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Biomedical subjects

R Virdis

Publications and source records attributed to R Virdis.

At least 37 records · Page 2Linked to original sources

Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism.

Previous studies have documented the association of insulin resistance and hyperandrogenism in adult women with functional ovarian hyperandrogenism (FOH) or polycystic ovary syndrome (a form of FOH). However, the possible impact of adrenal hyperandrogenism development during childhood in premature pubarche (PP) patients on postpubertal insulin secretion patterns remains unclear. The fasting insulin to glucose ratio, C peptide, early insulin response to glucose (IRG), mean blood glucose, mean serum insulin (MSI), glucose uptake rate in peripheral tissues (M), and insulin sensitivity indexes (SI) in response to a standard oral glucose tolerance test were evaluated in 13 PP girls with FOH (group A; age, 17.2 +/- 0.5 yr), 11 eumenorrheic nonhirsute PP girls (group B; age, 16.6 +/- 0.5 yr), and 21 age-matched controls (group C). Body mass indexes (BMI) were similar in the 3 groups (group A, 23.3 +/- 0.8; group B, 22.5 +/- 0.6; group C, 20.6 +/- 0.5 kg/m2). MSI values were significantly higher in FOH patients than in controls (74.7 +/- 17.6 vs. 45.7 +/- 4.1 mU/L; P < 0.01), but were not different from those in group B (63.3 +/- 11.1 mU/L). Thirty-eight percent of FOH patients (group A) and 27% of non-FOH patients (group B), all of whom had normal BMI, showed MSI levels well above the upper normal limit for controls (> 83.3 mU/L). MSI correlated with the degree of ovarian hyperandrogenism [defined by an abnormal 17-hydroxyprogesterone response to challenge with the GnRH analog leuprolide acetate; group A] and with the free androgen index [testosterone (nanomoles per L)/sex hormone-binding globulin (nanomoles per L) x 100; groups A and B)]. Although IRG, glucose uptake rate in peripheral tissues, mean blood glucose, and SI values were not significantly different in the 3 groups, 3 patients in group A and 1 patient in group B showed decreased insulin sensitivity and/or an enhanced early IRG. Among others, significant correlations between MSI and free androgen index values (r = 0.6; P < 0.002; groups A and B) and between BMI and SI (r = -0.53; P < 0.05; groups A and B) were found. Peak 17-hydroxyprogesterone responses to ACTH at PP diagnosis correlated positively with SI in both groups of patients (r = 0.53; P < 0.007). Hyperinsulinemia is a common feature in adolescent PP patients with FOH and appears to be directly related to the degree of androgen excess. Long term follow-up of PP patients into adulthood is warranted to ascertain whether hyperinsulinemia actually precedes FOH development and whether overt insulin resistance ensues.

Adolescent↗

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.

17-alpha-Hydroxyprogesterone↗

Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test.

The effects of a single injection (500 micrograms sc) of the GnRH agonist leuprolide acetate on gonadotropin secretion and those induced by a GnRH test were analyzed in 32 children (11 males and 21 females) referred for possible pubertal developmental disorders and in 9 prepubertal controls [group C; 4 males and 5 females; chronological age (CA), 7.4 +/- 1.2 yr]. The pituitary-gonadal secretory responses to the GnRH agonist were characterized in all subjects and in a control group in early puberty [10 females (Tanner breast stage II; CA, 11.3 +/- 1.1 yr) and 6 males (Tanner pubertal stage II; CA, 13.5 +/- 0.4 yr); group D]. Twelve girls (CA, 7.1 +/- 0.7 yr) presented with precocious breast development, 11 patients [6 boys (CA, 10.9 +/- 0.4 yr) and 5 girls (CA, 9.3 +/- 0.5 yr)] had advanced puberty and predicted adult heights below -2.0 SD score, and 9 patients [5 boys (CA, 14.6 +/- 0.3 yr) and 4 girls (CA, 14.4 +/- 1.1 yr)] had delayed puberty. Less than 6 months had elapsed since the appearance of pubertal signs in all patients with pubertal development. After a follow-up period of 12.9 +/- 2.0 months, 20 patients showed progression of pubertal signs (group A, progressive puberty), and in 12, puberty regressed or did not progress (group B, nonprogressive puberty). The results of hormonal tests in all patients were analyzed retrospectively according to their clinical outcome. Patients in group A had a mean plasma peak LH response significantly higher after leuprolide acetate stimulation than after GnRH challenge (13.1 +/- 0.2 vs. 7.3 +/- 0.9 IU/L; P < 0.003). Those in groups B and C had similar peak LH responses after both tests (3.3 +/- 0.2 vs. 3.1 +/- 0.4, and 1.5 +/- 0.1 vs. 1.8 +/- 0.4 IU/L, respectively). No differences in basal and poststimulated LH levels were found between boys and girls in the same group. In patients in groups A and D, LH consistently peaked 3 h postleuprolide acetate challenge; in those in groups B and C, the LH peak occurred 3-6 h postinjection. Maximal gonadal responses were elicited 24 h poststimulation. No overlap in poststimulated estradiol or testosterone values occurred between patients in groups A and D and those in groups B and C.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗

[Tables of the arterial hypertension in children in Italy (from 0 to 18 years)].

