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Biomedical subjects

G Mazzardo

Publications and source records attributed to G Mazzardo.

5 recordsLinked to original sources

Leptin, cortisol, and GH secretion interactions in short normal prepubertal children.

The hormonal regulation of the ob gene and leptin secretion in humans is still unclear. To investigate the interactions among leptin, cortisol, and GH, we analyzed and time-cross-correlated their spontaneous 24-h secretion in 12 short normal prepubertal children of both sexes (6 females and 6 males). Time-cross-correlation analyses demonstrated that leptin and cortisol were correlated in both a negative and positive fashion. The negative correlation, with cortisol leading leptin by 4 and 3 h for boys and girls, respectively, might reflect the stimulatory effect of CRH on the sympathetic system, which inhibits leptin secretion; the positive correlation, with leptin leading cortisol by 6 and 5 h for boys and girls, respectively, might reflect a direct effect of leptin on CRH secretion in the hypophyseal portal system. Time-cross-correlation analyses also showed a strong positive correlation between GH and leptin concentrations, with GH leading leptin by 5 and 2 h for boys and girls, respectively, suggesting a possible direct leptin-releasing effect of GH on adipocytes. We conclude that cross-correlation analyses of 24-h hormone secretions under baseline physiological conditions suggest that the hypothalamic-pituitary-adrenal axis might have a prevailing inhibitory effect on leptin secretion, whereas leptin might exert a positive effect on the hypothalamic-pituitary-adrenal axis. The relation between GH and leptin could be a direct one and characterized prevalently by a positive effect of GH on leptin secretion. Further investigations using different experimental systems are needed to ascertain the validity of these mathematically educed conclusions.

Body Height↗

[Treatment of thyroid dysfunction].

The treatment of hypothyroidism and hyperthyroidism is briefly reviewed. L-T4, which is the treatment of choice of hypothyroidism, should be administered once daily after an overnight fast at the dosage of 10-12 mg/kg/day in newborns and of 100 mg/m2 in older children. FT4 and TSH serum levels will normalize within few weeks from the beginning of treatment and should be maintained in the normal range thereafter by appropriate increases of the dosage during growth. The first choice treatment in children with hyperthyroidism due to Basedow disease is the administration of antithyroid drugs, i.e. methimazole at the initial dosage of 0.4-0.6 mg/kg/day b.i.d. or t.i.d.; after remission, the dosage of this drug can either be reduced or L-T4 added in order to avoid hypothyroidism. Treatment should be continued for at least 24 months and the patient followed thereafter to detect possible relapses. Side effects are rare, the most frequent are skin rashes and the most severe is agranulocytosis, so complete blood count should be evaluated frequently especially in the first months of treatment. Surgery (total or near-total thyroidectomy) should be considered in case of failure of medical therapy, even if radioiodine administration, used until now mainly in adults, is gaining favour also for children especially in the United States.

Humans↗

Final height in non-growth hormone deficient children treated with growth hormone. The Italian Multicentre Study Group.

