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Biomedical subjects

E Cacciari

Publications and source records attributed to E Cacciari.

At least 19 recordsLinked to original sources

Magnetic resonance imaging of the pituitary area in children treated for acute lymphoblastic leukemia with low-dose (18-Gy) cranial irradiation. Relationships to growth and growth hormone secretion.

OBJECTIVE: To determine the effects of 18-Gy cranial irradiation on growth, growth hormone (GH) secretion, and pituitary magnetic resonance imaging in children who underwent previous irradiation for treatment of acute lymphoblastic leukemia. DESIGN: Clinical survey. SETTING: Department of Pediatrics of the University of Bologna (Italy). PATIENTS: Ten boys and 18 girls who were treated for acute lymphoblastic leukemia; median age at diagnosis was 3.1 years and at the end of follow-up was 11.5 years. MEASUREMENTS AND RESULTS: Height was periodically measured from diagnosis until the end of follow-up, when GH secretion study and magnetic resonance imaging were performed. The mean height SD score was significantly lower than at diagnosis only at the end of treatment. Nocturnal mean GH concentration and GH response to pharmacological tests (arginine and levodopa [L-dopa]) were pathological in 22 cases (81.5%) and 18 cases (64.3%), respectively. Sixteen cases (59.2%) had a blunted GH release to the three tests. Mean pituitary anterior lobe height was reduced and seven subjects (25%) showed an empty sella. CONCLUSIONS: Cranial irradiation with 18 Gy does not seem to influence the growth pattern of most children who are treated for acute lymphoblastic leukemia, despite severe impairment of GH secretion and morphological abnormalities of the sellar area. However, a follow-up until final height is necessary.

Adolescent

Growth and thyroid function in children treated with growth hormone.

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.

Child

Growth response to recombinant human growth hormone of mammalian cell origin in prepubertal growth hormone-deficient children during the first two years of treatment.

In five clinical studies performed in Austria, France, the FRG, Italy, Switzerland, the UK and the USA, 304 growth hormone (GH)-deficient children were treated with recombinant human GH (rhGH) of mammalian cell origin. Two hundred and twenty-five patients were previously untreated (naive patients), and 79 were transferred from pituitary hGH after interruption of therapy for at least 6 months (transfer patients). Two treatment protocols, differing in both dose and frequency of injections, were used: (1) a dose of 0.6 IU/kg body weight per week was administered in 3 s.c. injections to 203 patients (178 naive, 25 transfer; group 1); and (2) a dose of 0.45 IU/kg body weight per week was administered in 7 s.c. injections to 101 patients (47 naive, 54 transfer; group 2). After 1 and 2 years of treatment, 143 and 109 naive, and 51 and 46 transfer patients, respectively, were still prepubertal, and their data were analyzed for efficacy. During the 1st year of treatment, both naive and transfer patients on daily injections (group 2) demonstrated better growth than those on 3 injections per week (group 1), with height velocities (HVs) of 10.6 +/- 2.7 cm/year (group 2) versus 8.6 +/- 2.0 cm/year (group 1) for naive patients (p < 0.001), and 9.9 +/- 1.9 cm/year (group 2) versus 7.2 +/- 2.7 cm/year (group 1) for transfer patients (p < 0.001). The corresponding changes in height standard deviation score (delta H SDS) for chronological age (CA) were +1.3 +/- 0.6 (group 2) versus +0.8 +/- 0.5 (group 1) for naive patients (p < 0.01), and +1.1 +/- 0.3 (group 2) versus +0.6 +/- 0.4 (group 1) for transfer patients (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pitfalls in diagnosing impaired growth hormone (GH) secretion: retesting after replacement therapy of 63 patients defined as GH deficient.

