Assay of growth hormone levels in human plasma using commercial kits: analysis of some factors influencing the results.

The reliability of growth hormone (GH) assays, performed in 39 different laboratories, using five different immunoassay kits was evaluated. It was found that the variability in GH levels measured by different commercial assay kits may be due to human factors, as well as differences between the kits. The influence of the variation in amount of circulating GH, during provocative testing and spontaneous secretory episodes, on the results of GH assay was also evaluated. It was found that large molecular weight forms of GH may be underestimated by some assay kits.

Dawn phenomenon in type 1 (insulin-dependent) diabetic adolescents: influence of nocturnal growth hormone secretion.

In order to reassess the role of growth hormone in the dawn phenomenon, we studied eight C-peptide negative diabetic adolescents, who are likely to exhibit important nocturnal growth hormone surges. The insulin infusion rate necessary to maintain euglycaemia was predetermined in each patient from 22.00 hours to 01.00 hours, and then kept constant until 08.00 hours resulting in stable free insulin levels. Blood glucose rose from 4.3 +/- 0.7 mmol/l at 01.00 hours to 7.1 +/- 1.1 mmol/l at 08.00 hours (p less than 0.01) secondary to an increased hepatic glucose production. All the subjects presented an important growth hormone secretion, ranging from 20 to 66 ng/ml (peak values) and from 3619 to 8621 ng.min.ml-1 (areas under the curve). The insulin infusion rate selected for each patient was positively correlated with the nocturnal growth hormone secretion (area under the curve) (r = 0.87, p less than 0.01). On the other hand, there was no relationship between the nocturnal growth hormone secretion and the magnitude of the early morning blood glucose rise (r = -0.48, p greater than 0.2). We conclude that, in Type 1 (insulin-dependent) diabetic adolescents, the dawn phenomenon exists but is moderate despite important growth hormone surges; the nocturnal growth hormone secretion influences the nocturnal insulin requirements but not the dawn phenomenon itself, if insulinisation is adequate.

Somatomedin-C/insulin-like growth factor 1: a differentiating factor of testicular function.

Using primary culture in a chemically defined medium of somatic testicular cells from immature pig, we were able to demonstrate synthesis and secretion of Somatomedin-C/Insulin-Like Growth Factor 1 (Sm-C/IGF-1) by Sertoli cells, a process that is stimulated by Fibroblast Growth Factor (FGF). The presence of IGF type 1 receptor was demonstrated on Sertoli cells. Sm-C/IGF-1 stimulates and potentiates the effects of FGF on both cell multiplication and secretion of plasminogen activator. The presence of both IGF type 1 and insulin receptors was also documented on immature Leydig cells. Pre-incubation of immature Leydig cells for 48 hours with Sm-C/IGF-1 resulted in a dramatic dose-dependent increment of both the LH receptor number and steroidogenic response to LH as well as a clear stimulation of DNA synthesis. These data provide new important insights on the role played by Sm-C, a growth and differentiating factor, on the maturation of the male gonad endocrine function.

[Somatocrinin and children in 1984. Application to the etiological diagnosis of somatotropin deficiencies]. / La somatocrinine et l'enfant en 1984. Application au diagnostic étiologique des déficits somatotropes.

A single acute IV injection (1 microgram/kg) of the synthetic replicate of Somatocrinin (GRF) in 40 children with growth hormone (GH) deficiency induces a marked plasma GH increase, although heterogeneous. Clinical tolerance is excellent. Compared to Propranolol + Glucagon (P + G), GRF induces a better GH response. It also discriminates better idiopathic GH deficiency (n = 13), where mean GH peak = 6.5 ng/ml (3.3 after P + G) from GH deficiency secondary to a brain tumor (n = 24) where mean GH peak = 15.5 ng/ml (5.0 after P + G) GRF induces a slight Prolactin (Prl) increase, more obvious when basal Prl is elevated. However there is no correlation between GH and Prl responses to GRF even with basal hyperprolactinemia. GH response to GRF seems to slowly decrease after radiation therapy. GRF is a new potent, well tolerated secretagogue of GH and improves the diagnostic quality of the etiology of GH deficiency.

