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ABSTRACT: We determined growth hormone (GH) and insulin-like growth factor I (IGF-I) levels after a 3 h infusion of escalating doses of growth hormone-releasing hormone (GHRH(1-29)) followed by a bolus injection in hypopituitary patients with marked differences in pituitary features at magnetic resonance imaging (MRI) in order to evaluate further the contribution of MRI in the definition of pituitary GH reserve in GH-deficient patients. Twenty-nine patients (mean age 14.5 +/- 4.0 years) were studied. Group I comprised 13 patients: seven with isolated GH deficiency (IGHD) (group Ia) and six with multiple pituitary hormone deficiency (MPHD) (group Ib) who had anterior pituitary hypoplasia, unidentified pituitary stalk and ectopic posterior pituitary at MRI, Group II consisted of eight patients with IGHD and small anterior pituitary/empty sella, while in group III eight had IGHD and normal morphology of the pituitary gland. Growth hormone and IGF-I levels were measured during saline infusion at 08.30-09.00 h, as well as after infusion of GHRH (1-29) at escalating doses for 3h: 0.2 micrograms/kg at 09.00-10.00 h, 0.4 micrograms/kg at 10.00-11.00 h, 0.6 micrograms/kg at 11.00-12.00 h and an intravenous bolus of 2 micrograms/ kg at 12.00 h. In the group I patients, the peak GH response to GHRH(1-29) was delayed (135-180 min) and extremely low (median 2mU/l). In group II it was delayed (135-180 min), high (median 34.8 mU/l) and persistent (median 37.4 mU/l at 185-210 min). In group III the peak response was high (median 30.8 mU/l) and relatively early (75-120 min) but it declined rapidly (median 14.4 mU/l at 185-210 min). In one group I patient, GH response increased to 34.6 mU/l. The mean basal value of IGF-I levels was significantly lower in group I (0.23 +/- 0.05 U/ml) than in groups II (0.39 +/- 0.13U/ ml, p < 0.01) and III (1.54 +/- 0.46 U/ml, p < 0.001) and did not vary significantly during the GHRH(1-29) infusion. The present study demonstrates that the impaired GH response to 3 h of continuous infusion of escalating doses of GHRH(1-29) was strikingly indicative for pituitary stalk abnormality, strengthening the case for use of GHRH in the differential diagnosis of GH deficiency. The low GH response, more severe in MPHD patients, might be dependent on the residual somatotrope cells, while the better response (34.6 mU/l) in the group Ia patients might suggest that prolonged GHRH infusion could help in evaluating the amount of residual GH pituitary tissue. Pituitary GH reserve, given the GH response to GHRH infusion in GH-deficient patients with small anterior pituitary/empty sella, seems to be maintained.
European Journal of Endocrinology 08/1996; 135(2):198-204. · 3.42 Impact Factor
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ABSTRACT: We determined the percentage of circulating natural killer (NK) cells, using the monoclonal antibodies anti-CD57 and anti-CD16, NK cytotoxic activity (lytic units/10(6)) and lymphokine-activated killer (LAK) activity in 25 IDDM patients aged 3-23 years, 12 with disease for < 1 year (Group I) and 13 with disease for > 3 years (Group II). Nine age-matched healthy subjects served as controls. The percentage of CD57+ cells was similar in IDDM patients and controls, while the percentage of CD16+ cells was lower in IDDM patients (P < 0.05) than in controls. NK cell cytotoxic activity was lower in IDDM patients than in controls (P < 0.01), in Group I and II compared with controls (P < 0.005). LAK activity was similar in IDDM patients and in controls. No correlation was found between NK cytotoxic activity and metabolic control, HLA typing, while a negative correlation was found between NK cytotoxic activity and insulin requirement (P < 0.05). The decreased NK cytotoxic activity observed in our patients, in particular in long-standing diabetics, with normal NK cell number, could be due to a qualitative defect of the NK cells, or to a deficient IL-2 and/or TNF-alpha production, or to a immunomodulatory or immunosuppressing effect of insulin.