Possible causes of error in the diagnosis of isolated GH deficiency are the variability of GH response to repeated tests, the existence of transient GH deficiencies, and the low GH levels found in short statured children with delayed puberty. Sixty-three patients with variously expressed GH deficiency were retested (1 sleep test and 2 pharmacological tests) after 1-3.9 yr of GH therapy (dose, 15 U/m2.week). Forty-eight subjects had arginine, L-dopa, and sleep tests (mean serum GH concentration) twice, while 15 had only arginine and L-dopa tests. All patients were retested 1 month after withdrawal from therapy. The criteria used to subdivide the patients were pubertal development and response to pharmacological and sleep tests at first diagnosis and on retesting. The initial diagnosis in 33 subjects (52.4%) was not confirmed, and 13 (20.6%) were no longer deficient on retesting. The percentage of normalization was high for the sleep test (43.9%), lower for the pharmacological test (24.5%), and lower still (12.9%) for pharmacological and sleep tests considered together. While none of the 28 subjects who remained prepubertal at retesting normalized in any of the tests, 13 of the 35 subjects retested during puberty did. When normalization was observed in pubertal subjects, it occurred predominantly in the sleep test. Growth velocity and height age/bone age increment ratio after the first year of therapy were no different for the groups of subjects classified according to GH secretion on retesting. Our study demonstrates that a number of children diagnosed as GH deficient do not have a true deficiency. However, such a diagnostic error seems to have little effect, at least in the first year of therapy, on the effectiveness of GH treatment.

Adolescent

What will be the adult height of coeliac patients?

We studied three groups of patients with coeliac disease: group 1 = 95 adult patients with gastro-intestinal symptoms diagnosed after reaching adult height, 41 of whom had had symptoms during childhood; group 2 = 23 adult patients with classic coeliac disease treated before or during puberty; group 3 = 11 coeliac children with short stature and no gastro-intestinal symptoms diagnosed and treated before or during puberty. We evaluated the adult height in groups 1 and 2 and the growth during the first years of diet in group 3. Our study leads us to the following conclusions. Dieting leads to a modest increase (on average not more than 3 cm) of the final height of coeliac patients. Subjects with gastro-intestinal symptoms who have been treated before adulthood reach a mean height similar to the normal population and have a slightly better adult height than non-treated subjects. This difference seems to exist only in men and this might be related to puberty evolving more rapidly in women receiving treatment. Subjects without symptoms during childhood reach a normal final height even without treatment. In our patients, early treatment seemed to have no great effect on adult height.

Adolescent

Growth hormone, insulin-like growth factor I, insulin and C-peptide during human fetal life: in-utero study.

Serum growth hormone (GH), insulin-like growth factor (IGF-I), insulin and C-peptide were measured by RIA in fetal blood collected in utero by umbilical cord puncture performed for a variety of indications. Eighty-four fetuses were aged 19-25 weeks and 14 were 26-37 weeks. IGF-I values were lower than the sensitivity of the method. The range for GH was 3-197 micrograms/l (GH-micrograms/l x 2 = mU/l), for insulin 14.3-117 pmol/l, for C-peptide 66.2-827.5 pmol/l. GH significantly increased from week 19 to 25; insulin and C-peptide levels increased from week 19 to 37. GH levels at 19-25 weeks were significantly higher in fetuses with femoral length less than the 5th compared with those with femoral length greater than the 95th centile for that age. GH and insulin levels did not correlate with weight at birth or with maternal hormone levels. These data provide evidence for a presence in living fetuses, from the 19th week, of high levels of GH and of insulin levels not very different from those in adults but these hormones do not seem to be directly responsible for fetal growth.

Birth Weight

[Diet-induced changes as risk factors in obese children: arterial pressure, glycoregulation and lipid profile].

