We examined the effect of growth hormone (GH) therapy on thyroid function in 57 children with iso... more We examined the effect of growth hormone (GH) therapy on thyroid function in 57 children with isolated GH deficiency and whether this effect could influence their growth response. Thyroid function and insulin-like growth factor I levels were measured before and after 3, 6, and 12 months of recombinant-GH therapy (20 U/m2 per week, given subcutaneously), after a 1-month withdrawal from therapy, and after a further 6 months of GH administration. The serum concentration of triiodothyronine (T3) and the T3/T4 (thyroxine) ratio increased after 12 months of GH treatment, whereas total T4 and free T4 levels decreased; thyrotropin levels did not change significantly during treatment but increased after a 1-month withdrawal. After a further 6 months of GH therapy, an increase in T3 levels and in the T3/T4 ratio and a decrease in total T4 and free T4 levels were found again, and thyrotropin levels decreased. The increment in growth velocity after 12 months of therapy correlated positively with the T3/T4 ratio and negatively with total T4 and free T4 values. These data confirm in children a GH-induced enhancement of peripheral conversion of T4 to T3. This effect appears to be more evident in children who are most sensitive to GH in terms of growth-promoting activity.
Objective/Methods: To assess exocrine and endocrine testicular function in subjects with diabetes... more Objective/Methods: To assess exocrine and endocrine testicular function in subjects with diabetes, we evaluated serum inhibin B, gonadotrophins and testosterone levels in 33 male adolescent and young adult patients affected by type-1 diabetes (age 21.0 ± 5 years; range 14.2–33.3), with a mean disease duration of 12.7 ± 5.8 years (range 1.5–25.3) and various metabolic control (HbA1c 7.8 ± 1.5%; range 5.5–13.2) and compared them with those of an age-matched group of 36 healthy control subjects (age 19.5 ± 4.1 years; range 13.6–28.1). Both patients and controls had a testicular volume ≧15 ml. Inhibin B was measured by ELISA method. Results/Conclusion: Diabetics and controls had comparable inhibin B (203 ± 74 vs. 221 ± 69 pg/ml, respectively) and follicle-stimulating hormone (FSH) levels, while luteinizing hormone (LH) and testosterone levels were significantly higher in the diabetic group. Inhibin B was negatively correlated both in patients and controls with FSH, while a negative corr...
Objective: To evaluate self and parent reports on quality of life (QoL) and psychological adjustm... more Objective: To evaluate self and parent reports on quality of life (QoL) and psychological adjustment of youths with type 1 diabetes, in comparison to a general paediatric population, and identify relationships between disease duration, metabolic control and psychological parameters. Research design and methods: Participants included 70 youths with type 1 diabetes and their parents. They were compared with 70 non-diabetic subjects. Data were analyzed in the whole group and in subgroups aged 6-10, 11-13 and 14-18 yr. All cases performed pediatric QoL, Child Behaviour Checklist, filled in by parents, and Youth Self-Report, filled in by youths. Data were compared with haemoglobin A1c (HbA1c) values and disease duration. Results: Self-reports showed a psychological adjustment of youths with type 1 diabetes similar to that of controls. Parent reports showed that parents of children with type 1 diabetes were more worried than those of controls (p , 0.01). Adolescents showed a worse QoL and more frequent psychological disturbances. In this group, for youth and parent reports, HbA1c levels correlated positively with psychological problems (p , 0.05) and negatively with QoL (p , 0.05). Only for parent reports, in the whole group and in subgroups aged 6-10 and 11-13 yr, disease duration correlated positively with psychological adjustment (p , 0.05). Conclusions: Before adolescence, youths with type 1 diabetes showed only slight problems in psychological adjustment and QoL, with an association with disease duration reported by parents. In adolescence, both youths and their parents reported more emotional and behavioural problems, independent of disease duration. Better metabolic control and psychological well-being seemed directly related.
Mild insulin resistance appears to be an early metabolic defect in girls with Turner syndrome (TS... more Mild insulin resistance appears to be an early metabolic defect in girls with Turner syndrome (TS). Impaired glucose tolerance has been reported in 10–34% of patients with TS, and type 2 diabetes mellitus is 2–4 times more common and occurs at a younger age in girls with TS than in the general population. In a mixed longitudinal and cross-sectional study, we analysed carbohydrate tolerance and insulin sensitivity in 46 children and adolescents with TS who reached their final height after long-term treatment (mean 6.3 ± 2.5 years) with growth hormone (GH: 0.33 mg/kg/week [0.05 mg/kg/day]), and in 36 of these patients who were followed-up after the cessation of GH therapy (mean follow-up, 2.6 ± 2.5 years; range, 1–9.5 years). Patients with TS were compared with an age-matched female control group. Insulin sensitivity appeared to be lower in patients with TS than in controls, even before the start of GH therapy. As in controls, insulin sensitivity decreased with age in patients with TS...
We have studied the distribution of Y chromosomal haplotypes and haplogroups in two population sa... more We have studied the distribution of Y chromosomal haplotypes and haplogroups in two population samples from the Romagna region (North Italy) by analyzing male-specific markers that reflect past and recent history: SNPs and STRs. The population samples were collected in the urban area of Rimini, an ancient port in Roman age and in the near rural area of Valmarecchia, that is more isolated and geographically out of ancient trading ways. We analyzed 11 Y STRs by a commercial kit and 20 binary polymorphisms by minisequencing analysis. In spite of the different historical records and geographic locations, the two population samples showed high genetic affinities likely due to modern demographic migrations that might have eroded the past genetic substructure.
We evaluated basal somatomedin-C (SmC) leve& in 98 subjects 2 to 16.6 years of age, with height <... more We evaluated basal somatomedin-C (SmC) leve& in 98 subjects 2 to 16.6 years of age, with height <3rd eentile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height >lOth centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (>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 (~<0.25 IU/ml in those older than 6 years, and <0.1 1U/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 <0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response oniy 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 9 (J PEDIATk 106:891, 1985)
Journal of pediatric endocrinology & metabolism : JPEM, 2001
Turner syndrome (TS) is the most common sex-chromosome abnormality in females. Short stature and ... more Turner syndrome (TS) is the most common sex-chromosome abnormality in females. Short stature and hypogonadism are the classical clinical findings. The spontaneous final height (FH) ranges between 139 and 147 cm, representing a growth deficit of about 20 cm with respect to the unaffected population. GH therapy improves FH and should be started during childhood at a high dose of about 1 IU/kg/week (range 0.6-2 IU/kg/week). Some authors advocate combined therapy with an anabolic steroid at various doses (e.g. oxandrolone 0.05-0.1 mg/kg/day). This treatment results in a significantly increased FH, a large proportion of treated girls reaching a FH of more than 150 cm. Gonadal function is compromised during adolescence in about 80% of girls with TS, whilst in about 20% pubertal development occurs spontaneously. Oestrogen therapy should be started at the age of 13-14 years in hypogonadic patients; early onset of treatment (before 12 years) seems to compromise FH. Other concerns in these pa...
Congenital adrenal hyperplasia (CAH) is mainly caused by the deficiency of the 21-hydroxylase enz... more Congenital adrenal hyperplasia (CAH) is mainly caused by the deficiency of the 21-hydroxylase enzyme coded by the CYP21A2 gene. However, some alleles in the non-classical form (NC-CAH) remain without identified mutations, suggesting the involvement of regulatory regions. Our objective was to study an allele carrying the variant *13 G&amp;amp;gt;A in the 3&amp;amp;#39;UTR of the CYP21A2 gene identified in some patients with a mild form of NC-CAH in order to verify the possible implication of this variation with the phenotype observed. Among all the subjects in whom the CYP21A2 gene was analyzed, 14 patients and 7 relatives heterozygous or homozygous for the *13 G&amp;amp;gt;A substitution in 3&amp;amp;#39;UTR were selected. Sequencing of DNA, genotyping, multiplex ligation-dependent probe amplification (MLPA), in vitro studies and bioinformatic analysis were performed. The haplotype of the *13 G&amp;amp;gt;A allele was identical in all the subjects with a monomodular structure composed by one C4A gene and one CYP21A2 gene without a second module with the CYP21A1P pseudogene. No other concomitant mutations were found in the region extending from 3 kb in the promoter and encompassing the polyadenylation signal. Both bioinformatic analysis and in vitro studies predicted an alteration of the RNA folding and expression, but no miRNA target sequences were found in this region. The identification of a substitution in the 3&amp;amp;#39;UTR of the gene associated with a mild form of NC-CAH suggests the importance of analyzing the CYP21A2 untranslated regions to better characterize and treat this subgroup of patients.
We examined the effect of growth hormone (GH) therapy on thyroid function in 57 children with iso... more We examined the effect of growth hormone (GH) therapy on thyroid function in 57 children with isolated GH deficiency and whether this effect could influence their growth response. Thyroid function and insulin-like growth factor I levels were measured before and after 3, 6, and 12 months of recombinant-GH therapy (20 U/m2 per week, given subcutaneously), after a 1-month withdrawal from therapy, and after a further 6 months of GH administration. The serum concentration of triiodothyronine (T3) and the T3/T4 (thyroxine) ratio increased after 12 months of GH treatment, whereas total T4 and free T4 levels decreased; thyrotropin levels did not change significantly during treatment but increased after a 1-month withdrawal. After a further 6 months of GH therapy, an increase in T3 levels and in the T3/T4 ratio and a decrease in total T4 and free T4 levels were found again, and thyrotropin levels decreased. The increment in growth velocity after 12 months of therapy correlated positively with the T3/T4 ratio and negatively with total T4 and free T4 values. These data confirm in children a GH-induced enhancement of peripheral conversion of T4 to T3. This effect appears to be more evident in children who are most sensitive to GH in terms of growth-promoting activity.
Objective/Methods: To assess exocrine and endocrine testicular function in subjects with diabetes... more Objective/Methods: To assess exocrine and endocrine testicular function in subjects with diabetes, we evaluated serum inhibin B, gonadotrophins and testosterone levels in 33 male adolescent and young adult patients affected by type-1 diabetes (age 21.0 ± 5 years; range 14.2–33.3), with a mean disease duration of 12.7 ± 5.8 years (range 1.5–25.3) and various metabolic control (HbA1c 7.8 ± 1.5%; range 5.5–13.2) and compared them with those of an age-matched group of 36 healthy control subjects (age 19.5 ± 4.1 years; range 13.6–28.1). Both patients and controls had a testicular volume ≧15 ml. Inhibin B was measured by ELISA method. Results/Conclusion: Diabetics and controls had comparable inhibin B (203 ± 74 vs. 221 ± 69 pg/ml, respectively) and follicle-stimulating hormone (FSH) levels, while luteinizing hormone (LH) and testosterone levels were significantly higher in the diabetic group. Inhibin B was negatively correlated both in patients and controls with FSH, while a negative corr...
Objective: To evaluate self and parent reports on quality of life (QoL) and psychological adjustm... more Objective: To evaluate self and parent reports on quality of life (QoL) and psychological adjustment of youths with type 1 diabetes, in comparison to a general paediatric population, and identify relationships between disease duration, metabolic control and psychological parameters. Research design and methods: Participants included 70 youths with type 1 diabetes and their parents. They were compared with 70 non-diabetic subjects. Data were analyzed in the whole group and in subgroups aged 6-10, 11-13 and 14-18 yr. All cases performed pediatric QoL, Child Behaviour Checklist, filled in by parents, and Youth Self-Report, filled in by youths. Data were compared with haemoglobin A1c (HbA1c) values and disease duration. Results: Self-reports showed a psychological adjustment of youths with type 1 diabetes similar to that of controls. Parent reports showed that parents of children with type 1 diabetes were more worried than those of controls (p , 0.01). Adolescents showed a worse QoL and more frequent psychological disturbances. In this group, for youth and parent reports, HbA1c levels correlated positively with psychological problems (p , 0.05) and negatively with QoL (p , 0.05). Only for parent reports, in the whole group and in subgroups aged 6-10 and 11-13 yr, disease duration correlated positively with psychological adjustment (p , 0.05). Conclusions: Before adolescence, youths with type 1 diabetes showed only slight problems in psychological adjustment and QoL, with an association with disease duration reported by parents. In adolescence, both youths and their parents reported more emotional and behavioural problems, independent of disease duration. Better metabolic control and psychological well-being seemed directly related.
Mild insulin resistance appears to be an early metabolic defect in girls with Turner syndrome (TS... more Mild insulin resistance appears to be an early metabolic defect in girls with Turner syndrome (TS). Impaired glucose tolerance has been reported in 10–34% of patients with TS, and type 2 diabetes mellitus is 2–4 times more common and occurs at a younger age in girls with TS than in the general population. In a mixed longitudinal and cross-sectional study, we analysed carbohydrate tolerance and insulin sensitivity in 46 children and adolescents with TS who reached their final height after long-term treatment (mean 6.3 ± 2.5 years) with growth hormone (GH: 0.33 mg/kg/week [0.05 mg/kg/day]), and in 36 of these patients who were followed-up after the cessation of GH therapy (mean follow-up, 2.6 ± 2.5 years; range, 1–9.5 years). Patients with TS were compared with an age-matched female control group. Insulin sensitivity appeared to be lower in patients with TS than in controls, even before the start of GH therapy. As in controls, insulin sensitivity decreased with age in patients with TS...
