Francesca Righetti

Relationships Between Growth Factors (Somatomedin-C and Growth Hormone) and Body Development, Metabolic Control, and Retinal Changes in Children and Adolescents With IDDM

We used the radioimmunoassay (RIA) method to determine somatomedin-C (SmC) basal values in 59 diabetic children and adolescents (20 prepubertal and 39 pubertal subjects; age range 2.75–20.16 yr; duration of diabetes 0.08–15.83 yr) and in 274 control subjects. In comparing diabetic subjects with controls, we considered only those 50 diabetic subjects who were age matched with the controls, i.e., those not over 16 yr chronological age. SmC basal levels in pubertal diabetic patients were no different from those of pubertal age-matched control children, whereas in prepubertal diabetic patients SmC was significantly lower than in the respective control children (P < .001). No correlation was found between the z score for SmC (i.e., the number of standard deviations each SmC level is from the age- and sex-normalized mean) and duration of disease, velocity standard deviation score, severity of fluoroangiographic retinal changes, basal C-peptide values and HbA, levels. No differences were encountered in mean SmC and SmC z-score values in the separate groups of poorly, fairly, and well-controlled diabetic children, in the groups with and without residual pancreatic activity, and in the group with and without retinal changes. In 16 of the pubertal diabetics and in 15 pubertal controls, serum glucose, growth hormone (GH), and SmC concentrations were determined during the night. The integrated nocturnal secretion of SmC was no different in diabetics than in controls, whereas the integrated nocturnal secretion of GH was significantly (P < .025) higher in diabetics than in controls. These data suggest a partial block in somatomedin production, which would be compensated by a hypersecretion of GH through a negative-feedback relationship. On the other hand, it may be that GH hypersecretion is primary and that the normal or low SmC secretion is a response to low-efficiency GH.

Differences in somatomedin-C between short-normal subjects and those of normal height*

We evaluated basal somatomedin-C (SmC) levels in 98 subjects 2 to 16.6 years of age, with height less than 3rd centile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height greater than 10th centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (greater than 8 ng/ml) in at least one of three tests: arginine, L-dopa, and sleep. In control subjects, there was a significant positive correlation between SmC levels and chronologic age, bone age, and pubertal stage (pubic hair, breast or testicular volume). The same correlations were present in short-normal subjects, but SmC levels were significantly lower than in normal children. The percentage of subjects with very low SmC values (less than or equal to 0.25 IU/ml in those older than 6 years, and less than 0.1 IU/ml in those younger than 6 years) was higher in the short-normal group of children older than 6 years. In growth-retarded subjects, SmC values were significantly higher (P less than 0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response only during sleep. We conclude that short-normal subjects have, on average, low SmC values, which might indicate insufficient GH release. Therefore, current criteria to define GH deficiency and children needing treatment may be too restrictive.

Neuroendocrinological evidence of an anti‐dopaminergic effect of flunarizine

ABSTRACT— The effect of a one month treatment with flunarizine (5 mg/day) on pituitary responsiveness to gonadotrophin‐releasing hormone (GnRH), thyrotrophin‐releasing hormone (TRH) and arginine infusion was assessed in 17 adolescents (11 M, 6 F) treated with the drug to prevent migraine attacks. Basal prolactin concentrations as well as the prolactin response to TRH were significantly (p<0.05) increased after flunarizine treatment. Flunarizine had no effect on the folliclestimulating and luteinising hormone response to GnRH stimulation, growth hormone response to arginine infusion or thyrotrophin response to TRH stimulation. Our data suggest that flunarizine may interfere with the hypothalamic‐pituitary‐prolactin axis decreasing dopaminergic inhibitory tonus.

The association between preeclampsia and placental disruption induced by chorionic villous sampling.

The objectives of this study were (1) to evaluate if the elevation of maternal serum α‐feto protein (MSAFP) and pregnancy‐associated placental protein‐A (PAPP‐A) in the maternal blood after chorionic villous sampling (CVS) is associated with a higher preeclampsia (PE) rate and (2) to verify the clinical utility of the analytes elevation for predicting PE.