For the first time in Italy, the results of a multicentre study of the Study Group into Juvenile Hypertension of the Italian Society of Paediatrics in 16.772 subjects from 0 to 18 years, are presented. Percentile charts (tables) of juvenile blood pressure (BP) levels according respectively to age and height of the subjects divided by sex, have been elaborated. Also pressure curves have been calculated and drawn that are based on standard deviations (DS). Normal levels are between + and -2DS. The relationship of BP levels with age permits the comparison with the Task force Tables, whilst the relationship with height permits comparison with the European data.

Adolescent↗

Blood pressure tracking in adolescents with insulin-dependent diabetes mellitus.

Hypertension, one of the most frequent and important complications of insulin-dependent diabetes mellitus (IDDM), usually begins in the second decade of the disease and is rare in childhood. We analysed the blood pressure (BP) levels of 106 patients (48 males, 58 females, aged 2-16 years) in relation to sex and age and we studied the modification of BP with years (tracking). BP levels, registered every three to six months, were compared with the local standard levels for age and expressed as standard deviation scores (SDS) of the means. For each subject a regression line describing the change of the SDS over time was calculated by the method of least squares. The slope of this line is called trend and represents the tendency of BP to increase or decrease with time, i.e. to develop (or not) hypertension. All patients, except one 16 year old girl, had normal BP and no microalbuminuria but ten of them presented with mean levels in the upper quartile and/or a constantly upward BP trend and were considered at risk. After a three year follow-up four of these ten patients became frankly hypertensive with increased microalbuminuria. These results agree with previous findings and with the hypothesis that an increase of intraglomerular and/or systemic BP may precede the appearance of (and even could be responsible for) microalbuminuria. The BP tracking study in IDDM children and adolescents could be useful for an early recognition of patients at risk of developing hypertension and diabetic nephropathy.

Aging↗

Hypertension in children with neurofibromatosis.

Hypertension in neurofibromatosis is mostly a consequence of a stenosis of the renal artery or is due to phaeochromocytoma. Riccardi pointed out primary hypertension in patients with several cervical neurofibromas in the absence of phaeochromocytoma and he noticed that the elevation of BP was often already present in children. Nine (15.8%) of 57 neurofibromatosis patients (age from 1.5 to 23 years) examined, presented BP levels above the 95th percentile on several occasions and three in particular had severe hypertension with compromised target organs. Two of them had a stenosis of the renal artery, in the third an organic origin of hypertension was not demonstrated, but there was an asymptomatic glioma of the hypothalamus. The other six children had a labile or borderline hypertension and two of them had, respectively, a glioma of the thalamus and of the optical chiasm. Elevation of the catecholamine metabolites or other causes of hypertension were not found in any of these patients. These preliminary data show a high incidence of hypertension in neurofibromatosis, primary or due to organic causes and overall they point out a possible correlation between hypertension and cerebral neoplasia.

Adolescent↗

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.

Adolescent↗

Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism.

