Raffaele Virdis

Blood pressure in childhood and adolescence: The Italian normal standards

OBJECTIVES To develop a national standard level of blood pressure (BP) for Italian children on the basis of a large sample of the population. DESIGN We analyzed data available from 21 Italian studies conducted according to the recommendations of the American Task Force between 1988 and 1994. Percentile curves of systolic and diastolic BP were constructed by fitting a third-order polynomial model of BP on age and height using multiple regression analysis. PARTICIPANTS BP was measured in 11 519 healthy individuals (6258 boys and 5261 girls) aged 5-17 years in various locations throughout Italy. All measurements were performed at school. RESULTS Percentile curves (5th, 10th, 25th, 50th, 75th, 90th and 95th) of systolic and diastolic BP are reported by age and by height for males and females. CONCLUSIONS With respect to the American standards, the levels in Italy for the 90th and 95th percentiles were 3-8 mmHg higher for systolic and diastolic BP in both sexes between 5 and 12 years of age, and 2-3 mmHg higher in older males. With respect to Northern Europe, in the lower ages, levels in Italy were quite similar, although slightly higher, whereas in late adolescence, the Northern European levels were much higher, especially in males, with differences of 4-5 mmHg for the mean values and 8-12 mmHg for the 95th percentile.

Precocious puberty in girls adopted from developing countries

Nineteen girls adopted from developing countries were referred for signs of idiopathic precocious puberty. After adoption, the catch up in linear and weight growth, together with improved nutritional and psychological conditions, may trigger the onset of puberty. Precocious puberty is a frequent and unnatural event in these girls. Treatment with gonadotrophin releasing analogues is indicated in patients diagnosed early, and when height prediction is poor.

Focus on prevention, diagnosis and treatment of hypertension in children and adolescents

The European Society of Hypertension has recently published its recommendations on prevention, diagnosis and treatment of high blood pressure in children and adolescents. Taking this contribution as a starting point the Study Group of Hypertension of the Italian Society of Pediatrics together with the Italian Society of Hypertension has conducted a reappraisal of the most recent literature on this subject. The present review does not claim to be an exhaustive description of hypertension in the pediatric population but intends to provide Pediatricians with practical and updated indications in order to guide them in this often unappreciated problem.This document pays particular attention to the primary hypertension which represents a growing problem in children and adolescents. Subjects at elevated risk of hypertension are those overweight, with low birth weight and presenting a family history of hypertension. However, also children who do not present these risk factors may have elevated blood pressure levels. In pediatric age diagnosis of hypertension or high normal blood pressure is made with repeated office blood pressure measurements that show values exceeding the reference values. Blood pressure should be monitored at least once a year with adequate methods and instrumentation and the observed values have to be interpreted according to the most updated nomograms that are adjusted for children’s gender, age and height. Currently other available methods such as ambulatory blood pressure monitoring and home blood pressure measurement are not yet adequately validated for use as diagnostic instruments. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child’s age and directly proportional to blood pressure levels. Medical history, clinical data and blood tests may guide the differential diagnosis of primary versus secondary forms. The prevention of high blood pressure is based on correct lifestyle and nutrition, starting from childhood age. The treatment of primary hypertension in children is almost exclusively dietary/behavioral and includes: a) reduction of overweight whenever present b) reduction of dietary sodium intake c) increase in physical activity. Pharmacological therapy will be needed rarely and only in specific cases.

Pituitary-ovarian responses to leuprolide acetate testing in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