A First-Trimester Biomarker Panel for Predicting the Development of Gestational Diabetes:

OBJECTIVE Serum markers measured early in pregnancy have been associated with the later diagnosis of gestational diabetes mellitus (GDM). This study aims to explore the performance of a panel of first-trimester biochemical markers for the prediction of GDM. METHODS A case-control study was performed that included 12 women who developed GDM and 60 controls matched for maternal and gestational age at blood collection. Levels of pregnancy-associated plasma protein A (PAPP-A), soluble endoglin, pregnancy protein 13, and adiponectin (Adipo) were measured on residual sera used in first-trimester screening for Down syndrome. Data were analyzed by nonparametric methods. A receiver operating characteristic curve was used to calculate the detection rate (DR) obtained with a panel of significant predictors for GDM. RESULTS Multiples of the median values for Adipo and PAPP-A were significantly reduced in GDM cases versus matched controls. Combination of Adipo and PAPP-A yielded a DR of 63.6% at a false-positive rate of 10%. Addition of body mass index (BMI) to this panel increased DR to 72.7%. CONCLUSION This study suggests that first-trimester screening with Adipo, PAPP-A, and BMI may effectively identify women at high risk for the development of GDM.Objective: Serum markers measured early in pregnancy have been associated with the later diagnosis of gestational diabetes mellitus (GDM). This study aims to explore the performance of a panel of first-trimester biochemical markers for the prediction of GDM. Methods: A case–control study was performed that included 12 women who developed GDM and 60 controls matched for maternal and gestational age at blood collection. Levels of pregnancy-associated plasma protein A (PAPP-A), soluble endoglin, pregnancy protein 13, and adiponectin (Adipo) were measured on residual sera used in first-trimester screening for Down syndrome. Data were analyzed by nonparametric methods. A receiver operating characteristic curve was used to calculate the detection rate (DR) obtained with a panel of significant predictors for GDM. Results: Multiples of the median values for Adipo and PAPP-A were significantly reduced in GDM cases versus matched controls. Combination of Adipo and PAPP-A yielded a DR of 63.6% at a false-positive rate of 10%. Addition of body mass index (BMI) to this panel increased DR to 72.7%. Conclusion: This study suggests that first-trimester screening with Adipo, PAPP-A, and BMI may effectively identify women at high risk for the development of GDM.

Author's response to the letter by Basaran et al.

This letter by Basaran comments on our article about serum pregnancy associated plasma protein A (PAPPA) and serum alpha-fetoprotein (AFP) before and after chorionic villus sampling (CVS). The title of Basaran’s letter is misleading, as our paper does not affirm any reliable association between serum markers and preeclampsia (PE) but, instead, a rise in serum levels before and after CVS as a possible correlation with the degree of villus disruption. Of course, as villus disruption has been associated with PE, a correlation between the degree of marker aberration and PE might be possible, but that is not to say it is clearly demonstrated. Basaran’s letter contains several criticisms, basically addressing the results and the statistical method. However, the second part does not at all relate to our paper as it reports some analyses advanced by other studies about the risk of PE and CVS. I, thus, fail to grasp the real purpose of this letter, which seems no more than a cursory reanalysis of other studies. However, I am more than happy to clarify the items that regard our paper. One point of confusion may be that Basaran did not read the conclusion or the aim of our paper carefully. He focused on the following items:

Somatomedin-C levels related to gestational age, birth weight and day of life.

Capillary blood samples on filter paper were assayed by means of an RIA method (Kit Nichols Institute USA) from 1096 newborns divided into full term, preterm and small-for-date infants. The somatomedin-C (Sm-C) mean value, which did not differ in the three groups, was 0.15±0.09 IU/ml. One hundred and ten (10%) showed Sm-C disc values ≤0.075 IU/ml, the minimum value measurable by our method. The day of life and birth weight had a significant influence on Sm-C levels. Gestational age did not have any significant effect. No significant interaction was found among the parameters considered. All the groups presented a progressive increase of Sm-C. Unlike preterm and small-for-date infants, in full term infants the latter increase seemed already to be evident from 5th day of life and reached higher levels from the 7th day of life onwards. In conclusion, Sm-C rates were reduced in the neonatal phase of life, but showed a tendency to rise later.