Diabetes Research and Clinical Practice 02/1994; 23(1):37-42. · 2.75 Impact Factor
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ABSTRACT: In the attempt to define possible causes of false positive GH deficiency, the role of caloric intake on GH determination was explored. The serum GH responses to insulin-induced hypoglycemia or arginine were assessed before and after 3 days of a hypocaloric diet in 23 prepubertal children of normal weight, aged 6.7-11.9 yr. Seventeen had short stature and a GH response to insulin and arginine below 10 micrograms/L, and 6 controls had normal stature and a GH peak above 10 micrograms/L in response to arginine. After diet, the serum peak GH and the area under the curve increased in both the patients (P < 0.0005 and P < 0.0005) and the controls (P < 0.005 and P < 0.025) with a GH peak greater than 10 micrograms/L in 11 of 17 patients. The patients with a persistent GH response below 10 micrograms/L also had lower mean 12-h overnight GH levels (P < 0.0005), whereas those with a normal GH response after diet had an overnight GH level greater than 3 micrograms/L. In the patients, the mean nighttime GH concentrations correlated with the serum GH peak (r = 0.85; P < 0.005) and with the area under the curve after the diet (r = 0.65; P < 0.025). The diet induced changes in plasma insulin-like growth factor-I, GH-releasing hormone levels, basal blood sugar and the nadir level obtained during insulin stimulation, total T3, and rT3. Height increased significantly during 1 and 2 yr (P < 0.005) of GH treatment only in patients with a GH response below 10 micrograms/L after the diet. These data are consistent with the hypothesis that the GH response to stimulation is strongly calorie dependent and that 3 days of a hypocaloric diet can increase the number and height of GH peaks and the total GH responses to insulin and arginine. The clear correlation of the GH response to stimulation after a hypocaloric diet with the mean nighttime GH and also with the growth response to GH treatment indicates that GH deficiency may be overdiagnosed in many children with short stature.
Journal of Clinical Endocrinology & Metabolism 11/1993; 77(5):1372-8. · 6.50 Impact Factor
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ABSTRACT: We describe a mentally retarded 12-year-old girl with ataxia in whom diagnostic evaluation for short stature revealed isolated growth hormone (GH) deficiency and multiple central nervous system (CNS) lesions. Assessment of immunologic status, performed because of the persistence of recurrent respiratory tract infections, showed associated deficiencies of IgG2-IgG4 and specific antibody response; in addition, in vitro lymphocyte response to mitogens was low, in vitro production of interleukin-2 and of IgM was absent, and natural killer activity was decreased. The possibility that association of the CNS lesions, GH deficiency and immune defects could be due to alterations of the neuro-immuno-endocrine network secondary to a disturbance of neurotransmitters induced by precocious CNS damage of a viral or ischemic nature is discussed.
Thymus 10/1992; 20(2):69-76.
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ABSTRACT: The in vitro effect of synthetic human growth hormone-releasing hormone (GHRH) on mitogen-induced lymphocyte proliferation and lymphokine secretion was investigated. Peripheral blood mononuclear cells (PBMC) of healthy adults were incubated in the presence and absence of increasing concentrations (from 0.006 to 50 micrograms/ml) of two forms of GHRH differing in amino-acid sequence (GHRH 1-44 and GHRH 1-29) or of increasing concentrations (from 0.0012 to 20 U/ml) of recombinant human insulin (rh-insulin). Low concentrations of GHRH 1-29 increased phytoemoagglutinin (PHA)-induced lymphoproliferation, while high concentrations inhibited lymphocyte response, interleukin-2 (IL-2) secretion and IL-2 receptor expression on activated cells. A toxic effect was excluded since no differences in cell viability were observed between cells cultured with and without hormone. GHRH 1-44 did not affect PHA-induced lymphoproliferation, IL-2 production and IL-2 receptor expression. Low concentrations of rh-insulin increased PHA-elicited lymphoproliferation, while high concentrations did not decrease lymphocyte response. The present study suggests that GHRH modulates in vitro human T lymphocyte functions.
Thymus 09/1991; 18(1):51-9.
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ABSTRACT: No further reports of associated X-linked hypogammaglobulinemia and isolated growth hormone deficiency have appeared in the literature since the description of the first affected family, two brothers and two maternal uncles, by Fleisher et al. in 1980. We report here a 13-year-old boy with X-linked agammaglobulinemia and isolated growth hormone deficiency, also probably inherited as an X-linked trait. The height of an older agammaglobulinemic brother who died at 6 years of age was below the third percentile.