In 52 both sex obese children (mean age was 9.7 +/- 2.5), blood pressure and biochemistry parameters in blood were studied after controlled hypocaloric diet. The data, collected in two out patient visits in intervals of one year and half and four years, were: blood pressure; total, HDL and LDL cholesterol; apoproteins A1 and B; NEFA; triglycerides; phospholipids; haematocrit; haemoglobin; glycosylated haemoglobins A1 and A1C; glucose; insulin; seric proteins: fibrinogen; platelets; Quick time and activated partial thromboplastin time. The group of obese children with a successful response to the hypocaloric diet treatment (significant loss of weight) showed a decrease in the plasmatic levels of Apoproteins A1 and B, triglycerides, NEFA and insulin together with an increase in the level of HDL cholesterol. These changes weren't so significant in the group of obese children who didn't lose weight. When we took into account plasmatic cholesterol, the obese patients with normal plasmatic level of cholesterol showed a significant descend in the risk factors. However, in the obese children with high cholesterol despite the dietetic treatment, the pathologic plasmatic profile didn't show any change. Finally, while the group with maintained high level of insulin showed a significant increase of apoproteins A1 and B, and total and HDL cholesterol, the group where the insulin levels became normal after treatment showed a good development of the biochemistry parameters studied. The fibrinogen level and blood precision which remained high in both visits were studied taking into account age and growth pattern.

Adolescent

Bronchial reactivity and sex hormone: study in a Turner's population.

Respiratory function and bronchial reactivity was studied by carbachol challenge in 41 patients with Turner's syndrome and in 46 controls. In patients and controls the personal and family history of atopic illnesses was evaluated; reactivity to skin allergen tests was studied in patients only. Patients with Turner's syndrome had less allergy skin test reactivity; no difference was found in allergic symptoms between patients and controls despite the patients having a more positive family history of atopy (P less than 0.05). Respiratory function variables were higher in patients than in controls, and bronchial reactivity as expressed by the results of carbachol testing was higher in Turner's patients than in controls (P less than 0.01). Bronchial reactivity was significantly reduced after 6 months of estrogenic therapy (P less than 0.05) in subjects with Turner's syndrome, while the same did not occur in patients who did not receive estrogen treatment. This study of pulmonary function and bronchial reactivity in Turner's patients may help understand the effects of sex hormones in the regulation of bronchial tone and of bronchial response to constrictive agents.

Adolescent

Effects of sport (football) on growth: auxological, anthropometric and hormonal aspects.

There are very few data available on the relationship between sporting activities, endocrine levels and changes in anthropometric measurements during growth. In order to study these relationships, we have made measurements of growth, changes in physical conformation and the plasma levels of several hormones [cortisol, dehydroepiandrosterone sulphate (DHEA-S), testosterone, growth hormone, somatomedin C, insulin, glycaemia and haemoglobin A1C] in 175 boys, aged 10-16 years, who have played football at a competitive level and in 224 boys, severing as controls, who have never performed sporting activities regularly. The football players were divided into prepubertal and pubertal subjects (10-11.99 years, 12-13.99 years and 14-16 years, chronological and bone age groups). Our results showed no significant differences in the growth indices between prepubertal athletes and controls, but the plasma level of DHEA-S was significantly higher (P less than 0.05) in the athletes. Pubertal football players, however, were significantly taller than the control subjects, particularly at 14-16 years chronological age. There were no such significant differences when bone age was considered. The pubertal football players were also more advanced in all biological indices of maturity, i.e. pubic hair, testicular volume and bone age. The increase in DHEA-S in pubertal football players, already seen in prepubertals, was also combined with a significant increase in testosterone, growth hormone and cortisol levels. Thus, in football players the DHEA-S level is already higher during prepuberty. This increase thus precedes all other indices of growth and maturation associated with puberty. We hypothesize that, while not excluding the possible influence of selection, as ours is a cross-sectional study, adrenal hyperactivity may be mainly responsible for the earlier onset of pubertal growth and maturity in exercising males.

Adolescent

Isolated dehydroepiandrosterone sulphate hypersecretion: a case report.

The case of a 17-year-old male with isolated hypersecretion of dehydroepiandrosterone sulphate (DHEAS) is described. Cushing syndrome, congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency, an androgen producing adrenal tumour, and elevated plasma DHEAS due to an increased renal threshold were excluded. Selective renal vein catheterization confirmed bilateral, isolated adrenal DHEAS hypersecretion. The dexamethasone suppression suggests a functional nature of this alteration. This condition has to be considered in the differential diagnosis of excessive adrenal androgen production in males, or of hirsutism in females.