To assess whether patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit a steroidogenic response to GnRH agonist consistent with functional ovarian hyperandrogenism (FOH) and elucidate the relationship between adrenal and ovarian hyperandrogenism, the LH, FSH, estradiol, 17-hydroxyprogesterone (17-OHP), androstenedione, total testosterone, dehydroepiandrosterone, and 17-hydroxypregnenolone responses to a sc dose of leuprolide acetate (500 micrograms) were evaluated in 10 patients with classic CAH (mean age, 18.4 +/- 0.95 yr), 7 of whom had oligomenorrhea, pretreated with dexamethasone (2 mg/day for 5 days, including the day of the test). The results were compared with those obtained in 11 patients with FOH (mean age, 18.7 +/- 0.46 yr) and 17 normal women (mean age, 19.68 +/- 0.59 yr) not pretreated with dexamethasone. Leuprolide acetate stimulation caused a significant augmentation of plasma E2, 17-OHP, androstenedione, testosterone, and 17-hydroxypregnenolone concentrations in all CAH patients. However, in only 6 (60%) of them, all with oligomenorrhea, was the 17-OHP response (posttest minus pretest value) similar to that of FOH patients and significantly higher than that in controls. In this subset of CAH patients, LH plasma levels after stimulation were significantly higher than those of CAH subjects with 17-OHP responses in the normal range, controls, and FOH patients, whereas FSH levels were similar to those of controls. In this latter group, plasma FSH concentrations after stimulation were significantly higher than those in FOH. In conclusion, the results of the present study indicate that LH-dependent functional ovarian hyperandrogenism is frequent in patients with classic CAH. As ovarian hyperandrogenism might be partially responsible for the menstrual irregularities that are common complications in such patients, all classic CAH patients with oligomenorrhea should undergo short term stimulation with GnRH agonists to ascertain the presence of ovarian hyperandrogenism and receive appropriate treatment.

Neurofibromatosis type 1 and precocious puberty.

Since neurofibromatosis type 1 (NF1) is a well known cause of precocious puberty (PP), we reviewed 412 NF1 pediatric patients to evaluate the prevalence of PP, the association with optic pathway tumors (OPT), and other clinical, auxological and hormonal data. Thirty-one of 412 patients had OPT (7.5%), 10/412 PP (2.4%), and in seven of these PP was associated with OPT (7/31, 22.6%). OPT in patients with PP involved the chiasm in four patients, and the optic nerves alone in three patients. The age at the onset of puberty (or better at diagnosis) ranged from 5.2 to 7.5 yr in girls (n=6) and from 7.9 to 8.9 yr in boys (n=4). LHRH agonist therapy was used in only three children because in the others the predicted height at diagnosis was good, treatment was refused or the patients were referred to us too late. The three treated patients attained a final height within the familial range. In the untreated patients the progression of puberty was not too rapid and final height was slightly below the genetic target in four patients; however, three patients had a final height markedly below the familial range. In conclusion, the prevalence of PP is increased in children with NF1, and frequently but not exclusively is associated with OPT. Moreover, sexual precocity does not seem to be necessarily bound to chiasmatic OPT. Treatment seems to be useful in the children with younger age at the onset of puberty or with a progressive decline in predicted final height.

Changes and relationships of IGFS and IGFBPS and cytokines in coeliac disease at diagnosis and on gluten-free diet

Objective  To evaluate changes and relationships of IGFs and IGFBPs, serum interleukin 6 (IL‐6) and tumour necrosis factor (TNF)‐α, and auxological parameters at diagnosis of coeliac disease (CD) and at 6 months and 12 months after starting a gluten‐free diet (GFD), compared with a control population.

Blood Pressure Behaviour and Control in Turner Syndrome

UNLABELLED Adult Turner syndrome (TS) patients frequently present hypertension. To clarify the pathogenesis of this hypertension we examined the blood pressure (BP) behaviour and the renin-angiotensin-aldosterone system in 31 TS patients (2-22 years of age). BP levels were occasionally elevated in 47% of the subjects and constantly elevated in 23%. Most of the patients were on estrogen replacement therapy, but 26% of them presented with elevated levels since childhood. Supine and upright plasma renin activity (PRA) values were higher in TS compared to controls and more elevated in hypertensive TS than in the normotensive ones. At Captopril challenge TS showed different PRA responses regardless of the karyotype and clinical features. Patients on estrogen therapy, however, exhibited higher increments of PRA after Captopril. CONCLUSIONS TS patients show high frequency of hypertension in pediatric age. Estrogen therapy is an outbreaking and worsening factor. An estrogen independent role of the renin-angiotensin-aldosterone system in the pathogenesis of TS hypertension is still uncertain.

Adrenal steroid and adrenocorticotropin responses to human corticotropin-releasing hormone stimulation test in adolescents with type I diabetes mellitus.

