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  • Author: Domenico Valle x
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Stefania Bonadonna, Anna Burattin, Monica Nuzzo, Giovanna Bugari, Enrico Agabiti Rosei, Domenico Valle, Nicoletta Iori, John P Bilezikian, Johannes D Veldhuis and Andrea Giustina

Objective: Spontaneous parathyroid hormone (PTH) secretory dynamics include tonic and pulsatile components. It is not known how glucocorticoids might alter these secretory dynamics.

Design: The aim of our study was to evaluate spontaneous fluctuations in serum PTH levels in six adult male patients (aged 31–64 years) receiving chronic (>6 months) therapy with glucocorticoids (daily dosage >7.5 mg of prednisone or dose equivalent of other corticosteroid) as compared with a control group of 10 age- and sex-matched normal subjects.

Methods: Peripheral venous blood sampling was performed every 3 min for 6 h from 0900 to 1500 h. Plasma PTH release profiles were subjected to deconvolution analysis, a method that resolves measured hormone concentrations into secretion and clearance components, and to an approximate entropy (ApEn) estimate, that in turn provides an integrated measure of the serial regularity or orderliness of the release process.

Results: In the glucocorticoid-treated group, the PTH tonic secretory rate was reduced (4.3±0.74 vs 8.8±1.4 pg/ml per min in controls, P = 0.017). There was, however, an increase in the fractional pulsatile PTH secretion (42±8.2 vs 18.3±3.9 pg/ml per min, P = 0.006) in glucocorticoid-treated vs normal subjects. Mean overall PTH concentration, as well as mean integrated area, was similar among normal and glucocorticoid-treated subjects.

Conclusions: These results demonstrate, for the first time, that chronic glucocorticoid treatment induces a redistribution of spontaneous PTH secretory dynamics by reducing the amount released in tonic fashion and increasing the amount released as pulses.

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Ginevra Corneli, Carolina Di Somma, Flavia Prodam, Jaele Bellone, Simonetta Bellone, Valentina Gasco, Roberto Baldelli, Silvia Rovere, Harald Jörn Schneider, Luigi Gargantini, Roberto Gastaldi, Lucia Ghizzoni, Domenico Valle, Mariacarolina Salerno, Annamaria Colao, Gianni Bona, Ezio Ghigo, Mohamad Maghnie and Gianluca Aimaretti

Objective

To define the appropriate diagnostic cut-off limits for the GH response to GHRH+arginine (ARG) test and IGF-I levels, using receiver operating characteristics (ROC) curve analysis, in late adolescents and young adults.

Design and methods

We studied 152 patients with childhood-onset organic hypothalamic–pituitary disease (85 males, age (mean±s.e.m.): 19.2±0.2 years) and 201 normal adolescents as controls (96 males, age: 20.7±0.2 years). Patients were divided into three subgroups on the basis of the number of the other pituitary hormone deficits, excluding GH deficiency (GHD): subgroup A consisted of 35 panhypopituitary patients (17 males, age: 21.2±0.4 years), subgroup B consisted of 18 patients with only one or with no more than two pituitary hormone deficits (7 males, age: 20.2±0.9 years); and subgroup C consisted of 99 patients without any known hormonal pituitary deficits (60 males, age: 18.2±0.2 years). Both patients and controls were lean (body mass index, BMI<25 kg/m2). Patients in subgroup A were assumed to be GHD, whereas in patients belonging to subgroups B and C the presence of GHD had to be verified.

Results

For the GHRH+ARG test, the best pair of highest sensitivity (Se; 100%) and specificity (Sp; 97%) was found choosing a peak GH of 19.0 μg/l. For IGF-I levels, the best pair of highest Se (96.6%) and Sp (74.6%) was found using a cut-off point of 160 μg/l (SDS: −1.3). Assuming 19.0 μg/l to be the cut-off point established for GHRH+ARG test, 72.2% of patients in subgroup B and 39.4% in subgroup C were defined as GHD. In patients belonging to group B and C and with a peak GH response <19 μg/l to the test, IGF-I levels were lower than 160 μg/l (or less than 1.3 SDS) in 68.7 and 41.6% of patients respectively predicting severe GHD in 85.7% of panhypopituitary patients (subgroup A).

Conclusions

In late adolescent and early adulthood patients, a GH cut-off limit using the GHRH+ARG test lower than 19.0 μg/l is able to discriminate patients with a suspicion of GHD and does not vary from infancy to early adulthood.