The postpubertal outcome of a group of girls diagnosed of premature pubarche during childhood was assessed 1) to determine the incidence of functional ovarian hyperandrogenism (FOH) through the ovarian-steroidogenic response to the GnRH agonist leuprolide acetate, 2) to validate leuprolide acetate stimulation in FOH diagnosis, and 3) to ascertain whether FOH-predictive biochemical markers exist at the diagnosis of premature pubarche. Of 35 patients (age, 15.4 +/- 1.5 yr), 16 showed hirsutism, oligomenorrhea, and elevated baseline testosterone and/or androstenedione (delta 4-A) levels. Subcutaneous administration of leuprolide acetate (500 micrograms) produced similar increases in gonadotropin levels in oligomenorrheic patients, regularly menstruating patients (n = 19), and controls (n = 12; age, 15.3 +/- 1.3 yr) when tested at 6 h. Of all of the steroids measured, 17-hydroxyprogesterone (17-OHP) and delta 4-A levels 24 h postleuprolide acetate stimulation were significantly higher in oligomenorrheic patients than in the other two groups (P < 0.0001). No overlapping in 17-OHP responses occurred between oligomenorrheic patients and the other groups. Baseline dehydroepiandrosterone sulfate and delta 4-A levels at the diagnosis of premature pubarche correlated with 17-OHP values postleuprolide acetate challenge (r = 0.47; P < 0.005 and r = 0.67; P < 0.0001, respectively). These results show a distinct leuprolide acetate challenge response in 45% of the postpubertal premature pubarche girls studied, suggestive of an increased incidence of FOH, and support the need for continued routine postmenarcheal evaluation of this group of patients. Responses of 17-OHP to leuprolide acetate challenge facilitate the identification of FOH patients, establish this test as a reliable diagnostic tool in FOH diagnosis, and confirm the ovaries as the source of hyperandrogenemia in most patients with androgen excess. Although increased 17-OHP responses after leuprolide acetate stimulation seem to occur more frequently in girls with elevated dehydroepiandrosterone sulfate and/or delta 4-A levels at the diagnosis of premature pubarche, specific biochemical markers predictive of FOH in this group of patients are still lacking.

Androgens↗

Natural history of premature pubarche: an auxological study.

The natural history of girls with premature pubarche is reported to be normal, but the effects on puberty and on final height are not well documented. We assessed the outcome of a group of girls with premature pubarche from two Latin populations in whom 21-hydroxylase deficiency had been ruled out by an ACTH test. Patients comprised 127 girls (70 Northern-Italian and 57 Northern-Spanish), of whom 69 had entered puberty and 38 had attained adult height. Height, bone age, onset and progression of puberty, height prognosis, adult height, and baseline plasma androgen levels were evaluated. Advanced skeletal maturation and tall stature were constant features during the first years of follow-up and subsequently declined. Puberty began at 9.7 +/- 0.9 yr, and age at menarche (12.0 +/- 1.0 yr) was comparable to maternal and population menarcheal ages. The appearance and chronology of pubertal milestones in both populations were very similar. Adult heights correlated with the height prognosis at diagnosis and at onset of puberty, and were above midparental heights. Premature pubarche produces a transient acceleration in growth and bone maturation with no negative effects on the onset and progression of puberty and final height.

Adolescent↗

Blood pressure tracking in juvenile insulin dependent diabetes mellitus: preliminary data.

One of the most frequent and important complications of IDDM is hypertension. It begins usually in adulthood and is rare in children. In order to study the behaviour and control of BP in IDDM children and adolescents we analyzed the BP levels of 106 patients (48 males, 58 females; age 1.5-16 yrs) in relation to sex, age, duration of the disease, and different parameters of metabolic control; moreover we studied the modifications of BP levels with years (tracking). BP levels, registered every 3-6 mos, were compared to the standard levels for age of the local population (2000 students between 7 and 16 yrs of age) and expressed as standard deviation scores (SDS) of the means. For each subject a line describing the change of the SDS over time was calculated by the method of least squares: the slope of this line is called trend and represents the tendency of the BP to increase or maintain stable or decrease with time, i.e to develop or not hypertension. All patients, except one 16 y. old girl, had normal BP and no microalbuminuria, but 10 of them presented with mean levels in the upper quartile and a constantly upward BP trend. Two of these patients showed after a 2 year follow-up stable hypertension and microalbuminuria. Moreover, an analytical and statistical study pointed out that BP levels of IDDM children seem to be influenced in addition to age, sex, height, weight, ponderal excess, as the general population, by the duration of the disease the insulin dose and some metabolic parameters (HbA1, HbA1c, glycemia, creatininemia).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effectiveness of growth-promoting therapies. Comparison among growth hormone, clonidine, and levodopa.

The ability of growth hormone, clonidine, and levodopa to stimulate growth was compared in short and slowly growing children randomly assigned to different treatment regimens for 6 months. There were 10 children in each group, and 10 additional subjects served as controls. Growth hormone improved mean height velocity, height velocity SD score, and height SD score. The mean height velocity and height velocity SD score were significantly increased by clonidine, while levodopa only enhanced the mean height velocity SD score of the treated children. Moreover, in nine patients (90%) receiving growth hormone, two (20%) receiving clonidine, and one (10%) receiving levodopa, the height velocity was raised by more than 2 cm/y. The increments in height velocity and height SD score were greatest in the growth hormone group. Clonidine induced an increase in height velocity significantly different from that in control children only. In the control group, there was a significant reduction of height SD score with time.