Acta paediatrica 06/1991; 80(5):563-6. · 1.77 Impact Factor
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ABSTRACT: To delineate the effects of human chorionic gonadotropin (hCG) administration on immune responsiveness, immunological parameters including serum immunoglobulins, total and differential white blood cell count T and B lymphocyte membrane phenotype, in vitro, proliferative response to phytohaemagglutinin, Concanavalin A (ConA) and pokeweed mitogen were studied in 13 prepubertal cryptorchid boys before, during, and 3 months after hCG therapy. Before treatment, all the immunological parameters were normal except for an unexpected high percentage of T suppressor-cytotoxic cells (CD8+). During therapy, the absolute number of total peripheral blood lymphocytes, and that of total T-cells, T helper-inducer cells and of CD8+ subsets were diminished. The percentage of CD8+ cells and lymphocyte response to ConA decreased significantly and returned to normal after hCG withdrawal. The possible effects of long-term hCG treatment remain to be determined.
European Journal of Pediatrics 03/1991; 150(4):238-41. · 1.88 Impact Factor
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Bone Marrow Transplantation 02/1991; 8 Suppl 1:60. · 3.75 Impact Factor
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ABSTRACT: Surface phenotype of peripheral blood lymphocytes (PBL) from preterm infants was evaluated using monoclonal antibodies which define T cell membrane antigens associated with processes of maturation and activation of these cells. In the majority of preterm infants born during the 25th and 26th week of gestation, PBL included higher percentages of cells bearing an immature/activated surface phenotype characterized by the presence of CD1, CD38, and CD71 surface antigens than in term newborns. In these gestational age groups, PBL included, in particular, very high percentages of lymphocytes (range: 22-60) expressing the p55 chain of interleukin-2 receptor (IL-2R). After the 26th week of gestation, PBL of some preterm neonates included, as well, high percentages of lymphocytes bearing immature/activated phenotype; their median values, however, were not significantly different from those observed in term newborns. Our data suggest that the presence of the p55 chain of IL-2R on the surface of neonatal lymphocytes could be correlated with the immaturity of these cells.
Biology of the Neonate 02/1991; 59(4):213-8. · 1.90 Impact Factor
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ABSTRACT: Exogenous corticoids are known to be potent inhibitors of linear growth in children. We investigated the mechanisms underlying growth failure by evaluating growth hormone (GH) release during short-term high-dose prednisone treatment (40 mg/m2/day given orally in 3 divided doses) and 7 days after steroid withdrawal in 7 prepubertal children (4 males, 3 females, age range 3-12 years), affected by acute lymphoblastic leukemia. Patients also received weekly administrations of vincristine (1.5 mg/m2 i.v.), daunomycin (20 mg/m2 i.v.) and L-asparaginase (6,000 IU/m2 i.m.). Corticoid therapy suppressed GH secretion during deep sleep as well as in response to arginine, insulin and GH-releasing hormone (GHRH) administration. A significant recovery of GH responsiveness after drug discontinuation was observed during deep sleep (14.03 +/- 3.47 vs. 1.49 +/- 0.43 ng/ml, p less than 0.025) as well as in response to arginine (13.63 +/- 2.73 vs. 4.95 +/- 1.54 ng/ml, p less than 0.025) and GHRH (32.62 +/- 4.59 vs. 7.27 +/- 3.52 ng/ml, p less than 0.005) but not to insulin (7.12 +/- 0.88 vs. 4.47 +/- 0.96 ng/ml, p = NS). Insulin-like growth factor 1 levels during deep sleep (0.61 +/- 0.13 IU/ml/min) were found to be low in the course of steroid therapy and did not increase after drug withdrawal (0.41 +/- 0.07 IU/ml/min). Our preliminary data suggest that recovery of adrenergic response to insulin does not immediately follow corticosteroid discontinuation.
Hormone Research 02/1991; 36(5-6):183-6. · 2.48 Impact Factor
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Journal of Pediatrics 11/1990; 117(4):596-9. · 4.11 Impact Factor
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Metabolism 03/1989; 38(2):193-4. · 2.66 Impact Factor
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Journal of endocrinological investigation 02/1989; 12(8 Suppl 3):123-4. · 1.57 Impact Factor
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ABSTRACT: The ability of growth hormone (GH) to influence certain immune functions has been studied in 21 GH-deficient children aged 1.8-17.7 years, before and during therapy with biosynthetic methionyl-hGH (12 IU/m2) injected intramuscularly 3 times weekly. Blood was collected prior to GH treatment, then after 1 week, again at 3-6 months, and finally at 9-12 months of therapy. We studied (1) the distribution of the T lymphocyte subpopulations: T total (CD3), helper/inducer (CD4) and suppressor/cytotoxic (CD8) cells, using monoclonal antibodies (OKT3, OKT4, OKT8) and (2) the in vitro IgM production stimulated by pokeweed mitogen. Pretreatment CD3, CD4, CD8 values were within the normal range. They did not change after 1 week of GH therapy. Following 3-6 months of GH treatment, CD3 significantly increased (p less than 0.001), CD4 decreased (p less than 0.01), CD8 increased (p less than 0.001) and the CD4/CD8 ratio decreased (p less than 0.001). At 9-12 months of therapy, the percentages of the different groups of T cells was not significantly different from the pretreatment values. In vitro IgM production before and following 3-6 months of GH treatment was significantly lower (p less than 0.005) than that of 15 age-matched controls. At 9-12 months, GH therapy restored the in vitro IgM production. No variations in the levels of serum immunoglobulins were observed throughout the treatment period. These data suggest that GH plays a role in the development of the immune function in children.
Hormone Research 02/1989; 31(4):153-6. · 2.48 Impact Factor
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ABSTRACT: The effect of long-term human chorionic gonadotropin (HCG) therapy on the linear growth and biological growth parameters was studied in six thalassaemic boys aged 14.5-15.5 years old with hypogonadotropic hypogonadism. A significant (P less than 0.001) increase in growth velocity (from 3.3 +/- 0.3 to 7.6 +/- 0.6 cm/year) was found after 6-12 months of therapy, without acceleration of bone age. A striking improvement in pubertal development was observed. The treatment significantly increased growth hormone (GH) response to L-dopa administration (P less than 0.025) as well as sleep GH secretion (P less than 0.025). Serum growth factors, evaluated as thymidine activity during deep sleep, increased (P less than 0.001), but somatomedin C (Sm-C) levels did not. Prior to treatment, baseline and peak values of plasma growth hormone releasing hormone (GH-RH) following L-dopa were low. After HCG therapy, GH-RH response to L-dopa increased significantly (from 9.2 +/- 5.6 to 20.2 +/- 6.2 pg/ml; P less than 0.05), but remained (P less than 0.001) lower than in normal prepubertal children. This study suggests that in thalassaemia major an impaired GH-RH release can be observed, in addition to the described alteration in Sm-C generation.
European Journal of Pediatrics 02/1989; 148(4):300-3. · 1.88 Impact Factor
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ABSTRACT: We investigated the influence of human growth hormone (hGH) on mitogen-stimulated lymphoproliferation, in vitro IgM production, serum levels of immunoglobulins, somatomedin-C (Sm-C) values and serum growth-promoting activity (Thymidine Activity, TA) in 18 short children, aged between 6.6-14.5 years, undergoing a 3-month course of hGH therapy. Blood was collected the day before treatment (Group A), on the 5th day after patients were administered hGH daily (0.1 U/kg) i.m. for 4 days (Group B), after a 3-month course of hGH injected three times weekly, and finally before (Group C) and 24 h after an extra injection (Group D). In vitro IgM production from the patients' unstimulated lymphocytes decreased from 277 +/- 41 (Group A) to 168 +/- 38 (Group B), to 119 +/- 43 (Group C) and then to 119 +/- 28 ng/ml (Group D) (p less than 0.05). Using PWM-stimulated lymphocytes in vitro IgM production decreased from 2,015 +/- 464 (Group A) to 1,116 +/- 316 (Group B), then to 511 +/- 170 (Group C) and 968 +/- 295 ng/ml (Group D) (p less than 0.02). The variation of this decrease could be correlated with the variation of growth velocity during treatment (r = 0.619, p less than 0.05). In contrast, no significant changes were found following therapy either in serum levels of IgA, IgE, IgG, IgM, Sm-C and TA, or in phytohemagglutinin, concanavalin A and pokeweed mitogen-stimulated lymphoproliferation. Our data suggest that there is some relationship between growth hormone, growth and immunity.
