F. Vaccaro

Is IGF binding protein-3 assessment helpful for the diagnosis of GH deficiency?

OBJECTIVE The measurement of serum immunoreactive IGFBP‐3 levels has been proposed as a screening test to Identify children with growth hormone deficiency (GHO). We tested the sensitivity and specificity of the IGFBP‐3 assessment In comparison with the measurement of IGF‐I.

Anti‐cardiolipin antibodies in autoimmune thyroid diseases

OBJECTIVE In recent years anti‐phospholipid antibodies have gained much attention since they are frequently associated with thrombosis, recurrent abortion, and thrombocytopenia. Besides disease‐specific autoantibodies, other autoantibodies reactive with both organ and non‐organ specific autoantigens have been found in patients with autoimmune thyroid diseases. Therefore the objective of this study was to evaluate the presence and significance of anti‐phospholipid antibodies in untreated patients with different forms of autoimmune thyroid diseases.

Twelve-hour Spontaneous Nocturnal Growth Hormone Secretion in Growth Retarded Patients

Twelve-hour nocturnal GH secretion was studied in 30 children with familial short stature (FSS), constitutional growth delay (CGD), total growth hormone deficiency (TGHD), partial growth hormone deficiency (PGHD), or idiopathic short stature (ISS). No difference was observed between subjects with FSS and children wtih CGD. The mean 12-hour serum GH concentration was significantly lower in patients with TGHD (p < 0.001), children with PGHD (p < 0.01), and subjects with ISS (p < 0.01) than in subjects with FSS and CGD. No overlap was observed between the range of mean concentration values of children with TGHD and that of subjects with FSS. A significant correlation was found between growth velocity expressed as SD from the mean for bone age and GH concentration (p < 0.001). All patients with a growth velocity <3rd percentile for bone age showed a mean nocturnal concentration <4 ng/ml. These data suggest that evaluation of 12-hour spontaneous nocturnal GH secretion with GH sampling every 30 minutes can be usefully employed in the diagnosis of GH deficiency.

Reduced growth hormone secretion in Turner syndrome: is body weight a key factor?

The age-related decline in spontaneous growth hormone (GH) secretion has been suggested to cause growth failure in girls with Turner syndrome (TS). We studied 23 girls (mean age +/- SD: 11.1 +/- 2.7 years) diagnosed to have TS by karyotype analysis. The control group consisted of 18 prepubertal age-matched subjects (10.7 +/- 2.5 years) with growth retardation due to familial short stature and/or constitutional growth delay. In addition, 18 children (10.9 +/- 3.3 years) diagnosed to have GH deficiency by two different provocative tests were chosen as a further comparison group. Spontaneous 12-hour nocturnal GH secretion was assessed by RIA at 30-min intervals. Plasma insulin-like growth factor 1 (IGF-1) levels were determined by RIA after acid-ethanol extraction. Girls with TS had a percentage of ideal body weight significantly higher than controls (p < 0.0001) and showed spontaneous GH secretion significantly lower than controls (mean +/- SD: 3.2 +/- 1.6 in TS vs. 5.5 +/- 1.3 microgram/l in controls; p < 0.0001) but higher than GH-deficient patients (1.3 +/- 0.8 microgram/l; p < 0.0001). No significant difference was found in IGF-1 levels between TS patients and controls, whereas GH-deficient children showed IGF-1 levels significantly lower than those of TS patients (p < 0.0005). As expected, GH concentrations correlated with bone age in controls (r = 0.51, p < 0.05), whereas no relationship was seen in TS. interestingly, in TS, GH levels were negatively related to the percentage of ideal body weight (r = -0.43, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Is obesity-related insulin status the cause of blunted growth hormone secretion in Turner's syndrome?

Growth hormone (GH) secretion is reduced in girls with Turners syndrome (TS) at pubertal age. We have recently proposed that the impairment of GH release in TS girls might be secondary to obesity. In the present study, we assessed the influence of overweight-related insulin status on spontaneous GH secretion in a group of 15 TS girls. Eighteen age-matched short normal subjects and six short obese prepubertal children were chosen as controls. Anthropometry, spontaneous GH secretion, insulin-like growth factor-I (IGF-I) serum levels, basal fasting insulin, and glucose concentrations were determined. The percentage of ideal body weight (IBW) was used as an index of nutritional status. Baseline fasting glucose (milligrams per deciliter) to insulin (milliunits per liter) ratio (G/I) was chosen as an index of insulin resistance. GH secretion was significantly lower in TS girls than in non-obese children (P < .005), whereas no significant difference was seen between TS and obese subjects. IGF-I levels were not statistically different in all groups. GH secretion was confirmed to be related to the degree of overweight (r = -.52, P < .05 in TS girls and r = -.74, P < .0001 in control group). G/I was closely related to both the percentage of IBW (r = -.59, P = .02) and GH level (r = .57, P = .03) in TS patients. These results confirm that the blunted GH secretion in TS patients is dependent on nutritional status, and suggest that insulin resistance secondary to overweight might represent the pathophysiologic link between the obesity-related metabolic status and impaired GH secretion.

Growth Hormone Secretion in Noonan's Syndrome

Growth hormone (GH) secretion was studied in eight children with Noonans syndrome: while GH response to pharmacologic stimulation was normal in all subjects, low spontaneous nocturnal GH secretion and/or low levels of IGF-1 were found in some patients. Two children received GH therapy for six months: a significative increase in height velocity was observed and no side effects were noted.

GROWTH HORMONE INSUFFICIENCY IN TURNER SYNDROME: IS BODY WEIGHT THE KEY FACTOR?

The age related decline in spontaneous growth hormone (GH) secretion has been suggested to cause growth failure in girls with Turner syndrome (TS). We studied 23 girls (mean age: 11.1 yrs with 95% confidence intervals (CI) 9.9 to 12.3) diagnosed to have Turner syndrome by karyotype analysis. 15 prepubertal age-matched subjects (mean age: 11.6 yrs with CI 10.4 to 12.8) with growth retardation due to familial short stature and/or constitutional growth delay were chosen as controls. Spontaneous 12-hour nocturnal GH secretion was assessed by RIA at 30 minutes intervals. Plasma IGF-1 levels were determined by RIA after acid-ethanol extraction. In TS, the percentage of ideal body weight was significantly higher than controls (mean: 127.5 with CI 116 to 139 in TS, and 100.3 with CI 96 to 104.5 in controls; P = 0.0005), and correlated with bone age (r= 0.62, P < 0.005). Spontaneous GH secretion was significantly lower in TS than controls (mean: 3.2 ng/ml with CI 2.5 to 3.9 in TS, and 5.4 ng/ml with CI 4.8 to 6.0 in controls; P < 0.0001). No significant difference was found in IGF-1 levels. In controls, GH concentrations correlated with bone age (r= 0.56, P < 0.05), whereas in TS no correlation was found. Interestingly, in TS GH levels negatively correlaled with percentage of ideal body weight (r= - 0.43, P < 0.05). Our results, confirming that obesity is a common finding in girls with TS, at least in the age range of our patients, suggest that overweight might be the key factor in determining the subnormal spontaneous GH secretion. On the basis of our previous observations showing a close inverse relationship between body weight and serum IGFBP-1 levels in TS, it might be hypothesized that obesity, probably by increasing insulin secretion, would reduce IGFBP-1 levels eventually leading to an enhancement of IGF negative feed-back effect on GH secretion.

IDENTIFICATION OF RESPONSIVE AND UNRESPONSIVE SHORT CHILDREN TO GROWTH HORMONE THERAPY USING A MULTIVARIATE DISCRIMINANT ANALYSIS OF PRE-TREATMENT AUXOLOGICAL DATA

BACKGROUND: Growth hormone (GH) has been proved to increase height velocity (HV) in some shoit children who are not GH deficient. OBJECTIVE: Multivariate discriminant analysis was employed to identify, using pre-treatment auxological data, the children responsive to GH. DESIGN: Open prospective study. SETTING: University hospital. SUBJECTS: Fifty-five (35 males) patients that met the following criteria were studied: birth weight >2.500 Kg; no signs of dysmorphic disease; stature below the 3rd centile for chronological age (CA); height velocity below the 25th centile for bone age (BA); no signs of puberty; growth hormone response to pharmacological stimulation >10 ng/ml; no evidence of organic disease; treatment with daily subcutaneous administrations of GH at the dosage of 12-16 UI/m2/week. MAIN OUTCOME MEASURES: Eight pre-treatment auxological variables; HV increase after six months of therapy. A HV increase >2.5 cm/y was considered as a positive response.RESULTS: Thirty-tvvO (58.2%) patients were responsive. Using univariate analysis, the variables found to have predictive value (p<0.001) were: height velocily (SD for CA) and bone age (SD). These variables were employed in the multivariate discriminant analysis. The equation obtained was: Score=1.09X1 - 0.83X2 + 0.19 (X1=HV, X2=BA). Using this scoring system we obtained a sensitivity of 95.7% and a specificity of 91.0% in predicting responsiveness to GH (X2 with Yates correction=36.78, p<0.0001). No correlation was found between responsiveness and GH dosage. CONCLUSIONS: Discriminant analysis may permit the pre-treatment prediction of response to GH therapy in short children and therefore the identification of patients in which GH would be useless.

GROWRH HORMONE THERAPHY IN NON GH-DEFICIENT SHORT CHILDREN

The growth response during Growth Hormone (GH) treatment was evaluated in a heterogeneous group of 1? prepubertal non GH-deficient short children. Diagnosis were: familial short stature (3), constitutional delay of growth associated with familial short stature (3), intrauterine growth retardation (3), sporadic primary microcephaly (3), and idiophatic short stature (5).Mean height (±SEM) was -2.98±0.08 SD, mean bone age was -2.84±0.27 years, end growth rate was 3.45±0.15cm/year. All children showed a normal GH response to standard pharmacologic stimulation tests. Biosynthetic GH was administered for 6-12 months at o dose of 7-14 IU/m2 b.s./week, 3 or 6 times weekly, i.m. or s.c. Mean growth rate increase was 2.50±0.31 cm/year, 12 children showing an increase >2 cm/year. Growth rate increase was not correlated with height, bone age or GH dose and was weekly correlated with pretreatment height velocity (r=-0.58, p<0.05); a lack of correlation was also demonstrated with mean nocturnal spontaneous GH concentration (arithmetical mean of GH levels in blood samples drawn every 30 min. from 8 p.m. to 8 a.m.) and SmC levels. As suggested by several Authors, a diagnostic-therapeutic trial of GH therapy, with auxological monitoring may be the only means of identifying the non GH-deficient short children who will benefit from treatment.