Pregnancy-associated plasma protein A (PAPP-A), a macromolecular glycoprotein associated with pregnancy, was shown to inhibit complement-induced haemolysis and to bind heparin reversibly. Because of the inhibitory effects of heparin on the complement cascade it was not clear if the inhibition of complement activity observed with PAPP-A (isolated from heparin plasma) was attributable to the heparin moiety bound to PAPP-A. This work demonstrates that heparin exerts an inhibitory effect on complement activity but that heparin-free PAPP-A is also inhibitory. PAPP-A specifically inhibits C3 by binding to this complement subcomponent and not by inhibiting C3 convertase as demonstrated for C3 inactivator.

Complement C3↗

PubMedDate not supplied

Turner's syndrome and hypogonadotrophic hypogonadism: thalassemia major and hemochromatosis.

We report here the first case of an association between thalassemia major, hemochromatosis, hypogonadotrophic hypogonadism and Turner's syndrome. The patient is an Albanese girl born in 1980; thalassemia major was diagnosed at 1 year and she was started on a transfusion program; in 1987 iron chelation therapy was started. Six years ago, at 7 years of age, her short stature was observed and she was referred to the endocrinology clinic for evaluation; the basal and stimulation tests done at that time failed to reveal growth hormone deficiency, hypothyroidism or any other disease. Nevertheless, at 12 years old, she was still prepubertal and there was a bone age delay of 1.5 years; a gonadotropin-releasing hormone (GnRH) stimulation test showed no response of either FSH (basal: 0.2 mU/ml; peak: 0.8 mU/ml) or LH (basal: < 0.1 mU/ml; peak: 0.6 mU/ml), suggesting hypogonadotrophic hypogonadism. Small dysmorphies called our attention to the possibility of Turner's syndrome which was confirmed by the karyotype (45 XO/46 XX). In this patient, thalassemia major and its lifelong consequences, namely the hemochromatosis-related hypogonadotrophic hypogonadism, masked the usual hormonal findings of Turner's syndrome.

Adolescent↗

PubMedDate not supplied

Should we monitor more closely the dosage of 9 alpha-fluorohydrocortisone in salt-losing congenital adrenal hyperplasia?

In salt-losing congenital adrenal hyperplasia (CAH), continuous therapy with glucocorticoids and 9 alpha-fluorohydrocortisone (9 alpha-F) remains the golden rule. Previous reports showed a growth promoting effect of 9 alpha-F therapy. In addition, 9 alpha-F seemed to have a negligible glucocorticoid action. To confirm these facts, we analyzed the clinical data and the biological markers of control of therapy in two groups of patients with salt-losing CAH aged from 2 to 12 years: group I: before (time 0) and 6 months after the increase in 9 alpha-F dosage (time +6); group II: at time 0 and time +6 but without change in 9 alpha-F dosage. Groups were similar in terms of mean age, bone age and hydrocortisone dose. The mean dose of 9 alpha-F was 68.2 +/- 5.0 micrograms/m2/d at time 0 and was increased to 98.6 +/- 7.7 micrograms/m2/d at time +6 in group I; it remained similar in group II. In group I, height velocity decreased significantly from 8.1 +/- 0.6 at time 0 to 6.3 +/- 0.3 cm/yr at time +6 (p < 0.01) while in group II there was no significant change. In group I, plasma renin activity decreased from 10.4 +/- 1.6 at time 0 to 3.9 +/- 1.1 ng/ml/h at time +6 (p < 0.005) and showed no change in group II. These preliminary results suggest that careful monitoring of 9 alpha-F is essential to control a proper growth rate.

Adrenal Hyperplasia, Congenital↗

PubMedDate not supplied

Human insulin induces a higher glucagon response to induced hypoglycemia in short normal children, compared to porcine insulin.

After transfer of diabetic patients from porcine to human insulin, many reports emerged supporting an increased hypoglycemia unawareness. Several studies were then undertaken in both diabetic and healthy adults to investigate counterregulatory hormone responses to both porcine and human insulin-induced hypoglycemia as a possible underlying cause for this different hypoglycemia awareness. Most studies demonstrated similar neuroendocrine responses to both insulin species in adults. However, no such studies have ever been performed in healthy children. We undertook a double-blinded study of counterregulatory hormone responses to both porcine and human insulin-induced hypoglycemia in 17 short normal children randomly assigned to two groups, one receiving human and the other porcine insulin. We found similar responses of growth hormone, cortisol, epinephrine, norepinephrine and dopamine to both porcine insulin- and human insulin- induced hypoglycemia. Interestingly, we observed a significantly higher glucagon secretion when hypoglycemia was induced by human insulin. In conclusion, human insulin induces a higher glucagon secretion in healthy children than porcine insulin. Evidently, this observation cannot be extrapolated to diabetic patients. This study, however, further underlines the importance of performing investigations in children, since results found in adults differ from those observed in children.

Adolescent↗

PubMedDate not supplied