in a girl with small stature.