We have studied the distribution of Y chromosomal haplotypes and haplogroups in two population sa... more We have studied the distribution of Y chromosomal haplotypes and haplogroups in two population samples from the Romagna region (North Italy) by analyzing male-specific markers that reflect past and recent history: SNPs and STRs. The population samples were collected in the urban area of Rimini, an ancient port in Roman age and in the near rural area of Valmarecchia, that is more isolated and geographically out of ancient trading ways. We analyzed 11 Y STRs by a commercial kit and 20 binary polymorphisms by minisequencing analysis. In spite of the different historical records and geographic locations, the two population samples showed high genetic affinities likely due to modern demographic migrations that might have eroded the past genetic substructure.
We evaluated basal somatomedin-C (SmC) leve& in 98 subjects 2 to 16.6 years of age, with height <... more We evaluated basal somatomedin-C (SmC) leve& in 98 subjects 2 to 16.6 years of age, with height <3rd eentile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height >lOth centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (>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 (~<0.25 IU/ml in those older than 6 years, and <0.1 1U/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 <0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response oniy 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 9 (J PEDIATk 106:891, 1985)
Journal of pediatric endocrinology & metabolism : JPEM, 2001
Turner syndrome (TS) is the most common sex-chromosome abnormality in females. Short stature and ... more Turner syndrome (TS) is the most common sex-chromosome abnormality in females. Short stature and hypogonadism are the classical clinical findings. The spontaneous final height (FH) ranges between 139 and 147 cm, representing a growth deficit of about 20 cm with respect to the unaffected population. GH therapy improves FH and should be started during childhood at a high dose of about 1 IU/kg/week (range 0.6-2 IU/kg/week). Some authors advocate combined therapy with an anabolic steroid at various doses (e.g. oxandrolone 0.05-0.1 mg/kg/day). This treatment results in a significantly increased FH, a large proportion of treated girls reaching a FH of more than 150 cm. Gonadal function is compromised during adolescence in about 80% of girls with TS, whilst in about 20% pubertal development occurs spontaneously. Oestrogen therapy should be started at the age of 13-14 years in hypogonadic patients; early onset of treatment (before 12 years) seems to compromise FH. Other concerns in these pa...
Congenital adrenal hyperplasia (CAH) is mainly caused by the deficiency of the 21-hydroxylase enz... more Congenital adrenal hyperplasia (CAH) is mainly caused by the deficiency of the 21-hydroxylase enzyme coded by the CYP21A2 gene. However, some alleles in the non-classical form (NC-CAH) remain without identified mutations, suggesting the involvement of regulatory regions. Our objective was to study an allele carrying the variant *13 G&amp;amp;gt;A in the 3&amp;amp;#39;UTR of the CYP21A2 gene identified in some patients with a mild form of NC-CAH in order to verify the possible implication of this variation with the phenotype observed. Among all the subjects in whom the CYP21A2 gene was analyzed, 14 patients and 7 relatives heterozygous or homozygous for the *13 G&amp;amp;gt;A substitution in 3&amp;amp;#39;UTR were selected. Sequencing of DNA, genotyping, multiplex ligation-dependent probe amplification (MLPA), in vitro studies and bioinformatic analysis were performed. The haplotype of the *13 G&amp;amp;gt;A allele was identical in all the subjects with a monomodular structure composed by one C4A gene and one CYP21A2 gene without a second module with the CYP21A1P pseudogene. No other concomitant mutations were found in the region extending from 3 kb in the promoter and encompassing the polyadenylation signal. Both bioinformatic analysis and in vitro studies predicted an alteration of the RNA folding and expression, but no miRNA target sequences were found in this region. The identification of a substitution in the 3&amp;amp;#39;UTR of the gene associated with a mild form of NC-CAH suggests the importance of analyzing the CYP21A2 untranslated regions to better characterize and treat this subgroup of patients.
Uploads
Papers by A. Cicognani