OBJECTIVE: To evaluate the final height of nongrowth hormone deficient (N-GHD) children treated with growth hormone (GH). DESIGN: Multicentre retrospective study. PATIENTS: 71 (54M/17F) N-GHD children (peak GH after pharmacological stimulation > 14-24 mU/l) who had been treated for 4.19 +/- 0.14 years with GH (0.69 +/- 0.02 IU/kg/week). MEASUREMENTS: Height (H) and height velocity (HV) expressed as standard deviation score (SDS) for chronological age (CA) and bone age (BA), BA/CA ratio, and predicted adult height (PAHSDS) were evaluated before and during treatment, and at each pubertal stage. Target height (TH), and final height (FH) were also calculated, and expressed as SDS. RESULTS: In the whole group, HSDS for CA increased significantly after the first year on GH, and remained significantly increased for 4 years. This did not occur to HSDS for BA, owing to a significant increase in BA/CA after the first year of therapy. In addition, this increase coincided with stages 4 and 5 of puberty. HVSDS for CA and BA also increased significantly after the first year of treatment, and remained significantly elevated for 4 years. PAHSDS did not change significantly during treatment. FHSDS (-1.69 +/- 0.07) was similar to PAHSDS (-1.6 +/- 0.12) and target height (THSDS) (-1.46 +/- 0.08). FHSDS was > or = THSDS in 36.6% of the patients, and > or = initial PAHSDS in 34.5%. Male patients were subdivided into 2 groups (A and B). Patients in Group A (n = 26) started treatment at puberty, while group B (n = 28) consisted of subjects who started therapy during prepubertal years. Height, height velocity and predicted adult height showed the same pattern as in the whole group, in each subgroup. BA/CA advanced significantly in group A after the second year on GH and in group B, after at least 3 years of therapy. FHSDS, THSDS, and PAHSDS were similar in both groups (-1. 7 +/- 0.13, -1.29 +/- 0.2 and -1.39 +/- 0.15 in group A and -1.48 +/- 0.11, -1.85 +/- 0.15 and -1.36 +/- 0.12 in group B, respectively). However, in group B (prepubertal), FHSDS was > or = initial PAHSDS in 60% of the patients and > or = THSDS in 40.7%, while in group A (pubertal), FHSDS was > or = initial PAHSDS only in 22.7% of the patients and > or = THSDS in 34.6%. FHSDS was found to be correlated with THSDS, PAHSDS at the onset of treatment, and after 1 year of treatment. The age at the beginning of puberty, and the duration of puberty were appropriate in all groups. CONCLUSIONS: GH treatment was effective in increasing height velocity of short non-GH-deficient children, but final height was not definitely improved with respect to initial predicted adult height.

Adolescent↗

Spontaneous thyrotropin and cortisol secretion interactions in patients with nonclassical 21-hydroxylase deficiency and control children.

Both exogenous and endogenous hypercortisolism result in reduced TSH secretion and mild hypothyroidism. However, little is known about the relation between endogenous TSH and cortisol secretion under physiological or slightly disturbed conditions. To examine this, we evaluated the pulsatility and circadian rhythmicity and time-cross-correlated the 24-h secretory patterns of cortisol and TSH in eight prepubertal children with nonclassical congenital adrenal hyperplasia (NCCAH) and eight age-matched short normal children. In both groups, TSH and cortisol were secreted in a pulsatile and circadian fashion, with a clear nocturnal TSH surge. Although no difference in mean 24-h TSH levels was observed between the two groups, daytime TSH levels were lower in the NCCAH group than in control children (P < 0.05). The cross-correlation analysis of the 24-h raw data showed that TSH and cortisol were negatively correlated, with a 2.5-h lag time for both groups, with cortisol leading TSH. This correlation might reflect a negative glucocorticoid effect exerted on the hypothalamic-pituitary-thyroid axis under physiological conditions. A significant positive correlation with TSH leading cortisol was observed at 8.5 and 5.5 h lag times for the control and NCCAH groups, respectively. The substantially shorter lag time of this positive correlation in NCCAH children than in controls suggests that in the latter, the nocturnal TSH peak occurs temporally closer to their compromised morning cortisol peak. These data indicate that the hypothalamic-pituitary-adrenal axis has a primarily negative influence on endogenous TSH secretion and that even mild disturbances in cortisol biosynthesis are associated with slight alterations in TSH secretion.

Adrenal Hyperplasia, Congenital↗

Growth hormone treatment in short normal children.

The efficacy of growth hormone (GH) therapy in short normal children (i.e. children without classical growth hormone deficiency [GHD]) is still under debate. This paper presents the preliminary data of a retrospective Italian multicenter study on children treated with GH until adult height was reached. Final adult height (FAH), however, is not significantly different from the predicted adult height (PAH) calculated at the beginning of treatment. This result is in agreement with those reported in the majority of other similar international surveys. In conclusion, GH should be administered to short normal children only within the framework of well designed prospective experimental studies, which should consider several auxological, clinical and biochemical parameters capable of influencing the therapeutic results.

Adolescent↗