Body Height↗

Adrenal steroid, cortisol, adrenocorticotropin, and beta-endorphin responses to human corticotropin-releasing hormone stimulation test in normal children and children with premature pubarche.

To determine whether CRH affects adrenal androgen, beta-endorphin (B-E), and ACTH secretion in normal children during sexual maturation, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), DHEA sulfate (DS), cortisol, B-E, and ACTH were measured after an iv injection of 1 microgram/kg human CRH. Children with premature pubarche were similarly analyzed to establish whether this condition is accompanied by altered hormonal responses to CRH. CRH produced consistent increases in ACTH, B-EP, and cortisol blood levels, which were comparable at all age intervals in all groups. 17-OHP increased after CRH injection, but its response linearly with age. D4-A levels were not influenced, while DHEA and DS levels were only partially influenced by CRH. The stimulated D4-A to 17-OHP ratio increased with sexual maturation, whereas ratios of cortisol to 17-OHP and D4-A to DHEA remained constant. Children with premature pubarche had hormonal responses similar in magnitude to those of prepubertal children of comparable age. In conclusion, an increase in 17,20-desmolase efficiency occurs with postnatal maturation after CRH challenge. Moreover, CRH does not appear to play an important role in premature pubarche.

17-alpha-Hydroxyprogesterone↗

Final height in a group of untreated children with constitutional growth delay.

We retrospectively evaluated the growth of 41 children with constitutional growth delay followed till adulthood and never treated with growth-promoting therapies. Final height has been correlated with prepubertal height, genetic target and height prediction calculated in both prepuberty and puberty. All patients showed a significant improvement of their height standard deviation score (HSDS) from prepuberty to adulthood, and the great majority of them achieved a final height above the 3rd percentile. Moreover, we found a good correlation between final height and both genetic target and height prediction, even if the latter overestimated final height in 25% of the patients. In conclusion, our data confirm that constitutional growth delay is a normal variant of growth. Therefore, caution should be paid in considering pharmacological treatment of this condition.

Adolescent↗

Prolactin, growth hormone and thyrotropin-thyroid hormone secretion during stress states in man.

Changes in hormone secretion and/or metabolism almost constantly accompany stressful events. The hormonal response to stress is directly related to the intensity of the stimulus, and greatly depends on the individual's perception of potentially stressful situations. Hypoglycaemia, surgery and exercise represent physical, metabolic and psychological stressful events where the activation of the endocrine system plays a great role. These endocrine responses also include the secretion of GH and prolactin, but the response pattern varies with the stimulus. Hypoglycaemia, exercise and surgery are potent stimuli to GH and prolactin release, both in men and women. The available data suggest that prolactin is more responsive than GH to surgical stress, whereas physical exercise and hypoglycaemia preferentially stimulate GH secretion. Prolactin levels during hypoglycaemia rise solely when symptomatic neuroglycopenia is achieved. By contrast, prolactin and GH responses to purely psychological stress are rarely seen, although some forms of reproductive stress may potentiate prolactin release in women. A teleologically satisfactory rationale for the acute GH and prolactin rise in response to these stressful stimuli is not clearly apparent in man. No definite metabolic activity of prolactin on intermediate metabolism has been demonstrated, although prolactin is mildly diabetogenic. The known metabolic actions of GH do not appear to be critical during surgery or acute hypoglycaemia, although GH probably participates in the regulation of metabolic homeostasis during chronic hypoglycaemia and chronic exercise. Changes in secretion and/or metabolism of hypothalamic neurotransmitters can increase the secretion of GH by increasing the secretion of GHRH or by decreasing the secretion of somatostatin. The prolactin rise is brought about by either a decrease in dopamine activity, an increased secretion of a hypothetical PRF, or by both mechanisms. Since multiple neuronal pathways converge on the hypothalamus from many other parts of the brain, the pronounced effects of hypoglycaemia, exercise and surgery on the secretion of GH and prolactin also reflect the action of different and complex neural inputs on the activity of the hypothalamic-pituitary axis. However, the morpho-functional mapping of these excitatory pathways still remains incomplete. TSH secretion is tightly regulated by the negative feed-back mechanism exerted by thyroid hormones. The small changes in TSH level observed during surgery and physical exercise seem to reflect mainly alterations in peripheral T4 metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Growth Hormone↗

Hormones and handedness: left-hand bias in female congenital adrenal hyperplasia patients.

An excess of left-handers among males has been attributed to early androgen exposure. This theory was supported by our observation that girls with congenital adrenal hyperplasia (CAH) are more left-biased than their normal sisters. Male CAH patients, with prenatal androgen exposure similar to that of unaffected brothers, had typical male-handedness patterns.

Adolescent↗