To determine whether abnormalities of hypothalamic-pituitary-adrenal axis function occur in type I diabetes mellitus, corticotropin, cortisol, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), and DHEA sulfate (DS) levels were measured after an intravenous (IV) injection of 1 microgram/kg human corticotropin-releasing hormone (CRH) in diabetic adolescents and normal age-matched subjects. CRH produced a consistent increase in corticotropin blood levels that was comparable in the two groups. In contrast, both baseline and stimulated cortisol concentrations were greater in diabetic patients. Levels of 17-OHP increased after CRH administration, and the magnitude of increase was similar in all subjects. Stimulation with CRH determined an attenuated integrated DS response in diabetics compared with normal subjects with a different pattern of the hormone secretion, whereas no differences in D4-A concentrations were detected between the two groups. DHEA serum levels of subjects from both groups underwent similar changes following administration of CRH. In conclusion, patients with type I diabetes have a discrete response of adrenal steroids to CRH stimulation that appears to be independent of corticotropin secretion. This phenomenon might be related to a direct effect of insulin on enzyme systems involved in the biosynthetic pathway of adrenal steroids or, alternatively, to an intra-adrenal CRH/corticotropin mechanism acting on the adrenal cortex in a paracrine manner.

Dynamics of 24-hour pulsatile cortisol, 17-hydroxyprogesterone, and androstenedione release in prepubertal patients with nonclassic 21-hydroxylase deficiency and normal prepubertal children

To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (17-OHP), and androstenedione (D4A) secretion in patients with nonclassic congenital adrenal hyperplasia (NCCAH) differ from those in normal children, 24-hour serum concentrations of these steroids were measured in five prepubertal patients with NCCAH and five normal prepubertal children. Adrenal steroid profiles obtained by 30-minute sampling were analyzed by the Pulsar program. In comparison to normal children, the 24-hour quantitative parameters of 17-OHP and D4A secretion were significantly greater in NCCAH patients, but serum cortisol concentrations were similar in the two groups. When daytime and nighttime hormone releases were separately analyzed, a significant nocturnal elevation of the cortisol area under the curve above zero level (AUCo) and 12-hour mean and 17-OHP AUCo, AUC above baseline, mean peak height, amplitude, area, and 12-hour mean was detected in normal subjects only. Conversely, NCCAH patients exhibited an increased frequency and number of 17-OHP secretory peaks at night together with a reduction of the interpeak interval. No significant day/night differences in D4A concentrations were detected either in normals or in the patients. In conclusion, the results of the present study indicate that patients with NCCAH have a distinct pattern of adrenal steroid secretion characterized by a high-frequency 17-OHP release accompanied by a relative nocturnal cortisol deficiency.

Leuteinizing hormone responses to leuprolide acetate discriminate between hypogonadotropic hypogonadism and constitutional delay of puberty

OBJECTIVE To assess if leuprolide acetate stimulation discriminates between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty (CDP) in males. DESIGN Case-control study. SETTING Patients attending an academic research environment. PATIENTS Only male patients were studied: 10 with HH (group 1, age 16.5 +/- 6.0 years), 8 prepubertal with CDP (group 2, age 14.3 +/- 1.2 years), 6 healthy prepubertal (group 3, age 9.5 +/- 3.3 years), and 8 healthy late-pubertal (group 4, age 15.1 +/- 3.1 years). INTERVENTION(S) Blood samples were obtained after an overnight fast. Leuprolide acetate was then administered SC, and blood samples were drawn at 0, 30, 60, 120, 180 minutes, and 6 and 24 hours after stimulation. MAIN OUTCOME MEASURE(S) Clinical follow-up evaluations of data and serum levels of LH, FSH, 17-hydroxyprogesterone, and testosterone. RESULT(S) Basal LH levels were similar in groups 1 through 3 and differed significantly from those in group 4. Peak serum LH levels were significantly higher in CDP compared with HH (8.9 +/- 1.4 vs. 1.4 +/- 0.2 IU/L). Baseline FSH levels were significantly higher only in pubertal boys (versus the HH group); peak levels did not differ among the groups. Basal and peak testosterone levels were significantly higher only in the control pubertal group when compared to the other groups; peak 17-hydroxyprogesterone concentrations were significantly higher in pubertal controls compared with HH and CDP. CONCLUSION(S) Peak LH responses clearly discriminate HH from CDP. Timing for blood sampling should be fixed at 0, 60, 120, 180 minutes after stimulation.