Adolescent

Long term growth hormone (GH)-releasing hormone and biosynthetic GH therapy in GH-deficient children: comparison of therapeutic effectiveness.

Twenty-five GH-deficient children were treated with GHRH (1-44), once daily sc for 6-24 months. At the 6th month of therapy, 40% of our patients showed a catch-up growth (responders), while the remaining 60% did not (nonresponders). No differences in auxological and biological variables at inclusion were found between the two groups. However, integrated GH secretion elicited by iv GHRH at inclusion was significantly (p less than 0.025) higher in responders than in non responders. During GHRH therapy, no significant increase in IGF 1/SmC was found in both groups. In all patients treatment was discontinued after 6-24 months, when its effect on growth rate failed. After a wash-out period of at least 6 months, patients were submitted to biosynthetic GH therapy. After 6 months of GH treatment a significant catch-up growth was found in both responder and non-responder children. Although the majority of GH-deficient children have hypothalamic rather than pituitary dysfunction, GHRH therapy is found to be less effective than GH treatment. Other methods of GHRH administration are worth investigating.

Adolescent

Microalbuminuria in diabetic children and adolescents. Relationship with puberty and growth hormone.

Urinary albumin excretion (UAE) was determined by radioimmunoassay in two 24 h urine collections from 125 diabetic children and adolescents and from 71 normal children matched for age and sex. Thirteen patients (10.4%) aged greater than 12 years had microalbuminuria, i.e. log transformed UAE levels above the upper normal range (24.5 mg/24 h). UAE values were positively correlated with age, GH secretion, but not with duration of disease, glycosylated hemoglobin, renal size or N-acetyl-beta-glucosaminidase excretion. Diabetic normoalbuminuric children aged 10 years and older had significantly higher UAE than controls and than younger diabetic patients matched for duration of disease. HLA DR3/DR4 heterozygosity frequency was significantly higher (p less than 0.01) in the microalbuminuric group than in the normoalbuminuric. All microalbuminuric subjects (n = 8) with short duration of disease (3.92 +/- 3.43 yr) developed diabetes at puberty. In conclusion, our cross-sectional study suggests: if a number of factors are combined, i.e. HLA DR3/DR4 heterozygosity, onset of disease at puberty and higher GH values, the probability of developing abnormal levels of UAE will increase.

Adolescent

Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance.

Evaluation of the sellar area was performed with magnetic resonance imaging in 101 patients (age range 0.8-27 years) with hypopituitarism, isolated diabetes insipidus, hypogonadotrophic hypogonadism, and central precocious puberty. The hypopituitary patients (n = 70) included multiple pituitary deficiency (n = 23), pituitary deficiency with diabetes insipidus (n = 5), and isolated growth hormone deficiency (n = 42). The patients with multiple pituitary deficiency showed pathological morphological findings in all cases, with stalk and posterior lobe always involved. The group with associated diabetes insipidus had abnormal stalk in four of five cases and posterior lobe not visible in all cases. Only five of 42 (12%) patients with isolated growth hormone deficiency had abnormalities of the sellar area. In two out of four patients with isolated diabetes insipidus posterior lobe was not seen. All patients with hypogonadotrophic hypogonadism (three with Kallmann's syndrome, one Prader-Willi syndrome, and two idiopathic hypogonadism) appeared normal. In precocious puberty (n = 21) the three patients with onset of symptoms before age 2 years exhibited a hypothalamic hamartoma, whereas in the others with onset of puberty between age 2 and 7 the magnetic resonance image was normal in 17 of 18 patients. The probability of finding a pathological magnetic resonance image was considerably high in our patients with multiple pituitary deficiency, isolated diabetes insipidus, and precocious puberty with very early onset of symptoms. On the contrary, purely functional abnormality is suggested in most patients with isolated growth hormone deficiency, hypogonadotrophic hypogonadism, and precocious puberty with later onset of symptoms.