Acta paediatrica 10/1988; 77(5):675-80. · 1.77 Impact Factor
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ABSTRACT: The growth response during short-term growth hormone (GH) treatment was evaluated in eight prepubertal non-GH-deficient (non-GHD) children and compared with six prepubertal GH-deficient (GHD) patients. Standard doses of GH can improve growth rate in GHD and in some non-GHD patients. In neither group the growth response can be predicted by the acute increase in Thymidine Activity or Somatomedin-C levels. A diagnostic trial of GH treatment may be the only certain method of selecting the short non-GHD patients who may benefit from long-term GH therapy.
European Journal of Pediatrics 05/1988; 147(3):248-51. · 1.88 Impact Factor
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ABSTRACT: To study physiological variations in serum growth factors during peripartal period, we have measured levels of a serum growth-promoting activity (thymidine activity, TA) and radioimmunoassayable somatomedin C (Sm-C) during labor in 39 women who delivered spontaneously (group A), by caesarean section (group B) and by legal abortion (LA) (group C). TA values were higher in the group A than in the group B and C, suggesting an important effect of uterine contractions in TA generation. A major role in Sm-C production seems to be played by the length of gestation since Sm-C concentrations were significantly higher in mothers delivered by caesarean section than in LA women. During labor influence of estrogens and progesterone in growth factor production seems unlikely because of the lack of correlation with TA and Sm-C levels. The lower TA values in placental flow than in the capillary blood of newborn suggest that serum growth factors, measured as TA, are produced by the newborn and do not cross through the placenta. These data suggest that the absolute dependence of the fetus on the mother does not preclude instances of fetal autonomy.
Biological research in pregnancy and perinatology 02/1987; 8(2 2D Half):60-4.
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ABSTRACT: GH response to an iv bolus of growth-hormone-releasing hormone (GHRH 1-44, 2 micrograms/kg iv) was evaluated in 17 prepubertal children with total GH deficiency (GHD), 6 with partial GHD and in 7 prepubertal normal but short children tested as control. GH response to conventional pharmacological (insulin and arginine or L-Dopa) and physiological stimuli (sleep test) and to GHRH test was also compared. GHRH-induced GH peak occurred at variable times and marked heterogeneity in magnitude of the individual responses to this peptide was observed in GHD patients and in controls. GH increases after GHRH with a peak greater than 10 ng/ml suggested an hypothalamic origin of the GHD in 12 patients (8 with total GHD and 4 with partial GHD). A significant difference (p less than 0.025) of GH peak mean following GHRH administration between total GHD children and normal short children was found. GH response to GHRH injection was usually higher than to conventional stimuli. Nevertheless GH peak following GHRH administration was lower than GH peak following conventional stimuli in 6 children (2 partial GHD children and 4 normal ones). A normal short child failed to respond to GHRH test performed twice. GHRH test is an important diagnostic tool in order to point out hypothalamic GHD.
Journal of endocrinological investigation 01/1987; 9(6):503-6. · 1.57 Impact Factor
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ABSTRACT: In order to investigate the ability of growth hormone (GH) to modulate lymphoproliferation, peripheral blood mononuclear cells (PBMC) from healthy adults were stimulated with phytohaemagglutinin (PHA) in the presence of increasing concentrations of pituitary (Crescormon) and biosynthetic (Somatonorm and Genotropin) GH (from 0.425 x 10(3) to 501.5 x 10(3) ng/ml) as well as biosynthetic insulin (rhinsulin, Humulin 1 Eli Lilly: from 0.0012 to 20 U/ml). The results obtained show that low doses of GHs and insulin increase lymphoproliferation. In contrast, high concentrations of GHs (8.5 x 10(3) ng/ml) induce a progressive decrease of PHA-induced lymphoproliferation, while insulin does not. No differences in cell viability were observed with and without GHs. Comparable percentages of lymphocytes bearing interleukin-2 receptor (CD25) and comparable values of interleukin-2 (IL-2) pr oduction were found in all conditions tested. Nevertheless, when exogenous recombinant IL-2 (R IL-2) was added to PHA-induced PBMC cultures with high doses of GH, a reconstitution of lymphoproliferation was observed. Further experiments seem to exclude the presence of suppressor T lymphocyte induction by GH. The present results suggest that hypothesis that high concentrations of GH may interfere with the binding between IL-2 and its membrane receptor on activated lymphocytes.
Thymus 12(3):157-65.