A method for early detection of graft failure in pancreas transplantation.

Pancreatic transplantation is intended to normalize carbohydrate metabolism in insulin-dependent diabetics by restoring endogenous insulin release, and it is usually performed together with kidney transplantation in patients with end-stage renal failure. A major problem in these patients is the daily control of the grafted pancreas because traditional measurements do not appear to be adequate to evaluate pancreatic function. Aiming at early detection of graft failure, we have analyzed in 8 such patients and in 20 nondiabetic kidney-grafted patients (a control group) the following variables: 24-hr glycosuria (absolute values, or values after natural logarithmic transformation) and 24-hr urinary C-peptide excretion (corrected for 24-hr urinary creatinine). These measurements, considered alone, did not detect pancreatic graft failure; for instance, glycosuria can depend on immunosuppressive steroid treatment, and it was often found even in the control group. On the contrary, the ratio Ln 24-hr glycosuria: 24-hr urinary C-peptide varied from 0.00 to 0.18 in the control group and in normally working pancreatic grafts; when the pancreatic grafts failed, however, as confirmed by arteriographic evidence, histologic findings, or dynamic endocrine tests, this ratio rose far higher than 0.18, reaching values as high as 12.2. Use of this ratio provides a simple technique for daily evaluation of pancreatic graft function and for early detection of graft failure.

Endocrine responses of type 1 (insulin-dependent) diabetic patients following successful pancreas transplantation.

The aim of the present study was to evaluate the insulin and glucagon responses to various stimuli in patients following pancreatic transplantation. Four Type 1 (insulin-dependent) diabetic patients with end-stage renal failure who had received a cadaveric segmental, neoprene-injected, pancreas transplant, in association with kidney transplantation, were investigated. Free-insulin, pancreatic glucagon, and growth hormone concentrations were measured after both oral and intravenous glucose tolerance tests, and following tolbutamide, arginine and arginine plus somatostatin infusions. Tests were performed 1 month (three cases) and 30 months (one case) after surgery, when no insulin administration was required. Four non-diabetic kidney grafted patients, matched for duration of graft survival and immunosuppressive treatment (steroids, azathioprine and anti-lymphocyte-globulins), served as control subjects. Impaired glucose tolerance was present in all diabetic and control patients. This was possibly related to immunosuppressive treatment. In comparison with control subjects, insulin release was normal in response to arginine and tolbutamide but was reduced in response to oral and intravenous glucose, while glucagon and growth hormone release were similar in both groups. Somatostatin was less effective in diabetic patients than in control subjects in suppressing insulin and glucagon release.

Effect of oral lipid administration on glucose homeostasis in small-for-gestational-age infants.

The metabolic effect of feeding with 1.3 g/kg bw lipids (67% medium chain triglycerides) was studied in 15 small-for-gestational age (SGA) term infants. It was compared to a control group of 7 SGA term infants, to 7 term infants with an appropriate birth weight (AGA) and to 7 AGA preterm infants. Plasma glucose concentration rose from (M +/- SE) 3.6 +/- 0.2 to 4.4 +/- 0.3 mmol/l at 30 min in SGA term infants (p less than 0.01). A similar increase was observed in AGA term and preterm infants. The lipid load produced no change in plasma glucagon concentration but a significant increase in insulin/glucagon molar ratio was observed in AGA term infants only. In term SGA infants, the disappearance rate of glucose in plasma after the lipid load was similar to the control: 1.24% per min. The evolution of blood pyruvate and lactate concentration was not modified by the lipid load. Despite lower concentrations of free fatty acids and ketone bodies (KB) in SGA infants than in AGA term infants, the lipid load induced a 120% increase of ketone bodies in SGA infants and a 40% increase only in AGA infants. These data show that these lipids produce a hyperglycemic response in SGA infants as in AGA infants without any change of the disappearance rate of glucose. They suggest that these lipids can stimulate gluconeogenesis and ketogenesis in SGA infants.