Adolescent

Influence of growth hormone on thymic endocrine activity in humans.

The thymus produces humoral factors that induce the proliferation and differentiation of T cells which are responsible for cell-mediated immunity. Experimental data have suggested that this thymic hormone production is modulated by the neuroendocrine network and, in particular, by growth hormone (GH) and thyroid hormones. To study the role played by GH in thymic endocrine activity in humans, the circulating level of one of the best known thymic peptides, i.e. thymulin (Zn-FTS), has been determined, after a washout period of 2 weeks without GH treatment, in GH-deficient children before and after a single injection of GH. The basal thymulin level is consistently lower in GH-deficient children than in healthy age-matched controls. A single injection of GH induces a significant increment of the thymulin level for at least 48 h. Since thymulin activity may also depend on zinc bioavailability, on thyroid hormone turnover and on the eventual presence of thymulin-inhibitory substances, all these aspects have been checked. No supporting evidence regarding the existence of these kinds of interferences in GH-deficient children has been substantiated. A positive correlation has been found between the serum level of insulin-like growth factor I, but not of GH, and thymulin activity. These data suggest that GH may directly or indirectly modulate the thymic endocrine function in humans. Whether and to what extent such a modulation is relevant to the functioning of the immune system remains to be ascertained.

Adolescent

Variability of growth hormone response to pharmacological and sleep tests performed twice in short children.

Forty-nine children with short stature (age range, 4.1-15.9 yr) were examined. Twenty-four (group 1) were submitted twice to an arginine and a sleep test (12-h overnight GH profile). Twenty-five patients (group 2) were submitted twice to an arginine and L-dopa test. Coefficients of variation were calculated between both the results of pharmacological (peak and area under the curve) and sleep tests [mean GH concentration (MGHC), peak, area under the curve, number of peaks above 5 micrograms/L, and peak area]. In group 1 the coefficient of variation of sleep test parameters was significantly lower than that of pharmacological tests (P less than 0.01 to less than 0.001). In the sleep test the area under the curve and MGHC were the most constant parameters. Group 2 showed no difference between the coefficients of variation of the two pharmacological tests. Considering groups 1 and 2 together, the coefficients of variation of the sleep test, in particular the MGHC and area under the curve, were lower than those of the two pharmacological tests. Eight of 24 subjects in group 1 showed a low GH level in 1 series of tests, and a normal level in the other series. Five of 18 subjects in group 2 showed an abnormally low GH response to the arginine and L-dopa tests and a normal response to the 2 repeated tests. Therefore, to prevent an erroneous interpretation of the GH test results, it is very important to perform a sleep test and repeat it whenever GH secretion seems to be deficient or at the lower limits of normalcy.

Adolescent

Incidence of intratubular germ cell neoplasia in androgen insensitivity syndrome.

Gonadal histology was investigated by means of conventional microscopy in 6 patients with complete androgen insensitivity syndrome, in 11 with incomplete androgen insensitivity syndrome, and in 3 with 5 alpha-reductase syndrome. Twelve subjects were prepubertal and 8 pubertal. In all patients gonadal tissue was removed as a prophylactic measure and no patients gave rise to any clinical suspicion of a tumour. Eight patients with incomplete androgen insensitivity syndrome, 5 of whom (62.5%) were prepubertal, showed intratubular germ cell neoplasia and in 6 of them it was bilateral. Histochemical and immunohistochemical analysis showed considerable agreement between atypical morphological aspects and positive response to Schiff's periodic acid and to staining with the anti-placenta alkaline phosphatase antibody. Our patients were characterized by one of the highest reported incidences of intratubular germ cell neoplasia, particularly at prepubertal age. These findings would seem to indicate that a rethink is needed concerning the general opinion that patients with androgen intensivity syndrome have practically no risk of developing malignancy, and that orchidectomy is not advisable before puberty is completed.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase