IGFBP-3 measurement had poor sensitivity in detecting growth hormone deficient patients, offering no diagnostic advantage over IGF-I, even in the first years of life, although, due to the high specificity, the finding of subnormal levels of IGFBP-3 was strongly suggestive of growth hormone deficiency. The presence of low IGFBP-3 and IGF-I levels in a short child with normal GH response to provocative tests should prompt further investigations, such as the determination of spontaneous GH secretion or assessment of the GH binding proteins together with an IGF-I and/or IGFBP-3 generation test, in order to identify neurosecretory dysfunction or GH receptor deficiency. Finally, we believe that there is no definitive test for diagnosing or excluding growth hormone deficiency and detailed analysis of the results of endocrine tests, clinical findings and other laboratory and radiological information is necessary to maximize diagnostic accuracy.

Summary 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. PATIENTS AND METHODS Thirty‐one patients (26 females, five males; mean age 42.5 years) affected by different autoimmune thyroid diseases were studied. Fourteen patients were affected by Graves' disease, eight by silent thyroiditis, five by Hashimoto's thyroiditis. Four patients with Graves' disease in remission were also evaluated. Anti‐cardiolipin antibodies were detected by enzyme linked immunosorbent assay. In five Graves' disease patients anti‐cardiolipin antibodies were evaluated before and after 3 months of therapy with methimazole. RESULTS Seventeen out of 31 patients were positive for IgG and/or IgM anti‐cardiolipin antibodies, the highest levels occurring in three Graves' disease patients with severe thyrotoxicosis. In four of five Graves' patients evaluated before and after methimazole therapy, anti‐cardiolipin antibodies decreased following treatment. None of the patients with increased IgG and/or IgM anti‐cardiolipin antibodies showed clinical manifestations of the anti‐phospholipid syndrome during our observation which ranged from 1 to 5 years. CONCLUSIONS Our results showed an increased incidence of anti‐cardiolipin antibodies in patients affected by autoimmune thyroid diseases. However, these autoantibodies seem merely to represent a non‐specific marker of immune dysregulation.

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 with CGD. The mean 12-hour serum GH concentration was significantly lower in patients with TGHD (p less than 0.001), children with PGHD (p less than 0.01), and subjects with ISS (p less than 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 less than 0.001). All patients with a growth velocity less than 3rd percentile for bone age showed a mean nocturnal concentration less than 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.

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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 µg/l in controls; p < 0.0001) but higher than GH-deficient patients (1.3 ± 0.8 µg/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). The finding of GH levels intermediate between control and GH-deficient patients together with normal IGF-1 concentrations, questions the existence of a ‘classical’ GH insufficiency in TS girls. This study confirms that weight excess is a common feature of TS girls at pubertal age and suggests that the reduced GH secretion might be due, at least in part, to obesity.