Clinical experience with renal and neoprene-injected segmental pancreatic allografts in man.

We describe 22 clinical cases of segmental pancreatic grafts that were prepared with neoprene injection in the pancreatic duct. Complete correction of the diabetes is obtained during the period of function of the graft. The surgical procedure is a safe one and does not lead to a higher surgical risk than the usual kidney transplantation. Progress should be made by early detection and effective treatment of the pancreatic graft rejection. Corticoids should be avoided to suppress the diabetogenic effect. Cyclosporine A will probably be the immunosuppressive of choice.

Effect of oral administration of lipids with 67% medium chain triglycerides on glucose homeostasis in preterm neonates.

Since hypoglycemic responses to medium chain triglycerides (MCT) have been reported in adults we studied the effect of an acute oral load of lipids (2,8 g/kg) with 67% MCT on glucose homeostasis in 21 preterm infants in comparison to 14 age-matched control preterm infants. A hyperglycemic response from (mean +/- SEM) 57 +/- 1.1 to 74 +/- 2.5 at 30 min (p less than 0.01) and to 80.5 +/- 2.5 mg/dl at 60 min (p less than 0.01) was observed after administration of the lipids whereas no change in plasma glucose concentration was observed in the control group. After administration of the lipids there was no change in the concentration of insulin and glucagon in plasma. An intravenous glucose tolerance test (1 g/kg) was similar in the control group and 60 min after administration of the lipids. After administration of the lipids free fatty acid concentration remained unchanged while a significant decrease from 304 +/- 56 to 199 +/- 28 muEq/l was observed in 60 min in the control group. At 60 min beta-hydroxybutyrate concentration was higher after lipid administration (630 +/- 86 mumol/l) than in the control group (436 +/- 66 mumol/l) (p less than 0.05). A more rapid decrease in blood lactate concentration was found after lipid administration than in the control group while no change in plasma alanine concentration was observed in either groups. In five additional preterm infants, plasma glucose concentration increased from 56 +/- 0.6 to 75 +/- 0.9 mg/dl (p less than 0.01) 60 minutes after gastric administration of glycerol (0.3 g/kg). These data show that in preterm infants, a lipid load with 67% TCM produces a hyperglycemic response through gluconeogenesis without changing the peripheral rate of glucose disappearance.

[Combined test for assessment of anterior pituitary function using glucagon-propranolol, TRH and LHRH (author's transl)]. / Test combiné d'exploration fonctionnelle anté-hypophysaire utilisant le glucagon-propranolol, la TRH et la LHRH.

Combined Glucagon-Propranolol test used for study of growth hormone is advantages. The combined administration of TRH and LHRH is possible. In 53 children, the hormone responses (GH, TSH, FSH, LH and prolactin) were studied. This combined test allows the rapid assessment of anterior pituitary function.

Studies of growth hormone secretion in juvenile diabetes.

To further investigate the GH secretion in juvenile diabetics, blood glucose (BG) and plasma growth hormone (GH) were determined during controlled exercise performed in basal condition and under glucose infusion, in 7 controls and 22 juvenile diabetics aged 12--35 years, 10 of them with fundal vascular lesions. In controls, glucose infusion significantly lowered the exercise induced GH rise observed under basal conditions. In diabetics, under basal conditions, diabetics with low basal BG (BG less than 100 mg/100ml) had higher GH secretion than those with high basal BG (BG greater than 140 mg/100 ml; p less than 0.05). Under glucose infusion, diabetics with normal BG peak values (not different from controls: BG = 284 +/- (SK) 45 mg/100 ml) had significantly higher plasma GH levels than controls (p less than 0.01). In contrast, in diabetics with BG peak value higher than controls (BG greater than 374 ng/100 ml), plasma GH levels were not different from control values. This study indicates that exercise induced GH secretion in diabetics is mainly related to actual BG levels. Furthermore, we found no relation between the magnitude of GH secretion and the presence of retinopathy in diabetics.

Effect of intravenous hydrocortisone administration on glucose homeostasis in small for gestational age infants.

The effects of I.V. hydrocortisone (H) (10 mg/kg) on glucose homeostasis were evaluated at 25 to 85 hours of age in 14 infants who were small for gestational age (SGA) in comparison to 17 control SGA infants. Three hours after H administration, higher levels of plasma glucose than in controls were detected (mean +/- S.E.M.): 4.78 +/- 0.2 vs. 2.88 +/- 0.2 mmol/l (p less than 0.01), while lower levels were found for blood pyruvate (38 +/- 7 vs. 89 +/- 12 mumol/l--p less than 0.01), plasma insulin (6.4 +/- 0.5 vs. 12 +/- 0.8 muIU/ml--p less than 0.05) and plasma glucagon (62.25 +/- 6.6 vs. 81.6 +/- 6.6 pmol/l--p less than 0.05). Three hours after H administration, I.V. injection of L-alanine (150 mg/kg) produced a significant rise over baseline of plasma glucose concentration from 4.78 +/- 0.2 to 5.94 +/- 0.2 mmol/l at 50 min (p less than 0.05), whereas no significant change was observed in controls. There was no significant change in plasma glucagon and insulin concentrations after L-alanine injection in either group. These results show that in SGA infants primed with H, the rise of plasma glucose concentration after L-alanine administration is observed with low plasma insulin levels and without stimulation of glucagon secretion. They suggest that H induced a reduced peripheral utilization of glucose by lowering the plasma levels of insulin and a production of glucose from alanine through gluconeogenesis.

Effect of intravenous L-alanine administration on plasma glucose, insulin and glucagon, blood pyruvate, lactate and beta-hydroxybutyrate concentrations in newborn infants. Study in term and preterm newborn infants.

Ten term and eleven preterm newborn infants with appropriate weights for their gestational age were infused for one minute with L-alanine (150 mg/kg) at the age of 29 to 76 hours (mean 48 hours) and circulating levels of glucose, lactate, pyruvate, D-betahydroxybutyrate (D-BOHB), insulin and glucagon were monitored. Plasma glucose concentrations increased from 2.7 +/- 0.16 (mean +/- S.E.M.) to 3.7 +/- 0.2 mmol/l after 50 min (p less than 0.01) in term infants. In preterm infants, after an initial decrease of the glucose level from 3.1 +/- 0.16 to 2.6 +/- 0.16 mmol/l (p less than 0.05), it returned to the baseline level at 50 min: 3.0 +/- 0.2 mmol/l. The blood concentration of D-BOHB decreased in term infants from 192 +/- 37 to 112 + 6 micrometer/l (p less than 0.01) after 40 min. In preterms, its decrease was not significant (p greater than 0.05). Plasma glucagon level rose from 53 +/- 5 to 70 +/- 8 pmol/l after ten minutes (p less than 0.01) in terms infants and from 61 +/- 6 to 75 +/- 9 after 20 min (p less than 0.01) in preterm infants. There were no significant changes in plasma insulin concentrations in either group. Forty minutes after L-alanine infusion, I/G ratios were lower in preterm infants (1.26 +/- 0.14) than in term infants (1.71 +/- 0.25) (p less than 0.01). There was no relationship between the glycemic responses to L-alanine and the basal levels of D-BOHB. The data suggest that the glycemic effect of L-alanine infusion and circulating glucagon depends upon a specific stage in maturation. The antiketogenic effect of L-alanine infusion is observed in term infants as in adults.

[A new method of pancreatic transplantation. 1 - Effects on the dog pancreas of the intraduct injection of neoprene (author's transl)]. / Une nouvelle méthode de transplantation pancréatique. I. Effet sur le pancréas du chien de l'injection intracanalaire de néoprène.

Injection into the pancreatic ducts of a synthetic liquid gum (neoprene), which polymerises when it comes into contact with the fluid secreted by the gland, would appear to be a simple and effective means of suppressing exocrine secretion of the pancreas in the dog. Endocrine secretion was remained in the short and mid-term. The therapeutic implications of this new technique in the preparation of pancreatic transplants are discussed.